WO2022061262A1

WO2022061262A1 - Systems and methods for non-invasive solute measurement

Info

Publication number: WO2022061262A1
Application number: PCT/US2021/051187
Authority: WO
Inventors: Lishan Aklog; Richard YAZBECK; Randal Chinnock; George Grubner; David GADDY
Original assignee: PAVmed Inc.
Priority date: 2020-09-21
Filing date: 2021-09-21
Publication date: 2022-03-24
Also published as: WO2022061262A8

Abstract

A method for non-invasive monitoring of a solute within a patient is provided. The method includes emitting, from each of a plurality of emitters, light at individually identifiable wavelengths through tissue or body fluid of the patient identifying, by at least one receiver, a transmittance of individually identifiable wavelengths received through the tissue or body fluid of the patient and determining, by a processor, a concentration of a solute for the patient based on the level of transmittance of each wavelength of light. The system also includes a controller having logic computations for activating and deactivating the light source and for controlling parameters of the light beam being emitted, and at least one receiver positioned to detect a designated wavelength from the light beam that has been transmitted across the layer of tissue or body fluid of the patient.

Description

SYSTEMS AND METHODS FOR NON-INVASIVE SOLUTE MEASUREMENT

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is an International PCT Application which claims priority to and the benefit of U.S. Provisional Application No. 63/080,961, filed September 21, 2020, the entire contents of which are hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present disclosure relates to systems and methods suitable for non-invasive measurement of a substance within a fluid. In particular, the present disclosure relates to measuring target substances within blood of a patient using non-invasive methods and systems.

BACKGROUND

[0003] Generally, a combination of systems and methods can be used to measure different substances within different materials. In the medical field it is often desirable to measure different levels of substances (i.e., solutes) to monitor for different conditions. For example, blood glucose monitoring is often performed to measure the concentration of glucose in blood for managing diabetes in patients. Traditionally, a blood glucose test is performed by puncturing or pricking the skin, for example, a tip of the patient’s finger to obtain a blood sample and testing the blood sample. The sample can be tested using a combination of techniques, however, it is common to measure an electrical characteristic of the blood sample to determine a concentration of glucose within the blood. For example, a glucose meter can have multiple conductive contacts which can be used to transmit an electrical signal through the blood sample (e.g. via a test strip) to determine a glucose concentration. Patients with diabetes can require testing multiple times a day to monitor and manage their diabetes. Although such repetitive testing can be an inconvenience in day to day testing, it can be exacerbated when patients are constantly being monitored, for example, during recovery from a procedure. Constantly having to prick finger to get glucose can both cause greater discomfort to a patient while interrupting their recovery, for example, when they should be resting.

SUMMARY

[0004] There is a need for improvements for monitoring substance levels within a patient. The present disclosure is directed toward further solutions to address this need, in addition to having other desirable characteristics.

[0005] In accordance with example embodiments of the present invention, method for non- invasive monitoring of a solute within a patient is provided. The method includes emitting, from each of a plurality of emitters, light at individually identifiable wavelengths through tissue or body fluid of the patient identifying, by at least one receiver, a transmittance of individually identifiable wavelengths received through the tissue or body fluid of the patient and determining, by a processor, a concentration of a solute for the patient based on the level of transmittance of each wavelength of light.

[0006] In accordance with one embodiment of the present invention, a system for non- invasive monitoring of a solute within a patient is also provided. The system includes a light source designed to emit at least one light beam with one or more wavelengths for transmission across a layer of tissue or body fluid of the patient. The system also includes a controller having logic computations for activating and deactivating the light source and for controlling parameters of the light beam being emitted, and at least one receiver positioned to detect a designated wavelength from the light beam that has been transmitted across the layer of tissue or body fluid of the patient. A processor is also provided for determining a concentration of a solute in the tissue or body fluid based on the level of transmittance of the wavelength detected by the receiver.

[0007] In accordance with aspects of the present invention, at least a first emitter or the plurality of emitters and a second emitter or the plurality of emitters are positioned on opposing sides of the tissue or body fluid. The at least one receiver can include a first receiver and a second receiver positioned on opposing sides of the tissue. The plurality of emitters can be directed to adjacent locations on the tissue. At least a first wavelength of light and a second wavelength of light of the plurality of emitters can be directed to adjacent locations on the tissue and converge at a location within the tissue. At least a first wavelength of light and a second wavelength of light of the plurality of emitters can be directed to adjacent locations on the tissue in an alternating pattern. In accordance with aspects of the present invention, the method further includes redirecting a direction of the light entering the tissue or exiting the tissue. In accordance with aspects of the present invention, the method can further include transforming at least one of a shape, power or energy, power or energy distribution, angle of incidence, polarization, spectral content, and area of the light entering the tissue or exiting the tissue. The at least one shape can be a fan shape.

[0008] In accordance with example embodiments of the present invention, method for non- invasive monitoring of a solute within a patient is provided. The method includes emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light through tissue or body fluid of the patient, performing spectral separation of the plurality of individually identifiable wavelengths of light, identifying, by a plurality of receivers, the power or energy of the individually identifiable wavelengths of light received through the tissue of the patient, and determining, by a processor, a concentration of a solute for the patient based on the power or energy of the individually identifiable wavelengths of light.

[0009] In accordance with example embodiments of the present invention, method for non- invasive monitoring of a solute within a patient is provided. The method includes emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light, performing spectral separation of the single light beam into the plurality of individually identifiable wavelengths of light, and combining, by a collimator, the plurality of wavelengths into a single light beam having the plurality of individually identifiable wavelengths of light. The method also includes identifying, by at least one receiver, a level of the individually identifiable wavelengths of light received through tissue of the patient and determining, by a processor, a concentration of a solute for the patient based on the power or energy each individually identifiable wavelength of light.

[0010] In accordance with aspects of the present invention, each of the spectrally separated plurality of wavelengths of light are directed to different receivers of the at least one receiver. [0011] In accordance with example embodiments of the present invention, a method for non-invasive monitoring of a solute within a patient or sample tissue or body fluid from a patient is provided. The method includes simultaneously activating a first emitter, a second emitter, and a third emitter, each emitting light at individually identifiable wavelengths through tissue or body fluid of the patient, deactivating the second emitter and the third emitter for a first period of time, activating the second emitter and deactivating the first emitter for a second period of time, and activating the third emitter and deactivating the second emitter for a third period of time. The method also includes reactivating all emitters, identifying, by at least one receiver, the transmittance through the tissue or body fluid of each of the individually identifiable wavelengths of light, and determining, by a processor, a concentration of a solute for the patient based on the transmittance of each wavelength of light through the tissue or body fluid.

[0012] In accordance with example embodiments of the present invention, method for non- invasive monitoring of a solute within a patient is provided. The method includes emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light through tissue or body fluid of the patient, identifying, by at least one receiver, a transmittance of individually identifiable wavelengths received through the tissue or body fluid of the patient, and determining, by a processor, a concentration of a solute for the patient based on the level of transmittance of each wavelength of light.

BRIEF DESCRIPTION OF THE FIGURES

[0013] These and other characteristics of the present disclosure will be more fully understood by reference to the following detailed description in conjunction with the attached drawings, in which:

[0014] FIGS. 1A and IB example diagrams of non-invasive measurement of a substance within a fluid in accordance with the present invention;

[0015] FIGS. 2A, 2B, 2C, and 2D are example illustrations of an operation of non-invasive measurement system in accordance with the present invention;

[0016] FIG. 3 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0017] FIGS. 4 A, 4B, 4C, and 4D are example illustrations of an operation of non-invasive measurement system in accordance with the present invention;

[0018] FIG. 5 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0019] FIG. 6 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0020] FIG. 7 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention; [0021] FIGS. 8 A, 8B, and 8C are example illustrations of an operation of non-invasive measurement system in accordance with the present invention;

[0022] FIGS. 9 A and 9B are example illustrations of an operation of non-invasive measurement system in accordance with the present invention;

[0023] FIG. 10 is a graph showing the absorption difference spectrum between water and various concentrations of aqueous solutions of glucose;

[0024] FIG. 11 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0025] FIG. 12 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0026] FIG. 13 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention;

[0027] FIG. 14 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention; and

[0028] FIG. 15 is an example illustration of an operation of non-invasive measurement system in accordance with the present invention.

DETAILED DESCRIPTION

[0029] An illustrative embodiment of the present disclosure relates to systems and methods for monitoring substance within a patient without having to draw a physical sample from the patient. Specifically, the systems and methods of the present disclosure utilize a combination of emitters and receivers capable of transmitting and detecting a plurality of wavelengths through a sampling site. The detected wavelengths can then be used to determine a concentration level of a target substance found within the sampling site. In some embodiments, the systems and methods of the present disclosure can be used to determine concentrations of glucose within blood of a patient through non-invasive means. The present disclosure can be modified for use with any combination of substances and measurements. For example, the present disclosure can be used to measure a concentration of potassium, sodium, hemoglobins, CO2, etc. in different fluids.

[0030] FIGS. 1 A through 15, wherein like parts are designated by like reference numerals throughout, illustrate an example embodiment or embodiments of improved systems and methods for detecting particular substances within a patient, according to the present disclosure. Although the present disclosure will be described with reference to the example embodiment or embodiments illustrated in the figures, it should be understood that many alternative forms can embody the present disclosure. One of skill in the art will additionally appreciate different ways to alter the parameters of the embodiment(s) disclosed, such as the size, shape, or type of elements or materials, in a manner still in keeping with the spirit and scope of the present disclosure.

[0031] Referring to FIGS. 1A and IB, in some embodiments, a monitoring system 100 for generating one or more light beams can be utilized for use in accordance with the present disclosure. The monitoring system 100 can include any combination of components for emitting, controlling, and detecting light beams, laser beams, light, etc. at various wavelengths. For purposes of this disclosure, the terms emitting, light, light beams, laser beams, light, light waves, photons, energy, electro-magnetic radiation, optical sensors, etc. may be used interchangeably depending on the systems and methods being described. The present invention provides a combination of devices that can be used in-vivo and/or in biomedical applications to leverage light absorption by the substance of interest. Similarly, systems and methods using different light emitting sources may substitute components without departing from the scope of the present disclosure. For example, a system using a light amplification by stimulated emission of radiation (laser) may be designed to implement the methods of the present invention in a similar manner as a system using light emitting diodes (LEDs) using similar steps discussed herein. Broadband light sources, which emit electromagnetic radiation over a wide spectrum, may also be used, with specific wavelengths selected by optical devices such as bandpass filters, diffraction gratings, prisms, etc.

[0032] In some embodiments, the system 100 can include a light generating device 102 including one or more emitters 104 for outputting light in one or more wavelengths. For example, the system 100 can include a single laser emitter, LED emitter, etc. capable of generating light at one wave length or light at multiple different wavelengths (simultaneously or sequentially), or a plurality of laser emitters, LED emitters, etc. each capable of generating light at one wavelength or generating light at multiple wavelengths (simultaneously or sequentially). The light generating device 102 can include a power source (not shown) or otherwise be coupled to a power source to provide energy to power the one or more emitters 104 and other components of the system 100.

[0033] In some embodiments, the light generating device 102 can include a controller 106 responsible for controlling operation of the one or more emitters 104. The controller 106 can include any combination of electronic components and logic computations capable of activating and deactivating the one or more emitters 104. The controller 106 can also include electronic components and logic computations for controlling the parameters of the light being emitted from the one or more emitters 104. For example, the controller 106 can be designed to control any combination of optical power and power modulation, wavelengths, polarization, etc. of the light being emitted by the one or more emitters 104.

[0034] In some embodiments, the light generating device 102 can include one or more control receivers 108 for sampling the light emitted by the one or more emitters 104. In some embodiments, the sampling occurs at or near the surface of the tissue, i.e., within sensor 112, to most accurately measure incident light. In some embodiments, the one or more control receivers 108 can also be designed to include filters and/or detectors to measure specific wavelengths or combination of wavelengths. In some embodiments, the one or more control receivers 108 can include a beam modifier(s).

[0035] In some embodiments, the light generating device 102 includes or otherwise be connected to a communication pathway 110 for transmitting light to and from a sensor 112. The communication pathway 110 can include any combination of devices and/materials capable of transmitting light emitted by the one or more light generating device 102. For example, the communication pathway 110 can simply be air, or it can comprise one or more lenses, one or more optical fibers arranged in a ring, a bundle, an array, or other geometry: one or more optical waveguides; or any other combination of optical materials known in the art. In some embodiments, the sensor 112 can be a device designed to be positioned on a subject for conveying the light received from the communication pathway 110 to and from the subject. For example, the sensor 112 can be a clip designed with one or more lenses or mirrors or other optical components for directing light through the sample and receiving the light back from the sample. In some embodiments, the light generating device 102 can be a sensor itself and does not require use of a communication pathway 110 for transmitting light to and from a separate sensor 112. Similarly, the communication pathway 110 can include any combination of devices and/materials capable of transmitting light emitted by the one or more emitters 104 to one or more receivers 108.

[0036] In some embodiments, the light generating device 102 and/or the sensor 112 can include one or both of a collimator 114 and a beam modifier 116. The collimator 114 can include any combination of devices designed to combine or narrow a beam of light or light waves to be more aligned in a specific detection and/or cause the cross section of the beam to become narrower in dimension. The beam modifier 116 can include any combination of devices designed to expand, modify, or separate a beam into different sets of waves or wavelengths to be distributed in different detections and/or cause the cross section of the beam to become more expanded in dimension. For example, the beam modifier 116 can be a spectral separator to separate light into a plurality of beams, each with different wavelengths. The beam modifier 116 can also include or can be designed as a filter designed to filter out particular wavelengths from a beam.

[0037] In some embodiments, the system 100, as illustrated in FIG. IB, can be used for non-invasive monitoring of a target substance or solute within tissue 200 or blood of a patient (or other gases or liquids). For example, the system 100 can be used for non-invasive monitoring of glucose within blood of a patient. For non-invasive glucose monitoring the light generating device 102 and/or the sensor 112 can be setup adjacent to a target tissue 200 on a patient. In some instances, it may be preferable to setup portions of the light generating device 102 and/or the sensor 112 on two sides of a target location that has a measurable thickness such that detectable light can be transmitted therethrough. For example, the light generating device 102 and/or the sensor 112 can be positioned on thin parts of the hand, feet, lips, ears, nostrils, etc. [0038] In some embodiments, when the light generating device 102 and/or the sensor 112 is in a desired position the monitoring process can be initiated. The monitoring process can include emitting light 120 from the one or more emitters 104. The light generating device 102 can include any combination of light emitters 104, for example, the light can be generated by a laser or by LEDs or any other combination of light sources. The light 120 being emitted can include one or more wavelengths that are selected to specifically identify or eliminate particular substances that are present in the light path 120. It can be advantageous to make measurements at wavelengths where absorption in the sample is highly sensitive to the amount of substance present in the light path (Signal). Other specific wavelengths may be also used as reference points, i.e., they are selected because when they pass through the sample they are insensitive to the concentration of the substance being measured but are otherwise attenuated by the sample in the same way as the Signal wavelengths. For example, water has a nearly identical absorption spectrum as low concentration aqueous solution of glucose (as in tissue).

[0039] The Beer-Lambert Law relates the optical attenuation of a physical material containing a single attenuating species of uniform concentration to the optical path length through the sample and absorptivity of the species: Absorbance = e/c, where e is the molar attenuation coefficient or absorptivity of the attenuating species, I is the optical path length, and c is the concentration of the attenuating species. If the concentration of the attenuating species (in this example glucose) is to be calculated, the thickness I of the tissue being measured must either be known or eliminated from the calculation.

[0040] FIG. 10 shows the absorption difference spectrum between water and various concentrations of aqueous solutions of glucose ranging from 100 to 10,000 mg/dL. Clinical values of glucose concentration in tissue are in the range of 60-300mg/dL. In FIG. 10, large changes in signal vs. concentration are seen in the bands 1140-1160nm, 1300-1500nm, and 1550-1780nm. Good reference wavelengths (very small changes in signal vs. concentration) are seen in the wavelength band 1050-1070nm, and at the isosbestic points around 1530nm and 1800nm. By measuring absorbance at one or more of the signal wavelengths (Ai) and one or more of the reference wavelengths (A2), glucose concentration may be determined that is corrected for optical path length variations, i.e., the thickness of the tissue being sampled.

[0041] Continuing with FIGS. 1 A and IB, in some embodiments, the light 120 can be provided directly into the tissue 200 of a patient or it can be redirected into the tissue 200, for example, using a combination of optical elements. After the light 120 has passed through the tissue 200, the one or more receivers 109 can detect the amount of light that is not absorbed or scattered by the substances in the tissue. In other words, the one or more receivers 109 can identify a level or amount of transmittance, power, and/or energy by the light 120 through the tissue 200 or body fluid of each of the individually identifiable wavelengths of light 120. The controller 106 can then receive the measured values from the one or more detectors 109 for each wavelength being used and can calculate a concentration of the substance that is corrected for optical path length. In particular, the controller 106 can be designed to determine a concentration of a solute for the patient based on the transmittance, power, and/or energy of each individually identifiable wavelengths of light 120 through the tissue 200 or body fluid of the patient.

[0042] In some embodiments, accuracy of the measurements can be improved by performing repeated measurements and using statistical processing methods on the measurements. For example, the controller 106 can calculate the ratio of the mean (ROM) values of each wavelength, or it can calculate the mean of the ratios (MOR). It can compare the ROM to the MOR to determine the confidence in the measurement. Measurements with low confidence can be discarded. Measurements made with a control receiver 108 that are simultaneous with the measurements made by receivers 109 are used to normalize the measurements made with receivers 109. This eliminates noise in the measurements caused by temporal variations in output of the light generating device(s) 102.

[0043] In some embodiments, light from the one or more light generating devices 102 can be transitioned over a communication pathway 110 to a testing location. For example, light 120 can be emitted through a fiber optic communication pathway 110 to a tissue being monitored. Similarly, the light 120 can be returned over the communication pathway 110, before or after, being detected by the one or more receivers 109. [0044] Referring to FIG. 2 A, in some embodiments, the light 120 can be directed through the tissue 200 from one or more light generating devices 102 to one or more receivers 109 on the opposing side of the emitters 104. This configuration can be used with any combination of light generating devices 102 and receivers 109. For example, a plurality of light generating devices 102 can direct light 120 through the tissue 200 to a single receiver 109, multiple receivers 109, or a plurality of receivers 109 aligned with each of the plurality of light generating devices 102. In some embodiments, light 120 emitted from one emitter 104 can be broadband, and a beam modifier 116 can be used to pass only certain wavelengths into beam 120 and through the tissue 200.

[0045] In some embodiments, light 120 emitted from one or more emitters 104 can also be separated (e.g., by beam modifier 116) into multiple separate wavelengths directed to one or more receivers 109. The separation can occur before or after the light 120 enters the tissue 200. For example, the light 120 from an emitter 104 can pass through a beam modifier 116 comprised of prism, one or more beam splitters, a grating, an AOTF or other optical element or subsystem that separates the light 120 into three beams directed through the tissue 200 and to one or more receivers 109 on the opposing side of the tissue 200. In some embodiments, each side of the tissue can have a device having both a receiver(s) 109 and narrow band filters to receive the respective signals,

[0046] Referring to FIG. 2B, in some embodiments, the light 120 can be directed through the tissue 200 from one or more light generating devices 102 then reflected back, by a redirecting device 150, through the tissue 200 toward to one or more receivers 109 on the same side of the tissue as the light generating devices 102. For example, the redirecting device 150, such as a mirror, can be positioned on an opposing side of the tissue 200 from the light generating device(s) 102 and can reflect light 120 back in a direction toward one or more receivers 109.

This configuration can be used with any combination of light generating devices 102, redirecting devices 150, and receivers 109. For example, a plurality of light generating devices 102 can direct light 120 through the tissue 200 to a single redirecting device 150 or multiple redirecting devices 150 to direct light 120 back to a single receiver 109, or multiple receivers 109. In some embodiments, light 120 emitted from one or more emitters 104 can also be separated into multiple separate wavelengths before or after reaching the tissue 200 to be redirected to one or more receivers 109. In some embodiments, the redirecting device 150 can also modify the size, shape, shape, power or energy, power or energy distribution, angle of incidence, area of the light power distribution, directivity, polarization, spectral content of the light 120, or a combination thereof. For example, the redirecting device 150 can separate the light 120 into multiple wavelengths directed to one or more receivers 109.

[0047] Referring to FIG. 2C, in some embodiments, the light 120a and 120b can be directed through the tissue 200 from two or more light generating devices 102a and 102b respectively on opposing sides of the tissue 200 to one or more receivers 109a and 109b on the opposing side of the respective light generating devices 102a and 102b. This configuration can be used with any combination of light generating devices 102 and receivers 109. For example, a single light generating device 102a or 102b can be positioned on each side of the tissue 200 and each light generating device 102a or 102b can direct its respective light beam 120a or 120b through the tissue 200 to a single receiver 109a or 109b on the opposing side. Similarly, multiple light generating devices 102 and receivers 109 can be positioned on either side of the tissue 200. In some embodiments, each light generating device 102 and receiver 109 pair can be a single device, such that the device transmits first light 120 in a first direction and transmits a second light 120 from the opposing direction, as shown in FIG. 2C. Although the light beams 120a and 120b shown in FIG. 2C have separation between one another, any combination of spacing can be used without departing from the scope of the present disclosure. For example, the different lights 120 can be directed to be separate from one another and can be directed to be substantially adjacent to one another. The two light beams 120a and 120b can also be partially or fully coincident with the use of any combination of optical elements such as dichroic mirrors (e.g., mirror 150), beam splitters (e.g., modifier 116), and beam combiners (e.g., modifier 116) In some embodiments, the system 100 can be designed such that the emitters and receivers 109 are coincident, as depicted in FIG. 2D.

[0048] Referring to FIG. 3, in some embodiments, the system 100 can be designed to continuously emit, from each of a plurality of light generating devices 102, light 120 at individually identifiable wavelengths through the tissue 200 of a patient. FIG. 3 depicts an example illustration for how the system 100 can implement such a design. During operation, each of the light generating devices 102 producing the individually identifiable wavelength of the light 120 can be individually activated and deactivated one time each and for specific periods of time (e.g., .5 seconds). In the example illustration, the system 100 can include three light generating devices 102 designed to emit light 120 at 1220nm, 1064nm, and 1150nm respectively, although any number of emitters and light wavelengths can be used without departing from the scope of the present disclosure. For example, the number of emitters 104 and the selected wavelengths, and duration of activation of those wavelengths, can be varied depending on the substances being targets, the location of testing, etc. Once the light 120 has passed through the tissue 200, a level of each light wave of light 120 at the individually identifiable wavelengths is identified, by at least one receiver 109 (or detector), received through the tissue 200 of the patient. Based on the level of each light wave of light 120 the controller 106 (or other processor) can determine a concentration of a substance in the tissue, as discussed in greater detail herein.

[0049] Referring back to FIG. 2C, in some embodiments, light generating device 102a of system 100 can include at least a first emitter 104a or the plurality of emitters, and can include a second light generating device 102b having one emitter 104b or a plurality of emitters, where light generating device 102a and device 102b are positioned on opposing sides of the tissue 200. Each of the light generating devices 102a, 102b can be associated with a corresponding receiver 109a, 109b respectively. When activated, the light 120a can be emitted by light generating devices 102a to receiver 109a and the light 120b can be emitted by light generating devices 102b to receiver 109b. Each of the light generating devices 102a, 102b and receivers 109a, 109b can be connected to a common controller 106 for control of the light generating devices 102a, 102b and processing data based on information provided from the receivers 109a, 109b.

[0050] Referring to FIG. 4A, in some embodiments, the system 100 can include one or more devices for transforming at least one of a shape, density, and area of the light beam entering the tissue 200 or exiting the tissue 200. To modify a light 120 beam (or multiple light beams 120), the system 100 can be designed to emit light 120 into a beam modifier 116 to modify characteristics of the light 120, such as size, shape, divergence angle, power distribution, spectral content, polarization, etc. or a combination thereof. Referring to FIGS. 4B, 4C, and 4D, example shapes can include a fanned straight-line profile, a condensed circular profile, an expanded circular profile (e.g., end of a cone shape).

[0051] Referring to FIG. 5, in some embodiments, the system 100 can include one or more beam modifiers 116 for transforming light into a plurality of separate light beams 120 at different wavelengths. For example, as depicted in FIG. 5, the system 100 can include a beam modifier 116 that separates a single light 120 beam into three distinct light beams 120a, 120b, and 120c, each having distinct wavelengths. The one or more beam modifier 116 can include any combination of devices, such as a spectral separator, a prism, a filter, dichroic mirror(s), a diffraction grating, an acousto-optical tunable filter (AOTF), etc., or a combination thereof. The beam modifier 116 can be designed to separate light 120 after it has passed through the tissue 200, as depicted in FIG. 5 or it can be designed to separate light 120 before it passes through the tissue 200. [0052] Referring to FIG. 6, in some embodiments, the system 100 can include a single, broadband light generating device 102 capable of generating a output over a wide spectral range, e.g., 500-2000nm in beam 120, to be directed into a beam modifier 116 , which can includee one or more beam splitters, dichroic mirrors, bandpass filters, diffractive gratings, absorbing filters, and other optical elements to create multiple light beams 120a, 120b, 120c at desired wavelengths to be passed into an (optional) collimator 114 and then be transmitted as a single beam 120d to and through the tissue 200. The beam 120d can include only the wavelengths selected by beam modifier 116, rather than the broadband output of emitter 104. Thereafter, the beam 120d passes through tissue 200 toward one or more receivers 109.

[0053] Referring to FIG. 7, in some embodiments, the system 100 can include a plurality of light sources capable of generating a light 120a, 120b with particular wavelengths, optionally combined into single beams, directed into tissue 200, and separated into different wavelengths after passing through the tissue 200. As shown in FIG. 7, multiple beams 120a, 120b can be emitted from multiple emitters 104 to be directed into optional collimators 114 and/or beam modifiers 116 for optional combination into a combined beam 120 to be directed trough the tissue 200. After the beam 120 passes through the tissue 200, the beam 120 can enter a beam modifier 116 (e.g., bandpass separators/filters) to create multiple light beams at desired wavelengths to be detected by a receiver 109. In some embodiments, multiple sets of beams 120 can be emitted, optionally collimated, transmitted through tissue, modified and detected by receivers. For example, as depicted in FIG. 7, pairs of emitters 104a, 104b, collimators 114a 114b, modifiers 116a, 116b, and receivers 109a, 109b can be used. Although a pair of device paths are shown, any number of devices can be used without departing from the scope of the present disclosure. Similarly, pairs/multiples can be used for some devices in the system 100 while some devices can be singular or multiples of different numbers. For example, a single receiver 109 can be used to detected light 120 provided from multiple sources.

[0054] Referring to FIGS. 8A-8C, in some embodiments, a plurality of emitters 104 can emit light 120 to be directed to adjacent locations on the tissue 200. Referring to FIG. 8A, a plurality of emitters 104 can be designed to emit light 120 at a first wavelength and at least one other emitter 104 can be designed to emit light at a second wavelength, with each of the light beams 120 being directed to a surface of the tissue 200 to pass through the tissue 200 substantially parallel and adjacent to one another. In some embodiments, each of the light beams can be detected by one or more receivers 109.

[0055] Referring to FIG. 8B, in some embodiments, a plurality of emitters 104 can emit light beam 120 at a plurality of wavelengths to points on the tissue 200 in a predetermined pattem. For example, a first plurality of emitters 104 can emit at least a first plurality of light at a first wavelength and a second plurality of emitters 104 can emit at least a second plurality of light at a second wavelength with each of the light beams 120 being directed to adjacent locations on the tissue 200. In some embodiments, as shown in FIG. 8B, the plurality of light beams 120 can be arranged in a circular pattern while alternating between beams of a first wavelength to beams of a second wave length.

[0056] Referring to FIG. 8C, in some embodiments, at least a first light beam 120a at a first wavelength and a second light beam at a second wavelength of the plurality of emitters 104 are directed to adjacent locations on the tissue 200 and converge at a location within the tissue 200. One or more receivers 109 on the opposing side of the tissue 200 can detect both of the wavelengths 120a, 120b. In some embodiments, the one or more receivers 109 can detect an overlapping dispersion of both wavelengths 120a, 120b.

[0057] Referring to FIGS. 9A and 9B, in some embodiments, the system 100 can alternate which light 120 is being generated from each of a plurality of emitters 104 operating in “continuous wave” mode, or “CW” mode (not modulated in time). As shown in FIG. 9A, there can be three emitters 104a, 104b, 104c within the system 100, each emitting light at individually identifiable wavelengths in beams 120a, 120b, and 120c. The three beams 120a, 120b, 120c can pass through one or more beam modifiers 116 and (optionally) one or more collimators 114, then through tissue 200 of the patient. The three emitters 104a, 104b, 104c can be continuously on while detector 109 records total incident power “P” for the light beams 120a, 120b, and 120c that has passed through the tissue 200. This referred to as the “Measurement Period” and could last for an extended period of time. In a second, very brief period of time, emitters 104a and 104b are deactivated and the incident power “p_c”on the detector during this second period is recorded. This is used to determine how much of the total incident power on the detector 109 during the measurement period is from emitter 104c. This is referred to as a “Calibration Period”. In a third period of time, emitters 104a and 104c are deactivated and emitter 104b is calibrated to provide pb. In a fourth period of time, emitters 104b and 104c are deactivated and emitter 104b is calibrated to provide p_a. Thus P = p_a+pb+pc. The values of p_a, pb, and p_c are proportional to the transmittance through the tissue at each of the three wavelengths. From the transmittance, absorption may be calculated with the formula Absorbance = -logio(T). Concentration of glucose may be calculated as the ratio of power of a Signal wavelength to the power of a Reference wavelength. The Measurement Period plus the three Calibration Periods comprise 1 cycle. This cycle may be repeated periodically. [0058] Referring to FIG. 11, in some embodiments, the light generating device 102 can emit light of multiple wavelengths. This light 120 can be conducted over light path 110a, which can include one or more optical fibers, one or more waveguides, or as a beam of light through air. The light 102a exiting light path 110a forms beam 116a which passes through beam forming device 116a and the tissue 200 to form beam 120b, which can pass through a beam forming optic 116b and enter a light path 110b, which can include one or more optical fibers, one or more waveguides, or as a beam of light through air. In some embodiments, the light path 110b can enter a detector module 121. In some embodiments, inside the detector module 121, a beam forming optic 116c can collimate the light 120b to create beam 120c. The beam 120c can be divided at a dichroic mirror 117a, where light of one range of wavelengths is reflected to form beam 120e, and another range of wavelengths passes through to form beam 120d. Beam 120e can pass through a narrow band filter 119a and a beam modifier 116d to focus onto detector 109a. Similarly, beam 120d can be divided at a dichroic mirror 117b where light of one range of wavelengths can be reflected to form beam 120f, and another range of wavelengths passes through to form beam 120e. In some embodiments, beam 120f can pass through a narrow band filter 119b and a beam modifier 116e to focus onto a detector 109b. Beam 120e can then pass through a narrow band filter 119c and a beam modifier 116f to focus onto a detector 109c. Using the detectors 109a, 109b, 109c the detector module 121 may be configured to measure any number of wavelengths independently.

[0059] Referring to FIG. 12, in some embodiments, the light generating device 102 can emit light of multiple wavelengths. This light can be conducted over light path 110 to a wavelength selector 125, where light exiting the light path 110 can pass through a beam modifier 116a to forma beam 120a, which can pass through a variable filter 123a. The variable filter 123a can pass only a certain passband of light and any given location. As the variable filter 123a is translated in an axis perpendicular to the beam 120a, the passband of light can shift from longer to shorter wavelengths, enabling the sequential measurement of different passbands of light with a single detector 109. In some embodiments, the beam modifier 116b can condense the beam into light path 110b, which can transmit the light to sensor 112. Inside sensor 112, the light exiting light path 110b can pass through a beam modifier 116c, the tissue 200, a beam modifier 116d, and enter light path 110c. Light path 110c can transmit the light to detector module 121. In some embodiments, inside detector module 121, light exiting light path 110c can form beam 120c, and can be coupled by beam modifier 116e to the detector 109. In an alternative embodiment, variable filter 123b can be used instead of variable filter 123 a. [0060] Referring to FIG. 13, in some embodiments, the system 100 can include console 129, sensor 112, and light paths 110a, 110b, 110c, 1 lOd, and 1 lOe. Console 129 can include the light generating device 102, the controller 106, and a detector module 131. The light generating device 102 can emit light of multiple wavelengths. The light emitted by light generating device 102 can be transmitted by light path 110a to sensor 112. Inside sensor 112, the light exiting light path 110a can be collimated by lens 115a and enter a dichroic beam splitter 127a, where one range of wavelengths is reflected, forming beam 120a, and a second range of wavelengths is transmitted, forming beam 120b. In some embodiments, beam 120a can be condensed by lens 115b and enter light path 1 lOe, which transmits the light to control receiver 108. Beam 120b can pass through the tissue 200 and the light that is not absorbed or scattered by the tissue 200 can be collimated by lens 115c and enters beam splitter 127b, where one range of wavelengths can be reflected to form beam 120c, and one range of wavelengths can be transmitted, forming beam 120d. The beam 120d can be condensed by lens 115d and enter light path 110b. In some embodiments, beam 120c can enter a dichroic beam splitter 127c, where one range of wavelengths can be transmitted to form beam 120e, and a second range of wavelengths is reflected to form beam 120f. Beam 120e can be condensed and enter light path 1 lOd and then can be transmitted to detector 109a. Beam 120f can be condensed by lens 115f, can enter light path 110c, and can be transmitted to detector 109b. Sensor 112 may be configured to divide the light from light path paths 110b, 110c, 1 lOd, into any number of passbands and measure them independently with a matching number of detectors 109a, 109b, 109c.

[0061] Referring to FIG. 14, in some embodiments, the system 100 can include controller 106, electrical connection 133, and sensor 112. Sensor 112 can include multiple emitters 104, multiple beam modifiers 116, and multiple dichroic beam splitter prisms 113 to enable the individual measurement of multiple different wavelengths. The diagonal surface of each dichroic beam splitter prism can be coated with a thin film that enables the combining or separating of light according to wavelength. In some embodiments, there can be three optical paths. The first path can start with emitter 104a. The light exiting emitter 104a forms beam 120a, which can be passed through beam modifier 116a, dichroic prisms 113a and 113b, tissue 200, beam modifier 116d, and dichroic beam splitting prism 113c to form beam 120f, which passes through beam modifier 116f, and is measured by detector 109a. The first path can start with emitter 104b. The light exiting emitter 104b can form beam 120b which can pass through beam modifier 116b. The light 120b can enter dichroic prism 113a and can be reflected to join beam 120c, which passes through beam splitting prism 113b, tissue 200, and beam modifier 116d. The beam 120e can enter dichroic beam splitting prism 113c where it is reflected to join beam 120g. The beam 120g can enter dichroic beam splitting prism 113d where it is reflected to form beam 120i, which passes through beam modifier 116g and can be measured by detector 109b. The third path can start with emitter 104c. The light exiting emitter 104c can form beam 120d which can pass through beam modifier 116c. The light 120d can enter dichroic prism 113b and can reflected to join beam 120e, which passes through tissue 200, and beam modifier 116d. The beam 120e can enter dichroic beam splitting prism 113c where it can be reflected to join beam 120g. Beam 120g can pass through dichroic beam splitting prism 113d to form beam 120h, which passes through beam modifier 116e and can be measured by detector 109c. The embodiment of FIG. 14 may be configured to have any number of optical paths as described and is not intended to be limited to three paths as discussed herein. The embodiment of FIG. 14 has the advantage of being able to make measurements in the tissue at multiple wavelengths truly simultaneously, or it can be configured to make measurements at multiple wavelengths sequentially.

[0062] Referring to FIG. 15, in this embodiment, the system 100 can include controller 106 and sensor 112. Sensor 112 can include multiple emitters 104, multiple beam modifiers 116, and multiple dichroic beam splitter prisms 113 to enable the individual measurement of multiple different wavelengths in opposing directions. The diagonal surface of each dichroic beam splitter prism can be coated with a thin film that enables the combining or separating of light according to wavelength. In the embodiment of FIG. 15, there can be two optical paths. The first optical path can start with emitter 104a. The light exiting emitter 104a can form beam 120a, which can pass through beam modifier 116a, dichroic prism 113a, beam modifier 116c, tissue 200, beam modifier 116d, and dichroic beam splitting prism 113b to form beam 120d, which passes through beam modifier 116e, and can be measured by detector 109a. The second optical path can start with emitter 104b. The light exiting emitter 104b can form beam 120b which passes through beam modifier 116b. The light 120b can enter dichroic prism 113b and can be reflected to join beam 120c, which passes through beam modifier 116d, tissue 200, and beam modifier 116c. The beam 120c can enter dichroic beam splitting prism 113a where it can be reflected to form beam 120e, which passes through beam modifier 116e, and is measured by detector 109b. The embodiment of FIG. 15 may be configured to have any number of optical paths as described and is not intended to be limited to two paths as discussed herein.

[0063] The system 100, as discussed in FIGS. 1A-15 can be used in any combination of hardware and software for use for non-invasive monitoring of a solute within a patient. For example, the system 100 can be implemented as part of a portable wearable device that can be clipped or otherwise attached to a patient. In some instances, the system 100 can be wirelessly connected (portable) or wired (non-portable or semi-portable) to another system for controlling and/or receiving data from the system 100. For example, the system 100 can be connected to a control system within an ER/OR to work as part of a larger system. The system 100 can be modified based on the intended application. For example, for home use, the system 100 can be implemented as a smart/wearable device, whereas for institutional use, the device can be physically tethered to another system or machine so that the system 100 is not lost or stolen. The system 100 can also be modified according to other preferences. For example, communications to and from the system 100 can be performed over a wired connection for security and reliability or wirelessly for convenience to mobile user devices.

[0064] The system 100 can be designed to be communicatively attached to at least one processing system (such as controller 106) that can be programed to activate/deactivate the emitters 104 and receive and process data from the receivers 109. The processing system can be part of the system 100 itself or part of another system. The system 100 can also include any combination of wired and wireless communication means to receive and/or transmit data to a controlling system and/or it can perform any processing and calculating within a singular device. Similarly, the system 100 can provide data to a user using any combination of systems and methods. For example, the system 100 can transmit data to an application on a fixed or portable device for providing controls and displaying results to a user and/or can convey information to a user on a singular device (e.g., a wearable).

[0065] Any combination of designs of the system 100, discussed with respect to FIGS. 1 A- 15, can be used to provide non-invasive monitoring of a solute within a patient. For example, the system 100 can be placed at a location on a patient in any of the orientations provided by one of FIGS. 1 A-15 to measure a concentration or level of glucose in the tissue 200 or blood of the patient. The system 100 can use readings from the different wavelengths, as read by the one or more receivers 109/controller 106 to calculate the desired information for a target solute using any combination of methods known in the art. For example, the controller can use the received power, energy, level, etc. of the various wavelengths to calculate a ratio, delta between the different measured wavelengths to determine a level of solute (e.g., glucose) in a tissue, liquid, etc. Thereafter, in operation, the system 100 can convey the results to the user, for example, based on the level of each light wave.

[0066] As utilized herein, the terms “comprises” and “comprising” are intended to be construed as being inclusive, not exclusive. As utilized herein, the terms “exemplary”, “example”, and “illustrative”, are intended to mean “serving as an example, instance, or illustration” and should not be construed as indicating, or not indicating, a preferred or advantageous configuration relative to other configurations. As utilized herein, the terms “about”, “generally”, and “approximately” are intended to cover variations that may existing in the upper and lower limits of the ranges of subjective or objective values, such as variations in properties, parameters, sizes, and dimensions. In one non-limiting example, the terms “about”, “generally”, and “approximately” mean at, or plus 10 percent or less, or minus 10 percent or less. In one non-limiting example, the terms “about”, “generally”, and “approximately” mean sufficiently close to be deemed by one of skill in the art in the relevant field to be included. As utilized herein, the term “substantially” refers to the complete or nearly complete extend or degree of an action, characteristic, property, state, structure, item, or result, as would be appreciated by one of skill in the art. For example, an object that is “substantially” circular would mean that the object is either completely a circle to mathematically determinable limits, or nearly a circle as would be recognized or understood by one of skill in the art. The exact allowable degree of deviation from absolute completeness may in some instances depend on the specific context. However, in general, the nearness of completion will be so as to have the same overall result as if absolute and total completion were achieved or obtained. The use of “substantially” is equally applicable when utilized in a negative connotation to refer to the complete or near complete lack of an action, characteristic, property, state, structure, item, or result, as would be appreciated by one of skill in the art.

[0067] Numerous modifications and alternative embodiments of the present disclosure will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode for carrying out the present disclosure. Details of the structure may vary substantially without departing from the spirit of the present disclosure, and exclusive use of all modifications that come within the scope of the appended claims is reserved. Within this specification embodiments have been described in a way which enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the invention. It is intended that the present disclosure be limited only to the extent required by the appended claims and the applicable rules of law.

[0068] It is also to be understood that the following claims are to cover all generic and specific features of the invention described herein, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.

Claims

CLAIMS What is claimed is:

1. A method for non-invasive monitoring of a solute within a patient, the method comprising: emitting, from each of a plurality of emitters, light at individually identifiable wavelengths through tissue or body fluid of the patient; identifying, by at least one receiver, a transmittance of individually identifiable wavelengths received through the tissue or body fluid of the patient; and determining, by a processor, a concentration of a solute for the patient based on the level of transmittance of each wavelength of light.

2. The method of claim 1, wherein at least a first emitter or the plurality of emitters and a second emitter or the plurality of emitters are positioned on opposing sides of the tissue or body fluid.

3. The method of claim 1, wherein the at least one receiver comprises a first receiver and a second receiver positioned on opposing sides of the tissue.

4. The method of claim 1, wherein the plurality of emitters are directed to adjacent locations on the tissue.

5. The method of claim 4, wherein at least a first wavelength of light and a second wavelength of light of the plurality of emitters are directed to adjacent locations on the tissue and converge at a location within the tissue.

6. The method of claim 4, wherein at least a first wavelength of light and a second wavelength of light of the plurality of emitters are directed to adjacent locations on the tissue in an alternating pattern.

7. The method of claim 1, further comprising redirecting a direction of the light entering the tissue or exiting the tissue.

8. The method of claim 1, further comprising transforming at least one of a shape, power or energy, power or energy distribution, angle of incidence, polarization, spectral content, and area of the light entering the tissue or exiting the tissue.

9. The method of claim 8, wherein the at least one shape is a fan shape.

10 A method for non-invasive monitoring of a solute within a patient, the method comprising: emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light through tissue or body fluid of the patient; performing spectral separation of the plurality of individually identifiable wavelengths of light; identifying, by a plurality of receivers, the power or energy of the individually identifiable wavelengths of light received through the tissue of the patient; and determining, by a processor, a concentration of a solute for the patient based on the power or energy of the individually identifiable wavelengths of light.

11. A method for non-invasive monitoring of a solute within a patient, the method comprising: emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light; performing spectral separation of the single light beam into the plurality of individually identifiable wavelengths of light; combining, by a collimator, the plurality of wavelengths into a single light beam having the plurality of individually identifiable wavelengths of light; identifying, by at least one receiver, a level of the individually identifiable wavelengths of light received through tissue of the patient; and determining, by a processor, a concentration of a solute for the patient based on the power or energy each individually identifiable wavelength of light.

12. The method of claim 11, wherein each of the spectrally separated plurality of wavelengths of light are directed to different receivers of the at least one receiver.

13. A method for non-invasive monitoring of a solute within a patient or sample tissue or body fluid from a patient, the method comprising: simultaneously activating a first emitter, a second emitter, and a third emitter, each emitting light at individually identifiable wavelengths through tissue or body fluid of the patient; deactivating the second emitter and the third emitter for a first period of time; activating the second emitter and deactivating the first emitter for a second period of time; activating the third emitter and deactivating the second emitter for a third period of time; reactivating all emitters; identifying, by at least one receiver, the transmittance through the tissue or body fluid of each of the individually identifiable wavelengths of light; and determining, by a processor, a concentration of a solute for the patient based on the transmittance of each wavelength of light through the tissue or body fluid.

14. A method for non-invasive monitoring of a solute within a patient, the method comprising: emitting, from a single emitter, a single light beam having a plurality of individually identifiable wavelengths of light through tissue or body fluid of the patient; identifying, by at least one receiver, a transmittance of individually identifiable wavelengths received through the tissue or body fluid of the patient; and determining, by a processor, a concentration of a solute for the patient based on the level of transmittance of each wavelength of light.

15. A system for non-invasive monitoring of a solute within a patient, the system comprising: a light source designed to emit at least one light beam with one or more wavelengths for transmission across a layer of tissue or body fluid of the patient; a controller having logic computations for activating and deactivating the light source and for controlling parameters of the light beam being emitted; at least one receiver positioned to detect a designated wavelength from the light beam that has been transmitted across the layer of tissue or body fluid of the patient; and a processor for determining a concentration of a solute in the tissue or body fluid based on the level of transmittance of the wavelength detected by the receiver.

16. A system as set forth in claim 15, wherein the light source includes a plurality of light generating devices positioned on one side of the tissue or body fluid.

17. A system as set forth in claim 15, wherein the light source includes at least one light generating device situated on opposing sides of the tissue or body fluid.

18. A system as set forth in claim 15, wherein the receiver is situated on the same side of the tissue or body fluid as the light source and the system includes a redirecting device on the opposite side of the tissue or body fluid to reflect the light beam back across the tissue or body fluid to the receiver.

19. A system as set forth in claim 15, wherein the receiver is situated on the opposing side of the tissue or body fluid.

20. A system as set forth in claim 15 further including a beam modifier to modify characteristics of the light beam prior to its entry into the tissue or body fluid.

21. A system as set forth in claim 20, wherein the characteristics of the light beam includes one of size, shape, divergence angle, power distribution, spectral content, polarization or a combination thereof.

22. A system as set forth in claim 15, further including a control receiver for sampling incident light from the light beam at or near a surface of the tissue or body fluid.