GB2582358A

GB2582358A - Imaging device

Info

Publication number: GB2582358A
Application number: GB1903885.0A
Authority: GB
Inventors: King Simon; Benzie Philip; Zaccari Irene
Original assignee: Sumitomo Chemical Co Ltd
Current assignee: Sumitomo Chemical Co Ltd
Priority date: 2019-03-21
Filing date: 2019-03-21
Publication date: 2020-09-23
Also published as: GB201903885D0

Abstract

An imaging device for imaging a microfluidic chip, such as an organ-on-chip, comprising a light source 2 on an optical axis 4, a light absorbing baffle 12, 30 to remove wide-angle light and having first and second openings, wherein the first opening is oriented towards the light source, and a detector 19 arranged so that a face of the detector is oriented towards the second opening of the baffle. Preferably the baffle is an array comprising multiple baffles to provide narrow apertures, which may be tubular and have a square cross section. Preferably a light scattering panel 5 is positioned between the light source and the baffle. Preferably the light source is movable along the optical axis. Also claimed is a system comprising a light source on an axis, a light absorbing baffle with a longitudinal axis, a detector and an actuator configured to move the light source in line with the longitudinal axis of the baffle.

Description

IMAGING DE VICE BACKGROUND

Embodiments of the present disclosure relate to an imaging device. Embodiments of the present disclosure specifically relate to a lens-free imaging device for live cell imaging.

Lens-free imaging devices are known, for example, CN 203069533 U, by Shandong University describes a multi-purpose synchronous radiation coherence X-ray diffraction microimaging device. The utility model discloses a multi-purpose synchronous radiation coherence X-ray diffraction microimaging device which comprises a synchronous radiation X-ray light source, an undulator, a monochromator crystal, an X-ray shutter, a first lifting platform, a focusing device cavity, a vacuum pipeline, a second lifting platform, a multi-purpose sample chamber, a vacuum pipe II, a third lifting platform, a detector and a computer for acquiring data and controlling an electric control translation table to move which are sequentially and coaxially arranged along a forwarding direction of light beams, wherein the monochromator crystal is arranged on an electric i5 control rotating platform; the focusing device cavity, the vacuum pipeline and the second lifting platform are arranged on the first lifting platform; the multi-purpose sample chamber, the vacuum pipe II and the third lifting platform are arranged on the second lifting platform; and the detector and the computer are arranged on the third lifting platform.

US 2003/0067680 Al, by The Arizona Boards of Regents on behalf of The University of Arizona, describes an inter-objective baffle system comprising a multi-axis imaging system and method wherein a plurality of optical elements are arranged to produce in image space thereof respective images of respective regions in object space thereof, and a plurality of image sensing elements corresponding to respective optical elements are disposed in image space of the image sensing elements to capture images of the respective regions. At least one baffle is positioned along an optical pathway of at least one of the optical elements to block light from outside the field of view of the one of the optical elements from reaching a corresponding image sensing element.

US 2012/0243747 Al, by University of Louisville Research Foundation, describes a system and method for precision measurement of position, motion and resonances. A non-contact sensing system for measuring and analyzing an object's position, motion, and/or resonance utilizes optical capturing of image features, data extraction, and signal processing to determine changes in the object's motion or position according to changes in signals, which arc associated with the excitation of photons duc to the object's motion.

US 2017/0326551 Al, by IMEC VZW, describes a fluid analysis device which comprises a sensing device for analyzing a fluid sample, the sensing device comprising ro a micro-fluidic component for propagating the fluid sample and a microchip configured for sensing the fluid sample in the micro-fluidic component; a sealed fluid compartment containing a further fluid, the compartment being fluid-tight connected to the sensing device and adapted for providing the further fluid to the micro-fluidic component when the sealed fluid compartment is opened; and an inlet for providing the fluid sample to /5 the micro-fluidic component. Further, the present disclosure relates to a method for sensing a fluid sample using the fluid analysis device.

SUMMARY

Organ-on-chip and other microfluidic devices are typically monitored optically using a microscope or lens and camera system to either monitor the lifecycle of the cells or by using colorimetric stains and fluorescence assays to indicate a change to the properties of the cells, for example, the intracellular oxygen or glucose level.

To increase the throughput and reduce the cost of such cell imaging systems it would be desirable to remove the need for the complex microscope optics which are used to focus the emitted (or scattered) light from the object plane (i.e. the cells) to a detector at the image plane. One possible route to do this would be to remove the optical system and place the object plane on the detector directly. Thus the objects are imaged effectively by directly shadowing the pixels of the detector.

However, in an organ-on-chip or other microfluidic device, it is not usually possible to place the object(s) to be imaged (for example, live cells) directly on the detector due to the various biological requirements of the cells, for example, channels for fluid flow, substrates required for cell adhesion, and the requirement for no cytotoxic materials. As a result, the cells to be imaged could be up to a few millimetres from the detector.

The radial distribution of light from a chromophore or scatterer results in an effective maximum resolution of this type of lensless imaging system to be approximately equal to the distance between the object and the detector. This limits the resolution in a typical organ-on-chip device to approximately 1 mm. A higher resolution is desirable and often required for particular uses.

In some embodiments there is provided a microfluidic chip imaging device comprising a light source on an optical axis. The imaging device further comprises at least one light absorbing baffle having first and second openings arranged so that the first opening is oriented towards the second side of the light scattering panel and light source and a detector arranged so that the face of the detector is oriented towards the baffle second opening.

In some embodiments, the microfluidic chip imaging device further includes a microfluidic chip arranged on the optical axis between the light source and the at least one baffle.

In some embodiments, the light source is an organic light emitting diode.

a In some embodiments, the organic light emitting diode is moveable to excite a detector area abutting the second opening of the at least one light absorbing baffle.

In some embodiments, the normal of the plane of the light scattering panel is parallel to the optical axis and the normal of the plane of the detector is parallel to the optical axis.

o In some embodiments, the at least one light absorbing baffle has a baffle central axis from the centre of the first opening to the centre of the second opening which is parallel to the optical axis.

In some embodiments, the at least one light absorbing baffle is a tube having a square profile.

In some embodiments, the at least one light absorbing baffle is an array of baffles.

In some embodiments, a side of each light absorbing baffle in the array of baffles abuts a side of another light absorbing baffle.

In some embodiments, the array of baffles is square having five baffles along each axis.

In some embodiments, the light source is configured to excite each baffle central axis of each baffle in the array of baffles simultaneously.

In some embodiments, the transverse cross-section of the at least one baffle has a width and a height of 100 Inn and the length of the baffle is 500 tun.

In some embodiments, the light source, the scattering panel, the at least one baffle and a the detector are configured to move along the imagine axis.

In some embodiments, the light source may be a lamberti an light source. In some embodiments, the detector face abuts the second baffle opening. In some embodiments, the scatterer s a Mie scatterer.

In some embodiments, the imaging device further includes a light scattering panel 5 having first and second opposite sides arranged on the optical axis and between the light source and the at least one light absorbing baffle and so that the first side faces the light source and the second side faces the first opening of the at least one baffle.

In some embodiments there is provided a microfluidic chip imaging device comprising a light source on an optical axis. The imaging device further comprises at least one light absorbing baffle having first and second openings arranged so that the first opening is oriented towards the second side of the light scattering panel and light source and a detector arranged so that the face of the detector is oriented towards the baffle second opening. The imaging device further includes a light scattering panel having first and second opposite sides arranged on the optical axis and between the light source and the at least one light absorbing baffle and so that the first side faces the light source and the second side faces the first opening of the at least one baffle. The imaging device further includes a microfluidic chip arranged on the optical axis between the light scattering panel and the at least one baffle.

In some embodiments there is a method of using the imaging device comprising causing the light source to emit light and receiving a signal from the detector.

DESCRIPTION OF THE DRAWINGS

The disclosed technology and accompanying figures describe some implementations of the disclosed technology.

Figure 1 is a schematic side view of a first live cell imaging device; Figure 2 is a perspective view of a first cell imaging device; Figure 3 is a schematic side view of a second example of a first live cell imaging device; Figure 4 is a perspective view of a second example of a first cell imaging device; Figure 5A is a perspective view of a baffle; Figure 5B is a transverse cross-sectional view of the baffle shown in Figure 5A taken along the line A-A'; Figure SC is longitudinal cross-sectional view of the baffle shown in Figure 5A taken along the line B-B'; Figure GA is a perspective view of a baffle array; _u) Figure 6B is a transverse cross-sectional view of the baffle shown in Figure 6A taken along the line C-C'; Figure 6C is longitudinal cross-sectional view of the baffle shown in Figure 6A taken along the line D-D'; Figure 7 is a schematic of the incident light on the detector; Figure 8 is a schematic side view of a second live cell imaging device; Figure 9 is a perspective view of a second cell imaging device; Figure 10A is a modeled signal detection plot for a first live cell imaging device; Figure 10B is a modeled signal detection plot for a first live cell imaging device; Figure 10C is a modeled signal detection plot for a first live cell imaging device; Figure 11A is a modeled signal detection plot for a second live cell imaging device; Figure 11B is a modeled signal detection plot for a second live cell imaging device; Figure 11C is a modeled signal detection plot for a second live cell imaging device; Figure 12A is an intensity profile across an image for a first live cell imaging device; Figure 12B is an intensity profile across an image for a first live cell imaging device; Figure 12C is an intensity profile across an image for a first live cell imaging device; Figure 13 is a schematic side view of a third live cell imaging device; Figure 14 is a perspective view of a third cell imaging device; Figure 15 is a schematic of the incident light on the detector for the third imaging device; Figure 16 is a process flow diagram of a method of imaging sample.

The drawings are not drawn to scale and have various viewpoints and perspectives.

f() The drawings are some implementations and examples. Additionally, some components and/or operations may be separated into different blocks or combined into a single block for the purposes of discussion of some of the embodiments of the disclosed technology. Moreover, while the technology is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the technology to the particular implementations described. On the contrary, the technology is intended to cover all modifications, equivalents, and alternatives falling within the scope of the technology as defined by the appended claims.

DETAILED DESCRIPTION

Unless the context clearly requires otherwise, throughout the description and the claims, the words "comprise," "comprising," and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to." As used herein, the terms "connected," "coupled," or any variant thereof means any connection or coupling, either direct or indirect, between two or more elements; the coupling or connection between the elements can be physical, logical, electromagnetic, or a combination thereof Additionally, the words "herein," "above," "below," and words of similar import, when used in this application, refer to this application as a whole and not to any particular portions of this application. Where the context permits, words in the Detailed Description using the singular or plural number may also include the plural or singular number respectively. The word "or," in reference to a list of two or more items, covers all of the following interpretations of the word: any of the items in the list, all of the items in the list, and any combination of the items in the list.

ro The teachings of the technology provided herein can be applied to other systems, not necessarily the system described below. The elements and acts of the various examples described below can be combined to provide further implementations of the technology. Some alternative implementations of the technology may include not only additional elements to those implementations noted below, but also may include fewer elements.

These and other changes can be made to the technology in light of the following detailed description. While the description describes certain examples of the technology, and describes the best mode contemplated, no matter how detailed the description appears, the technology can be practiced in many ways. Details of the system may vary considerably in its specific implementation, while still being encompassed by the technology disclosed herein. As noted above, particular terminology used when describing certain features or aspects of the technology should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics, features, or aspects of the technology with which that terminology is associated. In general, the terms used in the following claims should not be construed to limit the technology to the specific examples disclosed in the specification, unless the Detailed Description section explicitly defines such terms. Accordingly, the actual scope of the technology encompasses not only the disclosed examples, but also all equivalent ways of practicing or implementing the technology under the claims.

To reduce the number of claims, certain aspects of the technology are presented below in certain claim forms, but the applicant contemplates the various aspects of the technology in any number of claim forms.

In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of implementations of the disclosed technology. It will be apparent, however, to one skilled in the art that embodiments of the disclosed technology may be practiced without some of these specific details.

Overview There is a need for live cell imaging of organ-on-chip and other microfluidic devices.

There are a wide range of applications from the use of organ-on-chip devices for drug development to the use of microfluidic chips for biosensing and assays. These devices are typically monitored optically using a microscope and/or camera system to either monitor the lifecycle of the cells or by using colorimetric stains and fluorescence assays to indicate a change to the properties of the cells such as the intracellular oxygen or glucose level.

In order to increase the throughput and reduce the cost of such cell imaging systems it would be desirable to remove the need for the complex and expensive microscope optics or camera lenses which are used to focus the emitted or scattered light from the object plane (for example, live cells or other samples) to a detector at the image plane.

One route to do this is to remove the optical system and place the object plane directly on the detector. Thus, the objects are imaged effectively by directly shadowing the pixels of the detector. This can be effective where the objects can be placed in direct proximity to the detector.

However, in a microfluidic or organ-on-chip device it is not usually possible to place the object to be imaged (for example, live cells) directly on the detector due to the various biological requirements of the cells. The biological needs of the cells (for example, channels for fluid flow, various substrates required for cell adhesion, the absence of cytotoxic materials) may require space to be left between the cells and the surface of the detector. As a result the cells to be imaged may be between zero and a few millimetres away from the surface of the detector.

With cells a few millimetres away from the detector, the radial distribution of light from a chromophore or scatterer results in an effective maximum resolution of this type of lensless imaging system to be approximately equal to the distance between the object and the detector. This would limit the resolution in a typical organ on chip device to approximately 1 mm.

However, a higher resolution is often desirable for cell imaging systems. Higher resolution images enable the monitoring of specific clusters of cells, for example, /0 when investigating the development of cancerous tumours. The present inventors have found that by adding light absorbing baffle structures to a lensless imaging device, the wide angle light incident on the detector is decreased. This has the effect of increasing the resolution of the imaging system without the use of a lens.

Imaging devices Figures 1 and 2 are schematic side and perspective views respectively of a first lensless (also referred to as "lens-free") live-cell imaging device I according to some embodiments of the present disclosure.

The first imaging system 1 includes a light source 2 having a light emitting side 3, arranged on an optical axis 4. The light source 2 may be a Lambertian source. The light source 2 may comprise at least one organic light emitting diode (OLED). The light source 2 might comprise at least one light emitting diode (LED). The light source 2 may emit light on all sides. The light emitting side 3 emits light along the x axis.

The imaging system 1 may, optionally, include a light scattering panel 5 having first and second opposite sides (also referred to as "first and second faces") 6, 7 and is also -0Or arranged on the imaging axis 4. The light scattering panel 5 may be formed from a polymer, for example PDMS. The light scattering panel 5 may be of any size or shape. Typically, the light scattering panel 5 will have a width and a length of between 1 mm and 100 mm. The normal of the plane of the first side 6 of the light scattering panel 5 may be parallel to the imaging axis 4. The first side 6 of the light scattering panel 5 is oriented towards the light source 2. The distance a between the first side 6 of the light scattering panel 5 and the light emitting side 3 of the light source 2 may be between 100 pm and 1 mm. The distance a between the first side 6 of the light scattering panel 5 and the light emitting side 3 of the light source 2 is typically 100 pm. The light scattering panel thickness &all may be between 100 pm and 1 mm. The light scattering panel thickness ts,:art may be 100 pm. The light scattering panel 5 may perform Mie scattering.

The imaging device 1 includes a sample 8 which is typically a microfluidic device (also referred to as a "microfluidic chip"). The sample 8 has first and second sides 9, /0 10. The sample 8 is also arranged on the imaging axis 4. Typically, the sample 8 will have a width and a length of between 1 mm and 100 mm, although the sample 8 may be any size. The normal of the plane of the first side 9 of the sample 8 may be parallel to the imaging axis 4. The first side 9 of the sample 8 is oriented towards the light source 2. The light from the light source 2 illuminates the sample 8 also on the /5 imaging axis 4. The microfluidic device may have one or more microfluidic channels.

A typical microfluidic channel may be between 200 pm and 5 mm wide and 10 mm and 50 mm long. The sample 8 may contain cells. If a light scattering panel 5 is used, the light scattering panel 5 is placed between the light source and the sample 8. The sample 8 may also have light-scattering properties. The sample thickness is may be between 100 pm and 1 mm. The sample thickness is may be 100 pm.

If the light scattering panel 5 is not included, the distance a between the sample 8 and the light emitting side 3 of the light source 2 may be between 100 pm and 1 mm. The distance a between the sample 8 and the light emitting side 3 of the light source 2 is typically 100 pm.

Or The first imaging device 1 also includes an array 11 of light absorbing baffles 12 also arranged along the optical axis 4. An individual light absorbing baffle 12 (also referred to simply as a "baffle") may take the form of a tube, channel or conduit having first and second openings 13, 14. The baffle 12 may take the form of a square or rectangular tube. The baffle 12 may take the form of a circular tube. The first baffle opening 13 is oriented towards the light source 2. The distance b between the sample 8 and the baffle array 11 is variable. The distance b may be between 0 mm and a few millimetres. The distance b may be between 100 pm and 2 mm. The distance b is dependent on the requirements of the sample 8 to be imaged, for example, a distance b of between 100 pm and 1 mm may be required to allow for the top of the microfluidic chip to keep the cells enclosed. The baffle 12 and the array of baffles 11 will be described in more detail later.

The first imaging device 1 also has a detector assembly 19 (also referred to simply as a "detector") having a detector face 20. The detector 19 is arranged on the optical axis 4. The normal to the plane of the detector 19 may be parallel to the optical axis 4. The face 20 of the detector 19 may abut the baffle second opening 14. The face 20 of the detector 19 may be separated from the baffle second opening 14 by a distance of between 0 and 20 pm. The face 20 of the detector 19 is oriented towards the light source 2. The detector may be a charge-coupled device (CCD), a complementary metal-oxide-semiconductor (CMOS) or may be an array of organic photodiodes.

rg Figure 3 and 4 are schematic side and perspective views respectively of a second example of a first lensless live-cell imaging device 12. In the second example, an object mask 21 is arranged adjacent to the second side 7 of the light scattering panel 5. The object mask 21 is used to model the resolution of the first imaging device 1. The results from the modelling of the first imaging device 1 will be discussed in more detail later.

Figure 5A is a perspective view of a single baffle 12. The single baffle 12 generally takes the form of a tube, channel or conduit having first and second openings 13, 14. The transverse cross-section of the single baffle 12 may have any regular or irregular shape. The transverse cross-section of the single baffle 12 may be square or Or rectangular, so that the single baffle 12 takes the form of an elongated square tube. The transverse cross-section of the single baffle 12 may be circular, triangular or hexagonal. The transverse cross-section of the single baffle 12 may take the form of shapes which tessellate with the same shapes or with different shapes. The single baffle 12 has a central baffle axis 22 which runs through the centre of the baffle void.

The single baffle has a length la of between 250 and 750 pm. The single baffle typically has a length of 500 pm. The single baffle 12 has a width Wb and height ho of between 50 and 200 Rm. Typically, the single baffle 12 has a width Wb and height Ito of between 100 pm and 140 pm.

Figure 5B is a transverse cross-sectional view of the single baffle 12 in Figure 5A taken along the line A-A'. In this example, the transverse cross-section of the single baffle 12 has a square shape. The void height h, and void width WI, between the internal surface 30 of the baffle walls 28 is typically between 60 and 120 Rm. The void height h, between the internal surface 30 of the baffle walls 28 is typically 100 Rm.

Figure SC is a longitudinal cross-sectional view of the single baffle 12 in Figure SA iu taken along the line B-B'. The longitudinal cross-section has a rectangular shape. The baffle walls 28 may be formed from an opaque material, for example, black plastic. The thickness to of the baffle walls 28 is between 10 and 30 pm. The thickness tow of the baffle walls 28 is typically 20 pm. The internal surface 30 of the baffle walls absorbs near infrared (NIR) and visible light, for example, electromagnetic waves between 400 and 900 nm.

Figure 6A is a perspective view of a baffle array 11. A baffle array 11 is formed from several single baffles 121. 122, 123. 12n. The single baffles 12 in the baffle array 11 may have the first baffle openings 13 arranged along a common plane. The single baffles 12 in the baffle array 11 may have second baffle openings 14 arranged along a common plane. The baffle array width wha and height ha, of may be any size.

Typically, the baffle array width wim and height him will be similar to the size of the detector 19 used. The baffle array 11 in Figure 6A has twenty-five single baffles 12 arranged in five rows and five columns. A baffle array 11 may have any number of rows and any number of columns. The rows and columns of the may be perpendicular to each other. Typically, the baffle array 11 will have a number of columns and a number of rows needed to cover the whole or part of the detector 19 area. The baffle array 11 may be comprised of tessellated single baffles 12. The baffle array 11 may be comprised of baffles having the same shape in the plane normal to the x axis. The baffle array 11 may be comprised of baffles having different shapes in the plane normal to the x axis. The baffle array 11 may be comprised of non-tessellated single baffles 12.

Figure 6B is a transverse cross-sectional view of the baffle array 11 in Figure SA taken along the line C-C'. Figure SC is a longitudinal cross-sectional view of the baffle array 11 in Figure SA taken along the line D-D'.

Figure 7 is a side schematic view of the effect each single baffle 12 has on the light from the light source 2 passing through the optional light scattering panel 5, passing through the sample 8 or object (for example, cells) through each single baffle 12 before reaching the face 20 of the detector 19. The shaded arrow illustrates the path of io light from the light emitting side 3 of the light source 2, illuminating the sample 8 or object in line with the single baffle 122 before passing through the baffle and reaching the face 20 of the detector 19. The white arrows illustrate the path of light emitted from the light source 2, scattering on the optional light scattering panel 5, but illuminating a part of the sample 8 in line with the single baffle 123 before being rg directed towards the first opening 13 of the single baffle 122. As the internal surface 30 of the baffle walls 28 is light absorbing, light that does not travel in a straight line from the sample 8 or object to the face 20 of the detector 19 will be at least partially absorbed by the internal wall surface 30 and will not reach the detector 19. This reduces the wide angle light incident on the detector 19 and therefore increases the resolution of the imaging device without the use of a lens.

Figures 8 and 9 are schematic side and perspective views respectively of a second lensless live-cell imaging device 35 without an array of baffles 11. This device 35 is similar to the first imaging device 1 having a light source 2 with a light emitting side 3, optionally, a light scattering panel 5 with first and second sides 6, 7 and a detector 19.

Or A difference between the first imaging device 1 and the second imaging device 35 is that there are no baffles 12 in the second imaging device 35.

The resolutions of the second example of the first lensless imaging device 12 and the second lensless imaging device 35 are evaluated by modelling using Zemax (RTM). A hypothetical object mask 21 is overlaid on the second surface 7 of the light scattering panel 5. The object mask 21 is a series of parallel bars. These bars are 100 pm apart and 100 pm from the light emitting surface 3 of the light source 2. In this case, the light source 2 is a Lambertian light source. The distance b between the detector plane and the object mask 21 is variable. Three different distances b are modelled, 0, where the object mask directly shadows the detector 19, 100 and 200 pm. The image projected on the detector 19 is calculated for each of these distances b.

Figures 10A to 11C are signal detection plots showing density images created using the modelling process outlined above. Figures 10A, 10B and 10C are the modelled Yo resolutions of the parallel bars of an object mask 21 at distances h of 0, 100 and pm respectively for the second example of the first imaging device 12 which has an array of baffles 12. The parallel bars are identifiable and clearly resolved at the detector 19 assembly at all three of the modelled distances b.

Figures 11A, 11B and 11C are the modelled resolutions of the parallel bars of an 7,5 object mask 21 at distances b of 0, 100 and 200 pm respectively for the second imaging device 35 without an array of baffles 11 or other collection optics. In Figure 11A, the parallel bars appear clear and well resolved at the detector 19 assembly at a modelled distance b of 0 pm, where the object mask directly shadows the detector 19. In Figure 11 B, the parallel bars are barely resolvable at the detector 19 assembly at a modelled distance b of 100 pm. In Figure 11C, no parallel bars are identifiable at the detector 19 assembly at a modelled distance b of 200 pm.

Figures 12A, 12B and 12C are intensity profiles horizontally across the images in Figures 10A, 10B and 10C respectively. These profiles clearly illustrate that the modelled images are resolvable for the second example of the first imaging device 12 Or at distances b of 0, 100 and 200 pm. The signal to noise ratio for the 200 pm distance b is approximately 2:1, confirming that the parallel bars are resolvable at this distance. At this signal to noise ratio, samples 8 (for example, cells), are can be imaged successfully. The Rayleigh condition determines that a greater than 26.5% dip in intensity between two bright objects allows the objects to be resolved form each other.

Therefore, the 2:1 signal to noise ratio is high enough to achieve an acceptable resolution.

Figures 13 and 14 are schematic side and perspective views respectively of a third lensless live-cell imaging device 40 according to some embodiments of the present disclosure.

The third imaging device 40 generally takes the form of the first imagine device 1, however, the light source 2 is replaced with at least one pixelated organic light emitting diode (OLED) 41. The pixelated OLED 41 is moveable to each central baffle axis 22, of each of the single baffles 121 in the baffle array 11. This allows the OLED 41 to illuminate the cells between the OLED 41 and the area of the detector 19 abutting the second opening 14 of each single baffle 12. The OLED 41 may be driven to the required position. The OLED 41 may be driven, for example, by a piezo actuator or a servo motor. The use of an OLED 41 driven to the central baffle axis 22 of each individual baffle 12 has the effect of reducing the non-incident light, that is, light which has not passed through an object 8, which reaches the detector 19. A potential object 8, such as cells, is included for illustration.

Figure 15 is a schematic side view illustrating light that passes through the optional light scattering panel 5 and the sample 8 (i.e. incident light 42) indicated by a shaded arrow, and light that does not pass through the optional light scattering panel 5 and the sample 8 (i.e. non-incident light 43) indicated by a white arrow. Incident light 42 and non-incident light 43 then enter a baffle through a first baffle opening 13. The incident light 42 travels through the baffle 12 until it reaches the surface 20 of the detector 19. The non-incident light 43 is absorbed by the internal walls 30 of the baffle 12. A signal to noise ratio can be calculated by dividing the incident light 42 detected by the detector 19 which passes through the sample 8 by the total amount of incident light (that is, the incident light 42 which passes through the sample 8 plus the non-incident light 43 which does not pass through the sample 8).

Table 1 gives the signal to noise ratio for different distances b from the baffle to the object 8 (for example, cells to be imaged) for the third imaging device 40. It is clear 30 that using a pixelated OLED 41 as the excitation source allows the image to be resolvable with a signal to noise ratio of close to 2:1 for a distance of 500 tun. This is a greater signal to noise ratio than when using either no baffles, an array of baffles 11 or single baffle 12 alone.

Distance (itm) Ratio 0 1200:1 7:1 3.7:1 400 2.5:1 500 1.7:1

Table 1

The greater the distance b, that is the distance between the second side 7 of the light scattering panel 5 and the baffle first opening 13, the more space there is to allow for equipment to meet the requirements of the samples to be imaged. This greater distance ti) 1) also allows for more flexible object (for example, the cell sample) manipulation.

This greater distance b also allows the imaging of thicker and/or more complex microfluidic chips.

Figure 16 is a process flow diagram illustrating a method of imaging sample 8. First, the light source is made to emit light (Si). The emitted light then passes through the sample 8 and then enters the first opening 13 of at least one baffle 12. The after passing through the baffle, the incident light 42 then reaches the face 20 of the detector 19. The detector 19 then generates an image signal based on the light which has reached the face 20 of the detector 19. The image signal is then output from the detector assembly 19 (S2) and may be received by either further processors or a user.

Modifications It will be appreciated that various modifications may be made to the embodiments hereinbefore described. Such modifications may involve equivalent and other features which are already known in the design, manufacture and use of imaging devices and component parts thereof and which may be used instead of or in addition to features already described herein. Features of one embodiment may be replaced or supplemented by features of another embodiment.

Although claims have been formulated in this application to particular combinations of features, it should be understood that the scope of the disclosure of the present iu invention also includes any novel features or any novel combination of features disclosed herein either explicitly or implicitly or any generalization thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention. The applicants hereby give notice that new claims may be formulated to such features and/or combinations of such features during the prosecution of the present application or of any further application derived therefrom.

Claims

Claims I. A microfluidic chip imaging device comprising: a light source on an optical axis; at least one light absorbing baffle arranged on the optical axis having first and second openings arranged so that the first opening is oriented towards the light source; and a detector arranged on the optical axis so that the face of the detector is oriented towards the baffle second opening.
2. The microfluidic chip imaging device of claim 1 further including a microfluidic chip arranged on the optical axis between the light source and the at least one baffle.
3. The microfluidic chip imaging device of claim 1 or 2 wherein the light source is an organic light emitting diode.
4. The microfluidic chip imaging device of claim 3 wherein the organic light emitting diode is moveable to excite a detector area abutting the second opening of the at least one light absorbing baffle.
5. The microfluidic chip imaging device of any one of claims 1 to 4 wherein the at least one light absorbing baffle has a baffle central axis from the centre of the first opening to the centre of the second opening which is parallel to the optical 25 axis.
6. The microfluidic chip imaging device of any one of claims 1 to 5 wherein the at least one light absorbing baffle is a tube having a square profile.
7. The microfluidic chip imaging device of any one of claims 1 to 6 wherein the at least one baffle is an array of baffles.
8. The microfluidic chip imaging device of claim 7 wherein the array of baffles is square having five baffles along each axis.
9. The microfluidic chip imaging device of claim 7 or 8 wherein the light source is configured to pass through each baffle central axis of each at least one baffle in the array of baffles simultaneously.
10. The microfluidic chip imaging device of any one of claims 1 to 9 wherein the transverse cross-section of the at least one baffle has a width and a height so of 100 i_ina and the length of the baffle is 500 um.
11. The microfluidic chip imaging device of any one of claims 1 to 10 wherein the light source, the at least one baffle and the detector are configured to move along the optical axis.
12. The microfluidic chip microfluidic chip imaging device of any one of claims 1 to 11 wherein the normal of the plane of the detector is parallel to the optical axis.
13. The microfluidic chip imaging device of any one of claims 1 to 12 further including a light scattering panel having first and second opposite sides arranged on the optical axis and between the light source and the at least one light absorbing baffle and so that the first side faces the light source and the second side faces the first opening of the at least one baffle.
14. The microfluidic chip microfluidic chip imaging device of claim 13 wherein the normal of the plane of the light scattering panel is parallel to the optical axis.
15. The microfluidic chip imaging device of claim 13 or 14 wherein the light source, the scattering panel, the at least one baffle and the detector are configured to move along the optical axis.
16. The microfluidic chip imaging device of any one of claims 13 to 15 wherein the light scattering panel is a Mie scatterer.
17. The microfluidic chip imaging device of any one of claims 1 to 16 wherein the light source is a Lambertian light source.
18. The microfluidic chip imaging device of any one of claims 1 to 17 wherein the detector face abuts the second baffle opening.
19. A method of using the microfluidic chip imaging device of any of claims 1 to 18 the method comprising: causing the light source to emit light and outputting a signal from the detector.
20. A computer program comprising instructions which when executed by one or more processors causes the one or more processors to perform the method of claim 19.
2c, 21. A computer program product comprising a computer-readable medium storing the computer program of claim 20.
22. A system comprising: a light source on an optical axis; at least one light absorbing baffle arranged on the optical axis having first and second openings arranged so that the first opening is oriented towards the light source; a detector arranged on the optical axis so that the face of the detector is oriented towards the baffle second opening; an actuator configured to move the light source in line with the longitudinal axis of the at least one baffle.