EA042016B1 - SYSTEMS AND METHODS FOR PROCESSING BIOLOGICAL FLUIDS - Google Patents

Description

Cross-reference to related applications

This application claims priority to US Provisional Application No. 62/612,314, filed December 29, 2017, the contents of which are incorporated herein by reference in their entirety.

Prerequisites for the creation of the invention

The present invention generally relates to systems and methods for treating biological fluids, including mixtures of biological fluids and photochemical reagents, with light.

Systems and methods for treating biological fluids with light are well known. For example, US Pat. Nos. 7,459,695, 6,986,867, and 5,593,823 describe a system for treating a biological fluid with light to inactivate pathogens in the biological fluid. Specifically, the system includes a treatment chamber with a slide-out panel for introducing a biological fluid into the treatment chamber and light sources in the treatment chamber for illuminating the biological fluid. The light sources emit light in a selected range of wavelengths that are effective in inactivating pathogens in a biological fluid, in particular by photochemically inactivating pathogens. Other systems and methods for treating body fluids with light may include, for example, the systems and methods described in US Pat. Med. Hemother. 41:309-325.

In the case of systems and methods for treating biological fluids, such as blood products, including, for example, platelets and plasma, it is important to ensure that the blood products are free of pathogens to minimize the risk of infection to the individual receiving the blood product. Testing for the presence of pathogens in the blood is limited by the pathogens being tested for and the sensitivity of the assay. As an alternative or addition to testing for pathogens, methods of inactivating pathogens using various compounds are known in the art, for example, methods based on chemical, photochemical inactivation (for example, those described in Schlenke et al., Transfus Med Hemother, 2014, 41, 309 -325 and Prowse, Vox Sanguinis, 2013, 104, 183-199). Photochemical pathogen inactivation systems using psoralens and ultraviolet light for processing blood products include the commercially available INTERCEPT® blood product processing system (Cerus Corporation), which uses amotosalen and ultraviolet A light, followed by treatment with a compound adsorption device (CAD) in order to remove residual amotosalen and its photoproducts.

While previous systems and methods for the treatment of biological fluids have generally produced satisfactory results, it is desirable to develop improved systems and methods for the treatment of biological fluids in order to more efficiently treat biological fluids, for example, to reduce levels (for example, in photoconversion) a pathogen-inactivating compound after photochemical treatment, while maintaining or improving the degree of pathogen inactivation, and/or to provide improved characteristics (e.g., quality) of the treated biological fluids, for example, by minimizing the deterioration of biological fluids that can be caused by various parameters of the processing process. In addition, improved monitoring and greater control of various processing parameters may be desirable.

The essence of the invention

Systems and methods are proposed for processing biological fluids with light. In one exemplary embodiment, the processing system may include a processing chamber for receiving a biological fluid and one or more light sensors designed to detect light in the processing chamber. The first array of light sources may be positioned to illuminate the biological fluid in the treatment chamber. The first light source array may include one or more light source channels that illuminate the biological fluid with light at specific peak wavelengths. For example, the first light source channel may emit light at a first peak wavelength, and the second light source channel may emit light at a second peak wavelength that differs from the first peak wavelength by at least 5 nm. In other examples, one or more light source channels may emit light at a first peak wavelength with a full width at half maximum (FWHM) of the emission bandwidth of less than 20 nm.

The present invention relates to systems for treating a biological fluid, including: a treatment chamber for receiving a biological fluid (eg, a biological fluid in a container); one or more sensors designed to detect (eg, measure) light (eg, light intensity) in the processing chamber; and a first light source array designed to illuminate the biological fluid in the treatment chamber (e.g., directed at the biological fluid), wherein the first light source array includes a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source channel light designed to emit light at a second peak wavelength, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

In some embodiments, the first matrix of light sources includes a plurality of classes

- 1 042016 light source masters, each light source cluster of the first light source matrix includes a first light source channel designed to emit ultraviolet light with a first peak wavelength and a second light source channel designed to emit light with a second peak wavelength. In some embodiments, the first light source channel and/or the second light source channel is designed to emit ultraviolet light. In some embodiments, the first peak wavelength is in the ultraviolet A region (eg, 315-400 nm). In some embodiments, the implementation of the first channel of light sources is designed to emit ultraviolet light with a first peak wavelength from about 315 nm to about 350 nm. In some embodiments, the implementation of the first peak wavelength is from about 315 nm to about 335 nm. In some embodiments, the first peak wavelength is from about 330 nm to about 350 nm. In some embodiments, the first peak wavelength is in the ultraviolet A region (e.g., 315-400 nm) and the second peak wavelength is in the ultraviolet C region (e.g., 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the first peak wavelength is in the ultraviolet A region (eg, 315-400 nm) and the second peak wavelength is in the ultraviolet B region (eg, 280-315 nm). In some embodiments, the first peak wavelength is in the ultraviolet A region (e.g., 315-400 nm) and the second peak wavelength is in the ultraviolet A region. In some embodiments, the first peak wavelength is in the ultraviolet A region, and the second peak wavelength is in the visible region of the spectrum (eg, 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet B region and the second peak wavelength is in the ultraviolet C region. In some embodiments, the first peak wavelength is in the ultraviolet B region and the second peak wavelength is in the visible region of the spectrum. In some embodiments, the first peak wavelength is in the ultraviolet C region and the second peak wavelength is in the visible region of the spectrum. In some embodiments, the first light source channel and the second light source channel include one or more (eg, a plurality) of light emitting diodes (LEDs). In some embodiments, the light intensity at 50% of the maximum peak light intensity emitted by the first channel of light sources is within a spectral width of less than 20 nm from the first peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the spectral width (e.g., emission bandwidth) of the light (e.g., spectral width at maximum peak intensity) emitted by the first channel of light sources is within 20 nm of the first peak wavelength ( for example, not more than 10 nm more, not more than 10 nm less than the first peak wavelength, within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the first array includes only/single processing chamber lights placed to illuminate the biological fluid in the processing chamber. In some embodiments, the systems further include a first platform (eg, tray, well, plate, platform) located in the processing chamber, designed to contain a biological fluid (eg, one or more containers of biological fluid). In some embodiments, one or more sensors designed to detect light in the processing chamber are placed on or in the first platform. In some embodiments, the systems further include a heat exchanger thermally coupled to the first array of light sources. In some embodiments, the implementation of the first platform is placed above the first matrix of light sources, while the first matrix of light sources is directed to the first platform. In some embodiments, the implementation of the first platform is placed under the first matrix of light sources, while the first matrix of light sources is directed to the first platform.

In some embodiments, the implementation of the light sources of the first matrix of light sources are placed on the matrix unevenly. In some embodiments, the first array has an inner region with a first density of light sources and an outer region with a second density of light sources, wherein the first density of light sources is different from the second density of light sources. In some embodiments, the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, with the inner region occupying less than 50% (e.g., less than 40%, 30%, 20%, 10%, 1050 %, 20-40%, 10-20%) of the surface area of the first matrix, while the outer region occupies the remaining percentage (for example, 50%, 60%, 70%, 80%, 90%) of the surface area of the first matrix. In some embodiments, the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, with the inner region occupying more than 50% (e.g., more than 60%, 70%, 80%, 90%, 5090 %, 60-80%) of the surface area of the first matrix, while the outer region occupies the remaining percentage of the surface area of the first matrix (for example, less than 50%, 40%, 30%, 20%, 10%,

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10-50%, 20-40%, 10-20%). In some embodiments, the outer region includes a first region constituting the outer boundary of the first matrix, and no light sources are placed in the first region. In some embodiments, the implementation of the first density of light sources placed in the outer region is greater than the second density of light sources placed in the inner region. In some embodiments, the implementation of the first density of light sources placed in the outer region is less than the second density of light sources placed in the inner region. In some embodiments, the first array is designed with light sources placed at a higher density in the outer 50% of the surface area of the array compared to a density of light sources near the center (e.g., in the inner 10%, 20% of the surface area) of the array. In some embodiments, the first array includes a first light source area designed to illuminate a first biological fluid (e.g., a first body fluid container) in a treatment chamber and a second light source area designed to light a second body fluid (e.g., a second body fluid container). liquid) in the processing chamber. In some embodiments, each of the first density of lights placed in the first region of the first matrix and the second density of lights placed in the second region of the first matrix is greater than the density of lights placed outside the first region and the second region of the first matrix. In some embodiments, the first array includes a first light source area designed to illuminate a first biological fluid (e.g., a first body fluid container) in a treatment chamber and a second light source area designed to light a second body fluid (e.g., a second body fluid container). liquid) in the processing chamber. In some embodiments, each of the first density of light sources placed in the first area of the matrix and the second density of light sources placed in the second area of the matrix is greater than the density of light sources outside the first area and the second area of the matrix. In some embodiments, the first matrix is designed such that the light sources illuminate the biological fluid in the treatment chamber with less than 25% irradiance variation across the entire surface of the biological fluid (e.g., fluid container, fluid container sectional plane) facing the first matrix. In some embodiments, the first array is designed such that the light sources illuminate any 5 cm surface area of the biological fluid (e.g., a container of biological fluid) in the treatment chamber with less than 25% variation from the integrated illumination (surface area average) of the cross-sectional plane of the entire biological fluid. (for example, a container with a biological fluid).

In some embodiments, the first light source array further includes a third light source channel designed to emit light at a third peak wavelength (e.g., where the first, second, and third peak wavelengths each differ by at least 5 nm). In some embodiments, each light source cluster of the plurality of light source clusters further includes a third light source channel designed to emit light at a third peak wavelength. In some embodiments, each light source cluster of the plurality of light source clusters further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. In some embodiments, the first light source array further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. In some embodiments, each of the first, second, third, and fourth peak wavelengths differ from each other by at least 5 nm. In some embodiments, the first peak wavelength is equal to the third peak wavelength, and wherein the second peak wavelength is equal to the fourth peak wavelength. In some embodiments, the systems further include a barrier (eg, light barrier, safety barrier) located in the processing chamber between the first array of light sources and the first platform. In some embodiments, the systems further include a barrier (eg, light barrier, safety barrier) placed in the treatment chamber between the first array of light sources and the biological fluid (eg, the biological fluid in the container). In some embodiments, the barrier is a light barrier (eg, light filter) designed to reduce (eg, minimize, attenuate, block) the transmission of light having a wavelength less than the wavelength of light in the UV-A spectrum. In some embodiments, the implementation of the barrier is a light barrier designed to reduce the transmission of light having a wavelength less than the wavelength of light in the UV-B spectrum. In some embodiments, the barrier is a light barrier (e.g., light filter) designed to reduce (e.g., minimize, attenuate, block) the transmission of light having a wavelength of at least 20 nm shorter (e.g., at least 25 nm less, at least 30 nm less) of the first peak wavelength and/or another peak wavelength (e.g., at least 20 nm less

- 3 042016 second, third or fourth peak wavelength). In some embodiments, the barrier is a light barrier (e.g., a light filter) designed to reduce the transmission of light having a wavelength of at least 20 nm longer (e.g., at least 25 nm longer, at least 30 nm longer ) the first peak wavelength and/or another peak wavelength (eg, at least 20 nm more than the second, third or fourth peak wavelength). In some embodiments, the barrier is transparent to light with a wavelength within 30 nm of the first peak wavelength (e.g., within 15 nm less, within 15 nm more than the first peak wavelength; no more than 15 nm more, no more than 15 nm less than the first peak wavelength). In some embodiments, one or more sensors designed to detect light in the processing chamber are placed on or in the barrier. In some embodiments, the first platform and the first array of lights are designed to move relative to each other to change the distance between the first array of lights and the first platform.

In some embodiments, the first platform has a first compartment and a second compartment that is isolated from the first compartment. In some embodiments, the first platform is designed to separate at least the first first body fluid container and the second second body fluid container. In some embodiments, the first platform is transparent to light within 100 nm (e.g., 75 nm, 50 nm, 40 nm, 30 nm, 20 nm) of the first peak wavelength and/or another peak wavelength (e.g., second, third, or fourth peak wavelength). In some embodiments, the first platform is transparent to ultraviolet light (eg, UV-A, UV-B, and/or UV-C). In some embodiments, the first platform may be slidable (eg, in a drawer configuration) to introduce and withdraw biological fluid (eg, a container of biological fluid) into and out of the chamber. In some embodiments, one or more interior surfaces of the plurality of interior surfaces of the treatment chamber are designed to absorb light. In some embodiments, each interior surface of the plurality of interior surfaces of the treatment chamber is designed to absorb light. In some embodiments, one or more interior surfaces of the plurality of interior surfaces of the processing chamber are designed to reflect light. In some embodiments, each interior surface of the plurality of interior surfaces of the processing chamber is designed to reflect light.

In some embodiments, the system (eg, the first platform) is designed to mix the biological fluid during processing. In some embodiments, the implementation of the first platform is designed for movement (eg, orbital, reciprocating, controlled movement, movement with a given speed) to mix the biological fluid during processing.

In some embodiments, the systems further include one or more thermal sensors located in the treatment chamber and/or one or more airflow sensors located in the treatment chamber. In some embodiments, one or more sensors are placed on the first array of light sources. In some embodiments, the systems further include one or more sensors for detecting the presence and/or type of body fluid (eg, body fluid container) in the chamber (eg, in contact/platform).

In some embodiments, the light sources of the first array of light sources are connected in series. In some embodiments, the light sources of the first array of light sources are connected in parallel. In some embodiments, the light sources in the first set of the first light source array are connected in parallel, and the lights in the second set of the first light source array are connected in series. In some embodiments, the light sources of the first array of light sources are connected by a combination of parallel and series connection of circuits.

In some embodiments, the systems further include a second array of light sources directed away from the direction of the first array of light sources, wherein each light source of the second array of light sources includes a third light source channel designed to emit light at a first peak wavelength, and a fourth a light source channel designed to emit light at a second peak wavelength. In some embodiments, the first array of lights and the second array of lights are designed to move relative to each other to change the distance between the first array of lights and the second array of lights. In some embodiments, the systems further include a first platform positioned in the treatment chamber between the first light source array and the second light source array, wherein the first platform is designed to receive a biological fluid (eg, a container of biological fluid). In some embodiments, the systems further include a barrier placed in the processing chamber between the second array of light sources and the first platform.

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In some embodiments, the systems further include a second array of lights directed in the same direction as the first array of lights, wherein each light of the second array of lights includes a third light source channel designed to emit light at a first peak wavelength, and a fourth light source channel designed to emit light at a second peak wavelength, wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array. In some embodiments, the systems further include a first platform located in the treatment chamber in the first region, designed to receive the first biological fluid; and a second platform located in the processing chamber outside the first area, designed to receive the second biological fluid, while the second array of light sources is directed to the second platform. In some embodiments, the systems further include a barrier placed in the processing chamber outside of the first region and between the second array of light sources and the second platform. In some embodiments, the first array includes single processing chamber lights positioned to illuminate the biological fluid in the first region of the processing chamber. In some embodiments, the first set of lights of the first array of lights is located on the first panel, and while the second set of lights of the first array of lights is located on the second panel, located next to the first panel. In some embodiments, the first set of lights of the second array of lights is located on the first panel, and wherein the second set of lights of the second array of lights is located on the second panel located adjacent to the first panel. In some embodiments, the first panel and the second panel are designed to move relative to each other to change the distance between the first panel and the second panel. In some embodiments, in the first set, the light sources are connected in series, in the second set, the light sources are connected in series, with the first panel and the second panel connected in parallel.

In some embodiments, the systems further include a control circuit (eg, a control circuit operatively coupled (wireless or wired) to the processing chamber, operatively coupled to one or more arrays). In some embodiments, the control circuit is designed to adjust or set the first peak wavelength of light emitted by each first light source channel, and to adjust or set the second peak wavelength of light emitted by each second light source channel. In some embodiments, the control circuitry is designed to adjust or set the intensity of each light source (eg, each light source independently) of the first array of light sources. In some embodiments, the control circuit is designed to adjust or set the first light intensity emitted by each first light source channel and to adjust or set the second light intensity emitted by each second light source channel. In some embodiments, the control circuitry is designed to adjust or set the duration of light emission by each light source of the first array of light sources (eg, each light source independently). In some embodiments, the control circuit is designed to adjust or set a first light emission duration for each first light source channel, and to adjust or set a second light emission duration for each second light source channel.

In some embodiments, the control circuit adjusts or sets the first peak light wavelength and the second peak light wavelength based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, airflow sensor, thermal sensor). , a sensor for detecting the presence of a biological fluid or its properties, a sensor for detecting a photochemical compound, a sensor placed to determine the depth of a biological fluid). In some embodiments, the control circuit adjusts or sets the first peak light wavelength and the second peak light wavelength based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light. In some embodiments, the control circuitry is designed to adjust or set the duration of light emission by each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, airflow sensor, thermal a sensor, a sensor for detecting the presence of a biological fluid or a property thereof, a sensor for detecting a photochemical compound, a sensor placed to determine the depth of a biological fluid). In some embodiments, the control circuit is designed to adjust or set the duration of light emission by each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more

- 5 042016 sensors designed for light detection. In some embodiments, the control circuitry is designed to adjust or set the light emission intensity of each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, airflow sensor, thermal a sensor, a sensor for detecting the presence of a biological fluid or a property thereof, a sensor for detecting a photochemical compound, a sensor placed for determining the depth of a biological fluid). In some embodiments, the control circuitry is designed to adjust or set the light emission intensity of each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light.

In some embodiments, the systems further include a depth sensor designed to determine the first depth of the first portion of the biological fluid placed in the treatment chamber. In some embodiments, the control circuitry is designed to adjust or set the intensity of light emitted from the first channel of light sources directed at the biological fluid based on the depth of the biological fluid. In some embodiments, the control circuitry is designed to adjust or set the intensity of light emitted from the second channel of light sources directed at the biological fluid based on the depth of the biological fluid. In some embodiments, the control circuitry is designed to adjust or set the first intensity of light emitted by each first light source channel directed at the first body fluid portion based on the depth of the first body fluid portion and to adjust or set the second light intensity emitted by each second source channel. light directed at the second portion of the biological fluid, based on the depth of the second portion of the biological fluid. In some embodiments, the systems further include one or more depth sensors located in the treatment chamber that are designed to determine the depth of the first bodily fluid and the depth of the second bodily fluid.

In some embodiments, the systems further include a first container positioned within the interior of the treatment chamber (e.g., a treatment container) to receive and process the body fluid, the first container being adapted to be connected to a source body fluid container, and the first container being adapted for connection with a second container receiving biological fluid from the first container.

The present invention also relates to systems for treating a biological fluid, including a treatment chamber for receiving a biological fluid (eg, a biological fluid in a container); one or more sensors designed to detect (eg, measure) light (eg, light intensity) in the processing chamber; and a first array of light sources placed to illuminate the biological fluid in the treatment chamber (e.g., directed at the biological fluid), wherein each light source of the first light source array includes a first light source channel designed to emit ultraviolet light with a first peak wavelength in ultraviolet spectral A, ultraviolet B and/or ultraviolet C (e.g., 315-400 nm), with full width at half maximum (FWHM) (e.g., emission bandwidth) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by the first channel of light sources, less than 20 nm, for example, within 10 nm less, within 10 nm more than the first peak wavelength; no more than 10 nm more, no more than 10 nm less than the first peak wavelength.

In some embodiments, each light source of the first array of light sources includes a first channel of light sources designed to emit ultraviolet light with a first peak wavelength of about 315 nm to about 350 nm. In some embodiments, each light source of the first array of light sources includes a first channel of light sources designed to emit ultraviolet light with a first peak wavelength of about 315 nm to about 335 nm (e.g., about 320 nm to about 330 nm, or about 325 nm). nm). In some embodiments, each light source of the first array of light sources includes a first channel of light sources designed to emit ultraviolet light with a first peak wavelength of about 330 nm to about 350 nm (e.g., about 335 nm to about 345 nm, or about 340 nm). In some embodiments, 50% of the maximum peak light intensity emitted by the first channel of light sources is within 10 nm of the first peak wavelength. In some embodiments, the light intensity at 50% of the maximum peak light intensity emitted by the first channel of light sources is within (e.g., limited to) a spectral width of less than 20 nm (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the first light source array further includes a second light source channel designed to emit

- 6 042016 readings of light (eg ultraviolet light) with a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, the second peak wavelength is in the ultraviolet A region (e.g., 315-400 nm), ultraviolet B (e.g., 280-315 nm), ultraviolet C (e.g., 100-280 nm, 200- 280 nm, 240-280 nm) or visible region of the spectrum (eg 400-800 nm). In some embodiments, 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the second peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the second peak wavelength; within 10 nm less, within 10 nm more than the second peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by the second channel of light sources is less than 20 nm, e.g., not more than 10 nm more, not more than 10 nm less than the second peak wavelength; within 10 nm less, within 10 nm more than the second peak wavelength). In some embodiments, the first light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source array includes a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source channel designed to emitting light (eg, ultraviolet light) with a second peak wavelength. In some embodiments, the first light source channel includes one or more (eg, multiple) LEDs. In some embodiments, the second light source channel includes one or more (eg, multiple) LEDs.

In some embodiments, the systems further include a first platform (eg, tray, well, plate, pad) placed in a processing chamber that is designed to contain a biological fluid (eg, one or more containers of biological fluid). In some embodiments, the systems further include a heat exchanger thermally coupled to the first array of light sources. In some embodiments, the implementation of the first platform is placed above the first matrix of light sources, and the first matrix of light sources is directed to the first platform. In some embodiments, the implementation of the first platform is placed under the first matrix of light sources, and the first matrix of light sources is directed to the first platform. In some embodiments, one or more sensors designed to detect light in the processing chamber are placed on or in the first platform.

In some embodiments, the light sources of the first array of light sources are unevenly placed on the array. In some embodiments, the first array has an inner region with a first density of light sources and an outer region with a second density of light sources, wherein the first density of light sources is different from the second density of light sources. In some embodiments, the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, with the inner region occupying less than 50% (e.g., less than 40%, 30%, 20%, 10%, 1050 %, 20-40%, 10-20%) of the surface area of the first matrix, while the outer region occupies the remaining percentage (for example, 50%, 60%, 70%, 80%, 90%) of the surface area of the first matrix. In some embodiments, the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, with the inner region occupying more than 50% (e.g., more than 60%, 70%, 80%, 90%, 5090 %, 60-80%) of the surface area of the first matrix, while the outer region occupies the remaining percentage of the surface area of the first matrix (for example, less than 50%, 40%, 30%, 20%, 10%, 10-50%, 20 -40%, 10-20%). In some embodiments, the implementation of the first density of light sources placed in the outer region is greater than the second density of light sources placed in the inner region. In some embodiments, the implementation of the first density of light sources placed in the outer region is less than the second density of light sources placed in the inner region. In some embodiments, the outer region includes a first region constituting the outer boundary of the first matrix, and no light sources are placed in the first region. In some embodiments, the first array includes a first light source area designed to illuminate a first biological fluid (e.g., a first body fluid container) in a treatment chamber and a second light source area designed to light a second body fluid (e.g., a second body fluid container). liquid) in the processing chamber. In some embodiments, each of the first density of lights placed in the first region of the first matrix and the second density of lights placed in the second region of the first matrix is greater than the density of lights placed outside the first region and the second region of the first matrix. In some embodiments, the first matrix is designed such that the light sources illuminate the biological fluid in the treatment chamber with less than 25% irradiance variation across the entire surface of the biological fluid (e.g., fluid container, fluid container sectional plane) facing the first matrix. In some variants

- 7 042016 max implementation the first matrix is designed so that the light sources illuminate any 5 cm of the surface area of the biological fluid (for example, a container of biological fluid) in the processing chamber with a variation of less than 25% of the integrated, or average, illumination of the cross-sectional plane of the entire biological fluid ( e.g. a container with biological fluid).

In some embodiments, the first light source array further includes a third light source channel designed to emit light at a third peak wavelength (e.g., where the first, second, and third peak wavelengths each differ by at least 5 nm). In some embodiments, each light source cluster of the plurality of light source clusters further includes a third light source channel designed to emit light at a third peak wavelength.

In some embodiments, each light source cluster of the plurality of light source clusters further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. In some embodiments, the first light source array further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. In some embodiments, each of the first, second, third, and fourth peak wavelengths differ from each other by at least 5 nm. In some embodiments, the first peak wavelength is equal to the third peak wavelength, and wherein the second peak wavelength is equal to the fourth peak wavelength.

In some embodiments, the systems further include a barrier (eg, light barrier, safety barrier) located in the processing chamber between the first array of light sources and the first platform. In some embodiments, the systems further include a barrier (eg, light barrier, safety barrier) placed in the treatment chamber between the first array of light sources and the biological fluid (eg, the biological fluid in the container). In some embodiments, the barrier is a light barrier (eg, light filter) designed to reduce (eg, minimize, attenuate, block) the transmission of light having a wavelength less than the wavelength of light in the UV-A spectrum. In some embodiments, the implementation of the barrier is a light barrier designed to reduce the transmission of light having a wavelength less than the wavelength of light in the UV-B spectrum. In some embodiments, the barrier is a light barrier (e.g., light filter) designed to reduce (e.g., minimize, attenuate, block) the transmission of light having a wavelength of at least 20 nm shorter (e.g., at least 25 nm less, at least 30 nm less) of the first peak wavelength and/or another peak wavelength (eg, at least 20 nm less than the second, third or fourth peak wavelength). In some embodiments, the barrier is a light barrier (e.g., a light filter) designed to reduce the transmission of light having a wavelength of at least 20 nm longer (e.g., at least 25 nm longer, at least 30 nm longer ) the first peak wavelength and/or another peak wavelength (eg, at least 20 nm more than the second, third or fourth peak wavelength). In some embodiments, the barrier is transparent to light with a wavelength within 30 nm of the first peak wavelength (e.g., within 15 nm less, within 15 nm more than the first peak wavelength; no more than 15 nm more, no more than 15 nm less than the first peak wavelength). In some embodiments, one or more sensors designed to detect light in the processing chamber are placed on or in the barrier. In some embodiments, the first platform and the first array of lights are designed to move relative to each other to change the distance between the first array of lights and the first platform.

In some embodiments, the first platform has a first compartment and a second compartment that is isolated from the first compartment. In some embodiments, the first platform is designed to separate at least the first first body fluid container and the second second body fluid container. In some embodiments, the first platform is transparent to light within 100 nm (e.g., 75 nm, 50 nm, 40 nm, 30 nm, 20 nm) of the first peak wavelength and/or another peak wavelength (e.g., second, third, or fourth peak wavelength). In some embodiments, the first platform is transparent to ultraviolet light (eg, UV-A, UV-B, and/or UV-C). In some embodiments, the first platform may be slidable (eg, in a drawer configuration) to introduce and withdraw biological fluid (eg, a container of biological fluid) into and out of the chamber. In some embodiments, one or more internal surfaces (eg, of a plurality of internal surfaces of the treatment chamber) are designed to absorb light. In some embodiments, each interior surface of the plurality of interior surfaces of the treatment chamber is designed to absorb light. In some embodiments, one or more internal

- 8 042016 of these surfaces (for example, from a plurality of internal surfaces of the processing chamber) are designed to reflect light. In some embodiments, each interior surface of the plurality of interior surfaces of the processing chamber is designed to reflect light.

In some embodiments, the system (eg, the first platform) is designed to mix the biological fluid during processing. In some embodiments, the implementation of the first platform is designed for movement (eg, orbital, reciprocating, controlled movement, movement at a given speed) to mix the biological fluid during processing.

In some embodiments, the systems further include one or more thermal sensors located in the treatment chamber and/or one or more airflow sensors located in the treatment chamber. In some embodiments, one or more sensors are placed on the first array of light sources. In some embodiments, the systems further include one or more sensors for detecting the presence and/or type of body fluid (eg, body fluid container) in the chamber (eg, in contact/platform).

In some embodiments, the light sources of the first array of light sources are connected in series. In some embodiments, the light sources of the first array of light sources are connected in parallel. In some embodiments, the light sources in the first set of the first light source array are connected in parallel, and the lights in the second set of the first light source array are connected in series. In some embodiments, the light sources of the first array of light sources are connected by a combination of parallel and series connection of circuits.

In some embodiments, the systems further include a second array of light sources directed away from the direction of the first array of light sources, wherein each light source of the second array of light sources includes a third light source channel designed to emit light at a first peak wavelength, and a fourth a light source channel designed to emit light at a second peak wavelength. In some embodiments, the first array of lights and the second array of lights are designed to move relative to each other to change the distance between the first array of lights and the second array of lights. In some embodiments, the systems further include a first platform positioned in the treatment chamber between the first light source array and the second light source array, wherein the first platform is designed to receive a biological fluid (eg, a container of biological fluid). In some embodiments, the systems further include a barrier placed in the processing chamber between the second array of light sources and the first platform.

In some embodiments, the systems further include a second array of lights directed in the same direction as the first array of lights, wherein each light of the second array of lights includes a third light source channel designed to emit light at a first peak wavelength, and a fourth light source channel designed to emit light at a second peak wavelength, wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array. In some embodiments, the systems further include a first platform located in the treatment chamber in the first region, designed to receive the first biological fluid; and a second platform located in the processing chamber outside the first area, designed to receive the second biological fluid, while the second array of light sources is directed to the second platform. In some embodiments, the systems further include a barrier placed in the processing chamber outside of the first region and between the second array of light sources and the second platform. In some embodiments, the first array includes single processing chamber lights positioned to illuminate the biological fluid in the first region of the processing chamber. In some embodiments, the first set of lights of the first array of lights is located on the first panel, and while the second set of lights of the first array of lights is located on the second panel, located next to the first panel. In some embodiments, the first set of lights of the second array of lights is located on the first panel, and wherein the second set of lights of the second array of lights is located on the second panel located adjacent to the first panel. In some embodiments, the first panel and the second panel are designed to move relative to each other to change the distance between the first panel and the second panel. In some embodiments, in the first set, the light sources are connected in series, in the second set, the light sources are connected in series, with the first panel and the second panel connected in parallel.

In some embodiments, the systems further include a control circuit (eg, a control circuit operatively coupled (wireless or wired) to the processing chamber, operatively coupled to one or more arrays). In some variants

- 9 042016 implementation the control circuit is designed to adjust or set the first peak wavelength of light emitted by each light source (for example, each light source independently) of the first matrix of light sources. In some embodiments, the control circuit is designed to adjust or set the first peak wavelength of light emitted by each first light source channel and to adjust the second peak wavelength of light emitted by each second light source channel. In some embodiments, the control circuitry is designed to adjust or set the intensity of each light source (eg, each light source independently) of the first array of light sources. In some embodiments, the control circuit is designed to adjust or set the first light intensity emitted by each first light source channel and to adjust or set the second light intensity emitted by each second light source channel. In some embodiments, the control circuitry is designed to adjust or set the duration of light emission by each light source of the first array of light sources (eg, each light source independently). In some embodiments, the control circuit is designed to adjust or set a first light emission duration for each first light source channel and to adjust or set a second light emission duration for each second light source channel.

In some embodiments, the control circuitry is designed to adjust or set the first peak wavelength of light from each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, air sensor). flow, a thermal sensor, a sensor for detecting the presence of a biological fluid or its properties, a sensor for detecting a photochemical compound, a sensor placed to determine the depth of a biological fluid). In some embodiments, the control circuitry is designed to adjust or set the first peak wavelength of light from each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to light detection. In some embodiments, the control circuit adjusts or sets the first peak light wavelength and the second peak light wavelength based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light. In some embodiments, the control circuitry is designed to adjust or set the duration of light emission by each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, airflow sensor, thermal a sensor, a sensor for detecting the presence of a biological fluid or a property thereof, a sensor for detecting a photochemical compound, a sensor placed to determine the depth of a biological fluid). In some embodiments, the control circuit is designed to adjust or set the duration of light emission by each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light. In some embodiments, the control circuitry is designed to adjust or set the light emission intensity of each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor (e.g., light sensor, airflow sensor, thermal a sensor, a sensor for detecting the presence of a biological fluid or a property thereof, a sensor for detecting a photochemical compound, a sensor placed to determine the depth of a biological fluid). In some embodiments, the control circuitry is designed to adjust or set the light emission intensity of each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light.

In some embodiments, the systems further include a depth sensor designed to determine the first depth of the first portion of the biological fluid, located in the processing chamber. In some embodiments, the control circuitry is designed to adjust or set the intensity of light emitted from the first channel of light sources directed at the biological fluid based on the depth of the biological fluid. In some embodiments, the control circuitry is designed to adjust or set the intensity of light emitted from the second channel of light sources directed at the biological fluid based on the depth of the biological fluid. In some embodiments, the control circuitry is designed to adjust or set the first intensity of light emitted by each first channel of light sources directed at the first bodily fluid based on the depth of the first bodily fluid and to adjust or set the second

- 10 042016 intensity of light emitted by every second channel of light sources directed to the second portion of the biological fluid, based on the depth of the second portion of the biological fluid. In some embodiments, the systems further include one or more depth sensors located in the treatment chamber that are designed to determine the depth of the first bodily fluid and the depth of the second bodily fluid.

In some embodiments, the systems further include a first container positioned within the interior of the treatment chamber (e.g., a treatment container) to receive and process the body fluid, the first container being adapted to be connected to a source body fluid container, and the first container being adapted for connection with the second container receiving the biological fluid from the first container.

The present invention also relates to methods for treating a biological fluid (eg, inactivating pathogens in a biological fluid), including: obtaining a biological fluid in a mixture with a pathogen-inactivating compound (eg, a photochemical reagent); illuminating (eg, exposing) the biological fluid with ultraviolet light at a first peak wavelength; and illuminating (e.g., exposing) the biological fluid with light (e.g., ultraviolet light) of a second peak wavelength, the first peak wavelength differing from the second peak wavelength by at least 5 nm, the illumination of the biological fluid occurring for a period time and at an intensity sufficient to inactivate pathogens in the biological fluid.

In some embodiments, ultraviolet light at a first peak wavelength is produced by a first light source (eg, in a processing chamber), while light at a second peak wavelength is produced by a second light source (eg, in a processing chamber). In some embodiments, 50% of the maximum peak light intensity emitted by the first light source is within 10 nm of the first peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by the first light source is less than 20 nm from the first peak wavelength (e.g., no more than 10 nm more , not more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the implementation of ultraviolet light with a first peak wavelength is in the ultraviolet A region of the spectrum (for example, 315-400 nm). In some embodiments, the light with the second peak wavelength is in the ultraviolet B region (e.g., 280-315 nm), ultraviolet C region (e.g., 100-280 nm, 200-280 nm, 240-280 nm), or the visible region. spectrum (for example, 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet A region (e.g., 315-400 nm) and the second peak wavelength is in the ultraviolet C region (e.g., 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the first peak wavelength is in the ultraviolet A region (eg, 315-400 nm) and the second peak wavelength is in the ultraviolet B region (eg, 280-315 nm). In some embodiments, the first peak wavelength is in the ultraviolet A region (e.g., 315-400 nm) and the second peak wavelength is in the ultraviolet A region. In some embodiments, the first peak wavelength is in the ultraviolet A region, and the second peak wavelength is in the visible region of the spectrum (eg, 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet B region and the second peak wavelength is in the ultraviolet C region. In some embodiments, the first peak wavelength is in the ultraviolet B region and the second peak wavelength is in the visible region of the spectrum. In some embodiments, the first peak wavelength is in the ultraviolet C region and the second peak wavelength is in the visible region of the spectrum. In some embodiments, illumination of the biological fluid with ultraviolet light at a first peak wavelength and illumination of the biological fluid with light at a second peak wavelength occur sequentially or simultaneously. In some embodiments, illuminating a biological fluid with ultraviolet light at a first peak wavelength includes illuminating the biological fluid with ultraviolet light at a first peak wavelength for a first period of time, and wherein illuminating the biological fluid with light at a second peak wavelength includes illuminating the biological fluid with light at a second peak wavelength. peak wavelength during the second time period. In some embodiments, the first time period is different from the second time period. In some embodiments, the first time period is equal to the second time period. In some embodiments, illumination of a biological fluid with ultraviolet light of a first peak wavelength is performed using a first set of light sources, while illumination of a biological fluid with light of a second peak wavelength is performed using a second set of light sources, and

- 11 042016 the first and second sets of light sources are located on the matrix of light source clusters. In some embodiments, the first light source and the second light source include an LED. In some embodiments, the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen (e.g., amotosalen ).

The present invention also relates to methods for treating a biological fluid (eg, inactivating pathogens in a biological fluid), including: obtaining a biological fluid in a mixture with a pathogen-inactivating compound (eg, a photochemical reagent); and illuminating (e.g., exposing) the biological fluid with ultraviolet light at a first peak wavelength provided by the first ultraviolet light source (e.g., in a processing chamber), wherein the full width at half maximum (FWHM) of the ultraviolet light spectrum width (e.g., the spectral width at peak intensity) emitted by the first ultraviolet light source is less than 20 nm from the first peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within within 10 nm greater than the first peak wavelength), and the illumination of the biological fluid occurs for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid.

In some embodiments, the implementation of ultraviolet light with a first peak wavelength is in the ultraviolet A region of the spectrum (for example, 315-400 nm). In some embodiments, the implementation of the first peak wavelength is from 330 nm to 350 nm (for example, 340 nm + 5 nm). In some embodiments, the implementation of ultraviolet light with a first peak wavelength is in the ultraviolet B region (eg, 280-315 nm). In some embodiments, the implementation of ultraviolet light with a first peak wavelength is in the ultraviolet C region of the spectrum (for example, 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the first light source is an LED. In some embodiments, illumination of the biological fluid with ultraviolet light at a first peak wavelength is performed using the first ultraviolet light source as the sole light source of the treatment chamber illuminating the biological fluid. In some embodiments, the first light source is the sole ultraviolet light source of the processing chamber, illuminating the biological fluid during processing. In some embodiments, the biological fluid is contained in a container, wherein the illumination of the biological fluid with ultraviolet light at a first peak wavelength is performed using a first set of light sources located on an array of light sources, and the first set of light sources is directed to only one side of the container. . In some embodiments, the biological fluid is contained in a container, wherein the illumination of the biological fluid with ultraviolet light at a first peak wavelength is performed using a first set of light sources located on an array of light sources (e.g., in a processing chamber), and the array is directed toward ( e.g. illuminates) one side of the body fluid container during processing. In some embodiments, the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen (e.g., amotosalen ).

The present invention also relates to methods for treating a biological fluid (e.g., inactivating pathogens in a biological fluid) comprising: introducing a biological fluid (e.g., a biological fluid in a container) mixed with a pathogen-inactivating compound (e.g., a photochemical reagent) into a treatment chamber comprising one or more photosensitive sensors designed to detect (e.g., measure) light (e.g., light intensity) in the processing chamber, and a first array of light sources designed to illuminate the biological fluid in the processing chamber, with each light source of the first array of light sources turned on into a first light source channel designed to emit ultraviolet light at a first peak wavelength, or into a second light source channel designed to emit light (e.g., ultraviolet light) at a second peak wavelength, wherein the first peak wavelength is different from a second peak wavelength of at least 5 nm; and illuminating the biological fluid by emitting light at a first peak wavelength from each first light source channel and emitting light at a second peak wavelength from each second light source channel for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid.

In some embodiments, the implementation of the methods further include determining the set of characteristics of the biological fluid; determining the processing mode based on the set of characteristics of the biological fluid; and adjusting or setting the processing camera parameter set according to the processing mode.

- 12 042016

In some embodiments, the implementation of the illumination of the biological fluid is carried out in accordance with the mode of processing. In some embodiments, the duration and intensity sufficient to inactivate pathogens is determined based on the treatment regimen. In some embodiments, the first light source array includes a plurality of light source clusters, where each light source cluster of the first light source matrix includes a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source channel designed to emit light with a second peak wavelength. In some embodiments, 50% of the maximum peak light intensity emitted by the first channel of light sources is within 10 nm of the first peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by the first channel of light sources is less than 20 nm from the first peak wavelength (e.g., no more than 10 nm more, not more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the set of biological fluid characteristics includes at least one of: the volume of the biological fluid, the type of the biological fluid, or the temperature of the biological fluid. In some embodiments, determining a processing mode based on a set of characteristics includes determining a first peak wavelength and a second peak wavelength. In some embodiments, determining a processing mode based on the property set includes determining a first intensity of ultraviolet light at a first peak wavelength and a second intensity of light at a second peak wavelength. In some embodiments, determining the processing mode based on the set of characteristics includes determining a first duration of exposure to ultraviolet light at a first peak wavelength and a second duration of emission of light at a second peak wavelength. In some embodiments, the treatment chamber also includes a first platform located in the treatment chamber, containing a biological fluid (eg, one or more containers of biological fluid). In some embodiments, the processing chamber further includes a heat exchanger thermally coupled to the first array of light sources. In some embodiments, adjusting or setting the processing camera parameter set includes adjusting or setting the distance between the first array of light sources and the first platform. In some embodiments, adjusting or setting a treatment chamber parameter set includes adjusting or setting a treatment chamber temperature. In some embodiments, the methods further include mixing the biological fluid. In some embodiments, adjusting or setting a set of treatment chamber parameters includes adjusting or setting a parameter related to agitation of the biological fluid.

The present invention also relates to methods for treating a biological fluid (e.g., inactivating pathogens in a biological fluid) comprising: introducing a biological fluid (e.g., a biological fluid in a container) mixed with a pathogen-inactivating compound (e.g., a photochemical reagent) into a treatment chamber comprising one or more photosensitive sensors designed to detect (e.g., measure) light (e.g., light intensity) in the processing chamber, and a first array of light sources designed to illuminate the biological fluid in the processing chamber, with each light source of the first array of light sources turned on into a first channel of light sources designed to emit ultraviolet light at a first peak wavelength of ultraviolet A, ultraviolet B, and/or ultraviolet C, with a full width at half maximum (FWHM) of the light spectrum (e.g. , spectral width at maximum peak intensity) emitted by the first channel of light sources is within less than 20 nm from the first peak wavelength (for example, not more than 10 nm more, not more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength); and illuminating the biological fluid by emitting light at a first peak wavelength from each first light source channel for a first period of time and at a first intensity is sufficient to inactivate pathogens in the biological fluid.

In some embodiments, each light source of the first array of light sources includes a first channel of light sources designed to emit ultraviolet light with a first peak wavelength of about 330 nm to about 350 nm (e.g., about 335 nm to about 345 nm, or about 340 nm). In some embodiments, the implementation of the methods further include determining the set of characteristics of the biological fluid; determining the processing mode based on the set of characteristics of the biological fluid; and adjusting or setting the processing camera parameter set according to the processing mode. In some embodiments, the implementation of the illumination of the biological fluid is carried out in accordance with the mode of processing.

- 13 042016

In some embodiments, the first duration and first intensity sufficient to inactivate pathogens is determined based on the treatment regimen. In some embodiments, 50% of the maximum peak light intensity emitted by the first channel of light sources is within 20 nm of the first peak wavelength (e.g., within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, each light source of the first light source array further includes a second light source channel designed to emit light at a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the second peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the second peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by the second channel of light sources is less than 20 nm from the first peak wavelength (e.g., no more than 10 nm more, not more than 10 nm less than the first peak wavelength; within 10 nm less, within 10 nm more than the first peak wavelength). In some embodiments, the first light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source array includes a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source channel designed to emitting ultraviolet light with a second peak wavelength. In some embodiments, the set of biological fluid characteristics includes at least one of: the volume of the biological fluid, the type of the biological fluid, or the temperature of the biological fluid. In some embodiments, determining the processing mode based on the set of characteristics includes determining the first peak wavelength. In some embodiments, determining a processing mode based on a set of characteristics includes determining a first intensity of light with a first peak wavelength. In some embodiments, determining a processing mode based on a set of characteristics includes determining a first duration of light emission at a first peak wavelength. In some embodiments, the treatment chamber further includes a first platform positioned within the treatment chamber, accommodating a biological fluid (eg, one or more containers of biological fluid). In some embodiments, the processing chamber further includes a heat exchanger thermally coupled to the first array of light sources. In some embodiments, adjusting or setting the processing camera parameter set includes adjusting or setting the distance between the first array of light sources and the first platform. In some embodiments, adjusting or setting a treatment chamber parameter set includes adjusting or setting a treatment chamber temperature. In some embodiments, the methods further include mixing the biological fluid. In some embodiments, adjusting or setting a set of treatment chamber parameters includes adjusting or setting a parameter related to agitation of the biological fluid.

In some embodiments of any of the above embodiments, the treatment method is sufficient to inactivate at least 1 log (eg, at least 2 log, at least 3 log, at least 4 log) pathogens in the body fluid. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) pathogens in the body fluid, and the body fluid after illumination is suitable. for infusion into a subject without further treatment to remove the residual pathogen-inactivating compound or photoproducts thereof. In some embodiments, illumination of the biological fluid in admixture with the pathogen inactivating compound reduces the concentration of the pathogen inactivating compound to 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) after illumination. In some embodiments, the body fluid contains 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of a pathogen-inactivating compound after illumination (e.g., without further processing to remove the residual pathogen inactivating compound, eg prior to any subsequent compound removal step, eg treatment of the body fluid using UAS). In some embodiments, the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is at least 10 μM (e.g., at least 15 μM, at least 20 μM, at least 30 μM, at least 40 μM, at least at least 50 µM, at least 60 µM, at least 70 µM, at least 80 µM, at least 90 µM, at least 100 µM, at least 110 µM, at least 120 µM, at least 130 μM, at least 140 μM or at least 150 μM). In some embodiments, the concentration

- 14 042016 pathogen inactivating compound in a mixture with a biological fluid before illumination is from about 10 μM to about 1500 μM, from about 10 μM to about 1000 μM, from about 10 μM to about 500 μM, from about 10 μM to about 250 μM, about 10 μM to about 200 μM, from about 10 μM to about 150 μM, from about 15 μM to about 150 μM, from about 15 μM to about 130 μM, from about 15 μM to about 110 μM, from about 15 μM to about 90 µM, from about 30 µM to about 150 µM, from about 30 µM to about 130 µM, from about 30 µM to about 110 µM, from about 30 µM to about 90 µM, from about 30 µM to about 60 µM, from about 60 μM to about 150 μM, from about 60 μM to about 130 μM, from about 60 μM to about 110 μM, or from about 60 μM to about 90 μM. In some embodiments, the concentration of the pathogen-inactivating compound in admixture with the body fluid prior to illumination is about 10 µM, about 15 µM, about 20 µM, about 25 µM, about 30 µM, about 35 µM, about 40 µM, about 45 µM, about 50 µM, about 55 µM, about 60 µM, about 65 µM, about 70 µM, about 75 µM, about 80 µM, about 85 µM, about 90 µM, about 95 µM, about 100 µM, about 110 µM, about 120 µM, about 130 μM, about 140 μM, or about 150 μM. In some embodiments, the concentration of the pathogen inactivating compound in admixture with the body fluid after illumination is at least 3 times (e.g., at least 4 times, at least 5 times, at least 10 times, or more) less than the concentration of the pathogen inactivating compound in admixture with the body fluid prior to illumination (eg, without further treatment to remove residual pathogen-inactivating compound, eg, prior to any subsequent compound removal step, eg, treatment of the body fluid using UAS).

The present invention also relates to a biological fluid with inactivated pathogens obtained by the methods of any of the above embodiments. In some embodiments, the body fluid contains 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of a pathogen-inactivating compound after illumination (e.g., before any subsequent connection deletion step).

The present invention also relates to methods for treating a biological fluid, including the introduction of a biological fluid in a mixture with a photoactive pathogen inactivating compound; and illuminating the biological fluid with ultraviolet light at a first peak wavelength of about 315 nm to about 350 nm emitted by a set of one or more first light sources, with each of the one or more first light sources emitting light at full width at half maximum (FWHM ) of a spectral width of less than 20 nm, and the illumination of the biological fluid occurs for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid.

In some embodiments, the implementation of the first peak wavelength is from about 315 to about 335 nm. In some embodiments, the first peak wavelength is from about 330 nm to about 350 nm. In some embodiments, the first peak wavelength is the peak wavelength of one first light source in a set of one or more first light sources. In some embodiments, the first peak wavelength is the peak wavelength of each of the plurality of first light sources in the set of one or more first light sources. In some embodiments, the first peak wavelength is the average peak wavelength in the set of one or more first light sources.

In some embodiments, the methods further comprise illuminating the biological fluid with ultraviolet light at a second peak wavelength emitted by a set of one or more second light sources, wherein each of the one or more second light sources emits full width at half maximum (FWHM) light. spectrum less than 20 nm, and while the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, the implementation of the second peak wavelength is the peak wavelength of one second light source in a set of one or more second light sources. In some embodiments, the second peak wavelength is the peak wavelength of each of the plurality of second light sources in the set of one or more second light sources. In some embodiments, the implementation of the second peak wavelength is the average peak wavelength in the set of one or more second light sources.

In some embodiments, the set of one or more first light sources includes one or more LEDs. In some embodiments, the body fluid is contained in a container and a set of one or more first lights are arranged in an array of lights, with the set of one or more first lights directed to only one side of the container. In some embodiments, the photoactive, pathogen inactivating compound is psoralen. In some embodiments, the photoactive, pathogen inactivating compound is amotosalen.

- 15 042016

In some embodiments, the methods further comprise, before illuminating the biological fluid with ultraviolet light at a first peak wavelength: introducing the biological fluid, admixed with a photoactive, pathogen-inactivating compound, into a treatment chamber comprising one or more light-sensitive sensors designed to detect light in the treatment chamber, and a first array of light sources designed to illuminate the biological fluid in the treatment chamber, wherein the first matrix of light sources includes a first light source channel including a set of one or more first light sources, wherein the illumination of the biological fluid includes light emission at a first peak wavelength from the first channel of light sources during the first period of time and at the first intensity sufficient to inactivate pathogens in the biological fluid. In some embodiments, each light source of the first light source channel is designed to emit ultraviolet light with a first peak wavelength of about 315 nm to about 350 nm. In some embodiments, the implementation of the methods further include determining the set of characteristics of the biological fluid; determining the processing mode based on the set of characteristics of the biological fluid; and adjusting or setting the processing camera parameter set according to the processing mode. In some embodiments, illumination of the biological fluid is performed in accordance with the treatment regimen, and the first duration and first intensity sufficient to inactivate pathogens is determined based on the treatment regimen. In some embodiments, the first light source array includes a second light source channel designed to emit light at a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, the second peak wavelength is in the ultraviolet A region, the ultraviolet B region, or the ultraviolet C region. In some embodiments, the second light source channel includes a set of one or more second light sources, each of one or more The second light source emits light with a full width at half maximum (FWHM) spectral width of less than 20 nm. In some embodiments, the set of biological fluid characteristics includes one or more of the group consisting of: volume of the biological fluid, type of the biological fluid, and temperature of the biological fluid. In some embodiments, determining a treatment mode based on a set of biological fluid characteristics includes determining a first intensity of light at a first peak wavelength or determining a first duration of light at a first peak wavelength. In some embodiments, the processing chamber further includes a first platform located in the processing chamber, containing the biological fluid. In some embodiments, adjusting or setting the processing camera parameter set includes adjusting or setting the distance between the first array of light sources and the first platform.

In some embodiments, the methods further include mixing the biological fluid. In some embodiments, the implementation of the total dose of ultraviolet light illuminating the biological fluid is from about 0.5 J/cm ² to about 50 J/cm ² . In some embodiments, the total dose of ultraviolet light illuminating the biological fluid, emitted from an array of one or more first light sources, is from about 0.5 J/cm ² to about 50 J/cm ² . In some embodiments, the treatments are sufficient to inactivate at least 1 log of pathogens in the body fluid, if present, and the body fluid, after illumination, is suitable for infusion into the subject without further treatment to remove the residual pathogen-inactivating compound or its photoproduct(s). ). In some embodiments, the treatments are sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) pathogens in the body fluid, if present, and the body fluid after illumination is suitable for infusion into a subject without passing the body fluid through a compound removal step (eg, passing the body fluid through the UAS) to remove residual pathogen-inactivating compound or photoproduct(s) thereof. In some embodiments, the treatments are sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) pathogens in the body fluid, if present, and the body fluid contains 5 μM or less (eg, 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of the pathogen inactivating compound after illumination. In some embodiments, the treatments are sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) pathogens in the body fluid, if present, and the body fluid contains 2 μM or less pathogen-inactivating compound after illumination. In some embodiments, the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is at least about 10 μM (e.g., at least about 30 μM, at least about 60 μM, at least about 90 μM, according to at least about 110

- 16 042016 μM). In some embodiments, the concentration of the pathogen-inactivating compound in admixture with the body fluid prior to illumination is from about 15 µM to about 150 µM (e.g., about 30 µM to about 110 µM, about 60 µM to about 90 µM, about 75 µM). In some embodiments, the concentration of the pathogen inactivating compound in the mixture with the body fluid after illumination is at least 3 times less than the concentration of the pathogen inactivating compound in the mixture with the body fluid before illumination. In some embodiments, the treatments are sufficient to inactivate at least 4 log pathogens in the body fluid, if present. In some embodiments, the treatment method is sufficient to inactivate at least about 4 log pathogens, if present, wherein the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is from about 30 μM to about 110 μM, and the biological the liquid contains approximately 5 μM or less of IPA after illumination. In some embodiments, the treatment method is sufficient to inactivate at least about 4 log pathogens, if present, wherein the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is from about 30 μM to about 110 μM, and the biological the liquid contains approximately 2 μM or less of IPA after illumination. In some embodiments, the implementation of the biological fluid after illumination retains sufficient biological activity, so that the biological fluid is suitable for infusion to the subject.

In some embodiments, the biological fluid is a blood product. In some embodiments, the biological fluid is a plasma preparation. In some embodiments, the fibrinogen concentration in the plasma preparation after illumination is at least 70% of the fibrinogen concentration in the plasma preparation before illumination. In some embodiments, the concentration of factor VIII in the plasma preparation after illumination is at least 70% of the concentration of factor VIII in the plasma preparation before illumination. In some embodiments, the concentration of factor II, factor V, factor X, factor XI, protein C and/or protein S in the plasma preparation after illumination is at least 70% of the concentration of the corresponding factor II, factor V, factor X, factor XI, protein C and/or protein S in the plasma preparation prior to illumination.

In some embodiments, the body fluid is a platelet preparation. In some embodiments, the body fluid further comprises a platelet supplement solution. In some embodiments, the number of platelets in the platelet preparation after illumination is at least 80% of the retained platelets. In some embodiments, the retention of platelets in the platelet preparation after illumination is at least 80% (eg, at least 80% relative to the platelet preparation before illumination). In some embodiments, the pH value at 22° C. of the platelet preparation after illumination (eg, after treatment) is at least 6.2 (eg, at least 6.4, 5 days post illumination, 7 days post illumination). In some embodiments, the methods include, prior to illumination, incubating the body fluid with a photoactive, pathogen-inactivating compound for a period of 30 minutes to 24 hours (e.g., about 2, 4, 6, 8, 10, 12, 16, 20, 24 h).

The present invention also relates to a biological fluid with inactivated pathogens obtained by the methods of any of the above embodiments. In some embodiments, the pathogen-inactivated body fluid contains 5 μM or less of the pathogen-inactivating compound. In some embodiments, the pathogen-inactivated body fluid contains 2 μM or less of the pathogen-inactivating compound.

The present invention also relates to systems for treating a biological fluid, including a treatment chamber for receiving a biological fluid; one or more sensors designed to detect light in the processing chamber; and a first array of light sources placed to illuminate the biological fluid in the treatment chamber, wherein the first array of light sources includes a first channel of light sources designed to emit ultraviolet light at a first peak wavelength of the first array from about 315 nm to about 350 nm, and This first light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral width of less than 20 nm.

In some embodiments, the implementation of the first peak wavelength of the first matrix is from about 315 nm to about 335 nm. In some embodiments, the implementation of the first peak wavelength of the first matrix is from about 330 nm to about 350 nm. In some embodiments, the first peak wavelength of the first array is the average peak wavelength of one or more light sources of the first light source channel. In some embodiments, the one or more light sources of the first light source channel include one or more light emitting diodes (LEDs). In some embodiments, the first source matrix

- 17 042016 kov light additionally includes a second channel of light sources designed to emit light with a second peak wavelength, the first matrix, while the second channel of light sources includes one or more light sources, each of which emits light with a full width at half maximum ( FWHM) of a spectral width of less than 20 nm, and wherein the second peak wavelength of the first matrix differs from the first peak wavelength of the first matrix by at least 5 nm. In some embodiments, the second peak wavelength of the first array is in the ultraviolet A region, ultraviolet B region, or ultraviolet C region. In some embodiments, the second light source channel includes one or more LEDs.

In some embodiments, the implementation of the light sources of the first matrix of light sources are placed in the matrix unevenly. In some embodiments, the systems are designed to mix the biological fluid during processing. In some embodiments, the first light source array includes two or more light source panels. In some embodiments, the first matrix is designed such that the light sources of the first matrix illuminate the biological fluid in the treatment chamber with less than 25% irradiance variation over the entire surface of the biological fluid facing the first matrix.

In some embodiments, the systems further include a first platform located in a treatment chamber designed to contain a biological fluid. In some embodiments, the first platform and the first array of lights are designed to move relative to each other to change the distance between the first array of lights and the first platform. In some embodiments, the first platform may be slidably movable to deposit and withdraw body fluid into and out of the treatment chamber. In some embodiments, the first platform is designed to separately receive at least the first body fluid container as the first body fluid container and the second body fluid container. In some embodiments, one or more of the one or more sensors are attached to, or placed in, the first platform.

In some embodiments, the systems further include a barrier placed in the treatment chamber between the first array of light sources and the biological fluid. In some embodiments, the barrier placed in the treatment chamber between the first array of light sources and the biological fluid is transparent to light with a wavelength within 30 nm of the first peak wavelength of the first array. In some embodiments, one or more of the one or more sensors are affixed to, or housed in, a barrier located in the processing chamber between the first array of light sources and the biological fluid. In some embodiments, the first array includes: a first light source area designed to illuminate a biological fluid as the first illuminated biological fluid in the treatment chamber, and a second light source area designed to illuminate the second illuminated biological fluid in the treatment chamber.

In some embodiments, the systems further include a control circuit. In some embodiments, the control circuitry is designed to adjust or set the intensity or duration of light emission from each light source of the first array of light sources. In some embodiments, the control circuitry is designed to adjust or set the intensity or duration of light emission from each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to light detection. In some embodiments, the systems further include one or more sensors designed to detect the presence of a biological fluid in the treatment chamber.

In some embodiments, the systems further include a second array of lights directed away from the direction of the first array of lights, wherein the second array of lights includes a first light source channel designed to emit light at a first peak wavelength of the second array, and when In this case, the first light source channel of the second array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) of the spectral width of less than 20 nm. In some embodiments, the implementation of the first peak wavelength of the second matrix is substantially the same as the first peak wavelength of the first matrix. In some embodiments, the second array of light sources includes a second light source channel designed to emit light at a second peak wavelength of the second array, wherein the second light source channel of the second array includes one or more light sources, each of which emits full width light. at half maximum (FWHM) of the spectral width less than 20 nm, and at the same time the second peak wavelength of the second matrix differs from the first peak wavelength of the second matrix by at least 5 nm. In some embodiments, the first array of lights and the second array of lights are designed to move relative to each other to change the distance between

- 18 042016 the first matrix of light sources and the second matrix of light sources. In some embodiments, the systems further include a second array of lights directed in the same direction as the first array of lights, wherein the second array of lights includes a first light source channel designed to emit light at a first peak wavelength, the second array, wherein the first matrix of light sources and the second matrix of light sources define the first area between the first matrix of light sources and the second matrix of light sources, and wherein the first light source channel of the second matrix includes one or more light sources, each of which emits light with a full width of half maximum (FWHM) of the spectral width less than 20 nm.

In some embodiments, the systems further include a first platform positioned in the treatment chamber between the first light source array and a second light source array designed to receive biological fluid. In some embodiments, the systems further include: a first platform located in the treatment chamber in a first region designed to receive a biological fluid as the first applied biological fluid; and a second platform located in the treatment chamber outside the first area, designed to receive the second applied biological fluid, while the second array of light sources is directed to the second platform. In some embodiments, one or more of the one or more sensors are attached to, or placed in, the second platform.

In some embodiments, the systems further include a barrier placed in the treatment chamber between the second array of light sources and the biological fluid. In some embodiments, the barrier placed in the treatment chamber between the second array of light sources and the biological fluid is transparent to light within 30 nm of the first peak wavelength of the first array. In some embodiments, one or more of the one or more sensors are attached to, or placed in, a barrier placed in the processing chamber between the second array of light sources and the biological fluid.

In some embodiments, the systems further include a control circuit designed to adjust or set the intensity or duration of light emission from each light source of the second array of light sources. In some embodiments, the control circuitry is designed to adjust or set the intensity or duration of light emission from each light source of the second array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to light detection. In some embodiments, the control scheme is designed to a) determine a set of biological fluid characteristics; b) determining the treatment mode based on the set of characteristics of the biological fluid; c) adjusting or setting a set of parameters of the processing chamber in accordance with the processing mode; and d) illuminating the biological fluid according to the treatment regimen.

In some embodiments, the systems are designed to illuminate the body fluid in admixture with a photoactive, pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate pathogens in the body fluid, if present. In some embodiments, systems are designed to illuminate a body fluid in admixture with a photoactive, pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 1 log of pathogens in the body fluid, if present, and the body fluid after illumination is suitable for infusion into a subject without further treatment to remove residual photoactive, pathogen inactivating compound or photoproduct(s) thereof. In some embodiments, systems are designed to illuminate a body fluid in admixture with a photoactive, pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 1 log of pathogens in the body fluid, if present, and the body fluid contains 5 μM or less photoactive, pathogen inactivating compound after illumination. In some embodiments, systems are designed to illuminate a biological fluid in admixture with a photoactive, pathogen inactivating compound for a period of time and at an intensity sufficient to reduce the concentration of a photoactive, pathogen inactivating compound in admixture with a biological fluid to at least 3 times the concentration of photoactive, pathogen-inactivating compound mixed with biological fluid prior to illumination. In some embodiments, the systems are designed to illuminate the body fluid in admixture with a photoactive, pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 4 log pathogens in the body fluid, if present.

In some embodiments, the biological fluid is a blood product. In some embodiments, the biological fluid is a plasma preparation. In some embodiments, the biological fluid is a platelet preparation. In some embodiments, the biological fluid further comprises additional

- 19 042016 platelet solution. In some embodiments, the photoactive, pathogen inactivating compound is psoralen. In some embodiments, the photoactive, pathogen inactivating compound is amotosalen.

Brief description of the drawings

In FIG. 1A-E are perspective views of an exemplary system for handling biological fluids.

In FIG. 2A-D show exemplary light source array configurations.

In FIG. 3 is a perspective view of an exemplary body fluid processing system including an array of light sources with a plurality of light source panels.

In FIG. 4 is a perspective view of an exemplary body fluid processing system including opposing arrays of light sources directed at a body fluid platform.

In FIG. 5 is a perspective view of an exemplary body fluid processing system incorporating multiple arrays of light sources pointing in the same direction.

In FIG. 6A,B are perspective views of an exemplary body fluid processing system including an array of light sources directed toward a body fluid platform.

In FIG. 7A,B are block diagrams showing exemplary methods for handling biological fluids.

In FIG. 8A is an illustrative spectral result for a light source, indicating the wavelength of maximum peak intensity, 50% of maximum peak intensity, and full width at half maximum peak intensity.

In FIG. 8B shows illustrative spectral results for three light sources with different maximum peak intensity wavelengths and wavelength distributions.

In FIG. 9 shows illustrative spectral results for a wide band fluorescent lamp UV light source and narrow band LED UV light sources.

Detailed description of the invention

The following description is provided to enable a person skilled in the art to make and use various embodiments of the invention. Descriptions of specific systems, devices, methods, and uses are provided by way of example only. Various modifications of the examples described herein will become apparent to those skilled in the art, and the general principles set forth herein may be applied to other examples and applications without departing from the scope and spirit of the various embodiments. Thus, the various embodiments should not be limited to the examples described and shown herein, but should fall within the scope of the claims.

Biological fluids, such as, for example, blood and blood products, may contain contaminating pathogen(s) due to an infected donor or introduction of the pathogen(s) during processing. As such, it may be desirable to subject such body fluids to a treatment process (eg, pathogen inactivation, pathogen reduction) that reduces the risk of pathogen contamination. Ideally, such a process results in the inactivation of a wide range of pathogens (eg, viruses, bacteria, parasites) that may be present in the biological fluid. The treatment process may also result in the inactivation of other unwanted substances, such as, for example, cells (eg, leukocytes) and nucleic acids that may be present in the biological fluid.

The present invention primarily relates to methods and systems that provide unexpectedly high levels of virus and/or bacterial inactivation (e.g., photochemical inactivation) with more efficient photoconversion of pathogen inactivating compounds, such as, for example, psoralen pathogen inactivating compounds (e.g., S-59) . In some embodiments, the methods and systems may be sufficient to inactivate at least 1 log (at least 2 log, at least 3 log, at least 4 log) of pathogens in a body fluid and provide a body fluid with inactivated pathogens (e.g., , blood product), with sufficient photoconversion of the pathogen-inactivating compound after illumination such that the body fluid is suitable for infusion into a subject without further processing to remove residual pathogen-inactivating compound or photoproducts thereof.

In some embodiments, the photoconversion of the pathogen inactivating compound (e.g., S-59) is defined as % (e.g., concentration, wt%) of the compound remaining after illumination relative to the amount (e.g., concentration, wt%) of the original pathogen inactivating compound. In some embodiments, the % compound remaining after illumination is less than about 40%, less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5 %. In some embodiments, the photoconversion of the pathogen inactivating compound is defined as

- 20 042016 concentration (eg, μm concentration) of the residual pathogen inactivating compound remaining after illumination.

In FIG. 1A is a perspective view of an exemplary body fluid treatment system 100. As used herein, the term biological fluid means any fluid that occurs in or is derived from a body (e.g., human, animal, plant, microorganism), or which contains one or more components (e.g., biological substances) found in the body, excreted from, or derived from, an organism, including their synthetic variants. Biological fluids may include, but are not limited to, blood and blood products, vaccines, cells (eg, primary cells, cell lines, cell cultures), naturally occurring and recombinant proteins (eg, therapeutics, antibodies), bacterial cultures, viral suspensions, and the like. similar. As used herein, the term blood product means blood (e.g., whole blood), or a blood component or derivative, e.g., erythrocytes, leukocytes, platelets, plasma, cryoprecipitate, and cryosupernatant (e.g., cryoprecipitate-depleted fraction) of plasma, or a combination of one or more of those components that have been isolated from the blood. In some embodiments, the body fluid may further include a non-body fluid, such as, for example, saline (e.g., a diluent solution), including, but not limited to, saline, buffer, nutrient solution, platelet supplemental solution (PAS) and/or anticoagulant solution. In some embodiments, the body fluid has a volume of about 50 ml to about 1000 ml (e.g., about 100 ml to about 750 ml, about 200 ml to about 600 ml, about 100 ml, about 200 ml, about 300 ml, about 400 ml, about 500 ml, about 600 ml).

In some embodiments, treatment system 100 may be used to inactivate pathogen(s) in one or more body fluids, preferably body fluids mixed with one or more pathogen inactivating compounds (e.g., photoactive pathogen inactivating compound, psoralen). In particular, treatment system 100 may illuminate a mixture of one or more pathogen-inactivating compounds and a biological fluid with light (e.g., ultraviolet light) at specific wavelengths, causing a photochemical reaction and inactivation of pathogens such as viruses, bacteria, parasites, and other contaminants, such as, for example, cellular impurities (eg, leukocytes) that may be present in the biological fluid. In some embodiments, treatment system 100 may illuminate a mixture of one or more pathogen inactivating compounds and a body fluid having a volume of from about 50 ml to about 1000 ml (eg, from about 100 ml to about 750 ml).

In some embodiments, after the treatment system 100 illuminates the mixture of one or more pathogen-inactivating compounds and the body fluid with light (e.g., ultraviolet light, ultraviolet A light) at specific wavelengths (e.g., from about 315 nm to about 350 nm, from about 315 nm to about 335 nm, from about 330 nm to about 350 nm), causing a photochemical reaction and inactivating pathogens, the biological fluid is suitable for infusion into a subject without additional processing, including without exposure to a compound adsorption device ( UAS) to remove residual components useful for photochemical inactivation of pathogens, such as a pathogen inactivating compound (IPC) or its photoproducts. In some embodiments, after the treatment system 100 illuminates the mixture of one or more pathogen-inactivating compounds and the body fluid with light (e.g., ultraviolet light) at specific wavelengths (e.g., from about 315 nm to about 350 nm, from about 315 nm to about 335 nm, from about 330 nm to about 350 nm), causing a photochemical reaction and inactivating pathogens, the biological fluid contains less than 5 μm IPA (for example, less than 2 μM IPA).

The term "pathogen inactivating compound" means any suitable compound, such as a small molecular weight organic compound, which can be used to inactivate pathogens that may be present in a biological fluid, such as, for example, blood or a blood product. A pathogen inactivating compound, which is a photoactive or photoactivated or photochemical or photosensitizing compound, is an appropriate compound that requires some level of illumination to successfully inactivate pathogens. Such compounds are preferred for the inactivation of pathogens in biological products because they allow control of the inactivation process. In some embodiments, the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen (eg, S-59). Such photoactivated, or photochemical, pathogen-inactivating compounds,

- 21 042016 described herein may include, but are not limited to, psoralens, isoalloxazins, alloxazins, phthalocyanines, phenothiazines, and porphyrins, it being understood that these terms cover a general class of compounds, i.e., the base compound and its corresponding derivatives. For example, psoralens or psoralen generally means the basic compound psoralen and any of its derivatives (e.g., amotosalen), isoalloxazines, or isoalloxazine, generally means the basic compound isoalloxazine and any of its derivatives (e.g., riboflavin), and so on. Such derivatives have the structure of the main compound, as well as additional substituents on the main structure. Descriptions of such compounds include any of their salts.

The term amotosalen means the compound 3-(2-aminoethoxymethyl)-2,5,9-trimethylfuro[3,2g]chromen-7-one and any salts thereof. The compound may also be referred to as 4'-(4-amino-2-oxa)butyl-4,5',8trimethylpsoralen. If the methods of the present invention include the addition of amotosalen-Hl (HCl-salt of amotosalen), the removal of this compound from a biological fluid, such as, for example, a blood product (for example, platelet preparation, platelet dose, plasma preparation, whole blood preparation, plasma preparation) , is not limited to the removal of amotosalen-HCl, since amotosalen may be present in solution as other salts or as a free base. When used in the methods described herein, the removal of amotosalen means the removal of a compound in any form, such as free base form or any salt form, as measured in the assays described herein.

In some embodiments, the pathogen-inactivating compound is a 4-primary amine-substituted psoralen, which is a psoralen compound having an NH ₂ group linked to the 4' position of the psoralen by a hydrocarbon chain having a total length of 2-20 carbon atoms, where 0-6 of these carbons are independently replaced by NH or O, and each substitution point is separated from every other substitution point by at least two carbon atoms and separated from psoralen by at least one carbon atom. The 4'-substituted primary amine psoralens may have additional substituents at the 4, 5' and 8 positions of the psoralen, these substituents include, but are not limited to, the following groups: H and (CH ₂ ) _n CH ₃ where n=0-6 . In some embodiments, the 4'-primary amine-substituted psoralen contains: a) an R ₁ substituent on the 4' carbon atom selected from the group consisting of: -(CH ₂ ) _u -NH ₂ , -(CH ₂ ) _w -R ₂ -(CH ₂ ) _z -NH ₂ , -(CH ₂ ) _w -R ₂ -(CH ₂ ) _x R ₃ -(Ch ₂ ) _z -NH ₂ and -(CH ₂ ) _w -R ₂ -(CH ₂ ) _x -R ₃ -(CH ₂ ) _y -R ₄ -(CH ₂ ) _z -NH ₂ ; where R ₂ , R ₃ and R ₄ are independently selected from the group consisting of O and NH, and where u is an integer from 1 to 10, w is an integer from 1 to 5, x is an integer from 2 to 5 , y is an integer from 2 to 5 and z is an integer from 2 to 6; and b) substituents R ₅ , R ₆ and R ₇ on 4, 5' and 8 carbon atoms, respectively, are independently selected from the group consisting of H and (CH ₂ ) _v CH ₃ , where v is an integer from 0 to 5 ; or its salt.

In some embodiments, the pathogen-inactivating compound is a 5-primary amine-substituted psoralen, which is a psoralen compound having an NH2 group linked to the 5' position of the psoralen by a hydrocarbon chain having a total length of 1-20 carbon atoms, where 0-6 of these carbon atoms are independently replaced by NH or O, and each replacement point is separated from every other replacement point by at least two carbon atoms and separated from psoralen by at least one carbon atom. The 5'-substituted primary amine psoralens may have additional substituents at the 4, 4' and 8 positions of the psoralen, these substituents include, but are not limited to, the following groups: H and (CH ₂ ) _n CH ₃ where n=0-6 . In some embodiments, the 5'-primary amine-substituted psoralen comprises: a) an R1 substituent on the 5' carbon atom selected from the group consisting of: -(CH2)u-NH2, -(CH2)w-R2-(CH2)z -NH2, -(CH2)w-R2-(CH2)xR3-(CH2)z-NH2 and -(CH2)w-R2-(CH2)x-R3-(CH2)y-R4-(CH2)z- NH2; where R2, R3 and R4 are independently selected from the group consisting of O and NH, and where u is an integer from 1 to 10, w is an integer from 1 to 5, x is an integer from 2 to 5, y is is an integer from 2 to 5 and z is an integer from 2 to 6; and b) substituents R ₅ , R ₆ and R ₇ on 4, 4' and 8 carbon atoms, respectively, independently selected from the group consisting of H and (CH ₂ ) _v CH ₃ , where v is an integer from 0 to 5 where if R ₁ is selected from the group consisting of -(CH ₂ ) _u -NH ₂ , R ₇ is (CH ₂ ) _v CH ₃ , and where if R ₅ , R ₆ and R ₇ are (CH ₂ ) _v CH ₃ , and is an integer from 3 to 10; or its salt. Exemplary psoralen compounds are described, for example, in US Pat. No. 5,593,823.

In some embodiments, the body fluid (eg, a platelet preparation) is admixed with a pathogen inactivating compound (IPA) in a platelet supplement solution (PAS). In some embodiments, the implementation of the IPA is mixed with PAS prior to mixing with the biological fluid. Platelet additive solutions are known in the art, for example, as described in Alhumaidan et al. and Ringwald et al. (Alhumaidan, H. and Sweeney, J., J Clin Apheresis, 27: 93-98 (2012); Ringwald et al., Transfusion Medicine Reviews, 20: 158-64 (2006)), which are incorporated herein by reference in full. In some embodiments, the platelet supplement solution (PAS) contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments, additional

- 22 042016 platelet solution (PAS) is a PAS approved by a regulatory body or accrediting body known in the art.

In some embodiments, the platelet supplement solution (PAS) contains one or more of sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, sodium gluconate, glucose, and sodium bicarbonate.

In some embodiments, the PAS contains chloride, citrate, phosphate, and potassium. In some embodiments, the implementation of the PAS contains chloride, citrate and acetate. In some embodiments, the PAS contains chloride, citrate, phosphate, and acetate. In some embodiments, the PAS contains chloride, citrate, acetate, magnesium, potassium, and gluconate. In some embodiments, the PAS contains chloride, citrate, phosphate, acetate, magnesium, and potassium. In some embodiments, the PAS contains chloride, acetate, magnesium, potassium, and gluconate. In some embodiments, the PAS contains chloride, citrate, phosphate, acetate, magnesium, potassium, and glucose.

In some embodiments, the PAS contains sodium chloride, sodium acetate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, the implementation of the PAS contains sodium chloride, sodium acetate and sodium citrate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, and sodium phosphate. In some embodiments, the PAS contains sodium chloride, sodium citrate, sodium phosphate, and potassium chloride. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium phosphate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, glucose, and sodium bicarbonate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, glucose, and sodium bicarbonate.

In some embodiments, the PAS is PAS-I. In some embodiments, the PAS is a PlasmaLyte. In some embodiments, the PAS is Pas-II. In some embodiments, PAS is T-Sol. In some embodiments, the PAS is PAS-III. In some embodiments, the PAS is Intersol. In some embodiments, the PAS is PASIIIM SSP. In some embodiments, the PAS is Composol PAS-G. In some embodiments, PAS is M-Sol. In some embodiments, the PAS is an Isoplate. In some embodiments, the PAS is PAS-A. In some embodiments, the PAS is PAS-B. In some embodiments, the PAS is PAS-C. In some embodiments, the PAS is PAS-D. In some embodiments, the PAS is PAS-E. In some embodiments, the PAS is PAS-F. In some embodiments, the PAS is PAS-G.

In some embodiments, a biological fluid (e.g., plasma preparation, platelet preparation, platelet preparation in PAS) is incubated with a photoactive, pathogen-inactivating compound until illumination: for a period of 30 minutes to 24 hours (e.g., 2 to 24 hours, from 4 to 24 hours, 8 to 24 hours, 12 to 24 hours).

Biological fluids such as, for example, blood products, including, for example, whole blood, containing red blood cells and platelets, as well as containing plasma, blood products (for example, platelet preparation, plasma preparation), may contain pathogens, or may be contaminated with pathogens in processing. Therefore, it is desirable to subject such biological fluids (eg, blood products) to a pathogen inactivation process to reduce the risk of transfusion-transmitted diseases. Various processes and methods have been used to reduce the risk of diseases associated with the transfusion of blood products such as platelet-containing and plasma-containing blood products. In addition to screening and detection of pathogens, followed by disposal of contaminated blood products, treatments are available to inactivate pathogens (ie, to inactivate pathogens) that may be present. Ideally, such a method results in the inactivation of a wide range of pathogens such as viruses, bacteria and parasites that may be present in the blood product. For example, pathogen inactivation may include adding a small molecule compound that inactivates various pathogens, the preferred method comprising adding a photosensitizing compound (e.g. photoactive compound, photochemical compound) which, when activated by illumination with light of appropriate wavelengths, will inactivate various pathogens, which may be present. Two preferred methods that are commercially available include the addition of amotosalen or riboflavin to a blood product (eg, platelets, plasma), followed by UV light illumination. Other methods include illumination with UV light without the addition of a photosensitizing compound (e.g. UV light germicidal treatments) as well as illumination with other photoactive compounds including psoralen derivatives other than amotosalen, isoalloxazins other than riboflavin, alloxazins, dyes such as phthalocyanines , phenothiazine kra

- 23 042016 carriers (e.g. methylene blue, azure B, azure C, thionine, toluidine blue), porphyrin derivatives (e.g. dihematoporphyrin ester, hematoporphyrin derivatives, benzoporphyrin derivatives, alkyl-substituted sapphirine) and merocyanine 540 (Prodouz et al., Blood Cells 1992, 18(1): 10114; Sofer, Gail, BioPharm, August 2002). Other pathogen inactivation systems include, for example, those described in the publications of international patent applications No. Wo 2012071135, Wo 2012018484, Wo 2003090794, Wo 2003049784, Wo 1998018908, Wo 1998030327, Wo 1996039815, Wo 1996039820, Wo 1996039, Wo 1996039, WO 1996039820, Wo 1996039, Wo 1996039815, WO 1996039820, Wo 1996039, Wo 1996039 1993000005, US Patent Application No. US 20050202395 and US Patent Nos. 8296071 and 6548242, the contents of which are incorporated herein by reference in part relating to the inactivation of pathogens in blood products. In some embodiments, the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen. When the addition of a compound to a biological fluid such as, for example, blood products (e.g., platelets, plasma) is used to inactivate pathogens, it is desirable in some cases to remove any residual pathogen-inactivating compound or its by-product (e.g., photoproduct, degradation product), for example, by more efficient photoconversion of the pathogen-inactivating compound.

Some of the methods used to remove pathogen inactivating compounds or by-products thereof include the use of a device for removing the pathogen inactivating compound, for example, a device for reducing the concentration of the pathogen inactivating compound, including a compound adsorption device (CAD), for example, a small molecular weight organic compound and its by-products. products, in the biological fluid, while retaining to a large extent the desired biological activity of the biological fluid. In some embodiments, the removal device includes porous adsorbent particles in an amount sufficient to reduce the amount of the pathogen inactivating compound to a level below the desired concentration, wherein the adsorbent particles have an affinity for the pathogen inactivating compound. Various adsorbent particles are known, including, in general, particles made from any natural or synthetic material capable of interacting with compounds to be removed, including particles made from natural materials such as activated carbon, silica, diatomaceous earth, and cellulose. as well as synthetic materials such as hydrophobic resins, hydrophilic resins or ion exchange resins. Such synthetic resins include, for example, carbonaceous materials, polystyrene, polyacrylic, polyacrylic ester, cation exchange resin, and polystyrene-divinylbenzene. Such removal devices and adsorbent particles are described in International Patent Application Publication Nos. WO 1996040857, WO 1998030327, WO 1999034914 and WO 2003078023, and include, for example, Amberlite (Rohm and Haas) XAD-2, XAD-4, XAD-7, XAD-16, XAD-18, XAD-1180, XAD-1600, XAD-2000, XAD-2010; Amberchrom (Toso Haas) CG-71m, CG-71c, CG-161m, CG161c; Diaion Sepabeads (Mitsubishi Chemicals) HP20, SP206, SP207, SP850, HP2MG, HP20SS, SP20MS; Dowex (Dow Chemical) XUS-40285, XUS-40323, XUS-43493 (also known as Optipore V493 (dry form) or Optipore L493 (hydrated form)), Optipore V503, Optipore SD-2; Hypersol Macronet (Purolite) MN-100 MN-102 MN-150 MN-152 MN-170 MN-200 MN-202 MN-250 MN-252 MN-270 MN-300 MN -400, MN-500, MN-502, Purosorb (Purolite) PAD 350, PAD 400, PAD 428, PAD 500, PAD 550, PAD 600, PAD 700, PAD 900, and PAD 950. Materials used to create the immobilized matrix typically include a low melting polymer such as nylon, polyester, polyethylene, polyamide, polyolefin, polyvinyl alcohol, ethylene vinyl acetate, or polysulfone. In one example, devices for removing amotosalen after pathogen inactivation in a blood product are commercially available, including, for example, removal devices containing Hypersol Macronet MN-200 adsorbent contained in a matrix made of metal powders by sintering, wherein the matrix made of metal sintered powders, includes PL2410 plastic as a binder.

Inactivation of pathogens in a body fluid may require compliance with various treatment parameters, which include the treatment mode for the body fluid. Accordingly, the systems and methods described herein can be controlled and used to process one or more biological fluids in accordance with their one or more respective processing modes. As used herein, the term treatment regimen for a biological fluid means a set of treatment parameters necessary to inactivate one or more types of pathogens present in a biological fluid. Such parameters may include, but are not limited to, one or more peak wavelengths of light used for (e.g., one or more peak wavelengths of light illuminating) the biological fluid, the period(s) during which the light with one or more peak wavelengths wavelengths are used to illuminate a biological fluid, the intensities at which light with one or more peak wavelengths is applied to one or more

- 24 042016 more portions of the biological fluid, doses of energy of one or more peak wavelengths applied to one or more portions of the biological fluid, the angle of incidence at which light is used to illuminate the biological fluid, the temperature during the processing of the biological fluid, the method of mixing/mixing the biological fluid, the amount of time the body fluid is agitated or mixed, the distance between light sources that are used to illuminate the body fluid, and the type of body fluid, and so on. As used herein, the term peak wavelength of a light source means the wavelength at which light is emitted at maximum intensity by the light source. In FIG. 8A shows an exemplary spectral result 802 (e.g., spectral trace) for a light source, with a vertical solid line 804 indicating the maximum peak intensity wavelength (e.g., peak wavelength) and a horizontal dotted line 806 corresponding to 50% of the maximum peak intensity, and vertical dotted lines 812 and 814 corresponding to points 816 and 818 on each side of the half-peak representing the full width (e.g., emission bandwidth), along with a line segment on the wavelength axis between these points (e.g., FWHM, 20 nm full width, 10 nm peak FWHM). Spectral curves, including, for example, spectral curves 850, 860, 870 from light sources with similar peak intensities as shown in FIG. 8B may have symmetrical (B) or asymmetrical (A, C) wavelength distributions and peak wavelengths of different light sources. An illustrative difference of 885 for peak wavelengths (eg, >5 nm) is also indicated.

Pathogens inactivated using the systems and methods of the present invention may include, for example, any number of viruses, bacteria and/or parasites. Exemplary pathogens may include enveloped viruses, non-enveloped viruses, DNA-containing viruses such as, for example, those of the families Papillomaviridae, Parvoviridae, Herpesviridae, Poxviridae, Hepadnaviridae, Polyomaviridae, RNA-containing viruses, such as, for example, viruses of the families Reoviridae, Picornaviridae , Caliciviridae, Togaviridae, Arenaviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Rhabdoviridae, Filoviridae, Coronaviridae, Astroviridae, Bornaviridae, Arteriviridae, Hepeviridae, Retroviridae, human immunodeficiency viruses (e.g. HIV-1), HTLV-1, HTLV-2, adenovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, yellow fever virus, Zika virus, hepatitis D virus, hepatitis E virus, West Nile virus, Lassa virus, Ebola virus, Marburg disease virus, alpha viruses chikungunya), Epstein-Barr virus, dengue fever virus, cytomegalovirus, BK virus, influenza virus, African bluetongue virus adki and/or adenovirus. Illustrative pathogens may include Gram-positive bacteria, Gram-negative bacteria, Anaerobic bacteria, Escherichia (eg, E. coli), Yersinia (eg, Y. enterocolitica), Klebsiella (eg, K. pneumoniae), Serratia (eg, S. marcescens), Staphylococcus (eg S. epidermidis, S. aureus), Streptococcus (eg S. pyogenes), Bacillus (eg B. cereus), Clostridium (eg C. perfringens), Propionibacterium (eg P. acnes), Treponema ( e.g. T. pallidum), Borrelia (e.g. B. burgdorferi), Listeria (e.g. L. monocytogenes), Pseudomonas (e.g. P. aeruginosa), Haemophilus (e.g. H. parainfluenzae), Rickettsia (e.g. R. rickettsia ), Anaplasma (eg A phagocytophilium), Acinetobacter (eg A baumannii). Exemplary pathogens may also include the parasites Plasmodium (eg Plasmodium falciparum), Babesia (eg Babesia microti), Trypanosoma (eg Trypanosoma cruzi), Leishmania (eg Leishmania braziliensis). In addition, the systems and methods of the present invention can inactivate one or more types of unwanted cells, such as, for example, leukocytes, in a biological fluid. It should be understood that treatment of the body fluid to inactivate pathogens that may be present does not necessarily completely inactivate all pathogens that may be present, but greatly reduces the number of pathogens, greatly reducing the risk posed by the presence of pathogens (e.g. associated with transfusion disease from a blood product transmitted by transfusion infection from a blood product). Pathogen inactivation can be analyzed by measuring the number of infectious pathogens (eg, viral particles, bacteria) in a certain volume, and the level of inactivation is usually presented as log reduction in pathogen infectivity or log reduction in titers. Methods for analyzing log titer reduction and measuring titer to assess levels of pathogen inactivation are well known in the art. When testing the inactivation method for various pathogens, the reduction in a particular pathogen is a titer reduction of at least about 1 log, at least about 2 log, at least about 3 log, at least about 4 log, or at least about 5 log or more. Such a pathogen-inactivated body fluid, in addition to being used to treat (e.g., transfusion, therapy) a subject in need, can also be further processed for other uses, e.g., further processed to produce a body fluid-derived product such as eg platelet lysate from a pathogen inactivated platelet preparation or cryoprecipitate from a pathogen inactivated plasma preparation.

In FIG. 1A, an exemplary body fluid processing system 100 includes a processing chamber 102 for receiving one or more body fluids 108 and 110, and an array of sources

- 25 042016 lights 104 placed to illuminate one or more body fluids 108 and 110. In some embodiments, the implementation of the matrix of lights 104 may include single lights in the chamber 102, placed to illuminate one or more body fluids 108 and 110. In other embodiments implementation described below with reference to FIG. 3-5, multiple arrays of light sources can be used to illuminate one or more body fluids placed in various embodiments of the chamber 102. As used herein, the term light source array means one or more light sources located on any two- or three-dimensional surface. (eg continuous surface, discontinuous surface).

One or more channels of lights 106 are included in a matrix of lights 104. Each channel of lights 106 may be a set of one or more lights with the same wavelength (eg, peak wavelength). In an exemplary set, one light source may have a peak wavelength. In another exemplary set, two light sources may have the same peak wavelength. In another exemplary set, the plurality of light sources may all have different peak wavelengths. In the following exemplary set, a first subset of one or more light sources may have one peak wavelength and a second subset of one or more light sources may have a different peak wavelength. In a light source channel having a plurality of lights, all of the lights may have respective peak wavelengths, all of which are within a wavelength range (e.g., 1-20 nm range; e.g., 1 nm, 2 nm, 3 nm , 4 nm, 5 nm, or more, more and/or less than a specific wavelength) for the light source channel. For example, in some embodiments, in a light source channel having a plurality of light sources, all of the light sources may have peak wavelengths within the range specified herein, such as, for example, from about 315 nm to about 350 nm (for example, from about 315 nm to about 335 nm, from about 330 nm to about 350 nm). In the light source channel 106, each light source can be any light source that provides light with desired properties (e.g., peak wavelength, emission spectrum width), including, but not limited to, solid state light source (SSL), light emitting diodes (LED) , organic light emitting diodes (OLED), polymer light emitting diodes (PLED) and laser diodes. The light source channels 106 of the light source array 104 may be connected in series, in parallel, or in a combination of series and parallel circuits. In a light source channel 106 having a plurality of lights, these lights may be controlled together or separately.

Each channel of light sources 106 may be tilted (eg, tilted in a controlled manner) relative to the normal direction of the surface (eg, perpendicular to the surface) on which each channel of light sources 106 is located. For example, each channel of light sources 106 may be tilted at an angle from > 0° to about 50°, e.g. up to about 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5°, 4°, 3°, 2° or up to about 1 °, or <50°, <45°, <40°, <35°, <30°, <25°, <20°, <15°, <10°, <5°, <4°, <3° , <2° or <1° relative to the normal direction of the surface 124, defined by the plane of the light source array 104. Each channel of light sources 106 (for example, the light source in it) can be independently tilted, for example, with one or more channels of light sources 106 (eg, the light source(s) therein) are tilted at a different angle than one or more other channels of light sources 106 (eg, the light source(s) therein). Tilt one or more channels of light sources 106 may be desirable to control the intensity of light and/or the angle of incidence of light illuminating the biological fluids 108 and 110.

Each channel of light sources 106 can be adjusted or set to emit light at different intensities (e.g., corrected radiation dose, corrected energy dose) in which light at one or more peak wavelengths illuminates one or more portions of the body fluid. For example, each channel of light sources may emit light at a maximum intensity (e.g., 100%) or at less than a maximum intensity (e.g., about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20% or less).

Each channel of light sources 106 may emit different types of light. For example, each channel of the light sources may emit ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, and/or visible light. In addition, each channel of the light sources 106 may emit light with different peak wavelengths. For example, the peak wavelength(s) of light may be in the ultraviolet A region (e.g., 315-400 nm), ultraviolet B (e.g., 280-315 nm), ultraviolet C (e.g., 100-280 nm, 200-280 nm, 240-280 nm) or the visible region of the spectrum (for example, 400-800 nm). In some embodiments, the peak wavelength(s) of the emitted light may be from about 240 nm to about 250 nm, from about 245 nm to about 255 nm, from about 250 nm to about 260 nm, from about 255 nm to about 265 nm, from about 260 nm to about 270 nm, from about 265 nm to about 275 nm, from about 270 nm to about 280 nm, or from about 275 nm to about 285 nm. In some embodiments,

- 26 042016 peak wavelength(s) of emitted light may be from about 280 nm to about 290 nm, from about 285 nm to about 295 nm, from about 290 nm to about 300 nm, from about 300 nm to about 310 nm, from about 305 nm to about 315 nm, or from about 310 nm to about 320 nm. In some embodiments, the peak wavelength(s) of the emitted light may be from about 315 nm to about 325 nm, from about 320 nm to about 330 nm, from about 325 nm to about 335 nm, from about 330 nm to about 340 nm, from about 335 nm to about 345 nm, from about 340 nm to about 350 nm, from about 345 nm to about 355 nm, from about 350 nm to about 360 nm, from about 355 nm to about 365 nm, from about 360 nm to about 370 nm, from about 365 nm to about 375 nm, from about 370 nm to about 380 nm, from about 375 nm to about 385 nm, from about 380 nm to about 390 nm, from about 385 nm to about 395 nm, from about 390 nm to about 400 nm. In some embodiments, the peak wavelength of the emitted light may be about 240 nm, about 245 nm, about 250 nm, about 255 nm, about 260 nm, about 265 nm, about 270 nm, about 275 nm, about 280 nm, about 285 nm , about 290 nm, about 295 nm, about 300 nm, about 305 nm, about 310 nm, about 315 nm, about 320 nm, about 325 nm, about 330 nm, about 335 nm, about 340 nm, about 345 nm, about 350 nm, about 355 nm, about 360 nm, about 365 nm, about 370 nm, about 375 nm, about 380 nm, about 385 nm, about 390 nm, about 395 nm, or about 400 nm. In some embodiments, the peak wavelength of the emitted light may be from about 255 nm to about 275 nm (eg, from about 260 nm to about 270 nm, 265 nm). In some embodiments, the peak wavelength of the emitted light may be from about 275 nm to about 295 nm (eg, from about 280 nm to about 290 nm, 285 nm). In some embodiments, the peak wavelength of the emitted light may be from about 300 nm to about 320 nm (eg, from about 305 nm to about 315 nm, 310 nm). In some embodiments, the peak wavelength of the emitted light may be from about 315 nm to about 335 nm (eg, from about 320 nm to about 330 nm, 325 nm). In some embodiments, the peak wavelength of the emitted light may be from about 330 nm to about 350 nm (eg, from about 335 nm to about 345 nm, 340 nm). In some embodiments, the peak wavelength of the emitted light may be from about 355 nm to about 375 nm (eg, from about 360 nm to about 370 nm, 365 nm). In some embodiments, the peak wavelength of the emitted light may be from about 375 nm to about 395 nm (eg, from about 380 nm to about 390 nm, 385 nm). In some embodiments, the peak wavelength(s) of the emitted light may be in (1) ultraviolet A (eg, 315-400 nm); and (2) ultraviolet B (eg, 280-315 nm) or ultraviolet C (eg, 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the peak wavelength of the emitted light is in the ultraviolet A region, from about 315 nm to about 350 nm (e.g., from about 320 nm to about 345 nm, from about 315 nm to about 335 nm, from about 330 nm to about 350 nm).

In some embodiments, all channels of the light sources 106 of the array of light sources 104 may emit light with approximately the same (eg, with variation within ±1 nm, ±2 nm, ±3 nm, ±4 nm, ±5 nm) peak wavelength. The light source channels may include multiple lights with different peak wavelengths (eg, measured peak wavelengths) within a range of variability. In some embodiments, the average peak wavelength of a plurality of lights in a single light source channel may be the same as a specific peak wavelength of a particular light source in a single light source channel. In other embodiments, the average peak wavelength of multiple light sources of a single channel of light sources may differ (e.g., be about 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or more, more, or less) from all specific peak lengths. waves of each light source in one channel of light sources. In some embodiments, some light source channels may emit light at a first peak wavelength, and other light source channels may emit light at a second peak wavelength. The first peak wavelength may differ from the second peak wavelength by at least (eg, more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more. For example, in a non-limiting embodiment, the first light source channel may emit light at a peak wavelength in the ultraviolet A region as described above (e.g., from about 330 nm to about 350 nm), and the second light source channel may emit light at a peak wavelength wavelengths in the ultraviolet C region as described above (for example, from about 250 nm to about 260 nm, from about 260 nm to about 270 nm) or ultraviolet B as described above (for example, from about 305 nm to about 315 nm). In another non-limiting embodiment, the first light source channel may emit light at a peak wavelength in the ultraviolet A region as described above (e.g., from about 330 nm to about 350 nm) and the second light source channel may emit light at a peak wavelength also in ultraviolet

- 27 042016 region of the spectrum A, as described above (for example, from about 315 nm to about 335 nm, from about 355 nm to about 375 nm). In some embodiments, the first peak wavelength is the average peak wavelength of one or more light sources of the first light source channel. In some embodiments, the light source array 104 may include first, second, and third light source channels, each of which, respectively, emits light at a first, second, and third peak wavelength. In some embodiments, the first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more, and/or the second peak wavelength may differ from a third peak wavelength of at least (eg, greater than) 5 nm, 10 nm, 15 nm, or 20 nm, or more.

Alternatively, each of the first, second, and third peak wavelengths may differ from each other by at least (eg, more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. In some embodiments, the light source array may include first, second, third, and fourth light source channels, each of which, respectively, emits light at a first, second, third, and fourth peak wavelength. In some embodiments, at least two, at least three, or at least four of the first, second, third, and fourth peak wavelengths may differ from each other by at least (e.g., more than) 5 nm, 10 nm, 15 nm or 20 nm or more. Alternatively, each of the first, second, third, and fourth peak wavelengths may differ from each other by at least (eg, more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more. Alternatively, the first peak wavelength may be about (e.g., equal to, within a range of variability of ±1 nm, ±2 nm, ±3 nm, ±4 nm, ±5 nm) the third peak wavelength, the second peak wavelength may be about the same as (eg, equal to) the fourth peak wavelength, and the first peak wavelength may differ from the second peak wavelength by at least (eg, more than) 5 nm, 10 nm, 15 nm, or 20 nm.

In some embodiments, each channel of the light sources 106 may emit light with a narrow spectral bandwidth. For example, the full width at half maximum (FWHM) of the light spectrum width (e.g., spectral width at maximum peak intensity) emitted by each channel of light sources 106 may be less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 nm, less than 8 nm, less than 7 nm, less than 6 nm, or less than 5 nm. In some embodiments, the full width at half maximum (FWHM) of the spectral width of the light emitted by each light source channel is within 10 nm less and/or within 10 nm more than the peak wavelength (e.g., no more than 10 nm more, no more than 10 nm less than the peak wavelength). In some embodiments, the full width at half maximum (FWHM) of the spectral width of the light emitted by each light source channel may be greater than 1 nm, greater than 2 nm, greater than 3 nm, or greater than 4 nm, or greater. In other examples, 50% of the maximum peak light intensity emitted by each light source channel is within 10 nm, within 9 nm, within 8 nm, within 7 nm, within 6 nm, within 5 nm, within 4 nm or within 3 nm of the peak wavelength (eg, no more than 10 nm more, no more than 10 nm less than the peak wavelength; within 10 nm less, within 10 nm more than the peak wavelength). In other examples, the light intensity at 50% of the maximum peak light intensity emitted by each light source channel is within a spectral width of less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 less than 8 nm, less than 7 nm, less than 6 nm, or less than 5 nm . Commercially available LED and laser diodes are non-limiting examples of light sources that can provide such a narrow bandwidth at the peak wavelengths described above.

The use of illumination of biological fluids with narrow-bandwidth light at various selected peak wavelengths can maximize the intensity of photochemical reaction and/or pathogen inactivation while minimizing unnecessary exposure of biological fluids to light at wavelengths that can adversely affect (e.g., reduce, damage) on the biological function and/or desirable characteristics (eg quality) of the biological fluid. In addition, maximizing the efficiency of the photochemical process may, in turn, result in a reduction in the amount of pathogen inactivating compound required and/or in reducing or eliminating the need to remove (e.g., adsorb) unreacted pathogen inactivating compound and/or photoproducts from body fluids following inactivation treatment. pathogens.

In addition, illuminating biological fluids with narrow bandwidth light at one or more peak wavelengths can have unexpected benefits and results. For example, when a body fluid in admixture with the psoralen pathogen-inactivating compound amotosalen is illuminated with narrow ultraviolet A light, such as from an LED (e.g., peak wavelength of about 315-350 nm, peak wavelength of about 315-335 nm , peak wavelength approx. 330-350 nm, peak wavelength approx.

- 28 042016

325 nm, peak wavelength approx. 340 nm, peak wavelength approx. 365 nm), increased levels of photoconversion can be observed compared to existing biological fluid processing systems (INTERCEPT® Blood Processing System, Cerus Corporation) illuminating the same mixture liquids with broader ultraviolet A (UV-A) light from fluorescent lamps (eg, typically peak wavelength in the 320-400 nm range, about 352 nm). In addition, increased levels of pathogen inactivation (e.g., increased log reduction, wider spectrum of pathogens) and/or improved photoproduct profiles can be achieved when narrow bandwidth light with selected peak wavelength(s) in the UV-A region applied to a biological fluid in a mixture with a pathogen inactivating compound, in comparison with the use of existing systems for treating biological fluids with light with a wider radiation spectrum in the UV-A region. In addition, such an improvement can be achieved while maintaining the desired function and/or characteristics of the biological fluid after treatment with a pathogen inactivating compound and narrow-bandwidth light compared to a biological fluid treated using existing broader-bandwidth light sources.

In view of the advantages and unexpected results of treating (e.g., photochemically treating) a biological fluid with the narrow bandwidth light sources provided herein, it may be desirable to control various parameters of the light sources capable of emitting light with such a narrow bandwidth. Accordingly, the peak emission wavelength, emission spectrum width, tilt angle, emission duration, and emission intensity of each channel of the light sources 106 can be adjusted or set.

Adjustment of these different light source channel parameters can be made using control circuitry 126 operatively coupled (e.g., communicatively coupled) to processing chamber 102, light source array 104, and/or computer system 128. As used herein, the term operative link means any wired or a wireless connection between two or more components that allows two or more components to exchange information, control instructions and/or control signals. As discussed in more detail below, control circuit 126 may receive control instructions and/or control signals from computer system 128 and send control instructions and/or control signals to various components of processing chamber 102 to adjust or set various parameters associated with various components of camera 102. Adjusting various parameters of camera 102 may be desirable to ensure that camera processing parameters are consistent with the processing modes of one or more body fluids 108 and 110. It should be understood that in some examples, control circuit 126 and/or the function of control circuit 126 may be included in computer system 128. In some examples, control circuit 126 may include computer system 128 and/or a function of computer system 128. or bottom top of the treatment chamber 102). In some examples, the control circuitry 126 may be integrated into the processing chamber 102 (eg, located within the processing chamber 126 or form part of the structure of the processing chamber 102).

Turning to additional or optional components of system 100, FIG. 1B shows that an array of light sources 104 may be thermally coupled to a heat exchanger 122 (eg, a heat sink structure heat exchanger, a heat sink that may be operatively coupled to, and controlled by, control circuitry 126). Heat exchanger 122 can remove thermal energy from matrix 104 directed to one or more biological fluids 108 and 110, thereby minimizing exposure of biological fluids 108 and 110 to thermal energy (eg, thermal energy that can be detrimental to biological function). Additional control of the temperature of chamber 102 and/or the temperature of one or more of the body fluids 108 and 110 may be provided by a heating/cooling unit 114 that may be operatively associated with, and controlled by, control circuit 126 and designed to adjust or set the temperature of chamber 102. /cooling block 114 may be any suitable device known in the art, such as, for example, a fan, a heat pump, a Peltier cooling element, and/or a heat pipe. The heating/cooling unit 114 may be outside, inside and/or integrated into the chamber 102.

Processing chamber 102 may further include multiple interior surfaces designed to absorb light (eg, each designed to absorb light). For example, the processing chamber 102 may have a top wall 116, a bottom wall 118, and four side walls 120a-d that are made of or coated with a material (e.g., black plastic, black silicate, black paint) that absorbs light to a significant extent with certain wavelengths. As used herein, the term "substantially absorbs" means that more than 50%, 60%, 70%, 80%, or 90% or more of the light incident on a surface is not reflected (absorbed) by the surface. For example, each wall 116, 118 and 120a-d can largely

- 29 042016 foams to absorb ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, visible light or light with a wavelength less than 500 nm, 450 nm, 400 nm, 375 nm, 350 nm, 325 nm, 300 nm, 280 nm or 260 nm.

In some examples, the wavelengths of light substantially absorbed by the multiple interior surfaces of the processing chamber 102 may be dependent on one or more peak wavelengths of light emitted by one or more light sources 106 of the light source array 104. For example, walls 116, 118, and 120a- d can absorb light with a wavelength equal to the peak wavelength of light emitted by one or more light sources 106 of the array of light sources 104. The walls can absorb light with a wavelength in the range of 100 nm, 75 nm, 50 nm, 40 nm, 30 nm, 20 nm or 10 nm from the peak wavelength of light emitted by one or more light sources 106.

Alternatively or additionally, in some embodiments, the processing chamber 102 may further include one or more interior surfaces designed to reflect light (eg, each designed to reflect light). For example, the processing chamber 102 may have a top wall 116, a bottom wall 118, and four side walls 120a-d, each or all of which is made of or coated with a material that highly reflects light at certain wavelengths. As used herein, the term highly reflective means that more than 50%, 60%, 70%, 80% or 90% or more of the light incident on a surface is reflected by the surface.

For example, each wall 116, 118, and 120a-d may substantially reflect ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, visible light, or light with a wavelength less than 500 nm, 450 nm, 400 nm, 375 nm, 350 nm, 325 nm, 300 nm, 280 nm or 260 nm.

Containers for biological fluid

As shown in FIG. 1C, body fluids 108 and 110 may be contained in body fluid containers 130 and 132, respectively. Containers 130 and 132 may include an identifier (eg, barcodes 134, RFID, label) to identify the body fluid contained. In one example, the body fluid containers 130 and 132 may be made from any translucent or transparent or other highly translucent (e.g., translucent ultraviolet light at the peak wavelength specified herein) material, which may also be sterilizable and/or flexible. When the body fluids are blood or a blood product, the body fluid containers may contain a blood-compatible material such as, for example, the polymeric material used in the art for blood product bags (e.g., plasma bags, platelet bags).

In some embodiments, the body fluid containers may be separate containers (eg, container 130) not associated with other containers. In some embodiments, the body fluid containers may be associated with one or more additional containers, such as, for example, a storage container and/or a compound adsorption device. In some embodiments, such body fluid containers may be introduced into a treatment chamber to expose the body fluid to the desired amount of light, and then removed after such light exposure. In other embodiments, the implementation of the biological fluid can flow in and out of the processing chamber 102 through the use of multiple containers. In particular, the treatment chamber may include a treatment container 132 positioned within the treatment chamber to contain and process a biological fluid. The treatment container 132 can be adapted to connect to a source container located outside of the treatment chamber and an outlet container located outside of the chamber 102 to receive the treated biological fluid from the treatment container 132. Connections between the source container, the treatment container 132, and the outlet container can be carried out by tubes connecting the source container, the processing container 132 and the output container. The pumps may be operatively coupled or otherwise connected to one or more of the source container, tubing, treatment container 132, and outlet container to move the biological fluid 110 between containers. The pumps may be operatively associated with the control circuit 126, and the control circuit 126 may control the volumetric flow rate of the biological fluid between the containers by controlling the pumps.

Platform for containing biological fluid

As shown in FIG. 1C, treatment chamber 102 may further include a platform 144 designed to hold one or more body fluids 108 and 110 (eg, body fluid containers). Platform 144 may be a tray, well, or any other support suitable for containing body fluids or body fluid containers. Platform 144 may be configured as a drawer so that it can be manually slid into and out of the chamber, 102.

- 30 042016 form 144 can be moved in a sliding motion automatically by any suitable drive, such as an electric motor or servo. A platform 144 containing body fluids 108 and 110 may be placed above the array of lights 104 with the array of lights 104 directed toward platform 144. However, in other embodiments, platform 104 containing one or more body fluids may be placed below the array. light sources 104, with the array of lights 104 directed toward the platform 144. In other embodiments, the lights may be located on the array parallel to one of the side walls 120a-d of the processing chamber 102 to provide illumination of one or more biological fluids 108 and 110 from different sides.

In some embodiments, platform 144 may have first compartment 146 and second compartment 148 isolated from each other (eg, by baffle 150). The first compartment 146 may be designed to contain the first body fluid 108, and the second compartment may be designed to contain the second body fluid 110. The first body fluid 108 may be the same or a different type of body fluid as compared to the second body fluid 110. In other embodiments, the implementation of the platform 144 may have more than two compartments isolated from each other (for example, by partitions). Each compartment can be designed to hold body fluids separately.

In embodiments where platform 144 is designed to accommodate two or more body fluids, two or more different body fluids requiring different processing modes may be processed in the same processing chamber. For example, as shown in FIG. 1C, the first set of lights 152 directed at the first body fluid 108 may be controlled to emit light according to the treatment mode of the first body fluid 108, and the second set of lights 154 directed at the second body fluid 110 may be controlled. for emitting light in accordance with the processing mode of the second biological fluid 110.

In some embodiments, platform 144 may be translucent or transparent to light at selected wavelengths. In particular, platform 144 may be made of materials such as plastic or glass to be transparent to light at selected wavelengths. These selected wavelengths may be determined by the peak wavelength of the light emitted from one or more light source channels 106 of the light source array 104. For example, the platform may be translucent or transparent to light having a wavelength in the range of 200 nm, 150 nm, 100 nm, 75 nm, 40 nm, 30 nm, or 20 nm from the peak wavelength of light emitted from the light sources channel of matrix 104. In other embodiments, platform 144 may be translucent or transparent to certain types of light. For example, platform 144 may be transparent to ultraviolet light, ultraviolet A, ultraviolet B, ultraviolet C, and/or visible light.

In examples where platform 144 is divided into multiple compartments, each compartment may be translucent or transparent to the selected wavelengths of light described above. In other words, each compartment of the multiple platform compartments 144 may be made from a separate material to provide the desired translucency or transparency. For example, as shown in FIG. 1C, in one embodiment in which the platform 144 has a first compartment 146 and a second compartment 148, the first compartment 146 may be translucent or transparent to light at the first selected wavelength range, while the second compartment 148 may be translucent or transparent to light. with the second selected wavelength range.

Platform 144 and array of lights 104 can move relative to each other to increase or decrease distance 156 between array of lights 104 and platform 144. In one example, distance 156 can be adjusted or set in the range of 0-19 centimeters. Control circuit 126, which may be operatively associated with platform 144 and/or light source array 104, may control this movement. For example, control circuitry 126 may control the relative position of platform 144 and array of lights 104 by controlling the actuator(s) (eg, motor, servo, and so on) that controls the placement and orientation of platform 144 and/or array of lights 104. In addition In addition, the control circuit 126 may separately control the movement of the array of lights 104 and the movement of the platform 144. Changing the distance 156 between the platform 144 and the array of lights 104 may be desirable to change the dose of light energy (for example, changing the intensity of light) incident on one or more biological fluids 108 and 110, and/or the degree of heat transfer between the array of light sources 104 and one or more of the biological fluids 108 and 110.

In some embodiments, it may be desirable to mix one or more body fluids 108 and 110 before, during, and/or after illumination. In particular, agitation of the biological fluid may be desirable so that the fluid is sufficiently and uniformly exposed to the emitted light and/or any pathogen-inactivating compound.

- 31 042016

Accordingly, platform 144 may be designed to agitate one or more of the body fluids 108 and 110 contained on platform 144. In particular, platform 144 may vibrate (eg, due to vibration of a motor connected to or associated with platform 144), move in an orbital rotation ( for example, by an electric motor or servo that moves platform 144 along a predetermined orbital or displacement path), or move in a reciprocating manner (eg, side to side) at a certain frequency (eg, by a reciprocating motor). The frequency, onset and type of such agitation may be dependent on instructions and/or control signals received from the control circuit 126 and any suitable electromechanical actuator coupled to or associated with the platform 144.

Barrier

Processing chamber 102 may further include a barrier 158 positioned between the light source array 104 and one or more body fluids 108 and 110. For example, barrier 158 may be placed between the light source array 104 and platform 144. Barrier 158 may be a security barrier such as such as, for example, a barrier separating one or more of the body fluids 108 and 110 from the light source array 104 to reduce the likelihood of contamination and/or the need to clean the light source array 104. Alternatively or additionally, the barrier 158 may be a light filter that passes or attenuates the transmission of light at certain wavelengths. Barrier 158 may be made of materials such as plastic or glass to transmit or attenuate transmission of all or some of the wavelengths of light. Barrier 158 may, for example, have a thickness in the range of 1-10 mm.

In some examples, barrier 158 may be designed to transmit at least 50%, 60%, 70%, 80%, 90%, 95%, 97%, or 99%, or more, of light at the desired wavelength (e.g., wavelengths light emitted from the channel of light sources 106, wavelengths of light that photoactivate the specific pathogen-inactivating compound). In some examples, the barrier 158 may be designed to reduce the transmission of light below a certain wavelength, such as wavelengths less than 320 nm, 310 nm, 300 nm, 290 nm, 280 nm, 270 nm, 260 nm, 250 nm, or 240 nm. . In other embodiments, barrier 158 may be designed to attenuate transmission of light above a certain wavelength (eg, greater than 350 nm, greater than 370 nm, greater than 400 nm, or greater). As used herein, the term attenuation may mean that less than 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2%, or 1% of the light passes through the barrier 158.

In some examples, one or more wavelengths of light transmitted or attenuated by light barrier 158 may be dependent on one or more wavelengths of light emitted from a channel of light sources 106. For example, barrier 158 may be designed to attenuate transmission of light with wavelengths of at least 5 nm, 10 nm, 20 nm, 25 nm or 30 nm, or more, more or less than the peak wavelength of light emitted by the channel of light sources 106. The barrier may be translucent or transparent to light with a wavelength within 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, or 30 nm from the peak wavelength of the light emitted by the light source channel 106 of the light source array 104.

In some examples, barrier 158 may be divided into multiple sections, with each section capable of attenuating light transmission at any of the wavelengths described above and/or to different levels. In other words, all parts of the multiple parts of the barrier 158 can be made of different materials or the same material to provide the desired transmission or attenuation of the transmission of light at certain wavelengths and/or to different levels. For example, in one embodiment in which the barrier 158 includes a first portion 160 and a second portion 162, the first portion 160 located under the first compartment 146 of the platform 144 may reduce the transmission of light with a selected wavelength range, while the second portion 162 of the barrier 158 placed under the second compartment 148 of the platform 144 may attenuate the transmission of light with a different selected wavelength range.

In embodiments where platform 144 and/or barrier 158 are selectively translucent or transparent and selectively attenuate light at selected wavelengths and/or to different levels, one or more body fluids 108 and 110 may be substantially illuminated only by light at wavelengths waves corresponding to their processing modes. Accordingly, wavelength-selective illumination can lead to a more efficient photochemical reaction and hence more effective pathogen inactivation. In addition, exposure of one or more of the biological fluids 108 and 110 to unwanted wavelengths of light, which can be detrimental to biological function, can be minimized.

Light Array Configurations

In FIG. 2A-2D show exemplary light source array configurations 104.

In FIG. 2A shows an exemplary light array configuration in which lights 202 are distributed on a light source array 200. In particular, lights 202 may be placed in clusters of lights 204. Each of the lights 202 belonging to the same light source channel , can emit light with the same wavelength (e.g., peak wavelength) in the visible region of the spectrum or in the ultraviolet region of the spectrum, on

- 32 042016 example, in ultraviolet A, ultraviolet B or ultraviolet C. In other words, each light source channel can be a set of one or more light sources 202 having the same wavelength. As shown in FIG. 2A, each light source cluster may include two or more (e.g., three or more, four or more, five or more, six or more) lights 202. In some examples, two or more lights 202 may emit light at peak wavelengths. , which differ from each other by at least (for example, more than) 5 nm, 10 nm, 15 nm or 20 nm, or more. In other examples, two or more light sources 202 may include one or more (eg, two or more, three or more) pairs of light sources. For example, as shown in FIG. 2A, each light source cluster 204 may include four light sources 202. A first pair of light sources from a common light source channel may emit light at a first peak wavelength, and a second pair of light sources from another common light source channel may emit light at a second peak wavelength. a wavelength that differs from the first peak wavelength by at least (eg, more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more. Alternatively, the first pair of light sources (for example, the first and second light sources, respectively, of the first and second light source channels) may emit light with a first peak wavelength, the other light source (for example, the third light source of the third light source channel) may emit light with second peak wavelength, and another light source (for example, the fourth light source of the fourth channel of light sources) can emit light with a third peak wavelength, wherein the first peak wavelength differs from the second peak wavelength by at least (for example, more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more, and the second peak wavelength differs from the third peak wavelength by at least (for example, more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more. Alternatively, the first light source (e.g., the first light source of the first light source channel) may emit light at the first peak wavelength, the other light source (e.g., the second light source of the second light source channel) may emit light at the second peak wavelength, the other light source (for example, the third light source of the third light source channel) may emit light at the third peak wavelength, and the other light source (for example, the fourth light source of the fourth light source channel) may emit light at the fourth peak wavelength, wherein the first peak wavelength differs from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more, and the second peak wavelength differs from the third peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm or 20 nm, or more, and the third peak wavelength differs from the fourth peak wavelength by at least (for example, more than) 5 nm, 10 nm, 15 nm or 20 nm or more.

In FIG. 2B shows another exemplary light array configuration in which lights 208 (eg, of the same light channel) are distributed on an array of lights 206. In particular, the light array 206 may have an inner region 210 and an outer region 212. region 210 may occupy less than 50% (e.g., less than 40%, less than 30%, less than 20%, less than 10%) of the surface area of matrix 206, while the outer region may occupy the remaining percentage of the surface area (e.g., 50%-90% or more) of the matrix 206. Alternatively, the inner region 210 may occupy less than 90% (e.g., less than 80%, less than 70%, less than 60%) of the surface area of the matrix 206, while the outer region may occupy the remaining percentage of the surface area (e.g., 10% - 50% or more) of the matrix 206. The density of light sources 208 placed in the inner region 210 (for example, the same channel of light sources) may be greater than the density of the source into lights 208 placed in outer region 212 (eg, the same channel of light sources). In other embodiments, as shown in FIG. 2D, the density of lights 208 placed in the inner region 210 (e.g., the same light source channel) may be less than the density of the light sources 208 placed in the outer region 212 (e.g., the same light source channel), in matrix of light sources 216. In these examples, the density of light sources placed in the inner region 210 and the density of light sources placed in the outer region 212 may differ by at least 1.2 times, 1.5 times, 2 times, 2, 5 times, 3.0 times, or more (for example, greater density in the inner region relative to the outer region, as in Fig. 2B, greater density in the outer region relative to the inner region, as in Fig. 2D).

As shown in FIG. 2B and 2D, in some embodiments, light sources 208 are not placed on (e.g., near) one or more outer boundaries 214 of array 206. In other embodiments, light sources 208 may be placed on (e.g., near) one or more outer boundaries 214. .

In FIG. 2C shows another exemplary light source array configuration in which the light source array 216 has a first area 218 and a second area 220 separated by a third area 222. Each of the densities of light sources 224 placed in the first area 218 and in the second area 220 may be greater than density of light sources placed in areas outside the first area 218 and second area 220 (eg, in the third area 222), for example, in the third area containing no light sources. In some embodiments, the third region does not include

- 33 042016 one or more light sources. Such a configuration of an array of light sources may be desirable in the embodiments described above, in which the treatment chamber 102 includes a first body fluid 108 and a second body fluid 110. 108, and the lights placed in the second area 220 may be directed to the second body fluid 110. The lights of the first area 218 may illuminate the first body fluid 108 in accordance with the processing mode for the first body fluid 108, and the lights of the second area 220 may illuminate the second body fluid 110 in accordance with the processing mode for the second body fluid 110. The light sources may not be placed, or placed at a lower density, in areas (for example, the third area 222) that are not directed to either the first or second , biological fluid. For example, lights may not be needed in third region 222 if third region is directed toward baffle 150 of platform 144. Alternatively, third region 222 may include lights inclined toward the first or second body fluid, or both.

On a particular array of light sources, the light sources can be evenly distributed. For example, in FIG. 2A shows clusters of lights 204 (e.g., sixteen clusters of lights 204) evenly distributed on an array of lights 200. In the case of an array of lights 200, there may be four channels of lights, with each channel of lights including one light 202 in one. and the same relative position within each cluster 204. Thus, each cluster 204 may include four lights, one from each of the four different light source channels. Alternatively, on a particular array of light sources, the arrangement of the light sources and the arrangement of the channels of the light sources may be non-uniform. The light sources themselves can be placed unevenly. Lights for a particular light channel may not be evenly placed. The one or more light sources of the light source array may be in any positional arrangement (eg, linear, curvilinear, in row(s) and column(s), in a regular manner, at irregular intervals, and so on). A uniform distribution can be created by regular spacing and even spacing of light sources throughout the array, as shown by way of example in FIG. 2A. A non-uniform distribution can be created, for example, by irregular arrangement and uneven spacing of light sources throughout the array, for example, with inner and outer regions having different light source densities, as shown in FIG. 2B and 2D.

The various light source configurations described above may be desirable for illuminating different biological fluids that require corresponding different processing modes. In addition, various configurations of light sources may be desirable to achieve a substantially uniform illumination of the surface of a biological fluid or the surface of a container of biological fluid. For example, various configurations of light source arrangements for a matrix are shown in FIG. 2A-2D, and various options for the distance of light sources from the biological fluid are presented in Figs. 4 and 6B. The surface of the biological fluid may be defined, for example, by the surface of a biological fluid container containing the fluid, or by a plane intersecting any portion of the biological fluid. In one example, light sources of an array of light sources 104 may be designed (e.g., placed in an array) such that the light sources illuminate the biological fluid with less than 25% irradiance variation (e.g., less than 20%, less than 15%, less than 10%) throughout. surface of the biological fluid 108 facing the matrix of light sources 104. In other words, the light intensity in any part of the surface of the biological fluid 108 facing the matrix of light sources 104 may differ from the light intensity in any other part of the surface of the biological fluid 108 facing the matrix of sources of light 104 by less than less than 25% (eg, less than 20%, less than 15%, less than 10%).

In another example, the light sources of the light source array 104 may be designed such that the light sources illuminate any 5 square centimeter area of the surface of the biological fluid 108 with an emission variation of less than 25% (e.g., less than 20%, less than 15%, less than 10%) from the average integrated radiation over the entire surface of the biological fluid 108. In other words, the light intensity received within a 5 square centimeter area of the surface of the biological fluid 108 facing the matrix 104 may differ from the total light intensity (averaged over the entire surface area) received by the surface of the biological fluid 108 facing the matrix 104 by less than 25% (eg, less than 20%, less than 15%, less than 10%).

In FIG. 3-6B provide further embodiments of exemplary light source array configurations in processing systems designed to process one or more biological fluids.

In FIG. 3 is a perspective view of an exemplary body fluid processing system 300 having a light source array configuration including a plurality of

- 34 042016 in the light source panels 302 and 304 in the processing chamber 308. Although only two light source panels are shown in FIG. 3, in other examples, the light source array may include more than two (eg, three, four, five, or more) light source panels. Processing chamber 308 may be operatively coupled to control circuitry 306 capable of adjusting or setting various parameters of processing chamber 308, such as adjusting or setting parameters of light sources (e.g., peak emission wavelength, emission spectral bandwidth, tilt angle, emission duration, intensity radiation) in the processing chamber.

Each panel of lights 302 and 304 may be independently retrieved from the processing chamber 308 (e.g., a matrix of lights) and operably linked to a control circuit 306. Each panel of lights 302 and 304 may include a matrix of lights, such as 310 and 312. The control circuit 306 may adjust or set various parameters for each light source 314 of each panel of light sources 302 and 304. light source panels 302 and 304. In addition, each of the respective light source arrays 310 and 312 can be independently designed with the different light source distributions described above for FIGS. 2A-D.

All of the lights 314 of each light source array 310 and 312 located on panels 302 and 304, respectively, may be daisy-chained within each panel. Each panel 302 and 304 may be connected in parallel with another panel.

In some embodiments, the control circuit 306 may correct or set the positions of the light source panels 302 and 304 in the processing chamber 308. In particular, the control circuit 306 may send control instructions and/or control signals to, for example, the electric motor(s), servo(s) or any suitable electromechanical actuator connected or associated with each panel of lights 302 and 304 and this causes the panels to move relative to each other, increasing or decreasing the distance between the panels of lights 302 and 304. For example, the first panel of lights 302 can move in parallel plane of the first panel of lights 302, and the second panel of lights 304 can move parallel to the plane of the second panel of lights 304. The first panel of lights 302 can move to increase or decrease the first distance 318 between the bottom plane 316 of the processing chamber 308 and the first source panel Likewise, the second panel of lights 304 can also be moved to increase or decrease the second distance 320 between the bottom plane 316 and the second panel of lights 304.

In some embodiments, the processing chamber 308 may include a platform 322 (eg, a platform having one or more compartments). The light source panel of the plurality of light source panels in the light source array may be directed to each compartment, for example in a straight alignment without lateral displacement. For example, as shown in FIG. 3, the platform 322 may have a first compartment 324 and a second compartment 326 isolated from each other by a baffle 328. The first compartment 324 may be designed to contain the first body fluid 330 and the second compartment may be designed to contain the second body fluid 332. First Source Panel of light 302 may be directed to the first compartment 324, and the second panel of light sources 304 may be directed to the second compartment 326.

The configuration of processing chamber 308 to include multiple independently controlled light source panels may be desirable in instances where multiple types of body fluids are to be processed in chamber 308. For example, if first body fluid 330 is a different type from second body fluid 332, it may be desirable different processing modes for the first and second biological fluids. To provide these different treatment modes, the first panel 302 directed to the first body fluid 330 and the second panel 304 directed to the second body fluid 332 may be independently designed and independently controlled by the control circuit 306. For example, the control circuit 306 may set or adjust the configuration light sources on the first panel 302 and/or configuration of the lights on the second panel 304 to be different from each other. In addition, the control circuit 306 may set or adjust the distance between the first panel 302 and the first body fluid 330 and/or the distance between the second panel 304 and the second body fluid 332 to be different from each other. In addition, the control circuit 306 can set or adjust the characteristics of the light (e.g., duration, wavelength, intensity, spatial pattern, and temporal pattern of light emission) emitted by the first panel 302 and/or the characteristics of the light emitted by the second panel 304 to be different. from each other.

In FIG. 4 is a perspective view of an exemplary system 400 for treating one or more body fluids 406 and 408, including opposing arrays of light sources 402 and 404 located in a processing chamber 412. Each of the opposing arrays of light sources 402 and 404 may be thermally coupled to, respectively, heat exchangers 414 and 416.

- 35 042016

Processing chamber 412 may include a platform 410 placed between opposing arrays of light sources 402 and 404, designed to hold one or more body fluids 406 and 408. Providing illumination of body fluids 406 and 408 from opposite sides may be desirable, for example, for more uniform illumination. biological fluids.

All of the processing chamber 412, opposing arrays of light sources 402 and 404, heat exchangers 414 and 416, and platform 410 may be operatively linked to a control circuit 418 that may adjust or set their respective parameters.

The first opposing light source array 402 may be a first light channel matrix 420, and the second opposing light source array 404 may be a second light channel matrix (not shown). Each light source channel 420 of the first opposing light source array 402 and each light source channel of the second opposing light source array 404 may be designed to emit light at different peak wavelengths as described above.

In some embodiments, one or more wavelengths of light emitted from the first opposing light source array 402 may be the same as one or more wavelengths of light emitted from the second opposing light source array 404. For example, the first light source channel and the second light source channel of the first opposing array 402 may, respectively, emit light with a first peak wavelength and a second peak wavelength that differs from the first wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more . The third light source channel and the fourth light source channel of the second opposing array 404 may respectively emit light with wavelengths the same as (eg, equal to) the first and second peak wavelengths.

In some embodiments, all light sources of the first opposing array 402 may emit light at the same peak wavelength (eg, the first peak wavelength). All light sources of the second opposing array 404 may also emit light at the same peak wavelength (eg, the first peak wavelength). The peak wavelength of light emitted by all light sources of the first opposition array 402 may be the same (e.g., equal) as the peak wavelength of light emitted by all light sources of the second opposition array 404. Alternatively, the peak wavelength of light emitted by all light sources of the first opposing array 402 may differ from the peak wavelength of light emitted by all light sources of the second opposing array 404 by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm, or more.

In some embodiments, all of the first opposition array 402, the second opposition array 404, and the platform 410 may be designed to move relative to each other to increase or decrease distances 422, 424, and 426 between any pair of the first opposition array 402, the second opposition array 404, and platform 410. This movement may be by any number of actuators (e.g., electric motor, servo, etc.) controlled by control circuit 418, which may separately control movement of first opposing array 402, second opposing array 404, and platform 410.

In FIG. 5 is a perspective view of an exemplary system 500 including a processing chamber 502 and multiple arrays of lights 504 and 506 pointing in the same direction. Each of the arrays of light sources 504 and 506, respectively, may be thermally coupled to heat exchangers 508 and 510. Processing chamber 502 may optionally include multiple platforms 512 and 514, each designed to accommodate one or more (e.g., multiple) body fluids 516 Such a configuration of system 500 may provide separate treatment areas in processing chamber 502, each with separate access (eg, separate openings, separate retractable platforms) for processing multiple biological fluids. Such a configuration may be desirable for high throughput processing of biological fluids and/or for processing biological fluids (eg, different biological fluids) under different conditions or at different times (eg, non-parallel processing cycles).

Processing chamber 502, each of a plurality of light source arrays 504 and 506, each of heat exchangers 508 and 510, and each of platforms 512 and 514 may be operatively coupled (directly or indirectly) to a control circuit 518 that may adjust or set their various parameters. .

As shown in FIG. 5, the first array of lights 504 may be directed in the same direction as the second array of lights 506. The first platform 512 may be placed in the first region 520 between the first array of lights 504 and the second array of lights 506. The first array of lights 504 may only include processing chamber lights 502 that illuminate one or more body fluids in first region 520. For example, processing chamber 502 may be designed (eg, with an opaque baffle) such that light from the second array of light sources 506 cannot illuminate area 520. The second platform 514 may

- 36 042016 be placed in the second area 522 outside the first area 520 (for example, above the second matrix of light sources 506). The second array of lights 506 may be directed toward the second platform 514. The second array of lights 506 may be a single processing chamber light 502 that illuminates one or more body fluids in the second region 522. For example, the processing chamber 502 may be designed (e.g., with an opaque baffle) so that light from the first array of light sources 504 cannot illuminate area 522.

Processing chamber 502 may optionally include a third array of lights and a fourth array of lights (not shown) directed in the same direction as the first array of lights 504 and the second array of lights 506. The third array of lights may be directed towards the third platform. (not shown) placed between the third and fourth arrays of light sources (for example, in the third area). A fourth array of light sources may be directed to a fourth platform (not shown). One of ordinary skill in the art will appreciate that processing chamber 502 can be enlarged to accommodate any number of arrays of lights pointing in the same direction and any number of platforms. Each additional array of light sources may provide an additional area (not shown), for example, each additional array of light sources provides a single light source of the processing chamber 502 that illuminates one or more body fluids in its respective area. Likewise, each separate treatment area in the processing chamber may have separate access (eg, separate openings, separate retractable platforms) for independent processing of multiple biological fluids.

The first light source matrix 504 may include one or more light source channels 524, and the second light source matrix 506 may include one or more light source channels 526. All of the light source channels 524 of the first light source matrix 504 and all of the light source channels 526 of the second the light source arrays 506 may be designed to emit light at different peak wavelengths as described above.

In some embodiments, the peak wavelengths of the light emitted by the light source arrays 504 and 506 may be the same. This may be desirable in instances where multiple body fluids 516 (e.g., body fluids of the same type) that require the same treatment regimen or treatment with light of the same peak wavelength are to be processed in the chamber. 502. For example, the first light source channel and the second light source channel of the first light source array 504 may respectively emit light with a first peak wavelength and a second peak wavelength different from the first wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm or 20 nm or more. The third light source channel and the fourth light source channel of the second light source array 506 may respectively emit light with wavelengths the same as (eg, equal to) the first and second peak wavelengths.

In some embodiments, all channels of the light sources 524 of the first array of light sources 504 may emit light at a single peak wavelength (eg, the first peak wavelength). All channels of the light sources 526 of the second array of light sources 506 may also emit light with a single peak wavelength (eg, the first peak wavelength). The peak wavelength of light emitted by all light source channels 524 of the first light source array 504 may be the same (e.g., equal) as the peak wavelength of light emitted by all light source channels 526 of the second light source array 506. Alternatively, the peak wavelength of light emitted by all channels of light sources 524 of the first array of light sources 504 may differ from the peak wavelength of light emitted by all channels of light sources 526 of the second array of light sources 506 by at least (for example, more than) 5 nm, 10 nm, 15 nm and 20 nm or more.

In some embodiments, all of the light source arrays 504 and 506 and all of the platforms 512 and 514 can move relative to each other to increase or decrease the distance between any pair of light source arrays 504 and 506 and platforms 512 and 514. Such movement can be performed in account for any number of actuators (e.g., motor, servo, etc.) controlled by control circuitry 518, which can separately control the movement of each of the light source arrays 504 and 506 and each of the platforms 512 and 514. Similarly, additional light source arrays and platforms (for example, the third and fourth arrays of light sources, the third and fourth platforms, not shown) can move relative to each other, and such movement is carried out by any number of actuators (for example, an electric motor, a servo, etc.) controlled by a control circuit 518.

In FIG. 6A is a perspective view of an exemplary system 600 for processing one or more body fluids 606 and 608, including an array of lights 604 located in a processing chamber 612. An array of lights 604 is directed toward a body fluid platform 610. Light source array 604 may be thermally coupled to heat exchanger 616. Process chamber 612 may include a platform 610 placed below light source array 604 designed to hold one or more body fluids 606 and 608. All of process chamber 612, light source array 604, heat exchanger 616 and platform 610

- 37 042016 may be operatively linked to the control circuit 618, which may adjust or set their respective parameters. In FIG. 6B, exemplary system 600 may also include barrier 658 and various sensors 612, 666, 668, 680 in processing chamber 612. Barrier 658 is positioned between an array of light sources 604 and one or more body fluids 606 and 608, and barrier 658 may have any of the characteristics described above for barrier 158 in FIG. 1D. Sensors 612, 666, 668 may be attached to, or placed in platform 610. Sensors 680 may be attached to (e.g., top or bottom), or placed in barrier 658.

The light source matrix 604 may be a light source channel matrix. All of the light source channels of the light source array 604 may be designed to emit light at different peak wavelengths, as described above, and designed in different light source and light source channel arrangements, as described above.

Both of the array of light sources 604 and the platform 610 can be designed to move relative to each other to increase or decrease the distance 626 between them, as in the case of the movement described above. The platform 610 may be lowered to the bottom of the processing chamber 612, which may be raised above (e.g., any structural base including any components such as sensors or circuits) or flush with an outer bottom surface (e.g., floor, ground, table, etc.). The array of light sources 604 can be raised to the top of the processing chamber 612. In FIG. 6B, all of the light source array 604, barrier 658, and platform 610 may be designed to move relative to each other to increase or decrease distances 626, 682, and 684 between any pair of light source array 604, barrier 658, and platform 610. This movement may be any number of actuators (e.g., motor, servo, etc.) controlled by a control circuit 618 that can separately control the movement of the light array 604, barrier 658, and platform 610. In some embodiments, one or two light source arrays 604, barrier 658 and platform 610 may be fixed in position in processing chamber 612. For example, barrier 658 may be fixed in position in processing chamber 612. In another example, barrier 658 and array of light sources 604 may be fixed in position relative to each other. fixed distance 682 cameras e processing 612, wherein platform 610 can be designed to move to increase or decrease distances 626 and 684. As another example, barrier 658 and platform 610 can be fixed in position relative to each other at a fixed distance 684 in processing chamber 612 , wherein the array of lights 604 can be designed to move to increase or decrease distances 626 and 682.

System 600 in FIG. 6A,B may be similar to system 100 in FIG. 1A-E in many ways, including, for example, both system 600 and system 100 provide illumination of the body fluid from one side: for example, illumination of one side of a container of biological fluid, illumination of one side of a platform. System 600 in FIG. 6A,B may differ from system 100 in FIG. 1A-E in many ways, including, for example, that system 600 provides illumination of bodily fluid light from above (e.g., above the body fluid container, above the platform) and system 100 provides illumination from below (e.g., below the body fluid container, below the platform).

System 600 in FIG. 6A,B may be similar to system 400 in FIG. 4 in many ways, including, for example, that both system 600 and system 400 provide illumination of the body fluid from above (eg, above the body fluid container, above the platform). System 600 in FIG. 6A,B may differ from system 400 in FIG. 4 in many ways, including, for example, that system 600 provides illumination of the body fluid from one side rather than from opposite sides as in system 400.

Providing illumination of the biological fluids 606 and 608 from above may be desirable for a variety of reasons. For example, due to downward gravity, the biological fluids 606 and 608 may be stationary and passive on the platform 610 (eg, in containers, in wells, in trays). Thus, the body fluids 606 and 608 can be illuminated by light emitted above the platform 610 and the light need not pass through the platform 610 to reach the body fluids 606 and 608. . In addition, platform 610 need not be transparent or translucent to emitted light. Platform 610 may be made of materials and/or structures that are opaque to emitted light.

Sensors

Exemplary embodiments of the systems described above may include one or more different types of sensors used in respective processing chambers. In FIG. 1E shows that each of the various types of sensors described below may be operatively coupled (directly or indirectly) to control circuitry 126 and/or computer system 128. While various sensors are described below with respect to FIG. 1E, one skilled in the art will appreciate that the description

- 38 042016 can also refer to any of the other embodiments of the systems described above, an example being the various sensors shown in FIG. 6B.

Various sensors that may be used for the processing chamber 102 include one or more photosensitive sensors 112 designed to measure the intensity of light in different parts of the processing chamber and/or the intensity of light incident on different portions of one or more biological fluids 108 and 110, one or more airflow sensors 164, one or more thermal sensors 166 to measure the temperature of the treatment chamber 102 and/or the temperature of one or more body fluids 108 and 110, one or more sensors 168 or 172 to detect the presence of one or more body fluids 108 and 110 (e.g., pressure sensors, optical reflex sensors, optical transmissive sensors, label reading sensors, barcode scanning sensors, RFID sensors, and so on), one or more sensors 172 to determine the type of one or more body fluids 108 and 110 (for example, sensors for reading labels, sensors that scan barcodes, etc.) RFID sensors), one or more sensors 174 for determining the properties (e.g., transparency) of a biological fluid (e.g., optical sensors, spectroscopic sensors), one or more sensors 174 for detecting a photochemical compound in a biological fluid (e.g., by fluorescence spectrometry), one or more sensors 174 (e.g., ultrasonic sensors) placed to determine fluid depth in a portion (e.g., different portions) of one or more biological fluids 108 and 110.

Any of these various sensors can be placed anywhere (eg, outside, inside, forming part of the processing chamber structure) when practicing the various embodiments of the processing chambers described above. For example, one or more light sensors 112, one or more thermal sensors 166, and one or more airflow sensors 164 may be placed on an array of light sources 104. As shown in FIG. 1E, in embodiments of processing chambers 102 that include platform 144, one or more light sensors 112 and one or more sensors 168 for detecting the presence of one or more body fluids 108 and 110 may be placed on platform 144. As shown in FIG. 6B, in embodiments of processing chamber 612 that include platform 610 and barrier 658, one or more light sensors 612, one or more thermal sensors 666, and one or more sensors 668 for detecting the presence of one or more body fluids 606 and 608 may be attached. to, or placed in platform 610. Sensors 680, which may represent any of the various sensors described above, may be attached to, or placed in barrier 658.

Control system and user input

The following describes mechanisms for controlling and adjusting or setting various parameters of various components of various embodiments of treatment systems for biological fluids. Although mechanisms for controlling and adjusting or setting various parameters of various components of the processing system 100 are described below, one skilled in the art will appreciate that the following description may also refer to adjusting various parameters of various other embodiments of the processing systems described above.

In some embodiments, various parameters of various components of processing system 100 may be dynamically or automatically adjusted or set based on feedback signals received in control circuit 126 and/or computer system 128 from one or more different types of sensors. Alternatively, or additionally, various parameters of various components of processing system 100 may be adjusted or set based on user input to computer system 128.

Computer system 128 may be operatively coupled (directly or indirectly) to control circuitry 126 and/or to any of the various sensors described above. The computer system may include one or more processors 176, memory 178, input/output (I/O) interface 180, and user interface (UI) 182. One or more processors 176 may be one or more of any type of general purpose computer processor. The storage unit, or computer-readable medium, 178 may include one or more readily accessible storage units, such as random access memory (RAM), read-only memory (ROM), floppy disk, hard disk, optical media (e.g., CD or digital video disc), flash memory card, or any other form of digital storage, local or remote. In some examples, a readable medium memory 178 may be used to store instructions for illuminating one or more body fluids in accordance with their one or more processing modes, as described below with reference to the flowcharts of FIG. 7A-7B. Computer system 128 may include a wide variety of computers, such as a personal computer (PC), desktop computer, laptop computer, computer terminal, server computer, tablet,

- 39 042016 smartphone, personal digital assistant (PDA) and so on. In some examples, control circuit 126 and/or a function of control circuit 126 may be included in computer system 128.

Control circuit 126 may be implemented as any suitable logic circuit that can coordinate its control functions described herein. Such control functions may be provided by executing instructions implemented in software. Suitable logic may include a processor-readable medium that stores instructions embodied in software and a processor(s) that performs control functions when the instructions are executed. In addition, such control functions may also be provided by appropriate logic implemented in a hardware logic circuit, such as a programmable logic device or an ASIC implementing logic circuits providing the control functions of the control circuit 126. In addition, such control functions may be provided by an implementation that integrates both the processor(s) running the software and the hardware logic. In some examples, control circuitry 126 may include computer system 128 and/or a function of computer system 128.

At UI 182, a user may enter one or more characteristics from a property set of one or more body fluids 108 and 110. Alternatively, or additionally, one or more characteristics from a property set of one or more body fluids may be determined based on feedback signals to the computer. system 128 and/or control circuit 126 from one or more sensors to processing chamber 102. Characteristics from the biological fluid property set may include, for example, the type of biological fluid (e.g., blood product such as plasma, platelets, red blood cells; cells such as eukaryotic cells; proteins such as antibodies; vaccines), the photochemical reagent in the body fluid (e.g., type, volume, concentration), the volume of the body fluid, the clarity of the body fluid, the type and/or shape of the container containing the body fluid, and the temperature of the body fluid .

On the UI 182, the user can enter one or more parameters that make up the processing modes of one or more biological fluids 108 and 110. Alternatively or additionally, the computer system 128 can automatically determine one or more parameters of one or more processing modes of one or more biological fluids 108 and 110 based on a respective set of characteristics of one or more body fluids 108 and 110. In particular, memory 178 may store a computer program containing instructions that relate one or more body fluid characteristics to one or more body fluid processing mode parameters for each body fluid. The instructions that relate one or more characteristics of the biological fluid to one or more parameters of the treatment mode of the biological fluid for each biological fluid may be implemented as a set of user-programmable rules.

The computer system 128 may send control instructions and/or control signals to the control circuit 126 to adjust or set various parameters of the processing chamber 102. In some embodiments, various parameters of the processing chamber 102 may be adjusted or set based on the processing modes of one or more biological fluids 108 and 110 placed in the processing chamber. Alternatively, or additionally, various parameters of treatment chamber 102 may be adjusted or set based on feedback from various sensors located in treatment chamber 102.

Control circuit 126 may adjust or set the peak wavelength of light emitted by each channel of light sources 106. Control circuit 126 may adjust or set the intensity of light emitted by each channel of light sources 106. In particular, control circuit 126 may adjust or set the intensity of light emitted each channel of lights 106, from off (0% intensity) to maximum intensity (100% intensity) in 0.4% increments. The control circuit 126 may correct or set the angle of each light channel 106 by physically reorienting the light channel 106 or by adjusting the output direction of the light channel 106. For example, the control circuit may correct or set the angle of each light channel relative to the normal direction of the surface ( e.g., perpendicular to the surface) on which each channel of light sources is located, from 0 to 5°. Control circuit 126 may adjust or set the duration of light emission emitted by each channel of light sources 106. Control circuit 126 may adjust or set the width of the spectrum of light emitted by each channel of light sources 106. Any of these parameters may be adjusted or set based on a set of parameters, obtained, for example, from one or more light sensors 112 located in the processing chamber 102, and/or any other sensors located in the processing chamber 102.

Ability to individually control one or more of the peak wavelength of the radiation,

- 40 042016 duration of emission, intensity of emission and angle of emission of light from each channel of light sources 106 allows you to program and control various time and/or space-varying characteristics of the light emitted by the matrix of light sources 104. These characteristics of light can represent an important processing parameter in modes of treatment of biological fluids may be programmed by the user in computer system 128 and stored in memory 178. Light characteristics for one or more biological fluids may be automatically determined in computer system 128 based on a corresponding set of characteristics of one or more biological fluids.

In an exemplary set of light characteristics, all lights of the light source array 104 can be turned on and off at the same time at a user-adjustable rate to create an output strobe pattern. In another exemplary set of light characteristics, the intensity of light emitted by each light source channel may be modulated in time to create an output pattern that is sinusoidal in intensity. In another exemplary set of light characteristics, the first set of lights 152 of the array of light sources 104 may illuminate a portion of the first body fluid 108 facing the first set of lights 152 at a first intensity, and the second set of lights 154 of the array of light sources 104 may illuminate the second body fluid 110 facing the second set of light sources 154 at a second intensity.

Adjustments to various parameters of treatment chamber 102 may be made by control circuitry 126 prior to lighting one or more body fluids 108 and 110 in treatment chamber 102. Such initial adjustments by control circuitry 126 may include, for example, instructing or controlling heating/cooling unit 114 to adjust or set the temperature. processing chambers 102, instructing or controlling an array of lights 104 to move closer or further relative to one or more body fluids 108 and 110, instructing or controlling pumps 142 to flow the body fluid from source container 136 to processing container 132, instructing or controlling platform 144 for mixing one or more body fluids 108 and 110, and instructing or controlling each channel of light sources 106 to adjust or set the light intensity from off to on. initial intensity.

Adjustment of various parameters by control circuit 126 may also be made during illumination of one or more body fluids 108 and 110. Such adjustments by control circuit 126 may be performed dynamically based on feedback received in computer system 128 and/or control circuit 126 from various sensors. described above. In particular, memory 178 may store a set of user-programmable rules for matching input data from various sensors with necessary adjustments to various components of processing chamber 102. The ability to dynamically respond to data received by various sensors allows control circuit 126 to quickly adjust processing parameters that deviate from the intended treatment regimens for one or more of the treated body fluids 108 and 110. This, in turn, can provide more effective inactivation of pathogens in the one or more of the treated body fluids while minimizing exposure of the one or more body fluids to conditions processing chambers that can adversely affect (eg, reduce, disrupt, impair) the biological function and/or desirable characteristics of the biological fluid.

The following are examples of how control circuit 126 dynamically monitors various parameters of processing chamber 102 based on feedback from various sensors.

In some examples, the adjustment of the intensity of light emitted by each channel of light sources 106 by control circuit 126 may be based on data received by computer system 128 from one or more light sensors 112. For example, if the intensity of light incident on a portion of biological fluid 108, determined by one or more light sensors 114 is greater than or less than a threshold value, control circuit 126 may decrease or increase the light intensity of one or more light sources of an array of light sources 104 directed at the portion of body fluid 108, respectively. Alternatively, or additionally, control circuit 126 may increase or decrease the distance 156 between the platform 144 containing the biological fluid 108 and the array of light sources 104 to change the intensity of light falling on this portion of the biological fluid 108. The intensity threshold value can be based, for example, on one or more of: the depth of that portion of the body fluid 108, the type of body fluid 108, the clarity of the body fluid 108, the clarity of the container containing the body fluid 108, and the type of pathogen-inactivating compound mixed with the body fluid 108. The intensity threshold can be determined in the mode biological fluid processing 108 and/or in the biological fluid characteristic set 108. Suitable photosensitive sensors are well known in the art, such as, for example, photodiodes with a spectral response range that corresponds to

- 41 042016 (for example, includes) the wavelength(s) of the light sources proposed in this document (for example, a photodiode with a spectral response range of 210-390 nm). Exemplary photodiodes may include silicon photodiodes, silicon carbide photodiodes, or other suitable photodiodes such as GaAsP photodiodes, GaP photodiodes, and GaN photodiodes.

In some examples, the intensity of light emitted by each channel of light sources 106 of light source array 104 may be adjusted or set by control circuitry 126 based on depth data received by computer system 128 from one or more depth sensors 174. Ability to control intensity based on depth may be desirable in embodiments where the container 130 containing the biological fluid 108 may differ in depth (e.g., maximum depth), e.g., due to different volumes of the biological fluid (e.g., volumes less than the capacity of the container containing the biological liquid) and/or the depth may be inhomogeneous (e.g. in a blood bag). In particular, due to the characteristic central bulge of the blood bag, the central portions of the body fluid in the blood bag may be deeper than the peripheral portions of the body fluid in the blood bag. Therefore, the intensity of illumination required to sufficiently inactivate pathogens in the central region of the body fluid may be required to be greater than the intensity of illumination required to sufficiently inactivate pathogens in the peripheral region of the body fluid. Accordingly, one or more depth sensors 174 can detect these variations in the depth of the liquid in the container 130, and the control circuit 126 can adjust or set the intensity of each light source directed at different portions of the biological fluid 108, based on the determined depth of such portions. Alternatively or additionally, a container with a specific capacity (e.g., 1000 ml) containing a body fluid volume less (e.g., 300 ml) than the capacity of the container may have a shallower depth than a body fluid volume closer to (e.g., 900 ml) container capacity. Therefore, the light intensity required to sufficiently inactivate pathogens in a larger volume body fluid may be greater than the light intensity required to sufficiently inactivate pathogens in a smaller volume body fluid contained in a container of similar size. Accordingly, one or more depth sensors 174 may determine the depth of the liquid in the container 130, and the control circuit 126 may adjust or set the intensity of each light source directed at the biological fluid 108 based on the determined depth.

Control of intensity with depth and dynamic adjustment of intensity by control circuit 126 may also be important in instances where it is desired to agitate the body fluids, either continuously or intermittently, during processing. In particular, in embodiments in which the biological fluid 108 is agitated during processing, an oscillatory or wave motion may occur in the biological fluid 108, resulting in a standard wave pattern. Such movement can lead to depth variations in different portions of the biological fluid 108, thus causing a change in the dose of light energy sufficient to inactivate pathogens in such portions. Accordingly, based on feedback from one or more depth sensors 174, control circuit 126 may dynamically adjust or set the intensity of light emitted from one or more light source channels 106. of biological fluid 108 may be dynamically increased or decreased by control circuitry 126 based on whether the depth of that portion of biological fluid 108, as determined by one or more depth sensors 174, is greater than or less than a threshold depth. The threshold depth may be determined in the body fluid processing mode 108 and/or in the body fluid property set 108. Alternatively or additionally, a standard waveform may be determined based on variables such as, for example, body fluid volume, body fluid type, container size. , container shape, agitation speed, agitation pattern, and agitation stroke length, and computer system 128 may send control instructions and/or control signals to control circuit 126 to adjust or set the intensity of light emitted from one or more light source channels using a set user-programmable rules based on such wave patterns.

In some examples, the temperature of treatment chamber 102 and/or the temperature of one or more body fluids 108 and 110 may be adjusted or set by control circuitry 126 based on data received by computer system 128 from one or more thermal sensors 166. Suitable thermal sensors are well known in the art. areas such as, for example, the LM74 temperature sensor (Texas Installations, Inc.). For example, if the temperature of the body fluid 108, as detected by one or more thermal sensors 166, exceeds a threshold temperature, the control circuit 108 may adjust or set various operating parameters of the processing chamber 102 to lower the temperature of the body fluid 108. For example, the control circuit

The control circuit 108 may increase the distance 156 between the array of light sources 104 and the body fluid 108 and/or instruct or control the heating/cooling unit 114 to lower the temperature of the treatment chamber 102. Alternatively or additionally, the control circuit 126 may instruct or control the heat exchanger 122 to increasing the rate of heat transfer between the light source array 104 and the heat exchanger 122.

While specific examples of how feedback signals from various sensors may cause control circuitry 126 to adjust or set various parameters of various components of processing chamber 102 have been described above, these examples are to be limiting. It should be understood that the control circuit 126 may adjust or set any of the various adjustable parameters of the possible components of the various embodiments of the processing systems described above based on data determined by any of the various sensors described above and/or based on any user input in PI 182 computer system 128.

Methods for processing biological fluids

The various methods used to treat biological fluids to successfully inactivate one or more pathogens present in biological fluids are described below. The methods described below may optionally be applied using various embodiments of the systems described above. However, the methods described below need not necessarily be applied using the various embodiments of the systems described above, and may be used using any system suitable for applying the methods described below.

In FIG. 7A,B are flow charts illustrating methods 700 for processing biological fluids, in accordance with some embodiments. In various embodiments, some of the steps in the method may be combined and/or the order of some of the steps may be changed relative to the order shown in FIG. 7A, B. In addition, in some embodiments, operations shown in separate blocks/figures and/or described in connection with separate methods can be combined to obtain other methods and operations shown in the same blocks/figures and/ or described in connection with the same method can be separated in different ways.

In FIG. 7A, in step 702, a body fluid in admixture with one or more pathogen inactivating compounds (hereinafter referred to as body fluid) can be provided or received. In embodiments in which a treatment chamber (such as chamber 102) is used to process a biological fluid, step 702 may include an optional step 703 in which the biological fluid is introduced into, or enters, treatment chamber 102. For example, in FIG. 1C, in embodiments in which the treatment chamber 102 includes a slidable platform 144, the slidable platform 144 may be extended out of the treatment chamber, a biological fluid 108 (e.g., a containerized body fluid) may be placed on the slidable platform. 144 and the platform can be pushed back into the processing chamber 102.

In another example, in embodiments involving multiple containers 132, 136, and 138, optional step 703 may include inflow of body fluid 110 into treatment chamber 102 from source container 136.

At an optional step 704, a set of biological fluid characteristics may be determined. The determination of one or more properties from a set of biological fluid properties may be based on user input to computer system 128 and/or based on feedback from the various types of sensors described above. For example, in embodiments where processing chamber 102 includes one or more types of body fluid sensors 170, one or more types of sensors 170 may determine the type of body fluid.

In another example, a set of biological fluid characteristics may be determined using a barcode scanner 172. In particular, a barcode sensor 172 may scan a barcode 134 on the body fluid container 130, determining the identifier of the biological fluid 108 and transmitting this identifier to the computer system 128. Computer system 128 may then determine the property set of body fluid 108 based on the list stored in memory 178 by matching the identifiers of one or more body fluids to their respective property set.

At an optional step 706, a treatment mode for the biological fluid may be determined. Determining the processing mode may include determining any one or more of the parameters constituting the processing mode described above. For example, determining a processing mode may include determining one or more peak wavelengths of light to be used to illuminate the biological fluid. Determining the processing mode may include determining one or more light intensities at which light with one or more peak wavelengths will be emitted. Determining the processing mode may include determining one or more durations of light emission with one or more peak wavelengths.

In some examples, determining a treatment mode for a biological fluid may be based on a set of characteristics of the biological fluid. For example, after defining

- 43 042016 computer system 128 set of characteristics of the biological fluid, the computer system 128 may use a set of programmable rules to determine the processing mode of the biological fluid. The set of programmable rules may determine one or more processing mode parameters based on one or more characteristics from the set of biological fluid characteristics. For example, a programmable rule may match a certain type of photochemical with a certain peak wavelength of light, a certain duration of radiation, and a certain intensity of radiation of such a peak wavelength of light, sufficient to inactivate pathogens in a biological fluid mixed with this photochemical. In another example, a programmable rule may match the depth of a portion of a body fluid with a specific light intensity sufficient to inactivate pathogens in that portion of the body fluid.

In other examples, one or more processing mode parameters may be entered by a user into computer system 128.

In FIG. 7B, in examples where treatment chamber 102 is used to treat a body fluid, at an optional step 708, the parameter set of treatment chamber 102 may be adjusted or set by control circuit 126 based on the treatment mode. The set of parameters that may be adjusted or set based on the treatment mode may include the need for agitation of the biological fluid, one or more parameters associated with the agitation of the biological fluid (e.g., the frequency of the agitation and the type of agitation), the temperature of the treatment chamber 102, and the distance between the light source array 104 and platform 144.

At 710, the body fluid mixture (e.g., the body fluid mixture with a photoactive, pathogen-inactivating compound) is illuminated for a period of time and at an intensity (e.g., to provide a dose of light, to provide a total dose of light) sufficient to inactivate one or more pathogens in biological fluid. In some embodiments, the implementation of the illumination of the biological fluid is in accordance with the mode of processing.

In some examples, step 710 may include step 711 where the biological fluid may be illuminated with light at a first peak wavelength and illuminated with light at a second peak wavelength. In some embodiments of any of the methods provided herein, the first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, 20 nm, or 25 nm, or more . In some embodiments of any of the methods provided herein, second peak wavelength light is emitted from one or more second light sources, each light emitted having a full width at half maximum (FWHM) of less than 20 nm, and the second peak wavelength differs from the first peak wavelength by at least 5 nm, for example by at least 10 nm, 15 nm, 20 nm, or 25 nm. The first peak wavelength may be in the visible region of the spectrum or in the ultraviolet region of the spectrum, for example, ultraviolet A, ultraviolet B or ultraviolet C. Similarly, the second peak wavelength may be in the visible region of the spectrum or in the ultraviolet region of the spectrum. , for example, ultraviolet A, ultraviolet B, or ultraviolet C. In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 240 nm to about 250 nm, from about 245 nm to about 255 nm, from about 250 nm to about 260 nm, from about 255 nm to about 265 nm, from about 260 nm to about 270 nm, from about 265 nm to about 275 nm, from about 270 nm to about 280 nm, or from about 275 nm to about 285 nm. In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 280 nm to about 290 nm, from about 285 nm to about 295 nm, from about 290 nm to about 300 nm, from about 300 nm to about 310 nm, from about 305 nm to about 315 nm, or from about 310 nm to about 320 nm. In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 315 nm to about 325 nm, from about 320 nm to about 330 nm, from about 325 nm to about 335 nm, from about 330 nm to about 340 nm, from about 335 nm to about 345 nm, from about 340 nm to about 350 nm, from about 345 nm to about 355 nm, from about 350 nm to about 360 nm, from about 355 nm to about 365 nm, from about 360 nm to about 370 nm, about 365 nm to about 375 nm, about 370 nm to about 380 nm, about 375 nm to about 385 nm, about 380 nm to about 390 nm, about 385 nm to about 395 nm, from about 390 nm to about 400 nm. In some embodiments, the first peak wavelength and/or the second peak wavelength may be about 240 nm, about 245 nm, about 250 nm, about 255 nm, about 260 nm, about 265 nm, about 270 nm, about 275 nm, about 280 nm, approx. 285 nm, approx. 290 nm, approx. 295 nm, approx. 300 nm, approx. 305 nm, approx. 310 nm, approx. 315 nm, approx. 320 nm, approx. , about 345 nm, about 350 nm, about 355 nm, about 360 nm, about 365 nm, about 370 nm, about 375 nm, about 380 nm, about 385 nm, about 390 nm, about 395 nm or about

- 44 042016

400 nm. In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 255 nm to about 275 nm (eg, from about 260 nm to about 270 nm, 265 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 275 nm to about 295 nm (eg, from about 280 nm to about 290 nm, 285 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 300 nm to about 320 nm (eg, from about 305 nm to about 315 nm, 310 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 315 nm to about 335 nm (eg, from about 320 nm to about 330 nm, 325 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 330 nm to about 350 nm (eg, from about 335 nm to about 345 nm, 340 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 355 nm to about 375 nm (eg, from about 360 nm to about 370 nm, 365 nm). In some embodiments, the first peak wavelength and/or the second peak wavelength may be from about 375 nm to about 395 nm (eg, from about 380 nm to about 390 nm, 385 nm). In some embodiments, the implementation of the first peak wavelength and/or the second peak wavelength may be from about 315 nm to about 350 nm.

In some embodiments of any of the methods provided herein, the total dose of ultraviolet light for illuminating a biological fluid emitted by an array of one or more first light sources is from about 0.5 J/cm ² to about 50 J/cm ² , for example, from about 0.5 J/cm ² to about 10 J/cm ² , from about 0.5 J/cm ² to about 15 J/cm ² , from about 0.5 J/cm ² to about 25 J/ ^cm2 , from about 1 J/ ^cm2 to about 10 J/ ^cm2 , from about 1 J/ ^cm2 to about 15 J/ ^cm2 , from about 1 J/ ^cm2 to about 25 J/ ^cm2 , from about 3 J/cm ² to about 10 J/cm ² from about 3 J/cm ² to about 15 J/cm ² from about 3 J/cm ² to about 25 J/cm ² from about 5 J/cm 2 cm ² to about 10 J/cm ² , from about 5 J/cm ² to about 15 J/cm ² , from about 5 J/cm ² to about 25 J/cm ² , from about 10 J/cm ² to about 30 J/cm ² from about 10 J/cm ² to about 20 J/cm ² from about 15 J/cm ² to about 50 J/cm ² , from about 15 J/cm ² to about 35 J/cm ² , from about 20 J/cm ² to about 30 J/cm ² , from about 25 J/cm ² to about 50 J /cm ² from about 30 J/cm ² to about 40 J/cm ² or from about 40 J/cm ² to about 50 J/cm ² . In some embodiments, the total dose of ultraviolet light for illuminating a biological fluid emitted by an array of one or more first light sources is about 0.5 J/cm ² or more, such as about 1 J/cm ² or more, 2 J /cm ² or more, 3 J/cm ² or more, 4 J/cm ² or more, 5 J/cm ² or more, 6 J/cm ² or more, 7 J/cm ² or more, 8 J/cm ² or more, 9 J/ ^cm2 or more, 10 J/ ^cm2 or more, 15 J/ ^cm2 or more, 20 J/ ^cm2 or more, 25 J/ ^cm2 or more, 30 J/ ^cm2 or more more, 35 J/cm ² or more, 40 J/cm ² or more, 45 J/cm ² or more, or 50 J/cm ² or more. In some embodiments, the total dose of ultraviolet light for illuminating a biological fluid emitted by a set of one or more first light sources is less than about 50 J/cm ² , less than about 40 J/cm ² , less than about 30 J/cm ² , less than about 25 J/cm ² , less than about 20 J/cm ² , less than about 15 J/cm ² , or less than about 10 J/cm ² . In some embodiments, illumination of the biological fluid occurs for a period of time and at an intensity sufficient to provide a total dose (e.g., the above total dose) of ultraviolet light to illuminate the biological fluid (e.g., any suitable combination of duration and intensity sufficient to provide total dose of light in the ultraviolet region of the spectrum). In some embodiments, the implementation of the intensity is from 1 to 1000 mW/cm ² (for example, from 1 to 100 mW/cm ² ). In some embodiments, the duration is from 1 second to 2 hours (eg, from 1 to 60 minutes).

In some embodiments of any of the methods provided herein, first peak wavelength light and second peak wavelength light may be provided by a first light source and a second light source, respectively. The first light source and/or the second light source may be, for example, a solid state light source (SSL), light emitting diodes (LED), organic light emitting diodes (OLED), polymer light emitting diodes (PLED) or laser diodes. In some examples, the first light source and the second light source may be included in the light source channels 106 of the light source array 104.

In some embodiments of any of the methods provided herein, the first and second light sources may emit light with a narrow emission spectrum. In some examples, the full width at half maximum (FWHM) of the light spectrum width (e.g., the spectral width at maximum peak intensity) emitted by the first light source and/or the second light source may be less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 nm, less than 8 nm, less than 7 nm, less than 6 nm or less than 5 nm. In some embodiments, the full width at half maximum (FWHM) of the spectral width of the light emitted by the first light source and/or the second light source is within 10 nm less, within

- 45 042016 lx 10 nm more than the peak wavelength of the first light source and/or the second light source, respectively (for example, not more than 10 nm more, not more than 10 nm less than the peak wavelength of the first light source and/or the second light source, respectively) . In some embodiments, the full width at half maximum (FWHM) of the spectral width of the light emitted by the first light source and/or the second light source may be greater than 1 nm, greater than 2 nm, greater than 3 nm, or greater than 4 nm, or greater. In other examples, the light intensity at 50% of the maximum peak light intensity emitted by the first light source and/or the second light source may be within 10 nm of the peak wavelength of the light emitted by the first and/or second light source.

In some examples, illumination of the biological fluid with light at the first peak wavelength and light at the second peak wavelength occurs sequentially. In other examples, illumination of the biological fluid with light at the first peak wavelength and light at the second peak wavelength occurs simultaneously. In other examples, illuminating the biological fluid with light at a first peak wavelength and illuminating the biological fluid with light at a second peak wavelength partially overlap (e.g., illuminating only (from the processing chamber lights) with light at the first peak wavelength for a period of time, then with light with both the first and second peak wavelengths for some period of time, then only (from the processing chamber light sources) light at the second peak wavelength for some period of time).

In some embodiments of any of the methods provided herein, illumination of the biological fluid with light at a first peak wavelength may occur during a first period of time, and illumination of the biological fluid with light at a second peak wavelength may occur during a second period of time. The first duration may be equal to, or different from, the second duration. In some examples, the first duration may be at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 times or more than the second duration. In other examples, the second duration may be at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 times or more than the first duration.

In some examples, the illumination of the biological fluid with light with a first peak wavelength and a second peak wavelength may be performed in accordance with the processing mode. For example, the processing mode may determine the light characteristics used in illuminating the biological fluid. An exemplary processing mode may define first illuminating the biological fluid with light at a first peak wavelength for a first period of time at a first intensity, and then illuminating the biological fluid with light at a second peak wavelength for a second period of time at a second intensity. Another exemplary processing mode may determine that the body fluid is illuminated with light of the first peak wavelength for a first period of time at the first intensity, and simultaneously (e.g., with at least partial overlap) the body fluid is illuminated with light of the second peak wavelength for the second period of time at the second intensity. In some embodiments, the processing mode may define one or more mixing conditions that are used before, during, and/or after illumination of the biological fluid. An exemplary processing mode may define one or more mixing conditions that are used before, during, and/or after illuminating the biological fluid with light of the first peak wavelength, and one or more mixing conditions that are used before, during, and/or after illuminating the biological fluid. liquid light with a second peak wavelength.

In some embodiments of any of the methods provided herein, the biological fluid may be illuminated with light at a single peak wavelength (eg, the first peak wavelength). In some examples, step 710 may include step 712, in which the biological fluid can be illuminated with light with a single peak wavelength (eg, the first peak wavelength). One peak wavelength (for example, the first peak wavelength) may be in the visible region of the spectrum or in the ultraviolet region of the spectrum, ultraviolet A, ultraviolet B, ultraviolet C. In other examples, one peak wavelength (for example, the first peak wavelength) may be from about 240 nm to about 250 nm, from about 245 nm to about 255 nm, from about 250 nm to about 260 nm, from about 255 nm to about 265 nm, from about 260 nm to about 270 nm , from about 265 nm to about 275 nm, from about 270 nm to about 280 nm, or from about 275 nm to about 285 nm. In some embodiments, one peak wavelength (e.g., the first peak wavelength) may be from about 280 nm to about 290 nm, from about 285 nm to about 295 nm, from about 290 nm to about 300 nm, from about 300 nm to about 310 nm, from about 305 nm to about 315 nm, or from about 310 nm to about 320 nm. In some embodiments, one peak wavelength (e.g., the first peak wavelength) may be from about 315 nm to about 325 nm, from about 320 nm to about 330 nm, from about 325 nm to about 335 nm, from about 330 nm to about 340 nm, from about 335 nm to about 345 nm, from about 340 nm to about 350 nm, from about 345 nm to about 355 nm, from about 350 nm to about

- 46 042016

360 nm, from about 355 nm to about 365 nm, from about 360 nm to about 370 nm, from about 365 nm to about 375 nm, from about 370 nm to about 380 nm, from about 375 nm to about 385 nm, from about 380 nm to about 390 nm, from about 385 nm to about 395 nm, from about 390 nm to about 400 nm. In some embodiments, one peak wavelength (e.g., the first peak wavelength) may be about 240 nm, about 245 nm, about 250 nm, about 255 nm, about 260 nm, about 265 nm, about 270 nm, about 275 nm, approx. 280 nm, approx. 285 nm, approx. 290 nm, approx. 295 nm, approx. 300 nm, approx. 305 nm, approx. 310 nm, approx. 315 nm, approx. nm, about 345 nm, about 350 nm, about 355 nm, about 360 nm, about 365 nm, about 370 nm, about 375 nm, about 380 nm, about 385 nm, about 390 nm, about 395 nm, or about 400 nm. In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 255 nm to about 275 nm (eg, from about 260 nm to about 270 nm, 265 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 275 nm to about 295 nm (eg, from about 280 nm to about 290 nm, 285 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 300 nm to about 320 nm (eg, from about 305 nm to about 315 nm, 310 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 315 nm to about 335 nm (eg, from about 320 nm to about 330 nm, 325 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 330 nm to about 350 nm (eg, from about 335 nm to about 345 nm, 340 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 355 nm to about 375 nm (eg, from about 360 nm to about 370 nm, 365 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 375 nm to about 395 nm (eg, from about 380 nm to about 390 nm, 385 nm). In some embodiments, one peak wavelength (eg, the first peak wavelength) may be from about 315 nm to about 350 nm.

In some embodiments of any of the methods provided herein, light with a single peak wavelength (eg, a first peak wavelength) may provide the first light source. In some examples, the first light source may be the sole light source of the processing chamber 102 used to illuminate the biological fluid. The first light source may be, for example, one or more solid state light sources (SSL), light emitting diodes (LED), organic light emitting diodes (OLED), polymer light emitting diodes (PLED) or laser diodes. For example, the first light source may be included in the light source channels 106 of the light source array 104. As shown in FIG. 1A1E, the channels of the light sources 106 may only be directed to one side of the container 130 containing the biological fluid 108.

The first light source may emit light with a narrow emission spectrum. In particular, the light intensity at 50% of the maximum peak intensity of the light emitted by the first light source may occur at a wavelength within less than 10, 20, 30, or 40 nm of the peak wavelength of the light emitted by the first light source. In other examples, the full width at half maximum (FWHM) of the spectral width of the light emitted by the first light source may be less than 20 nm, 18 nm, 16 nm, 14 nm, 12 nm, 10 nm, 9 nm, 8 nm, 7 nm, 6 nm, 5 nm or less than 5 nm.

In some embodiments of any of the methods provided herein, the treatment method is sufficient to inactivate at least about 1 log of pathogens, if present (e.g., when present), such as at least about 2 log, 3 log , 4 log, 5 log, 6 log, 7 log, 8 log, 9 log, or 10 log (eg, after exposing the mixture to light sufficient to photochemically inactivate pathogens). In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogens, if present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log , 7 log, 8 log, 9 log, or 10 log, and wherein the biological fluid contains about 5 μM or less, for example, about 4 μm or less, 3 μm or less, 2 μM or less, or 1 μm or less ISI, after illumination. In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogens, if present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log , 7 log, 8 log, 9 log, or 10 log, wherein the concentration of the pathogen-inactivating compound in admixture with the biological fluid before illumination is from about 15 μM to about 150 μM, and wherein the biological fluid contains about 5 μM or less, for example, about 4 μM or less, 3 μM or less, 2 μM or less, or 1 μM or less ISI, after illumination. In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogens, if present (e.g., when present), e.g.

- 47 042016 at least about 2 logs, 3 logs, 4 logs, 5 logs, 6 logs, 7 logs, 8 logs, 9 logs, or 10 logs, wherein the concentration of the pathogen-inactivating compound in admixture with the biological fluid before illumination is from about 15 µM to about 150 µM (for example, from about 30 µM to about 110 µM, from about 60 µM to about 90 µM, about 75 µM), while the total dose of ultraviolet light illuminating the biological fluid is from about 0.5 J/ cm ² to about 50 J/cm ² (for example, from about 3 J/cm ² to about 15 J/cm ² ), and while the biological fluid contains about 5 μm or less, for example, about 4 μm or less, 3 μM or less, 2 μM or less, or 1 μM or less IPS, after illumination. In some embodiments, the treatment method is sufficient to inactivate at least about 4 log pathogens, if present (e.g., when present), wherein the concentration of the pathogen-inactivating compound in admixture with the body fluid prior to illumination is from about 30 μM to about 110 μM, and while the biological fluid contains approximately 5 μm IPA after illumination. In some embodiments of any of the above methods, the body fluid, after illumination, is suitable for infusion into a subject without further processing to remove residual pathogen-inactivating compound or photoproduct(s) thereof.

In some embodiments of any of the methods provided herein, the biological fluid is a blood product. In some embodiments, the biological fluid is a whole blood preparation. In some embodiments, the implementation of the biological fluid is a preparation of erythrocytes. In some embodiments, the body fluid is a platelet preparation (eg, platelets). In some embodiments, the biological fluid is a plasma preparation (eg, plasma). In some embodiments, the biological fluid is a platelet preparation (eg, platelets) and a plasma preparation (eg, plasma). In some embodiments, the body fluid (eg, platelet preparation) contains a supplemental solution for platelets. In some embodiments, the body fluid is a platelet preparation, wherein the platelet preparation comprises a platelet supplement and plasma (e.g., about 5-50% plasma and about 95-50% supplement; about 30-50% plasma and about 70 up to 50% supplemental platelet solution). For example, in some embodiments, the processing methods include preparing a platelet preparation suitable for infusion into an individual using the systems and methods disclosed herein.

In some embodiments of any of the methods provided herein, the treatment method described herein is sufficient to inactivate at least 1 log (e.g., at least 2 log, 3 log, 4 log or more) of pathogens (e.g., , when they are present), while the biological fluid after illumination is suitable for infusion into the subject without further processing to remove residual IP or its photoproducts. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, 3 log, 4 log, or more) pathogens (e.g., when present), wherein the platelet preparation after illumination contains 5 μM or less IPS. In some embodiments, the concentration of IPA in the mixture prior to illumination is at least 10 μM. In some embodiments, the concentration of IPA in the pre-illumination mixture is at least 30 µM, at least 50 µM, at least 70 µM, at least 90 µM, or at least 110 µM, or more. In some embodiments, the concentration of IPA in the mixture before illumination is from about 15 μM to about 150 μM. In some embodiments, the concentration of IPA in the mixture prior to illumination is from about 15 μM to about 110 μM, from about 30 μM to about 110 μM, from about 60 μM to about 110 μM, from about 30 μM to about 90 μM, or from about 60 µM to about 90 µM. In some embodiments, the concentration of IPA in the mixture prior to illumination is about 75 μM. In some embodiments, the methods for treating body fluids disclosed herein do not include further treatment of the body fluid, such as exposure to a compound adsorption device (CAD), after illuminating the body fluid for a period of time and at an intensity sufficient to inactivate one or more pathogens in the biological fluid, if present. In some embodiments, the methods for treating biological fluids disclosed herein do not include further processing of the biological fluid, such as subjecting a compound adsorption device (CAD) to remove residual IPA or its photoproducts after illuminating the biological fluid for a period of time and at intensity , sufficient to inactivate one or more pathogens in the biological fluid, if present (for example, when they are present), while the method is sufficient to inactivate at least 1 log of pathogens (for example, at least 4 log pathogens), and when this biological fluid after illumination in accordance with the methods disclosed herein, is suitable for infusion to the subject. In some embodiments, the implementation of the biological sample, after illuminating the biological sample in accordance with the

- 48 042016 as disclosed herein contains less than 5 μM IPS (eg, less than 2 μM IPS).

In some embodiments of any of the methods provided herein, the method for processing comprises preparing or pre-mixing the IPA with a platelet supplement solution (PAS) at the desired (e.g., standardized) concentration, and then adding the IPA/PAS solution to the platelet preparation, thus facilitating, for example, (i) increased processing flexibility and control, (ii) improved pathogen inactivation, including, for example, reducing the amounts of IPA used to inactivate pathogens, (iii) reducing the number of processing steps, no need for additional processing with Compound Adsorption Devices (CADs) to remove residual IPA or its photoproducts prior to administration to the individual, and/or (iv) improve platelet quality.

In some embodiments of any of the methods provided herein, the method for treatment further comprises, prior to illumination: incubating the body fluid with a photoactive, pathogen-inactivating compound for a period of 30 minutes to 24 hours (e.g., 2 to 24 hours, 4 to 24 hours, 8 to 24 hours, 12 to 24 hours).

As used herein, terms in the singular include the corresponding terms in the plural unless otherwise indicated.

It is understood that the aspects and embodiments of the invention presented herein include including, consisting of, and consisting essentially of aspects and embodiments.

It is clear that when you specify a range between two values, the endpoints of the range are included in the range. For example, a range from x to y or from about x to about y includes x and y.

The present invention is further illustrated by the following examples, which should not be taken as limiting the scope or spirit of the invention to the specific procedures described.

Examples

Example 1. System for the treatment of biological fluids.

An exemplary system for processing biological fluids was designed to contain two opposing arrays of light sources facing each other in the processing chamber, each containing 72 clusters of 4 LED channels, with each cluster including LEDs with a wavelength of both 340 nm and 365 nm (see, for example, Fig. 2A). The system also included a glass platform placed between two arrays as a means of illuminating the body fluid containers placed on the platform with ultraviolet light from opposite sides of the containers (see, for example, FIG. 4). The control devices of the system were used to adjust the LED and treat the biological fluid samples with light from either 340 nm LED or 365 nm LED, separately, or light with wavelengths of both 340 nm and 365 nm, simultaneously or sequentially, with control of both time (for example, duration), and intensity, lighting with LED.

Example 2 Photochemical Conversion of a Pathogen Inactivating Compound.

A study was conducted to determine the efficiency of photochemical conversion of the pathogen inactivating compound using the system of the present invention. Amotosalen photochemical reagent (also referred to as S-59) is a psoralen pathogen-inactivating compound used in a commercially available medical device for pathogen-inactivating treatment of blood components: plasma and platelets (INTERCEPT® Blood System, Cerus Corporation). To determine the photochemical conversion efficiency of amotosalen and the profile of photoproducts present after treatment with the LED lighting device described in Example 1, several wavelengths and light sources were compared in the studies. Illumination was performed using a 340 nm narrow band LED (device of example 1), a 365 nm narrow band LED (device of example 1), and a commercially available INTERCEPT® Blood System (INT-100) fluorescent UV illumination device. And lamps. The lamps in the INT-100 device generate light with a wide emission band across the entire UV-A spectrum (see, for example, Fig. 9), and the filter in the INT-100 device attenuates light with wavelengths below 320 nm, which thus leads to to illumination in the UV-A region at a wavelength of about 320-400 nm, with a peak wavelength of about 352 nm, as spectral curve 902. Exemplary narrow band peaks for 340 nm and 365 nm LED are also shown (not to scale) in FIG. 9 for comparison as spectral curves 904 and 906, respectively. For the data described in Examples 1-9 herein using prototype systems, light doses are expressed in Joules (J)/cm ² ±25%.

Three different suspension media were prepared for this study, including: 100% plasma, platelet supplement solution (PAS III), or a 35%/65% combination of plasma+PAS III. Amotosalen (S-59) was added to each type of slug at a concentration of 150 μM, followed by illuminating the slug with about 6.4 J/ ^cm2 UV light (100% plasma), about

- 49 042016

3.6 J/cm ² (PAS+plasma) or approximately 3 J/cm ² (PAS) UV light dose from an LED device at 340 nm or 365 nm (used with all types of portions), or UV light dose about 6.4 J/cm ² from the INT-100 device (used with plasma or PAS portions only). Samples taken before and after illumination were analyzed by HPLC as described previously (Schlenke et al., 2008, Transfusion, 48:697-705) to determine the S-59 photoconversion efficiency as well as the photoproduct profile.

The percentage of residual S-59 after illumination is shown in the following table. 1 for plasma doses, PAS or PAS+plasma (65/35). Notably, 340 nm S-59 LED illumination at about 6.4 J/ ^cm2 resulted in significantly greater S-59 photoconversion in each type of medium than either 365 nm LED or INT-100 illumination at the same dose. Sveta.

Table 1

Photoconversion of S-59 (% of the remainder of applied S-59)

PAS 365 nm PAS 340 nm PAS INT100 Plasma 365 nm Plasma 340 nm Plasma INT100 65/35 365 nm 65/35 340 nm S-59 (%) 36.8 13.4 26.2 66.8 33.1 60.5 46.2 9.1

In addition, HPLC analysis of samples after illumination was used to calculate areas and relative levels of residual S-59 and photoproducts after different processing conditions. As shown in the following table. 2, differences in the obtained profiles of photoproducts were observed in the case of illumination of 340 nm, 365 nm and INT-100.

table 2

Photo products after illumination

PAS PAS PAS Plasma Plasma Plasma 65/35 65/35 365 nm 340 nm INT100 365 nm 340 nm INT100 365 nm 340 nm Peak B 107 167 132 215 169 220 307 315 Peak C 161 217 211 210 739 334 229 786 Peak D 1314 1423 1377 146 133 153 438 385 S-59 4118 1436 2905 9675 4957 8513 5889 1249 PiE 204 213 199 0 32 0 69 FROM

Example 3 Virus inactivation.

The photochemical inactivation of the virus in human donated plasma was then evaluated using the illumination device of the present invention. Pathogen inactivation studies were performed on plasma supplemented with rhabdovirus, vesicular stomatitis virus (VSV) and then treated with amotosalen and UV-A light using a narrowband 340 nm and 365 nm LED device or a broadband INT-100 device described in examples 1 and 2.

The pooled ABO-matched plasma was aseptically divided into three portions of approximately equal volumes of 500 ml, and each portion was inoculated with VSV. Each of the VSV-supplemented plasma was combined with a commercially available INTERCEPT® blood processing kit, mixed with amotosalen at a concentration of 150 μM, and transferred to a container for illumination. Samples were taken from each portion prior to UV light illumination to determine pretreatment virus titers. The VSV-containing plasma portions were then exposed to UV-A light of ~6.4 Joules/cm ² with either an INT-100 device or a 340 nm or 365 nm LED light source (see eg Example 2). Samples were collected after illumination to determine post-treatment viral titers in the BHK cell plaque assay.

The results of determining the titers of the virus in the samples before and after illumination are given in the following table. 3, along with the achieved levels of virus inactivation (log of inactivation).

Table 3

Virus inactivation

LIGHTING DEVICE TITLE before PROCESSING (LOG PFU) TITER AFTER PROCESSING (LOG POU) LOG INACTIVATIONS INT-100 6.3 2.9 3.4 340 Nm 6.3 1.7 4.6 365 NM 6.3 3.3 3.0

The data obtained indicate unexpected differences in levels of photochemical inactivation, with higher levels of virus inactivation when using amotosalen and narrowband 340nm LED UVA illumination as light sources, compared to both narrowband 365nm LED UVA illumination and broadband UV-A illumination with INT-100 device. The level of inactivation at is

- 50 042016 using 365 nm LED was comparable to the level of inactivation when using the INT-100 device.

Virus inactivation and photoconversion.

An additional study compared VSV inactivation using a lower dose of 30 µM amotosalen (S-59) and UV-A light, in volumes of either 220 ml or 350 ml, and using 340 nm LED or INT-100 illuminators. Plasma was pooled to a volume of at least 1140 ml and inoculated with stock VSV at a final dilution of 1:100. The VSV-supplemented pooled plasma was then divided into four portions, two with a volume of 220 ml and two with a volume of 350 ml. A dose of amotosalen at a concentration of approximately 30 μM was added to each serving and controls were collected to determine VSV titer and amotosalen concentration prior to exposure to UV-A light. One 220 ml portion and one 350 ml portion were exposed to ~3.0 J/cm ² UV-A light using an INT100 illuminator, while the other 220 ml and 350 ml portions were exposed to ~3.0 J/cm 2 cm ² of UV-A light using a 340 nm LED illuminator. After photochemical processing, samples were taken from each portion to determine the VSV titer and the concentration of amotosalen after exposure to UV-A light. VSV titers (log ₁₀ ) were determined in a standard plaque assay and amotosalen concentrations (μM) were determined by HPLC as shown, on average, for three replicas in the following table. 3b.

Table 3b

Virus inactivation and photoconversion of amotosalen

VOLUME M TITR before PROCESSING ΙΝΤ 100 340 Nm TITER AFTER PROCESSING CI LOG INAC T. S-59 AFTER PROCESSED TKI TITER AFTER TREATMENTS AND LOG INAC T. S-59 AFTER PROCESSED TKI 220 6.60 4.58 2.02 6.53 4.32 2.28 0.84 ML 220 5.24 3.27 1.97 7.22 2.85 2.39 0.92 ML 350 6.60 4.93 1.76 9.32 4.26 2.34 2.21 ML 350 5.24 3.58 1.66 10.10 3.03 2.21 2.34 ML

These data also indicate a higher level of virus inactivation when using amotosalen and 340 nm LED UV-A illumination as light sources, compared to broadband UV-A illumination from the INT-100 device. In addition, the level of photoconversion of amotosalen using the 340 nm device was much greater than using the INT-100 device, resulting in levels after photochemical treatment below 1 µM in 220 ml servings and approaching 2 µM in 350 ml servings. .

Additional photochemical inactivation studies were performed on other viruses. Caliciviruses, e.g., feline calicivirus (FCV), which has been used as a model for hepatitis E virus, has been previously shown to be highly resistant to photochemical inactivation by amotosalen (S-59), with only about a 1.7-2.4 log ₁₀ reduction in titer (Irsch et al., Transfus Med Hemother, 38: 1931 (2011)). Conducted a study to assess the level of FCV inactivation in platelet preparations. More specifically, two portions of platelets prepared in 35% plasma/65% platelet supplement solution (PAS) were pooled to give a total volume of approximately 400 ml containing approximately 3.8x1011 platelets. Pooled platelets were inoculated with stock feline calicivirus (FCV) at a final dilution of 1:100. FCV-supplemented platelets were then divided into ten smaller portions of approximately 28.5 ml each. Nine of these servings were divided into amotosalen dose groups, in each case three servings in each dose group, to which amotosalen was added at one of three different concentrations: 90 μM, 30 μM, or 15 μM. Samples were taken from each portion prior to illumination. In each dose group, portions were incubated at room temperature for 4, 8, or 24 hours (T=4, 8, 24 hours) and then exposed to 340 nm UV-A light at about 3 J/cm ² using the apparatus described above. Amotosalen was added to the remaining portion at a concentration of 150 μM, a control sample was taken before illumination for analysis, and then the portion was exposed to 340 nm UV-A light without delay (T=0), inadvertently at a dose more than twice the dose of light for the remaining nine samples. After exposure to UV-A light, samples were taken from all portions and, along with pre-illumination controls, were used to determine FCV titers (in standard

- 51 042016 analysis of plaque formation) and concentrations of amotosalen (by HPLC), the data are given in table. 3c.

Table 3c

Virus inactivation and photoconversion of amotosalen

INITIAL CONCENTRATION S-59 TIME LOG INACTIVATION (PFU/ML) S-59 CONCENTRATION POST UV-A 150 MKM 0H 2.5 2.1 MKM 90 MKM 4 HOUR >5.6 3.8 MKM 90 MKM 8 HOUR >5.6 0.9 MKM 90 MKM 24 HOUR >5.6 3.3 MKM 30 MKM 4 HOUR 4.0 0.8 µm 30 MKM 8 HOUR >5.6 0.9 MKM 30 MKM 24 HOUR >5.6 0.8 µm 15 MKM 4 HOUR 2.7 0.6 µm 15 MKM 8 HOUR 4.2 0.6 µm 15 MKM 24 HOUR >5.6 0.6 µm

As can be seen from these data, photochemical inactivation of FCV with S-59 using the 340 nm LED illumination device of the present invention occurred at higher levels than the levels according to Irsch (ibid) for 150 μM S-59 using broadband ultraviolet light. A. In addition, incubation (e.g., pre-incubation) of FCV-containing platelets with S-59 for a period of time prior to illumination with an LED device resulted in higher levels of FCV inactivation, even at lower initial concentrations of the pathogen-inactivating compound S-59. In particular, pre-incubation for 4, 8 or 24 h in the case of both 90 μM and 30 μM concentrations of S-59; 8 or 24 h in the case of 15 μm concentration of S-59, resulted in inactivation of at least 4 log FCV when using the LED device. In the case of 150 μM S-59 without preincubation, an inactivation of 2.5 log was achieved. Under several conditions, inactivation greater than 5.6 log FCV was achieved, reflecting inactivation below the detection limit for the dilutions tested in the plaque assay. In addition, HPLC analysis to determine the amount (e.g., concentration) of S-59 remaining in the samples after UV-A light illumination and photoconversion showed that the residual concentrations of the pathogen-inactivating compound S-59 were reduced to less than 5 μM, and during in many cases, to less than 2 μM or less than 1 μM. These data indicate that treatment conditions for pathogen inactivation can be achieved based on the methods provided herein, resulting in higher levels of virus inactivation (e.g., >4 log, >5.6 log) as well as efficient photoconversion. S-59, with low levels of residual S-59.

Comparison of single-sided and double-sided lighting.

A follow-up study was performed to evaluate pathogen inactivation using either LED array illumination placed both above and below the body fluid container (e.g., double-sided illumination) or LED array illumination placed only above the body fluid container (e.g., single-sided illumination). ).

A portion of platelets in a volume of approximately 370 ml was prepared in a mixture of 35% plasma/65% PAS containing approximately 5.2x1011 platelets, which was inoculated with stock FCV at a final dilution of 1:100. FCV-supplemented platelets were then divided into ten smaller portions of approximately 28.5 ml each. Nine of these servings were divided into dose groups amotosalen, with the addition of amotosalen at a concentration of 150 μm in two servings, 30 μm in four servings and 15 μm in four servings. Portions of the 30 μM and 15 μM dose groups were incubated at room temperature for 8 or 24 h (T=8, 24 h), samples were taken from each portion until illumination, and then the portions were exposed to 340 nm UV-A light at about 3 s using the above device, emitted either by a combination of the upper and lower LED arrays, or only by the upper LED matrix. In the case of 150 μM portions, pre-illumination control samples were taken for analysis, and then the portions were illuminated with 340 nm UV-A light without delay (T=0), either in LED config J/cm ² guration top + bottom (2-sided), or in LED configuration on top only (1-sided). After exposure to UV-A light, samples were collected from all portions and, along with pre-illumination controls, used to determine FCV titers in a standard plaque assay and amotosalen concentrations by HPLC, the results are shown in the following table. 3d.

- 52 042016

table 3d

Virus inactivation and photoconversion of amotosalen_________

TIME INITIAL CONCENTRATION S-59 LOG INACTIVATION (PFU/ML) S-59 CONCENTRATION POST UV-A TOP BOTTOM ONLY TOP TOP/BOTTOM 3 ONLY TOP 0H 150 MKM 3.5 4.6 7.7 MKM 10.8 MKM 8 HOUR 30 MKM 6.3 >6.3 <1 µm <1MKM 8 HOUR 15 MKM 3.9 4.1 <1 µm <1MKM 24 HOUR 30 MKM >6.3 >6.3 <1 µm <1MKM 24 HOUR 15 MKM >6.3 >6.3 <1 µm <1MKM

As can be seen from these data, incubation of FCV-containing platelets with S-59 (e.g., 8.24 h), followed by illumination with an LED device, again resulted in higher levels of FCV inactivation, even at lower initial concentrations of the pathogen-inactivating compound S-59. . Again, greater levels of inactivation were observed than levels that could be achieved at a concentration of 150 μm S-59. In addition, the levels of inactivation were generally comparable regardless of whether the FCV-containing platelets were exposed to 340 nm LED illumination from both sides or from only one side. HPLC analysis also again showed efficient photoconversion and the ability to achieve very low levels (eg, <1 μM) of residual S-59 after a photochemical processing process using either 1-sided or 2-sided LED illumination.

Example 4 Inactivation of bacteria.

Inactivation of bacteria in human plasma by photochemical treatment was evaluated using the system of the present invention. Pathogen inactivation studies were performed on human donated plasma supplemented with E. coli bacteria and then treated with amotosalen and UV-A light using the LED based system described in Example 1 or the INT-100 device for comparison.

More specifically, pooled apheresis plasma (FFP) in a volume of approximately 3000 ml was aseptically divided into five portions of approximately equal volumes of 585 ml. Each batch was inoculated with an overnight culture of E. coli at ~6 log cfu/ml. Each batch of E. coli-supplemented plasma was then mixed with the pathogen-inactivating compound amotosalen (S-59) at one of three concentrations (150 μM for two portions, 15 μM for two portions, 1.5 μM for one portion) in a container for lights from the INTERCEPT® Blood Processing Kit. Samples were taken from each portion prior to UV light illumination to determine pre-treatment bacterial titers. The remaining E. coli-supplemented plasma was then exposed to UV-A light using either a commercially available INT-100 broadband device at a light dose of ~3 J/cm ² for batches containing both 150 μM and 15 μM amotosalen, or narrow band 340 nm LED as light source (device of example 1) for batches containing amotosalen at concentrations of 150 μM, 15 μM and 1.5 μM, which were then illuminated with UV-A light once (~3 J/cm ² ), two times (~6 J/cm ² ) or three times (~9 J/cm ² ) as shown in the following table. Samples were collected for each treatment condition to determine post-treatment bacterial titers using standard colony formation assays.

The results of determining bacterial titers before and after treatment with UV-A light are shown in the following table. 4, along with bacterial inactivation levels achieved (log reduction). In addition, the efficiency of the photoconversion of amotosalen (S-59) was determined and is shown as the percentage of S-59 remaining after each specified treatment condition. LOQ means limit of quantitation.

- 53 042016

Table 4

Bacteria inactivation. and S-59 conversion

DEVICE in S-59 DOSE (J/CM ² ) UP TO UFA (LOG CFU/ML) AFTER UV-A (LOG CFU/ml) LOG UPEN ENIA QUANTITY TBA % RESIDUE NOGO S-59 INT-100 150 MKM ~3 6.4 <-0.7 >7.1 63.0 340 NM 150 MKM ~3 6.3 <-0.7 >7.0 39.9 INT-100 15 MKM ~3 6.2 2.0 4.2 40.5 340 NM 15 MKM ~3 6.1 1.4 4.7 13.5 340 NM 15 MKM ~6 6.1 0.5 5.6 2.5 340 NM 15 MKM -9 6.1 0.5 5.6 <LOQ 340 Nm 1.5 MKM ~3 6.3 5.0 1.3 9.0 340 Nm 1.5 MKM ~6 6.3 4.8 1.5 <LOQ 340 Nm 1.5 MKM -9 6.3 4.9 1.4 <LOQ

These data indicate that slightly higher levels of photochemical inactivation of bacteria can be achieved using amotosalen and illumination with a narrow band UV-A light source, compared with illumination with a wide band INT-100 device. In addition, greater than 4 log bacterial reductions can be achieved using either the 150 μM concentration of amotosalen used in commercial devices or the much lower 15 μM concentration. In addition, the photoconversion efficiency of S-59 was significantly improved with the LED lighting device in these studies, resulting in much lower levels of S-59 in treated materials.

In another study, four portions of plasma were prepared from pooled plasma in volumes of either ~220 ml or ~350 ml. Each batch was inoculated with an overnight culture of E. coli at ~6 log CFU/mL. Each of the E. coli spiked plasma was then mixed with the pathogen inactivating compound amotosalen (S-59) at a concentration of 15 μM in an illumination container from the INTERCEPT® Blood Processing Kit. Samples were taken from each portion prior to UV light illumination to determine pre-treatment bacterial titers. The rest of the E. coli-supplemented plasma was then exposed to UV-A light at a light dose of ~6.4 J/cm ² using either a narrow band 340 nm LED device or a commercially available INT-100 device.

Bacterial titers were analyzed before and after UV-A light treatment to determine levels of bacterial inactivation, which are shown as log reduction in the following table. 5. In addition, the photoconversion of S-59 was determined by HPLC, the results are presented as both absolute concentration and residual percentage after each indicated treatment condition.

Table 5

Bacterial Inactivation and S-59 Conversion

VOLUME PLASMA LOG DECREASE AMOUNT OF E. COLI RESIDUAL S-59 (MKM) % RESIDUAL OGO S-59 INT-100 220 ml 5.3 4.0 26.0 340 Nm 220 ml 6.0 0.5 3.0 INT-100 350 ml 4.4 5.5 37.0 340 Nm 350 ml 4.6 1.1 8.0

Data are mean values for two samples tested (N=2).

These data also suggest that somewhat higher levels of photochemical

- 54 042016 Bacteria inactivation can be achieved using the S-59 and illumination with a narrow band UV-A light source compared to illumination with a wide band INT-100 device. In addition, the photoconversion efficiency of S-59 was significantly improved in the case of the LED lighting device, resulting in much lower levels of S-59 in processed materials.

To confirm that the E. coli inactivation described above was a photochemical process requiring a pathogen inactivating compound and not an effect mediated solely by UVA light from the LED device, a control experiment was performed with 340 nm LED illumination at increasing doses but without adding amotosalen. For this study, an E. coli culture was prepared and added to a ~585 ml portion of plasma at a titer of ~6 log cfu/ml. Plasma with bacteria added was transferred to the illumination bag from the INTERCEPT® Blood Processing Kit and sampled prior to illumination for baseline control titer determination. Plasma with added bacteria was then subjected to illumination at 340 nm, with sampling to determine the bacterial titer after application of each of the energy doses indicated in the following table. 6. Titres before and after illumination are shown, and log reductions are calculated. E. coli inactivation was not observed at various dose levels of 340 nm UV-A light in the absence of the pathogen inactivating compound.

Table 6

Inactivation of bacteria

source SVETA -DOSE (J/CM ² ) TITER TO UVLIGHT (LOG CFU/ML) TITER AFTER UV LIGHT (LOG CFU/ML) LOG REDUCTIONS QUANTITIES 340 Nm 0 6.2 HH HH 340 Nm 0.5 HH 6.3 -0.1 340 NM 0.9 HH 6.2 0.0 340 Nm 1.4 HH 6.2 0.0 340 NM 2.8 HH 6.2 0.0 340 Nm 3.8 HH 6.3 -0.1 340 Nm 4.7 HH 6.1 0.1

Example 5 Treatment of platelets in plasma and supplemental solution.

Platelets collected in a mixture of PAS/plasma (65% PAS III/35% plasma) were pooled and divided into three 285 ml portions for analysis. Amotosalen (S-59) was added at a concentration of 150 μM, and the portions were illuminated once (total dose ~3.6 J/cm ² ), twice (total dose ~7.2 J/cm ² ) or three times (total dose ~10.8 J/cm ² ) narrow band 340 nm LED or 365 nm LED using the device from Example 1, or the INT-100 device. The photoconversion efficiency of S-59, as well as the formation of photoproducts, was evaluated after illumination with UV-A light by the HPLC method as in the previous Examples. S-59 concentrations after illumination were 32 μM, 11 μM, and 5 μM for the INT-100 device (~3.6, 7.2, 10.8 J/ ^cm2 , respectively), 9 μM, 2 μM, and 0. 98 μM (<LOQ) in the case of 340 nm LED (~3.6, 7.2, 10.8 J/cm ² , respectively), and 42 μM, 15 μM and 7 μM in the case of 365 nm LED (~3. 6, 7.2, 10.8 J/ ^cm2 , respectively). These data indicate a greater degree of S-59 photoconversion in the case of a narrow band 340 nm LED illuminator, with residual levels of S-59 equal to, or less than, 2 μM after two or three illuminations (e.g., ~7.2 or 10.8 J / cm ² ).

HPLC analysis of samples after illumination was used to calculate the areas and relative levels of photoproducts obtained under different processing conditions. As shown in the following tables. 7-9, differences were observed in the obtained photoproduct profiles under 340 nm, 365 nm and INT-100 illumination, with lower levels of photoproducts typically observed after illumination with 340 nm narrowband light.

Table 7

Photo products under INT-100 illumination

INT 100 S-59 PIK B PEAKS PIKO PIQUE PEAKS 0 1753 0 0 0 0 0 3.6 396 19 24 127 27 9 7.2 129 18 338 102 26 AND 10.8 56 15 34 72 24 12

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Table 8

Photoproducts when illuminated with light with a wavelength of 340 nm

340 Nm S-59 PIK B PEAKS PIC D PIQUE PEAKS 0 1826 0 0 0 0 0 3.6 106 4 29 93 28 5 7.2 24 2 27 33 25 5 10.8 eleven 3 23 13 22 5

Table 9

Photoproducts when illuminated with light with a wavelength of 365 nm

365 NM S-59 PIK B PEAKS PIKO PIQUE PEAKS 0 1753 0 0 0 0 0 3.6 514 18 thirty 152 28 10 7.2 183 17 42 156 29 eleven 10.8 84 14 43 144 29 13

Platelets in PAS/plasma (65% PAS III/35% plasma) treated with 150 μM amotosalen, illuminated once (~3.6 J/ ^cm2 total dose), twice (~7.2 J/cm total dose) cm ² ) or three times (~10.8 J/cm ² total dose) used to compare 340 nm LED and broadband INT-100 device was also analyzed for photoconversion of S-59 and photoproducts after LC/mass treatment. spectrometry. Since the mass spectrometric extinction coefficients for photoproducts were considered identical to the extinction coefficients of S-59, only the relative difference in concentrations (μM) between the samples was compared in the following table. 9b rather than absolute concentrations.

Table 9b

Photo products after illumination

~3.6 J / cm ² ~7.2 J / cm ² ~10.8 J / cm ² INT100 340 nm INT100 340 nm INT100 340 nm Peak A 1.0 0.1 0.3 0.0 0.7 0.2 Peak B 21.1 4.7 9.9 3.4 19.1 1.9 PeakV1 1.3 0.1 0.6 0.2 1.1 0.3 Peak C 4.0 3.4 2.4 3.7 5.5 2.2 PiO 17.6 13.3 13.8 7.1 14.2 3.6 S-59 37.0 21.3 11.6 4.8 12.0 2.5 PiE 12.1 11.4 10.8 11.1 11.9 9.2 Peak G 12.3 2.8 6.1 2.9 11.1 2.3

In addition, various platelet quality parameters were assessed by standard methods immediately after three exposures to UV-A light (~10.8 J/cm ² ) to determine potential differences between light sources. As shown in the following table. 10, these platelet parameters remained similar under all lighting conditions.

Table 10

Platelet parameters after 3x illumination INT 100 340 Nm 365 NM QUANTITY PLATELETS ~1.2x10 ⁶ /ML ~1.2x10 ⁶ /ML ~1.2x10 ⁶ /ML pH (37°C) 6.60 6.61 6.74 LYSIS (%) 2.25 2.36 1.72 ATP mmol/hyu ⁸ 4D 4.0 4.8 % RESIDUE S-59 zd 0.5 4.9

Example 6 Treatment of Apheresis Collected Platelets in 100% Plasma or Plasma/PAS Mix.

A study was conducted to evaluate the photoconversion of amotosalen in a platelet preparation in 100% plasma, as well as platelet function for 7 days (day 3, day 7) after photochemical treatment with different doses of light using a 340 nm device of the present invention. Five portions of platelet apheresis in 100% plasma were pooled and divided into ~285 ml servings.

- 56 042016 for research. Amotosalen (S-59) was added at a concentration of 15 μM. Three portions were illuminated with the narrow band 340 nm LED device of Example 1 using one of three different doses of light, illuminating at ~3.6 J/cm ² once (1x), twice (2x, ~7.2 J/cm ² ) or three times (3x, ~10.8 J/cm ² ). Additional portions were illuminated with an INT-100 device at ~3.6 J/cm ² for comparison or left as an untreated control. The photoconversion of S-59 was evaluated after illumination with UV-A light by the HPLC method as in the previous examples. S-59 concentrations after illumination were 4.11 µM for the INT-100 device and significantly lower for the 340 nm LED lighting device: 0.86 µM (<LOQ) for 1x, 0.19 µM (<LOQ) for 2x and 0.00 μM (<LOQ) for 3 doses of light, indicating a higher degree of photoconversion.

In addition, various biochemical and/or functional parameters of platelet quality were assessed before and/or after exposure to UV-A light, as well as on Days 3, 5 and 7 after treatment. As shown in the following tables. 11-19, regarding platelet quality parameters, the results were generally similar for controls and experimental samples for INT-100 and 340nm, except for some parameters at 3x340nm dose.

Table 11

Platelet count ( ^x103 cells/µl)

BEFORE UV-A POST UV A DZ D5 D 7 CONTROL 1425 1487 1436 1453 INT-100 1481 1415 1395 1400 1439 340 NM (IX) 1453 1366 1391 1338 1391 340 NM (2X) 1448 1301 1317 1370 1376 340 NM (ZX) 1452 1322 1372 1550 1474

Table 12 pH at 37°C

BEFORE UV-A POST UV A DZ D5 D 7 CONTROL 6.91 6.62 6.70 6.62 INT-100 6.87 6.89 6.82 6.67 6.54 340 NM (IX) 6.90 6.89 6.84 6.70 6.58 340 NM (2X) 6.90 6.89 6.86 6.72 6.56 340 NM (ZX) 6.87 6.87 6.56 5.57 5.49

Table 13

Adenosine triphosphate (ATP; mmol/ ¹⁰⁸ platelets)

BEFORE UV-A DZ D5 D 7 CONTROL 4.2 3.6 3.7 3.3 INT-100 3.9 4.3 4.0 3.5 340 NM (IX) 4.0 4.4 4.0 3.7 340 NM (2X) 3.9 4.4 4.1 3.7 340 NM (ZX) 3.6 3.8 0.4 -0.1

Table 14

PCO2 at 37°C (mm Hg)

BEFORE UV-A POST UV A DZ D5 D 7 CONTROL 87.7 59.1 27.1 29.1 INT-100 101.1 91.4 55.8 36.4 35.0 340 NM (IX) 89.6 91.9 54.4 35.7 34.3 340 NM (2X) 88.5 94.1 54.5 37.5 36.4 340 NM (ZX) 98.2 98.1 62.5 13.9 4.4

- 57 042016

Table 15

PO2 at 37°C (mm Hg)

BEFORE UV-A POST UV-A DZ D5 D 7 CONTROL 35.0 15.3 37.3 37.6 INT-100 98.4 36.4 18.9 20.1 19.7 340 NM (IX) 41.8 14.3 11.8 22.5 16.6 340 NM (2X) 45.9 14.2 14.8 15.3 14.1 340 NM (ZX) 90.9 19.7 27.7 159.5 178.6

Table 16

Lactate (mmol/l)

POST UV-A DZ D5 D 7 CONTROL 8.76 19.37 21.31 22.27 INT-100 8.85 14.71 20.18 23.31 340 NM (IX) 9.05 15.17 19.81 21.83 340 NM (2X) 8.77 14.55 19.06 22.13 340 NM (ZX) 9.48 20.42 36.09 36.36

Table 17

Glucose (mmol/l)

POST UV-A DZ D5 D 7 CONTROL 16.96 11.48 9.59 8.22 INT-100 17.24 13.11 10.26 8.19 340 NM (IX) 17.45 13.49 10.27 8.32 340 NM (2X) 16.98 13.63 10.69 8.34 340 NM (ZX) 16.77 10.87 1.33 0.43

Table 18

Platelet lysis (%)

BEFORE UV-A POST UV-A DZ D5 D 7 CONTROL 4.30 5.01 6.73 5.63 INT-100 4.30 4.74 4.69 4.50 5.18 340 NM (IX) 4.30 4.48 4.90 4.43 5.23 340 NM (2X) 4.30 4.50 4.59 4.92 5.19 340 NM (ZX) 4.30 4.77 4.78 6.62 16.6

Table 19

LDH (LDH IU / 101 ¹ platelets) ________________

BEFORE UV-A POST UV-A DZ D5 D 7 CONTROL 10.7 12.0 17.1 17.1 INT-100 10.3 11.5 11.9 11.6 12.6 340 NM (IX) 10.5 11.3 12.1 12.1 13.1 340 NM (2X) 10.5 12.1 12.1 13.0 13.2 340 NM (ZX) 10.5 12.1 11.6 16.0 33.7

Treatment of platelets with amotosalen at different concentrations

A study was conducted to evaluate the photoconversion of amotosalen in a platelet preparation in 100% plasma, as well as platelet function for 7 days (day 3, day 7) after photochemical treatment using a 340 nm device of the present invention. Several portions of donor platelets in 100% plasma (5 portions, ~278-391 ml) were pooled and divided into 5 portions of ~285 ml each for use as an untreated control, or for treatment with amotosalen at different concentrations, with ultraviolet light illumination And using a 340 nm device. Amotosalen was added at a concentration of 30, 60, 90, or 110 μM, then samples were taken before illumination (pre-UV) for analysis, and the remaining portions were subjected to illumination at ~7.2 J/cm ² . Samples were then taken after illumination (post-UV) for post-treatment analysis. The parameters presented in the following tables. 20-29 (left side columns), for the untreated control and amotosalen/UV-A treated portions were measured using standard analytical methods known in the art, and in addition, the residual concentration of amotosalen was determined by HPLC.

- 58 042016

A similar study was performed to evaluate photoconversion of amotosalen in a platelet preparation in platelet supplement solution (35% plasma/65% PAS III) as well as platelet function for 7 days (day 4, day 7) after photochemical treatment using a 340 nm device according to the present invention. Several portions of donor platelets in plasma/PAS mixture (6 portions, -202-318 ml) were pooled and divided into 5 portions of -285 ml each for use as an untreated control, or for treatment with amotosalen at different concentrations, with illumination with ultraviolet light Spectrum A using a 340 nm device. Amotosalen was added at a concentration of 30, 60, 90, or PO μM, then samples were taken before illumination (pre-UV) for analysis, and the remaining portions were subjected to illumination at ~7.2 J/cm ² . Samples were then taken after illumination (post-UV) for post-treatment analysis. The parameters presented in the following tables. 20-29 (columns on the right side), for the untreated control and treated with amotosalen/UV-A portions were also measured using standard analytical methods known in the field, and, in addition, the residual concentration of amotosalen was determined by HPLC.

Table 20

Platelet count ( ^x103 cells/µl)

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTROL 1225 N/A 1132 1162 1389 HH 1360 1317 30 µm 1200 1115 1155 1155 1346 1308 1385 1392 60 µm 1160 1117 1152 1041 1344 1249 1379 1403 90 MKM 1165 1115 1157 1199 1344 1313 1373 1384 But micron 1209 1239 1103 1153 1308 1335 0 0

Table 21 pH at 37°C

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 before UV AFTER UV D4 D 7 CONTROL 7.14 HH 7.22 7.18 6.86 HH 6.93 6.95 30 MKM 7.14 7.15 7.21 7.10 6.85 6.84 6.88 6.86 60 µm 7.14 7.15 7.20 7.09 6.85 6.83 6.88 6.86 90 MKM 7.14 7.15 7.17 7.00 6.84 6.83 6.87 6.87 But micron 7.13 7.14 7.18 7.01 6.84 6.83 HH HH

Table 22 pH at 22°C

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTO l 7.36 HH 7.44 7.40 7.08 HH 7.15 7.18 30 µm 7.36 7.37 7.43 7.32 7.07 7.07 7,N 7.08 60 µm 7.36 7.37 7.43 7.32 7.08 7.06 7,N 7.08 90 MKM 7.37 7.37 7.39 7.23 7.06 7.06 7.10 7.10 But micron 7.36 7.37 7.40 7.24 7.07 7.05 HH HH

-59042016

Table 23 pCO ₂ at 37°C (mm Hg)

PLASMA PAS/PLASMA BEFORE UV POST UV DZ D 7 BEFORE UV POST UV D4 D 7 CONTROL 53.1 N/A 39.1 31.8 34.4 N/A 28.3 25.2 zokm 52.4 50.2 38.1 31.2 35.0 34.9 26.7 23.6 60 µm 52.4 49.2 38.1 31.2 33.7 35.1 26.6 23.1 90 MKM 50.8 48.5 40.3 33.5 34.9 33.7 26.9 22.6 But micron 51.8 48.1 38.6 31.7 33.7 34.2 N/A N/A

Table 24 pO ₂ at 37°C (mm Hg)

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTROL 41.2 N/A 47.7 56.9 38.6 N/A 20.3 43.8 ZOMKM 28.6 13.9 74.6 78.5 4.8 11.6 28.9 57.3 60 µm 32.7 20.4 65.8 78.0 29.4 8.0 28.8 61.0 90 MKM 54.6 24.1 82.2 87.9 9.0 29.3 25.7 61.8 But micron 88.6 189.7 69.9 90.5 6.3 16.1 N/A N/A

Table 25

Lactate (mmol/l)

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTROL 5.7 N/A 6.6 9.7 7.05 N/A 9.97 14.01 zokm 5.4 5.7 6.9 12.1 8.6 8.21 7.1 15.38 60 µm 5.4 5.6 6.8 11.8 6.72 6.93 10.11 15.16 90 MKM 5.3 5.7 7.3 13.6 6.95 7,N 9.83 14.62 But micron 5.3 5.4 7.3 13.8 6.85 7.18 N/A N/A

Table 26

Glucose (mmol/l)

PLASMA PAS/PLASMA BEFORE UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTROL 16.3 N/A 15.6 13.3 2.4 N/A 2.19 0.08 ZOMKM 16.0 15.9 14.9 11.9 5.2 5.45 3.27 0.16 60 MKM 16.2 15.9 15.0 11.6 5.16 5.04 2.92 0 90 MKM 15.9 15.9 14.9 10.6 4.9 4.95 2.97 0 BUT MKM 15.9 16.0 14.7 10.4 4.95 4.88 N/A N/A

-60042016

Table 27

Platelet lysis (%)

PLASMA PAS/PLASMA before UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTROL 5.09 HH 5.15 5.49 1.88 HH 2.65 3.06 30 µm 4.92 5.31 5.22 6.10 2.46 2.85 2.86 3.17 60 µm 4.71 5.10 5.15 11.82 2.68 2.65 3.10 3.37 90 MKM 4.97 5.13 4.88 5.42 2.76 2.64 3.23 3.53 110 micron 4.61 4.63 5.90 6.13 2.65 2.72 HH HH

Table 28

LDH (LDH IU/10 ¹¹ platelets)________________

PLASMA PAS/PLASMA before UV AFTER UV DZ D 7 BEFORE UV AFTER UV D4 D 7 CONTRO eh 13.8 N/A 15.3 16.2 5.11 HH 7.28 8.58 30 µm 13.7 15.0 14.5 17.4 7.13 7.80 7.44 8.26 60 µm 13.6 14.3 13.9 36.5 7.66 7.53 8.12 8.48 90 MKM 13.8 13.9 13.1 13.9 7.59 7.01 7.94 8.67 by µm 12.4 12.0 17.0 16.0 7.42 6.97 N/A HH

Table 29

Amotosalen concentration (μM)

PLASMA PAS/PLASMA BEFORE UV POST UV BEFORE UV POST UV 30 MKM 32.7 1.1 30.5 0.3 60 µm 62.0 2.3 61.2 0.7 90 MKM 89.7 4.0 90.5 1.0 by µm 105.8 5.5 120.7 1.2

These data show that the quality of platelets, either in 100% plasma or plasma+PAS, is adequately maintained when treated with amotosalen over a range of concentrations (e.g., 30 µM to 110 µM) compared to untreated control platelets and furthermore, post-treatment amotosalen levels can be reduced to <5 µM (including <1 µM) after illumination with a 340 nm device.

Additional studies also assessed platelet quality after pathogen inactivation under conditions that achieved a residual concentration of amotosalen <2 μM after treatment using either 340 nm LED illumination or the commercially available INTERCEPT blood product processing system, INT-100. Portions of platelets in 100% plasma were pooled to a volume of 750-900 ml, and then divided into several 250-300-ml portions for processing, while comparing three conditions: 1) 75 μM initial concentration of amotosalen, illumination with a 340 nm device at ~6, 4 J/cm ² ; 2) 75 µM initial concentration of amotosalen, illumination with 340 nm device at ~7.2 J/cm ² ; 3) 150 μM initial concentration of amotosalen, illumination with INT-100 device at ~3.6 J/cm ² (for example, standard conditions for this system). After treatment with INT-100, the illuminated portions were necessarily treated with UAS to reduce the residual content of amotosalen, while UAS was not necessary in the case of portions illuminated with a 340 nm device.

The parameters given in the following table. 30-34 were measured using standard and other assay methods known in the art, including pCO ₂ and pO ₂ (blood gas analyzer), morphology (Kunicki score), P-selectin (flow cytometry), degree of shape change ( aggregometer), hypotonic shock reaction (aggregometer); and the residual concentration of amotosalen was determined by HPLC.

- 61 042016

Table 30 pH

TREATMENT BEFORE UV-A POST UV A D5 D 7 RNPRI37°С INT-100 7.08 6.94 6.93 6.74 340/-6.4 7.06 7.07 6.92 6.72 340/-7.2 7.08 7.09 6.88 6.72 pH AT 22°C INT-100 7.31 7.17 7.16 6.96 340/-6.4 7.29 7.30 7.15 6.95 340/-7.2 7.31 7.32 7,P 6.94

Table 31

RSO ₂ AND RO ₂ (MM Hg)

PROCESSING A BEFORE UV-A POST UV A D5 D 7 RSO ₂ INT-100 54.43 54.60 31.83 28.47 340/-6.4 55.20 43.60 35.00 30.95 340/-7.2 54.43 47.23 37.47 32.70 RO ₂ INT-100 31.77 62.87 69.77 70.37 340/-6.4 37.60 42.90 59.75 61.80 340/-7.2 31.77 32.93 49.33 56.07

Table 32

P-selectin (CD62P) and degree of shape change (ESC)

PROCESSING A BEFORE UV-A POST UV A D5 D 7 CD62 INT-100 27.77 HH 39.07 58.77 340/-6.4 31.95 HH 51.70 67.65 340/-7.2 27.77 HH 45.00 56.93 ESC INT-100 23.50 HH 25.20 19.82 340/-6.4 20.60 HH 22.15 16.45 340/-7.2 23.50 HH 26.73 19.47

Table 33

Hypotonic shock response (HSR) and morphology_______

PROCESSING A BEFORE UV-A POST UV A D5 D 7 HSR INT-100 49.67 HH 55.10 46.00 340/-6.4 45.40 HH 56.50 45.98 340/-7.2 49.67 HH 51.87 49.47 MORPHOLOGIST AND I INT-100 279.33 HH 265.67 274.67 340/-6.4 265.50 HH 271.50 259.00 340/-7.2 279.33 HH 287.67 254.67

Table 34

Amotosalen concentration

PROCESSING A BEFORE UV-A POST UV A % REMAINDER AFTER UAS S-59 (MKM) INT-100 173.2 69.4 40.1 0.2 340/-6.4 93.3 2.4 2.5 HH 340/-7.2 94.0 1.9 2.0 HH

These data show that platelet quality is adequately maintained by amotosalen treatment under both conditions with 340 nm light illumination, and that post-treatment residual amotosalen levels were reduced to ~2 μM without additional treatment to reduce residual amotosalen.

Example 7 Plasma Processing

A study was conducted to evaluate the photoconversion of amotosalen in plasma derived from whole

-62042016 blood, as well as the properties of plasma after photochemical processing using either a broadband UV-A device (INT-100) or a 340 nm device of the present invention. Several portions of donated plasma (3-4 portions, ~250-350 ml each) were pooled and divided into three portions of ~285 ml each for use as an untreated control or for amotosalen treatment with either INT-100 or 340 nm illumination, devices . This merge and split format was repeated four times, resulting in four replicas. Amotosalen was added at a concentration of 50 μM, samples were taken before illumination (before UV-A) for analysis, and the remaining portions were subjected to illumination at ~6.4 J/cm ² . Samples were then taken after illumination (after UV-A) for post-treatment analysis. The parameters in the following table. 35 were measured using standard analytical methods known in the art, and in addition, the residual concentration of amotosalen was measured by HPLC, which was 17.06 μM using the INT-100 device and 4.65 μM using the 340 nm device.

Table 35

Plasma parameters before and after illumination

CONTROL INT-100 340 NM BEFORE UV A AFTER UV-A UP TO UFA AFTER UV-A pH AT 37°C 7.20 7.22 7.24 7.19 7.20 РСО ₂ AT 37°С (MM HG) 69.38 69.20 60.68 67.38 66.75 PO ₂ AT 37°C (MM HG) 139.18 141.95 41.55 131.80 42.88 TOTAL PROTEIN (MG/ML) 66.83 80.18 70.35 72.13 72.43 NTV (SEC) 11.95 11.48 12.28 11.68 12.03 APTT (SEC) 1 30.35 33.98 31.15 33.95 FIBRINOGEN (MG/DL) 301.25 278.75 261.50 290.00 259.75 FACTOR II (IU/DL) 94.13 91.45 110.93 93.43 84.00 FACTOR V (IU/DL) 101.73 98.55 90.25 97.08 88.83 FACTOR VIII (IU/DL) 139.50 154.25 108.85 165.50 127.18 FACTOR X (IU/DL) 89.93 92.40 84.53 96.68 84.68 FACTOR XI (IU/DL) 79.90 89.55 76.63 85.65 73.93 PROTEIN C (IU/DL) 118.88 98.55 109.30 133.90 122.33 PROTEIN S (IU/DL) 102.63 111.88 121.80 119.00 118.03

These data show that plasma quality after photochemical treatment is adequately maintained compared to untreated control plasma and furthermore, post-treatment amotosalen levels were reduced to <5 μM after illumination with a 340 nm device but not with an INT-100 device.

Example 8. System for the treatment of biological fluids.

Another exemplary system for processing biological fluids has been constructed, providing a processing chamber with interchangeable arrays of light sources in the device, each array having LED channels with single narrow bandwidth peak wavelengths (e.g., first peak wavelength) of 265 nm, 280 nm, 310 nm, 325 nm, 340 nm, 365 nm or 385 nm in the UV-A, UV-B or UV-C region. This system included single matrices directed (eg, opposed) to the platform, designed to illuminate the biological fluids placed on the platform (see, for example, Fig. 5). The system controls were used to adjust the LED during the processing of the biological fluid samples, controlling both the time and intensity of the LED illumination to achieve the desired dose of UV light. Photochemical conversion, photoproduct formation, pathogen inactivation, and plasma and/or platelet quality parameters were evaluated for each light source wavelength as described previously.

In one device study, photochemical inactivation of various bacteria was tested for each of the above LEDs used in conjunction with amotosalen. Bacteria included E. coli (gram negative), S. epidermidis (gram positive) and P. acnes (anaerobic). Since the germicidal effects of ultraviolet light with wavelengths in the UV-C and UV-B ranges are known, the study was controlled to determine for each wavelength

- 63 042016 LEDs of general levels of inactivation, as well as levels of inactivation that are the specific result of exposure to UV light (without the addition of amotosalen) or the photochemical processing process itself.

Bacterial cultures were inoculated at ~6 log CFU/mL into a portion of plasma from which a sample was taken to determine the initial bacterial titer in a standard colony formation assay, followed by separation of the bacterial-supplemented plasma into one of three portions: control or treated. The amotosalen treatment groups included 15 μM concentration groups for each of the three bacteria, as well as an additional 150 μM treatment group for E. coli.

Plasma + bacteria, without lighting.

Plasma + bacteria, with lighting.

Plasma + bacteria + amotosalen, with lighting.

Samples were taken and pre-illumination bacterial titers were determined for each bacterial-supplied portion, aliquots of the portions were added to six-well plates (2 ml/well) for illumination. The plates were illuminated with light at a wavelength of 265 nm, 280 nm, 310 nm, 325 nm, 340 nm, 365 nm, or 385 nm at a light dose of ~3 J/cm ² for E. coli and S. epidermidis, and ~6.4 J /cm ² for P. acnes, followed by determination of bacterial titers after illumination in a standard analysis of colony formation. In the following tables. 36-39 show the log total bacterial reduction as well as the log bacterial reduction due to photochemical inactivation with amotosalen (S-59) or due to UV light alone (without amotosalen). HPLC analysis was also used to determine the residual concentrations of amotosalen after illumination in the samples, as described previously.

Table 36

Treatment of E. coli with amotosalen (150 µM) and UV light_______

LENGTH WAVES LOG OF TOTAL REDUCTION LOG REDUCTION IN NUMBER DUE TO S-59 LOG REDUCTION DUE TO LIGHTING S-59 (MKM) TO UV S-59 (MKM) AFTER UV 265 NM 5.01 0.54 4.81 148.9 115.0 280 Nm 5.38 0.59 5.14 152.7 148.1 310 Nm 6.23 2.29 4.12 151.1 56.8 325 NM 5.70 5.36 0.53 141.6 52.1 340 Nm 5.64 4.93 0.50 142.2 48.1 365 NM 5.30 4.90 -0.38 153.2 79.8 385 NM 4.95 4.34 0.54 148.4 135.1

Table 37

Treatment of E. coli with amotosalen (15 µM) and UV light

LENGTH WAVES LOG TOTAL REDUCTION QUANTITY LOG NUMBER REDUCTION DUE TO ES-59 LOG REDUCED QUANTITY DUE TO LIGHTING I S-59 (MKM) TO UV S-59 (MKM) AFTER UV 265 NM 4.52 0 4.52 16.0 12.7 280 Nm 4.52 0 4.52 16.2 12.6 310 Nm 4.52 1.15 3.37 15.4 5.5 325 NM 4.52 3.81 0.71 15.8 4.0 340 Nm 4.52 2.94 1.58 16.0 3.7 365 NM 4.52 2.76 1.76 16.2 8.1 385 NM 1.5 0.49 1.75 15.3 14.3

-64042016

Table 38

Treatment of S. epidermidis with amotosalen (15 μM) and UV light

LENGTH WAVES LOG TOTAL REDUCTION QUANTITY LOG NUMBER REDUCTION DUE TO ES-59 LOG DOWN NIA KOLICES TVA AFTERSTAND VIEW LIGHTING S-59 (MKM) TO UV S-59 (MKM) AFTER UV 265 NM 5.23 0.89 4.35 14.4 13.0 280 Nm 5.02 1.56 3.51 14.8 11.8 310 Nm 7.19 6.68 0.55 14.3 5.2 325 NM 7.18 7.17 0.14 14.9 3.7 340 NM 7.28 7.18 0.16 14.8 3.6 365 NM 7.26 7.32 0.05 14.8 7.8 385 NM 1.76 1.85 0.07 15.0 15.1

Table 39

Treatment of P. acnes with amotosalen (15 µM) and UV light_______

LENGTH LOG LOG LOG S-59 (MKM) S-59 WAVES TOTAL REDUCTION NIA QUANTITY REDUCTION IN QUANTITY DUE TO ES-59 DOWN NIA KOLICES TVA NEXTST VIEW LIGHTING BEFORE UV (MKM) AFTER UV 265 NM 6.03 1.60 4.43 15.7 10.8 280 Nm 1.09 0.71 0.38 15.7 16.0 310 Nm 6.99 5.67 1.32 15.7 2.2 325 NM 6.69 6.54 0.15 15.7 1.1 340 NM 6.99 6.78 0.21 15.7 1.4 365 NM 6.99 6.67 0.32 15.7 5.5 385 NM 1.97 1.64 0.33 15.7 13.7

A high level of bacterial inactivation was observed. When comparing the effect of amotosalen+UV light with the effect of UV light alone (without amotosalen), the data indicated that photochemical inactivation (amotosalen+UV light) was generally higher for all three bacteria in the UV-A light treatment groups. with a wavelength of 325 nm, 340 nm and 365 nm. Photochemical inactivation in the 310 nm amotosalen+UV-B light treatment group appeared to be more variable and less effective than the 325 nm, 340 nm, or 365 nm amotosalen+UV-A light treatment group, with increasing direct bactericidal activity observed. effect of UV-B light compared to UV-A light. In the amotosalen+UV-C light treatment groups at 265 nm and 280 nm, minimal inactivation was observed due to amotosalen, with the main inactivation resulting from the direct bactericidal effects of UV-C light. When also taking into account the analysis of residual levels of amotosalen after treatment (after UV-A), these data show that photochemical inactivation of more than 4 log can be achieved, with a residual level of amotosalen of less than 5 μM, as under the conditions of treatment with amotosalen+325 nm light and amotosalen+340 nm light.

Example 9 Inactivation of pathogens by light with a combination of several wavelengths.

Additionally, any two or more wavelengths of light with a narrow spectral width were evaluated in combination, for example, photochemical treatment of a biological fluid using amotosalen, as well as ultraviolet light with a first peak wavelength and ultraviolet light with a second peak wavelength, sequentially or simultaneously. More con

Specifically, in one example, inactivation of the bacterial pathogens E. coli (gram-negative) and S. epidermidis (gram-positive) was assessed using amotosalen and an LED device with the wavelengths described in example 8. Bacterial cultures were inoculated at ~6 log cfu /ml in a portion of plasma from which samples were taken to determine the initial bacterial titer in a standard analysis of colony formation. Bacterial-supplemented plasma portions were divided into control (no amotosalen ± UV light) and treatment (with amotosalen) groups, with amotosalen used at a concentration of 15 μM. Aliquots of portions were added to six-well plates (5 ml/well) for illumination. Samples were taken prior to illumination and control bacterial titers were determined in a standard colony formation assay. The plates were exposed to two successive doses of light ~3 J/cm each, using a combination of a dose of 265 nm or 280 nm UV-C light with a dose of 325 nm, 340 nm or 365 nm UVA light, followed by determination of bacterial titers after illumination and analysis of residual amotosalen . Data for titers before illumination, titer after first illumination, titre after second illumination, and residual content of amotosalen (S-59) after treatment (after second illumination) are presented in the following table. 40-41.

Table 40

Treatment with amotosalen and UV light E.coli

UV 1 UV 2 TITR to UV TITLE AFTER FIRST LIGHTING TITLE AFTER SECOND LIGHTING S-59 (MKM) 265 NM 325 NM 6.57 3.58 <-0.11 4.76 265 NM 340 NM 6.57 3.86 <-0.11 3.89 265 NM 365 NM 6.57 2.95 <-0.11 8.07 280 Nm 325 NM 6.57 3.66 <-0.11 4.44 280 Nm 340 NM 6.57 4.15 <-0.11 3.62 280 Nm 365 NM 6.57 4.11 <-0.11 7.96 325 NM 265 NM 6.57 <-0.11 <-0.11 4.88 325 NM 280 Nm 6.57 <-0.11 <-0.11 4.66 340 Nm 265 NM 6.57 <-0.11 <-0.11 4.43 340 Nm 280 Nm 6.57 <-0.11 <-0.11 4.46 365 NM 265 NM 6.57 <-0.11 <-0.11 8.13 365 NM 280 Nm 6.57 <-0.11 <-0.11 8.00

Table 41

Treatment with amotosalen and UV light for S. epidermidis_________

LIGHT 1 LIGHT 2 TITR to TITLE AFTER TITLE AFTER S-59 UV FIRST SECOND (MKM) LIGHTING LIGHTING 265 NM 325 NM 7.51 4.19 <-0.11 4.82 265 NM 340 Nm 7.51 4.37 <-0.11 3.93 265 NM 365 NM 7.51 4.12 <-0.11 8.17 280 Nm 325 NM 7.51 4.13 <-0.11 4.50 280 Nm 340 Nm 7.51 4.51 <-0.11 3.77 280 Nm 365 NM 7.51 4.19 <-0.11 8.01 325 NM 265 NM 7.51 <-0.11 <-0.11 4.92 325 NM 280 Nm 7.51 <-0.11 <-0.11 4.63 340 Nm 265 NM 7.51 <-0.11 <-0.11 4.47 340 Nm 280 NM 7.51 0.73 <-0.11 4.46 365 NM 265 NM 7.51 <-0.11 <-0.11 8.39 365 NM 280 Nm 7.51 <-0.11 <-0.11 8.07

A high level of bacterial inactivation was observed. Similar pathogen inactivation studies are performed using other bacteria known to be less sensitive to amotosalen/UV and/or UV-C treatment. In addition, similar studies are performed with other combinations of sequential doses of light, including combinations of a dose of 310 nm UV-B light with a dose of 325 nm, 340 nm or 365 nm UV-A light (in any order), as well as combinations of a dose of 325 nm, 340 nm, or 365 nm UV-A light followed by a dose of UV-A light of another wavelength of 325 nm, 340 nm, or 365 nm (in any order). In addition, using these or other devices according to this ISO

- 66 042016 shaving in similar studies, it is possible to evaluate light with any of the above combinations of wavelengths under simultaneous illumination, rather than sequential illumination, and/or using different containers (for example, bags for blood products).

While specific components, configurations, features, and functions have been presented above, those skilled in the art will appreciate that other variations may be used. In addition, although a feature may be described in connection with a particular embodiment, those skilled in the art will appreciate that various features of the described embodiments may be combined. Moreover, the aspects described in connection with the embodiment may be stand-alone.

While the embodiments have been fully described with reference to the accompanying drawings, it should be noted that various changes and modifications will be apparent to those skilled in the art. It is to be understood that such changes and modifications are within the scope of the various embodiments as defined by the appended claims.

Variations on the embodiments provided herein may become apparent to those skilled in the art upon reading the foregoing description. It is expected that those skilled in the art will be able to use such variations appropriately and practice the compositions, methods and kits described herein in a manner other than specifically described herein. Accordingly, the systems and methods described herein include all modifications and equivalents of the subject matter defined in the appended claims, in accordance with applicable law. In addition, any combination of the above elements in all their possible variations is included in the scope of the description, unless otherwise indicated in this document or otherwise clearly follows from the context. The following is a list of specific embodiments of the present invention. The list is illustrative and is not intended to limit the invention described herein.

Embodiment 1. A system for treating a biological fluid, including a treatment chamber for receiving a biological fluid;

one or more sensors designed to detect light in the processing chamber; and a first array of light sources arranged to illuminate the biological fluid in the treatment chamber, the first array of light sources including a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source channel designed to emit light from a second peak wavelength. peak wavelength, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

Embodiment 2. The system of Embodiment 1, wherein the first light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source matrix includes a first light source of a first light source channel designed to emit ultraviolet light with a first peak length waves, and a second light source of the second light source channel designed to emit light with a second peak wavelength.

Embodiment 3. The system of Embodiment 1 or Embodiment 2, wherein the second light source channel is designed to emit ultraviolet light.

Embodiment 4 The system of any one of Embodiments 1-3, wherein the first peak wavelength is in the ultraviolet A region.

Embodiment 5. The system of any one of Embodiments 1-4, wherein the first peak wavelength is in the ultraviolet A region and the second peak wavelength is in the ultraviolet C region.

Embodiment 6. The system of any one of Embodiments 1-5, wherein the first light source channel and the second light source channel include an LED.

Embodiment 7. The system of any of Embodiments 1-6, wherein the light intensity at 50% of the maximum peak light intensity emitted by the first channel of light sources is within a spectral width of less than 20 nm from the first peak wavelength.

Embodiment 8. The system of any of Embodiments 1-6, wherein the full width at half maximum (FWHM) of the light emitted from the first channel of light sources is within 20 nm of the first peak wavelength.

Embodiment 9. The system of any one of Embodiments 1-8, further including a first platform located in a treatment chamber designed to contain a biological fluid.

Embodiment 10. The system of any one of Embodiments 1-9, wherein the light sources of the first array of light sources are unevenly distributed on the array.

Embodiment 11. The system of Embodiment 10, wherein the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, wherein the inner region occupies less than 50% of the surface area of the first die, and the outer the area occupies the remaining percentage of the surface area of the first matrix.

- 67 042016

Embodiment 12. The system of Embodiment 11 wherein the first density of light sources placed in the outer region is greater than the second density of light sources placed in the inner region.

Embodiment 13. The system of any one of embodiments 1-10, wherein the first array includes a first light source area designed to illuminate a first body fluid in a treatment chamber and a second light source area designed to illuminate a second body fluid in the treatment chamber.

Embodiment 14. The system of any of Embodiments 1-13, wherein the first matrix is designed such that the light sources illuminate the body fluid in the treatment chamber with less than 25% irradiance variation over the entire surface of the body fluid facing the first matrix.

Embodiment 15. The system of any one of Embodiments 1-14, wherein the first light source array further includes a third light source channel designed to emit light at a third peak wavelength.

Embodiment 16. The system of any one of Embodiments 1-15, wherein the first light source array further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. wavelength.

Embodiment 17. The system of any one of Embodiments 1-16, further including a barrier placed in the treatment chamber between the first array of light sources and the biological fluid.

Embodiment 18 The system of Embodiment 17 wherein the barrier is transparent to light within 30 nm of the first peak wavelength.

Embodiment 19. The system of any one of Embodiments 9-18, wherein the first platform and the first array of lights are designed to move relative to each other to change the distance between the first array of lights and the first platform.

Embodiment 20. The system of any one of embodiments 9-19, wherein the first platform is designed to separately contain at least a first first body fluid container and a second second body fluid container.

Embodiment 21. The system of any one of embodiments 9-20, wherein the first platform is slidable to deposit and withdraw body fluid into and out of the treatment chamber.

Embodiment 22. The system of any one of Embodiments 1-21, wherein the system is designed to agitate the body fluid during treatment.

Embodiment 23. The system of any one of Embodiments 1-22, further including one or more sensors for detecting the presence of a biological fluid in the treatment chamber.

Embodiment 24. The system of any one of Embodiments 1-23, further including a second light source array directed away from the direction of the first light source array, wherein the second light source array includes a third light source channel designed to emit light from the first peak wavelength, and a fourth light source channel designed to emit light at the second peak wavelength.

Embodiment 25. The system of Embodiment 24, wherein the first array of lights and the second array of lights are designed to move relative to each other to change the distance between the first array of lights and the second array of lights.

Embodiment 26. The system of Embodiment 24 or Embodiment 25, further comprising a first platform positioned in the treatment chamber between the first light source array and the second light source array, the first platform being designed to receive biological fluid.

Embodiment 27. The system of any one of Embodiments 1-23, further including a second light source array directed in the same direction as the first light source array, wherein the second light source array includes a third light source channel designed to emit light with a first peak wavelength, and a fourth light source channel designed to emit light with a second peak wavelength, and wherein the first matrix of light sources and the second matrix of light sources define the first region between the first matrix of light sources and the second matrix of light sources.

Embodiment 28. The system of Embodiment 27, further comprising:

the first platform placed in the processing chamber in the first area, designed to accommodate the first biological fluid; and a second platform located in the processing chamber outside the first area, designed to accommodate the second biological fluid, while the second array of light sources on

- 68 042016 fixed for the second platform.

Embodiment 29. The system of any one of Embodiments 1-28, further including a control circuit.

Embodiment 30. The system of Embodiment 29, wherein the control circuit is designed to adjust or set the intensity of each light source of the first array of light sources.

Embodiment 31. The system of embodiment 29 or 30, wherein the control circuit is designed to adjust or set the first light intensity emitted by each first light source channel and to adjust or set the second light intensity emitted by each second light source channel.

Embodiment 32. The system as in any one of Embodiments 29-31, wherein the control circuit is designed to adjust or set the duration of light emission by each light source of the first array of light sources.

Embodiment 33. The system as in any one of embodiments 29-32, wherein the control circuit is designed to adjust or set a first light emission duration for each first light source channel and to adjust or set a second light emission duration for each second light source channel.

Embodiment 34. The system of any one of embodiments 29-33, wherein the control circuit is designed to adjust or set the duration of light emission by each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one a sensor of one or more sensors designed to detect light.

Embodiment 35. The system of any one of embodiments 29-34, wherein the control circuit is designed to adjust or set the light emission intensity of each light source of a first array of light sources based at least in part on a first set of parameters determined by at least one a sensor of one or more sensors designed to detect light.

Embodiment 36. A system for treating a biological fluid, including a treatment chamber for receiving a biological fluid;

one or more sensors designed to detect light in the processing chamber; and a first array of light sources designed to illuminate the biological fluid in the treatment chamber, wherein the first array of light sources includes a first channel of light sources designed to emit ultraviolet light with a first peak wavelength in the ultraviolet A region, with full width at half maximum (FWHM) of the spectrum width of the light emitted by the first channel of the light sources is less than 20 nm.

Embodiment 37. The system of Embodiment 36, wherein the first light source array includes a first light source channel designed to emit ultraviolet light at a first peak wavelength of about 330 nm to about 350 nm.

Embodiment 38. The system of Embodiment 36 or Embodiment 37, wherein 50% of the maximum peak light intensity emitted by the first channel of light sources is within 10 nm of the first peak wavelength.

Embodiment 39. The system of embodiment 36 or 37, wherein the light intensity at 50% of the maximum peak light intensity emitted by the first light source channel is within less than 20 nm.

Embodiment 40. The system of any one of embodiments 36-39, wherein the first light source array further includes a second light source channel designed to emit light at a second peak wavelength.

Embodiment 41. The system of Embodiment 40, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

Embodiment 42. The system of Embodiment 40 or Embodiment 41, wherein the second peak wavelength is in the ultraviolet A region.

Embodiment 43. The system of Embodiment 40 or Embodiment 41, wherein the second peak wavelength is in the ultraviolet B region.

Embodiment 44. The system of Embodiment 40 or Embodiment 41, wherein the second peak wavelength is in the ultraviolet C region.

Embodiment 45. The system of any one of embodiments 40-44, wherein 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the second peak wavelength.

Embodiment 46. The system of any one of embodiments 40-44, wherein the full width at half maximum (FWHM) of the light emitted from the second channel of light sources is less than 20 nm.

Embodiment 47. The system of any one of Embodiments 40-46, wherein

The light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source matrix includes a first light source of a first light source channel designed to emit ultraviolet light at a first peak wavelength and a second light source of a second channel light sources designed to emit light with a second peak wavelength.

Embodiment 48. The system of any one of embodiments 36-47, wherein the first light source channel includes one or more LEDs.

Embodiment 49. The system of any one of embodiments 40-48, wherein the second light source channel includes one or more LEDs.

Embodiment 50. The system of any one of embodiments 36-49, further including a first platform located in a treatment chamber designed to contain a biological fluid.

Embodiment 51. The system of any one of embodiments 36-50, wherein the light sources of the first array of light sources are unevenly spaced on the array.

Embodiment 52. The system of Embodiment 51, wherein the first die has a continuous inner region constituting the center of the first die and a continuous outer region surrounding the inner region, wherein the inner region occupies less than 50% of the surface area of the first die, and the outer the area occupies the remaining percentage of the surface area of the first matrix.

Embodiment 53. The system of Embodiment 52 wherein the first density of light sources placed in the outer region is greater than the second density of light sources placed in the inner region.

Embodiment 54. The system of any one of embodiments 36-51, wherein the first array includes a first light source area designed to illuminate a first body fluid in the treatment chamber and a second light source area designed to illuminate a second body fluid in the treatment chamber.

Embodiment 55. The system of any one of embodiments 36-54, wherein the first matrix is designed such that the light sources illuminate the body fluid in the treatment chamber with less than 25% irradiance variation across the entire surface of the body fluid facing the first matrix.

Embodiment 56. The system of any of embodiments 40-55, wherein the first light source array further includes a third light source channel designed to emit light at a third peak wavelength.

Embodiment 57. The system of any one of embodiments 40-56, wherein the first light source array further includes a third light source channel designed to emit light at a third peak wavelength and a fourth light source channel designed to emit light at a fourth peak wavelength. wavelength.

Embodiment 58. The system of any one of Embodiments 36-57, further including a barrier placed in the treatment chamber between the first array of light sources and the biological fluid.

Embodiment 59. The system of Embodiment 58, wherein the barrier is transparent to light within 30 nm of the first peak wavelength.

Embodiment 60. The system of any one of embodiments 50-59, wherein the first platform and the first array of lights are designed to move relative to each other to change the distance between the first array of lights and the first platform.

Embodiment 61. The system of any one of embodiments 50-60, wherein the first platform is designed to separately contain at least a first first body fluid container and a second second body fluid container.

Embodiment 62. The system of any one of embodiments 50-61, wherein the first platform is slidable to introduce and withdraw body fluid into and out of the treatment chamber.

Embodiment 63. The system of any one of embodiments 36-62, wherein the system is designed to agitate the body fluid during processing.

Embodiment 64. The system of any one of embodiments 36-63, further including one or more sensors for detecting the presence of a biological fluid in the treatment chamber.

Embodiment 65. The system of any one of embodiments 36-64 further including a second light source array directed away from the direction of the first light source array, wherein the second light source array includes a second light source channel designed to emit light from the first peak wavelength in the ultraviolet region of the spectrum A.

Embodiment 66. The system of any one of Embodiments 36-65, further

- 70 042016 including a second matrix of light sources directed in the direction opposite to the direction of the first matrix of light sources, while the second matrix of light sources includes a second channel of light sources designed to emit light with a second peak wavelength, while the second peak wavelength differs from the first peak wavelength at least 5 nm.

Embodiment 67. The system of Embodiment 65 or Embodiment 66, wherein 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the first peak wavelength.

Embodiment 68. The system of Embodiment 65 or Embodiment 66 wherein the full width at half maximum (FWHM) of the light emitted from the second channel of light sources is less than 20 nm.

Embodiment 69. The system of any one of embodiments 65-68, wherein the first array of lights and the second array of lights are designed to move relative to each other to change the distance between the first array of lights and the second array of lights.

Embodiment 70. The system of any one of embodiments 65-69, further including a first platform positioned in the treatment chamber between the first light source array and the second light source array, wherein the first platform is designed to receive biological fluid.

Embodiment 71. The system of any one of embodiments 36-64, further including a second array of lights directed in the same direction as the first array of lights, wherein the second array of lights includes a second light source channel designed to emit ultraviolet light with a first peak wavelength in the ultraviolet region of spectrum A, and wherein the first matrix of light sources and the second matrix of light sources delimit the first region between the first matrix of light sources and the second matrix of light sources.

Embodiment 72. The system of Embodiment 71, wherein 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the first peak wavelength.

Embodiment 73 The system of Embodiment 71 wherein the full width at half maximum (FWHM) of the light emitted from the second channel of light sources is less than 20 nm.

Embodiment 74. The system of any one of embodiments 71-73, further comprising a first platform located in a treatment chamber in a first region designed to receive a first body fluid; and a second platform located in the processing chamber outside the first area, designed to receive the second biological fluid, while the second array of light sources is directed to the second platform.

Embodiment 75. The system of any one of Embodiments 36-74, further including a control circuit.

Embodiment 76. The system of Embodiment 75, wherein the control circuit is designed to adjust or set the intensity of each light source of the first array of light sources.

Embodiment 77. The system of Embodiment 75 or Embodiment 76, wherein the control circuit is designed to adjust or set the duration of light emission by each light source of the first array of light sources.

Embodiment 78. The system of any one of embodiments 15-11, wherein the control circuit is designed to adjust or set the duration of light emission by each of the light sources of the first array of light sources based at least in part on a first set of parameters determined at least one sensor of one or more sensors designed to detect light.

Embodiment 79. The system of any one of embodiments 75-78, wherein the control circuit is designed to adjust or set the intensity of each light source of the first array of light sources based at least in part on a first set of parameters determined by at least one sensor of one or more sensors designed to detect light.

Embodiment 80. A method for treating a biological fluid, comprising: obtaining a biological fluid in admixture with a pathogen inactivating compound; illuminating the biological fluid with ultraviolet light having a first peak wavelength; and illuminating the biological fluid with light of a second peak wavelength, wherein the first peak wavelength differs from the second peak wavelength by at least 5 nm, wherein the biological fluid is illuminated for a period of time and at an intensity sufficient to

- 71 042016 accurate for pathogen inactivation in biological fluid.

Embodiment 81. The method of Embodiment 80, wherein ultraviolet light at a first peak wavelength is generated by a first light source, and light at a second peak wavelength is generated by a second light source.

Embodiment 82. The method of Embodiment 81 wherein 50% of the maximum peak light intensity emitted by the first light source is within 10 nm of the first peak wavelength.

Embodiment 83. The method of Embodiment 81, wherein the full width at half maximum (FWHM) of the spectrum width of the light emitted by the first light source is less than 20 nm.

Embodiment 84. The method of any one of embodiments 80-83, wherein the ultraviolet light with the first peak wavelength is in the ultraviolet A region of the spectrum.

Embodiment 85. The method of any one of embodiments 80-84, wherein the second peak wavelength light is in the ultraviolet B region, the ultraviolet C region, or the visible region of the spectrum.

Embodiment 86. The method of any one of embodiments 80-85, wherein illuminating the biological fluid with ultraviolet light at a first peak wavelength and illuminating the biological fluid with light at a second peak wavelength occur sequentially.

Embodiment 87. The method of any one of embodiments 80-86, wherein illuminating the biological fluid with ultraviolet light at a first peak wavelength comprises illuminating the biological fluid with ultraviolet light at a first peak wavelength for a first period of time, and illuminating the biological fluid with light with the second peak wavelength includes illumination of the biological fluid with light with the second peak wavelength during the second period of time.

Embodiment 88. The method of Embodiment 87, wherein the first time period is different from the second time period.

Embodiment 89. The method of any one of embodiments 80-88, wherein illuminating the biological fluid with ultraviolet light at a first peak wavelength is performed using a first set of light sources, wherein illuminating the biological fluid with light at a second peak wavelength is performed using a second set light sources, and the first and second sets of light sources are located on the matrix of light source clusters.

Embodiment 90. The method of any one of Embodiments 80-89, wherein the first light source and the second light source comprise an LED.

Embodiment 91. The method of any one of embodiments 80-90, wherein the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540.

Embodiment 92 The method of Embodiment 91 wherein the pathogen inactivating compound is psoralen.

Embodiment 93. A method for treating a biological fluid, comprising obtaining a biological fluid in admixture with a pathogen inactivating compound; and illuminating the biological fluid with ultraviolet light at a first peak wavelength generated by the first ultraviolet light source, wherein the full width at half maximum (FWHM) of the ultraviolet light emitted by the first ultraviolet light source is less than 20 nm, and illuminating the biological fluid occurs for a period of time and at an intensity sufficient to inactivate pathogens in the body fluid.

Embodiment 94. The method of Embodiment 93, wherein the ultraviolet light with the first peak wavelength is in the ultraviolet A region of the spectrum.

Embodiment 95. The method of Embodiment 94 wherein the first peak wavelength is 330 nm to 350 nm.

Embodiment 96. The method of any one of Embodiments 93-95, wherein the first light source includes an LED.

Embodiment 97. The method of any one of embodiments 93-96, wherein the biological fluid is contained in a container, and wherein the illumination of the biological fluid with ultraviolet light of a first peak wavelength is performed using a first set of light sources positioned on an array of light sources directed to only on one side of the container.

Embodiment 98. The method of any one of Embodiments 93-97, wherein the pathogen inactivating compound is a photoactive, pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazin, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540.

Embodiment 99. The method of Embodiment 98 wherein the inactivating pa

- 72 042016 togens compound is psoralen.

Embodiment 100. A method for treating a biological fluid, comprising introducing a biological fluid in admixture with a pathogen inactivating compound into a treatment chamber comprising one or more light sensors designed to detect light in the treatment chamber and a first array of light sources designed to illuminate the biological fluid in the processing chamber, wherein the first light source array includes a first light source channel designed to emit ultraviolet light at a first peak wavelength, and a second light source channel designed to emit light at a second peak wavelength, wherein the first peak wavelength is different from the second peak wavelength by at least 5 nm; and illuminating the biological fluid by emitting light at a first peak wavelength from the first light source channel and emitting light at a second peak wavelength from the second light source channel for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid.

Embodiment 101. The method of Embodiment 100, further comprising determining a set of biological fluid characteristics;

determining the processing mode based on the set of characteristics of the biological fluid;

adjusting or setting a set of processing camera parameters in accordance with the processing mode.

Embodiment 102. The method of Embodiment 100 or Embodiment 101, wherein the illumination of the biological fluid is carried out in accordance with the processing mode.

Embodiment 103. The method of any one of embodiments 100-102, wherein the duration and intensity sufficient to inactivate pathogens is determined based on the treatment regimen.

Embodiment 104. The method of any one of embodiments 100-103, wherein the first light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source matrix includes a first light source of a first light source channel designed to emit ultraviolet light with a first peak wavelength, and a second light source of the second light source channel designed to emit light with a second peak wavelength.

Embodiment 105. The method of any one of embodiments 100-104, wherein 50% of the maximum peak light intensity emitted from the first channel of light sources is within 10 nm of the first peak wavelength.

Embodiment 106. The method of any one of embodiments 100-104, wherein the full width at half maximum (FWHM) of the light emitted from the first channel of light sources is less than 20 nm.

Embodiment 107. The method of any one of embodiments 100-106, wherein the set of biological fluid characteristics includes at least one of a body fluid volume, a body fluid type, or a body fluid temperature.

Embodiment 108. The method of any one of embodiments 100-107, wherein determining a processing mode based on a set of characteristics includes determining a first peak wavelength and a second peak wavelength.

Embodiment 109. The method of any one of embodiments 100-108, wherein determining the processing mode based on the set of characteristics includes determining a first intensity of ultraviolet light with a first peak wavelength and a second intensity of light with a second peak wavelength.

Embodiment 110. The method of any one of embodiments 100-109, wherein determining the processing mode based on the property set includes determining a first duration of ultraviolet light emission at a first peak wavelength and a second duration of light emission at a second peak wavelength.

Embodiment 111. The method of any one of embodiments 100-110, wherein the treatment chamber further includes a first platform positioned in the treatment chamber containing a biological fluid.

Embodiment 112. The method of Embodiment 111, wherein adjusting or setting the processing camera parameter set includes adjusting or setting a distance between the first light source array and the first platform.

Embodiment 113. The method of any one of embodiments 100-112, further comprising agitating the biological fluid.

Embodiment 114. The method of Embodiment 113, wherein adjusting or setting the treatment chamber parameter set includes adjusting or setting a parameter related to agitation of the body fluid.

Embodiment 115. A method for treating a biological fluid, comprising

- 73 042016 introducing a biological fluid mixed with a pathogen-inactivating compound into a treatment chamber, including one or more photosensitive sensors designed to detect light in the treatment chamber, and a first array of light sources designed to illuminate the biological fluid in the treatment chamber, the first matrix the light sources include a first light source channel designed to emit ultraviolet light with a first peak wavelength in the ultraviolet A region, wherein the full width at half maximum (FWHM) of the light spectrum width emitted by the first light source channel is less than 20 nm;

illuminating the biological fluid by emitting light at a first peak wavelength from the first channel of light sources for a first period of time and at a first intensity sufficient to inactivate pathogens in the biological fluid.

Embodiment 116. The method of Embodiment 115, wherein each light source of the first channel of light sources is designed to emit ultraviolet light with a first peak wavelength of about 330 nm to about 350 nm.

Embodiment 117. The method of Embodiment 115 or Embodiment 116, further comprising determining a set of biological fluid characteristics;

determining the processing mode based on the set of characteristics of the biological fluid;

adjusting or setting a set of processing camera parameters in accordance with the processing mode.

Embodiment 118. The method of Embodiment 117, wherein the illumination of the biological fluid is carried out in accordance with the processing mode.

Embodiment 119. The method of Embodiment 117 or Embodiment 118, wherein the first duration and first intensity sufficient to inactivate pathogens is determined based on the treatment regimen.

Embodiment 120. The method of any one of embodiments 115-119, wherein 50% of the maximum peak light intensity emitted by the first channel of light sources is within 20 nm of the first peak wavelength.

Embodiment 121. The method of any one of embodiments 115-120, wherein the first light source array includes a second light source channel designed to emit light at a second peak wavelength.

Embodiment 122. The method of Embodiment 121, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

Embodiment 123. The method of Embodiment 121 or Embodiment 122, wherein 50% of the maximum peak light intensity emitted by the second channel of light sources is within 10 nm of the second peak wavelength.

Embodiment 124. The method of Embodiment 121 or Embodiment 122, wherein the full width at half maximum (FWHM) of the light emitted from the second channel of light sources is less than 20 nm.

Embodiment 125. The method of any one of embodiments 121-124, wherein the first light source array includes a plurality of light source clusters, wherein each light source cluster of the first light source array includes a first light source of a first light source channel designed to emit ultraviolet light with a first peak wavelength, and a second light source of the second channel of light sources designed to emit ultraviolet light with a second peak wavelength.

Embodiment 126. The method of any one of embodiments 117-125, wherein the set of biological fluid characteristics includes at least one of: volume of the biological fluid, type of the biological fluid, or temperature of the biological fluid.

Embodiment 127. The method of any one of embodiments 117-126, wherein determining a processing mode based on a set of characteristics includes determining a first peak wavelength.

Embodiment 128. The method of any one of embodiments 117-127, wherein determining the processing mode based on the set of characteristics includes determining a first light intensity with a first peak wavelength.

Embodiment 129. The method of any one of embodiments 117-128, wherein determining a processing mode based on a set of characteristics includes determining a first duration of light emission at a first peak wavelength.

Embodiment 130. The method of any one of embodiments 115-129, wherein the treatment chamber further includes a first platform positioned in the treatment chamber containing a biological fluid.

Embodiment 131. The method of Embodiment 130, wherein adjusting or setting the processing camera parameter set includes adjusting or setting a distance between the first light source array and the first platform.

-

Claims (64)

Embodiment 132. The method of any one of Embodiments 115-131 further comprising agitating the biological fluid. Embodiment 133. The method of Embodiment 132, wherein adjusting or setting the treatment chamber parameter set includes adjusting or setting a parameter related to agitation of the biological fluid. Embodiment 134. The method of any one of embodiments 80-133, wherein the treatment is sufficient to inactivate at least 1 log of pathogens in the body fluid and the body fluid after illumination is suitable for infusion into a subject without further treatment to remove residual a pathogen-inactivating compound or photoproducts thereof. Embodiment 135. The method of any one of embodiments 80-133, wherein the treatment is sufficient to inactivate at least 1 log of pathogens in the body fluid and the body fluid contains 5 μM or less of the pathogen-inactivating compound after illumination. Embodiment 136. The method of Embodiment 134 or Embodiment 135, wherein the concentration of the pathogen-inactivating compound in admixture with the body fluid prior to illumination is at least 10 μM. Embodiment 137. The method of any one of embodiments 134-136, wherein the concentration of the pathogen inactivating compound in the mixture with the body fluid after illumination is at least 3 times less than the concentration of the pathogen inactivating compound in the mixture with the biological fluid before illumination. Embodiment 138. Pathogen inactivated body fluid obtained by the methods of any one of Embodiments 80-137. Embodiment 139. The pathogen-inactivated body fluid of embodiment 138, wherein the body fluid contains 5 μM or less of the pathogen-inactivating compound after illumination. CLAIM 1. A method for processing a biological fluid, including obtaining a biological fluid in a mixture with a photoactive pathogen-inactivating compound; illumination of a biological fluid with ultraviolet light at a first peak wavelength of about 315 nm to about 350 nm emitted by a set of one or more first light sources, with each of the one or more first light sources emitting light having a full width at half maximum (FWHM ) of a spectral width less than 20 nm, and the illumination of the biological fluid occurs for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid. 2. The method of claim 1, wherein the first peak wavelength is from about 315 nm to about 335 nm. 3. The method of claim 1, wherein the first peak wavelength is from about 330 nm to about 350 nm. 4. The method according to any one of claims 1 to 3, wherein the first peak wavelength is the peak wavelength of one first light source in a set of one or more first light sources; optionally, the first peak wavelength is the peak wavelength of each of the plurality of first light sources in the set of one or more first light sources. 5. The method according to any one of claims 1 to 3, wherein the first peak wavelength is the average peak wavelength in the set of one or more first light sources. 6. The method according to any one of claims 1 to 5, further comprising illuminating the biological fluid with ultraviolet light with a second peak wavelength emitted by a set of one or more second light sources, wherein each of the one or more second light sources emits light having a total width at half maximum (FWHM) of the spectral width is less than 20 nm, and the second peak wavelength differs from the first peak wavelength by at least 5 nm. 7. The method according to claim 6, wherein the second peak wavelength is the peak wavelength of one second light source in a set of one or more second light sources; optionally, the second peak wavelength is the peak wavelength of each of the plurality of second light sources in the set of one or more second light sources. 8. The method of claim 6, wherein the second peak wavelength is the average peak wavelength of the set of one or more second light sources. 9. The method according to any one of claims 1 to 8, wherein the set of one or more first light sources includes one or more LEDs. 10. The method according to any one of claims 1 to 9, wherein the biological fluid is contained in a container, and when - 75 042016 this set of one or more first light sources is arranged in the form of a matrix of light sources, and the set of one or more first light sources is directed to only one side of the container. 11. The method according to any one of claims 1 to 10, wherein the photoactive, pathogen inactivating compound is psoralen; optionally, the photoactive, pathogen inactivating compound is amotosalen. 12. The method according to any one of claims 1 to 11, further comprising, before illuminating the biological fluid with ultraviolet light of a first peak wavelength, introducing the biological fluid in admixture with a photoactive, pathogen-inactivating compound into a treatment chamber comprising one or more light-sensitive sensors designed to detect of light in the treatment chamber, and a first matrix of light sources designed to illuminate the biological fluid in the treatment chamber, wherein the first matrix of light sources includes a first channel of light sources, including a set of one or more first light sources, wherein the illumination of the biological fluid includes light emission with the first peak wavelength from the first channel of light sources during the first period of time and at the first intensity sufficient to inactivate pathogens in the biological fluid; optionally, each light source of the first channel of light sources is designed to emit ultraviolet light with a first peak wavelength of about 315 nm to about 350 nm. 13. The method according to claim 12, further comprising determining a set of characteristics of the biological fluid; determining the processing mode based on the set of characteristics of the biological fluid; and adjusting or setting the processing chamber parameter set according to the processing mode; optionally, illumination of the biological fluid is carried out in accordance with the treatment regimen, and wherein the first duration and the first intensity sufficient to inactivate pathogens are determined based on the treatment regimen. 14. The method according to any one of claims 12, 13, wherein the first matrix of light sources includes a second channel of light sources designed to emit light with a second peak wavelength; optionally, the second peak wavelength differs from the first peak wavelength by at least 5 nm; and/or wherein the second peak wavelength is in the ultraviolet A region, the ultraviolet B region, or the ultraviolet C region. 15. The method of claim 14, wherein the second channel of light sources includes a set of one or more second light sources, wherein each of the one or more second light sources emits light having a full width at half maximum (FWHM) of a spectral width of less than 20 nm. 16. The method according to any one of claims 13-15, wherein the set of characteristics of the biological fluid includes one or more of the group including the volume of the biological fluid, the type of the biological fluid, and the temperature of the biological fluid; and/or wherein determining the processing mode based on the set of characteristics of the biological fluid includes determining the first intensity of light with the first peak wavelength or determining the first duration of light emission with the first peak wavelength. 17. The method according to any one of claims 12-16, wherein the treatment chamber further includes a first platform located in the treatment chamber containing the biological fluid. 18. The method of claim 17, wherein adjusting or setting the processing camera parameter set includes adjusting or setting a distance between the first light source array and the first platform. 19. The method according to any one of claims 1 to 18, further comprising mixing the biological fluid. 20. The method according to any one of claims 1 to 19, wherein the total dose of ultraviolet light illuminating the biological fluid is from about 0.5 J/cm ² to about 50 J/cm ² , optionally the total dose of ultraviolet light illuminating biological fluid emitted by a set of one or more first light sources is from about 0.5 J/cm ² to about 50 J/cm ² . 21. A method according to any one of claims 1-20, which is sufficient to inactivate at least 1 log of pathogens in the biological fluid, if present, and wherein the biological fluid, after illumination, is suitable for infusion into a subject without additional treatment to remove a residual pathogen-inactivating compound or photoproduct(s) thereof; and/or which is sufficient to inactivate at least 1 log of pathogens in the body fluid, if present, and wherein the body fluid, after illumination, is suitable for infusion into a subject without passing the body fluid through a compound removal step to remove residual pathogen-inactivating compound, or its photographic product(s). 22. The method according to any one of claims 1 to 21, which is sufficient to inactivate at least 1 log of pathogens in the biological fluid, if present, and wherein the biological fluid contains 5 μm or less of the pathogen-inactivating compound after illumination; optionally which is sufficient to inactivate at least 1 log of pathogens in the biological - 76 042016 biological fluid, if present, and the biological fluid contains 2 μM or less of the pathogen-inactivating compound after illumination. 23. The method according to any one of claims 1 to 22, wherein the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is at least about 10 μM; optionally, the concentration of the pathogen-inactivating compound in admixture with the biological fluid prior to illumination is from about 15 μM to about 150 μM. 24. The method according to any one of claims 1 to 23, wherein the concentration of the pathogen-inactivating compound in the mixture with the biological fluid after illumination is at least 3 times less than the concentration of the pathogen-inactivating compound in the mixture with the biological fluid before illumination. 25. A method according to any one of claims 1-24 which is sufficient to inactivate at least 4 log pathogens in the biological fluid, if present. 26. The method according to any one of claims 1 to 25, wherein the biological fluid after illumination retains sufficient biological activity such that the biological fluid is suitable for infusion into a subject. 27. The method according to any one of claims 1 to 26, wherein the biological fluid is a blood product. 28. The method according to any one of claims 1 to 27, wherein the biological fluid is a plasma preparation; optionally, the concentration of fibrinogen in the plasma preparation after illumination is at least 70% of the concentration of fibrinogen in the plasma preparation before illumination; and/or wherein the concentration of factor VIII in the plasma preparation after illumination is at least 70% of the concentration of factor VIII in the plasma preparation before illumination. 29. The method according to any one of claims 1 to 28, wherein the biological fluid is a platelet preparation, optionally the biological fluid additionally contains an additive solution for platelets; and/or wherein the number of platelets in the platelet preparation after illumination is at least 80% of the retained platelets; and/or wherein the pH value at 22° C. of the platelet preparation after illumination is at least 6.2. 30. The method of any one of claims 1 to 29, which comprises, prior to illumination, incubating the biological fluid with a photoactive, pathogen inactivating compound for a period of 30 minutes to 24 hours. 31. A system for processing a biological fluid, including a processing chamber designed to receive a biological fluid; one or more sensors designed to detect light in the processing chamber; and a first array of light sources designed to illuminate the biological fluid in the treatment chamber, wherein the first array of light sources includes a first channel of light sources designed to emit ultraviolet light at a first peak wavelength of the first array from about 315 nm to about 350 nm, and This first light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral width of less than 20 nm. 32. The system of claim 31, wherein the first peak wavelength of the first array is from about 315 nm to about 335 nm. 33. The system of claim 31, wherein the first peak wavelength of the first matrix is from about 330 nm to about 350 nm. 34. The system of any one of claims 31-33, wherein the first peak wavelength of the first array is the average peak wavelength of one or more light sources of the first light source channel. 35. A system according to any one of claims 31-34, wherein the one or more light sources of the first light source channel include one or more light emitting diodes (LEDs). 36. The system according to any one of claims 31-35, wherein the first light source array further includes a second light source channel designed to emit light at a second peak wavelength of the first matrix, wherein the second light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral width of less than 20 nm, and while the second peak wavelength of the first matrix differs from the first peak wavelength of the first matrix by at least 5 nm; optionally, the second peak wavelength of the first matrix is in the ultraviolet A region, the ultraviolet B region, or the ultraviolet C region; and/or wherein the second light source channel includes one or more LEDs. 37. A system according to any one of claims 31-36, wherein the light sources of the first array of light sources are unevenly placed on the matrix. 38. A system according to any one of claims 31-37, which is designed to mix a biological fluid during processing. 39. A system according to any one of claims 31-38, wherein the first light source array includes two or more light source panels. - 77 042016 40. The system according to any one of claims 31-39, wherein the first matrix is designed such that the light sources of the first matrix illuminate the biological fluid in the treatment chamber with a radiation variation of less than 25% over the entire surface of the biological fluid facing the first matrix. 41. The system according to any one of claims 31 to 40, further comprising a first platform located in the processing chamber, designed to contain biological fluid; optionally, the first platform and the first array of light sources are designed to move relative to each other in order to change the distance between the first matrix of light sources and the first platform; and/or wherein the first platform is movable in a sliding motion to introduce and withdraw biological fluid into and out of the treatment chamber; and/or wherein the first platform is designed to separately accommodate at least the first container with said biological fluid as the first biological fluid and the second container with the second biological fluid; and/or wherein one or more of the one or more sensors are attached to, or placed in, the first platform. 42. The system according to any one of claims 31-41, further comprising a barrier placed in the processing chamber between the first matrix of light sources and the biological fluid; however, optionally, the barrier placed in the processing chamber between the first matrix of light sources and the biological fluid is transparent to light with a wavelength within 30 nm from the first peak wavelength of the first matrix; and/or wherein one or more of the one or more sensors are attached to, or placed in, a barrier placed in the treatment chamber between the first array of light sources and the biological fluid. 43. The system according to any one of claims 31-42, wherein the first matrix includes a first area of light sources designed to illuminate the biological fluid in the form of a first illuminated biological fluid in the processing chamber, and a second area of light sources designed to illuminate the second illuminated biological fluid in the processing chamber. 44. The system according to any one of claims 31-43, further comprising a control circuit; optionally, the control circuit is designed to adjust or set the intensity or duration of light emission from each light source of the first array of light sources; wherein optionally the control circuit is designed to adjust or set the intensity or duration of light emission from each light source of the first array of light sources based at least in part on the first set of parameters determined by at least one sensor of one or more sensors designed for detection Sveta. 45. The system according to any one of claims 31-44, further comprising one or more sensors designed to detect the presence of a biological fluid in the treatment chamber. 46. The system of any one of claims 31-45, further comprising a second array of light sources directed away from the direction of the first array of light sources, wherein the second array of light sources includes a first light source channel designed to emit light with a first peak length waves of the second array, and wherein the first light source channel of the second array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) of the spectral width of less than 20 nm. 47. The system of claim 46, wherein the first peak wavelength of the second array is substantially the same as the first peak wavelength of the first array. 48. The system of claim 46, wherein the second light source array includes a second light source channel designed to emit light at a second peak wavelength of the second matrix, wherein the second light source channel of the second matrix includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) of a spectral width of less than 20 nm, and wherein the second peak wavelength of the second array differs from the first peak wavelength of the second array by at least 5 nm. 49. The system of any one of claims 46-48, wherein the first light source array and the second light source array are designed to move relative to each other to change the distance between the first light source array and the second light source array. 50. The system of any one of claims 31-45, further comprising a second array of light sources directed in the same direction as the first matrix of light sources, wherein the second matrix of light sources includes a first light source channel designed to emit light from the first peak wavelength of the second matrix, and wherein the first matrix of light sources and the second matrix of light sources define the first region between the first matrix of light sources and the second matrix of light sources, and wherein the first channel of light sources of the second matrix includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral width of less than 20 nm. 51. The system of any one of claims 46 to 50, further comprising a first platform positioned in the treatment chamber between the first light source array and the second light source array, designed to receive the biological fluid. 52. The system of claim 50, further comprising - 78 042016 the first platform placed in the processing chamber in the first area, designed to contain the biological fluid in the form of the first treated biological fluid; a second platform located in the processing chamber outside the first area, designed to accommodate the second processed biological fluid, while the second matrix of light sources is directed to the second platform; optionally, one or more of the one or more sensors are attached to, or placed in, the second platform. 53. The system according to claims 46-52, further comprising a barrier placed in the processing chamber between the second matrix of light sources and the biological fluid; however, optionally, the barrier placed in the processing chamber between the second matrix of light sources and the biological fluid is transparent to light with a wavelength within 30 nm from the first peak wavelength of the first matrix; and/or wherein one or more of the one or more sensors are attached to, or placed in, a barrier placed in the treatment chamber between the second array of light sources and the biological fluid. 54. The system according to any one of claims 46 to 53, further comprising a control circuit designed to adjust or set the intensity or duration of light emission from each light source of the second array of light sources; wherein optionally the control circuit is designed to adjust or set the intensity or duration of light emission from each light source of the second array of light sources based at least in part on the first set of parameters determined by at least one sensor of one or more sensors designed for detection Sveta. 55. The system according to claim 44 or 54, while the control circuit is designed for a) determining a set of characteristics of the biological fluid; b) determining the treatment mode based on the set of characteristics of the biological fluid; c) adjusting or setting a set of parameters of the processing chamber in accordance with the processing mode; And d) illumination of the biological fluid in accordance with the mode of processing. 56. A system according to any one of claims 31-55, designed to illuminate a biological fluid in admixture with a photoactive pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate pathogens in the biological fluid, if present. 57. A system according to any one of claims 31-55, designed to illuminate a biological fluid in admixture with a photoactive pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 1 log of pathogens in the biological fluid, if present. and wherein the biological fluid, after illumination, is suitable for infusion into the subject without further processing to remove residual photoactive, pathogen-inactivating compound or photoproduct(s) thereof. 58. A system according to any one of claims 31-55, designed to illuminate a biological fluid in admixture with a photoactive pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 1 log of pathogens in the biological fluid, if present. , and wherein the biological fluid contains 5 μM or less of a photoactive pathogen-inactivating compound after illumination. 59. A system according to any one of claims 31-55, designed to illuminate a biological fluid in admixture with a photoactive, pathogen inactivating compound for a period of time and at an intensity sufficient to reduce the concentration of a photoactive, pathogen inactivating compound in admixture with a biological fluid of at least 3 times the concentration of a photoactive, pathogen-inactivating compound in a mixture with a biological fluid before illumination. 60. A system according to any one of claims 31-55, designed to illuminate a biological fluid in admixture with a photoactive pathogen-inactivating compound for a period of time and at an intensity sufficient to inactivate at least 4 log pathogens in the biological fluid, if present. . 61. The system according to any one of claims 31-60, wherein the biological fluid is a blood product. 62. The system according to any one of claims 31-61, wherein the biological fluid is a plasma preparation. 63. The system according to any one of claims 31-61, wherein the biological fluid is a platelet preparation; optionally, the biological fluid additionally contains an additive solution for platelets. 64. The system according to any one of claims 31-63, wherein the photoactive, pathogen inactivating compound is psoralen; optionally, the photoactive, pathogen inactivating compound is amotosalen. -