WO2024105343A1

WO2024105343A1 - Device with cartridge

Info

Publication number: WO2024105343A1
Application number: PCT/GB2022/052911
Authority: WO
Inventors: Hector ZENIL; Santiago ZENIL ARAIZA
Original assignee: Oxford Immune Algorithmics Ltd
Priority date: 2022-11-16
Filing date: 2022-11-16
Publication date: 2024-05-23

Abstract

A device for imaging a biological sample. The device comprises a sample carrier configured to be loaded with a biological sample; and a cartridge comprising a platform and a barrier at a periphery of the platform. The barrier extends away from the platform to a shoulder, and the cartridge is free of obstructions above the platform so that the sample carrier can be loaded onto the platform from above the platform. A casing is configured to enable the cartridge to be inserted into the casing after the sample carrier has been loaded onto the platform; and an imaging system is configured to image the biological sample in the casing.

Description

DEVICE WITH CARTRIDGE

FIELD OF THE INVENTION

[0001] The present invention relates to a device for imaging a biological sample, and a method of imaging a biological sample with the device.

BACKGROUND OF THE INVENTION

[0002] Conventional systems and methods for biological imaging usually require a microscopic setup operated by humans traversing slides in translational movements, or a very expensive technique such as spectroscopy, flow-cytometry, electrical impedance, or chemical assays. Such technologies are unaffordable for applications of high population impact. Such systems and methods also do not scale and generalise well as they require manual analysis and are based on expensive optics and often provide inaccurate or incompatible results.

[0003] US 2008/018888 discloses an apparatus for capturing an image of a sample retained by a sample acquiring device, comprises an image capturing unit comprising a lens arrangement with a fixed focal plane, a sample holder comprising a first magnet unit, and a second magnet unit. The sample holder is adapted to receive the sample acquiring device and is movable in relation to the lens arrangement to a first position. The sample holder is movable from the first position to a second position by means of magnetic interaction of the first magnet unit and the second magnet unit, and the image capturing unit is adapted to capture an image of the sample by means of the lens arrangement when the sample holder is in the second position.

SUMMARY OF THE INVENTION

[0004] A first aspect of the invention provides a device for imaging a biological sample, the device comprising: a sample carrier configured to be loaded with a biological sample; a cartridge comprising a platform and a barrier at a periphery of the platform, wherein the cartridge is free of obstructions above the platform so that the sample carrier can be loaded onto the platform from above the platform; a casing configured to enable the cartridge to be inserted into the casing after the sample carrier has been loaded onto the platform; an imaging system configured to image the biological sample in the casing, the imaging system having a focal plane; and a focus drive system configured to lift the sample carrier off the platform and into the focal plane of the imaging system. [0005] The open structure of the cartridge above the platform provides a number of advantages. Firstly, it makes the cartridge mechanically robust and less fragile than a cartridge designed to enable the sample carrier to be loaded onto the platform by sliding it through a slot of the cartridge. Secondly, it enables the sample carrier to be loaded easily and quickly onto the platform. Thirdly, it enables the focus drive system to lift the sample carrier off the platform by a large amount, if required.

[0006] A further aspect of the invention provides a method of imaging a biological sample with the device of any preceding claim, the method comprising: loading the sample carrier with a biological sample; loading the sample carrier onto the platform from above the platform; inserting the cartridge into the casing; operating the imaging system to image the biological sample; withdrawing the cartridge from the casing; and unloading the sample carrier from the platform.

[0007] Optionally the barrier extends away from the platform to a shoulder.

[0008] Optionally the shoulder defines a periphery of an opening above the platform, and the cartridge is configured to enable the sample carrier to be loaded onto the platform via the opening and unloaded from the platform via the opening.

[0009] Optionally all or some of the shoulder lies in a plane which is parallel with the platform.

[0010] Optionally the barrier is configured to engage with an edge of the sample carrier in order to inhibit sliding between the platform and the sample carrier.

[0011] Optionally the barrier comprises a plurality of barrier segments separated by openings.

[0012] Optionally the barrier runs around a full circumference of the platform.

[0013] Optionally the barrier comprises a side wall and a top wall, the side wall extends away from the platform to the shoulder, and the side wall meets the top wall at the shoulder.

[0014] Optionally the imaging system has a field of view, and the device further comprises a drive system configured to move the cartridge or the sample carrier within the casing so that the sample carrier moves between a series of positions or orientations, each position or orientation bringing a different area of the sample carrier into the field of view of the imaging system. The imaging system may be configured to image an area of the biological sample in the field of view of the imaging system for each position or orientation of the sample carrier. [0015] Optionally the sample carrier comprises a circular wafer, the barrier comprises a cylindrical wall, and the drive system comprises a rotary drive system configured to rotate the sample carrier relative to the cartridge so that the sample carrier rotates between a series of orientations, each orientation bringing a different area of the sample carrier into a field of view of the imaging system. The imaging system may be configured to image an area of the biological sample in the field of view of the imaging system for each orientation of the sample carrier.

[0016] Optionally the drive system comprises a lateral cartridge drive system configured to move the cartridge within the casing so that the cartridge and the sample carrier move together between a series of lateral positions within the casing, each lateral position bringing a different area of the sample carrier into the field of view of the imaging system. The imaging system may be configured to image an area of the biological sample in the field of view of the imaging system for each lateral position.

[0017] Optionally the imaging system comprises a camera configured to acquire an image of the biological sample.

[0018] Optionally the imaging system comprises a smartphone.

[0019] Optionally the cartridge is configured to enable the focus drive system to lift the sample carrier higher than the barrier.

[0020] Optionally the cartridge further comprises an opening in the platform, and the focus drive system is configured to move into contact with an underside of the sample carrier through the opening in the platform.

[0021] Optionally the casing comprises a slot, and the casing is configured to enable the cartridge to be inserted into the casing via the slot.

[0022] Optionally the device further comprises a battery for powering the imaging system.

[0023] Optionally the device is a portable device and/or a handheld device.

[0024] Optionally the device has a maximum dimension which is less than 50cm or less than 40cm or less than 30cm.

[0025] Optionally the device has a weight less than 1kg, or less than 700g or less than 500g.

[0026] Optionally the device comprises a processor configured to analyse image or video data to automatically classify sample features. [0027] Optionally the sample carrier is loaded onto the platform by lowering the sample carrier into contact with the platform and/or by raising the platform into contact with the sample carrier.

[0028] Optionally as the sample carrier is loaded onto the platform, a first end of the cartridge is inside the casing and a second end of the cartridge protrudes from the casing.

[0029] Optionally the imaging system generates image or video data, and the method further comprises analysing the image or video data to automatically classify features of the biological sample.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Embodiments of the invention will now be described with reference to the accompanying drawings, in which:

[0031] Fig. 1 is an isometric view of a device for imaging a biological sample;

[0032] Fig. 2 is an isometric view of a cartridge of the device of Fig. 1;

[0033] Fig. 3 is an end view of the cartridge of Fig. 2;

[0034] Fig. 4 is an exploded view showing various parts of the device of Fig. 1;

[0035] Fig. 5 shows a slide with a biological sample loaded onto the cartridge of Fig. 2;

[0036] Fig. 6 shows the slide being loaded onto the cartridge from above the platform;

[0037] Fig. 7 is a plan view of the top part of the casing;

[0038] Fig. 8 is an isometric view of the top part of the casing;

[0039] Fig. 9 is a cross-sectional view showing the device of Fig. 1 imaging a biological sample;

[0040] Fig. 10 is an isometric view of a drive system;

[0041] Fig. 11 is an isometric view of the frame and drive members of the focus drive system;

[0042] Fig. 12 is an isometric view from below showing the cartridge in an extended position;

[0043] Fig. 13 is an isometric view from below showing the cartridge in a retracted position;

[0044] Fig. 14 is a plan view showing the cartridge in a first extended position;

[0045] Fig. 15 is a plan view, partly in section and with hidden parts shown, with the cartridge in the first extended position of Fig. 14; [0046] Fig. 16A is a plan view, partly in section, with the cartridge in the first extended position of Fig. 14;

[0047] Fig. 16B is a plan view, partly in section, with the cartridge in a first intermediate position;

[0048] Fig. 16C is a plan view, partly in section, with the cartridge in a first retracted position;

[0049] Fig. 16D is a plan view, partly in section, with the cartridge in a second retracted position;

[0050] Fig. 16E is a plan view, partly in section, with the cartridge in a second intermediate position;

[0051] Fig. 16F is a plan view, partly in section, with the cartridge in a second retracted position;

[0052] Fig. 17A is a side view showing the slide in a lowered position resting on the platform of the cartridge;

[0053] Fig. 17B is a side view showing the slide in a raised position;

[0054] Fig. 18A is an end view showing the slide in a lowered position resting on the platform of the cartridge;

[0055] Fig. 18B is an end view showing the slide in a raised position;

[0056] Fig. 19 is an isometric view of a device for imaging a biological sample;

[0057] Fig. 20 shows a wafer with a biological sample loaded onto a cartridge of the device Fig. 19;

[0058] Fig. 21 is an exploded view showing various parts of the device of Fig. 19;

[0059] Fig. 22 is an isometric view showing the wafer being loaded onto the cartridge from above the platform;

[0060] Fig. 23 is a plan view of the cartridge;

[0061] Fig. 24 is a plan view of the top part of the casing;

[0062] Fig. 25 is an isometric view of the top part of the casing;

[0063] Fig. 26 is an isometric view of a wafer drive system;

[0064] Fig. 27 is an end view showing the drive members in a lowered position;

[0065] Fig. 28 is an end view showing the drive members in an engaged position; [0066] Fig. 29 is an isometric view from below with the drive members in the engaged position;

[0067] Fig. 30 is a cross-sectional view showing the device of Fig. 19 imaging a biological sample;

[0068] Fig. 31 is an isometric view showing an underside of the wafer;

[0069] Fig. 32 is a bottom view of the underside of the wafer;

[0070] Fig. 33 is a side of the wafer, including an enlarged view at the edge;

[0071] Fig. 34 is a plan view of the wafer;

[0072] Fig. 35 is a side view of the table and wafer from the side in a non-engaged position;

[0073] Fig. 36 is an isometric view of the table and wafer in a non-engaged position;

[0074] Fig. 37 is a side view of the table and wafer from the side in an engaged position;

[0075] Fig. 38 is a section along line A-A;

[0076] Fig. 39 s a sectional view showing the rotary drive teeth in the recesses;

[0077] Fig. 40 is an isometric view showing an underside of an alternative wafer;

[0078] Fig. 41 is a side view of the table and wafer from the side in a non-engaged position;

[0079] Fig. 42 is a sectional view of the table and wafer in an engaged position; and

[0080] Fig. 43 is a sectional view showing the rotary drive teeth in the recesses.

DETAILED DESCRIPTION OF EMBODIMENT(S)

[0081] Figure 1 shows a device 10 for imaging a biological sample. Certain elements of the device are shown in Figure 4, including a sample carrier (in this case a slide 16) for carrying the biological sample; a cartridge 22 carrying the slide 16; a camera 18; and a casing comprising a top part 12a and bottom part 12b.

[0082] The camera 18 may be a smartphone, for example. The camera 18 is configured to capture video and images. Typically, the camera 18 has a weight of approximately 200gm.

[0083] The top part 12a of the casing has a slot 15 at one end, shown in Figure 8, and the camera 18 is fitted into the top part 12a of the casing via the slot 15. The top part 12a of the casing (carrying the camera 18) is then fitted into the lower part 12b. The two parts of the casing have respective slots 14a, 14b which line up when the casing is in its fully assembled state shown in Figure 1. The top and bottom parts of the casing are then secured together by a fastener 8 with a cap 9 shown in Figure 4.

[0084] The casing 12a, 12b is configured to enable the cartridge 22 to be inserted into a chamber 33 in the casing via the aligned slots 14a, 14b after the slide 16 has been loaded onto the cartridge 22.

[0085] The slot 14a provides an opening into the chamber 33. As shown in Figure 16A and 16F, the chamber 33 has side walls 30a, 30b, a rear wall 30c, and a shelf 5 shown in Figure 8 with openings 6, 7 shown in Figure 7.

[0086] The side walls 30a, 30b have V-shaped projecting rails 29a, 29b which are received in V-shaped grooves 29c in the side of the cartridge, to guide the cartridge into the casing at the correct height. The rails 29a, 29b are shown most clearly in Figure 9 and the grooves 29c are shown most clearly in Figure 3. Each rail 29a, 29b runs from the slot 14a and terminates a short distance into the chamber 33 as shown most clearly in Figures 16A and 16E. The side walls 30a, 30b, and their respective rails 29a, 29b, extend at an oblique angle to each other so the width of the chamber 33 widens towards the rear wall 30c.

[0087] The cartridge 22 shown in Figures 2 and 3 has a platform 21 which carries the slide 16. Seven barrier segments 23 are provided at a periphery of the platform. The barrier segments 23 are separated by openings.

[0088] As shown in Figure 3, each barrier segment 23 comprises a planar inner side wall 24 and a top wall 25. The side wall 24 extends away from the platform 21 to a convex shoulder 26, and the inner side wall 24 meets the top wall 25 at the shoulder 26.

[0089] In this example, all of the barrier segments 23 are the same height, so that their shoulders 26 and top walls 25 all lie in a plane 27 which is parallel with the platform 21. In other examples, some of the barrier segments 23 may have different heights.

[0090] The shoulders 26 defines a periphery of an opening 28 above the platform 21, and the cartridge 22 is configured to enable the slide 16 to be loaded onto the platform via the opening 28 and unloaded from the platform via the opening 28.

[0091] The cartridge 22 is free of obstructions above the platform 21, so that the slide 16 can be loaded onto the platform from above the platform as shown in Figure 6. The barrier segments 23 collectively provide a barrier which is configured to engage with an edge of the slide 16 in order to inhibit sliding between the platform 21 and the slide 16, after the slide has been loaded as shown in Figure 5.

[0092] The slide 16 can be loaded onto the platform 21 from above the platform in a variety of ways. For example, the cartridge 22 may be fully removed from the casing 12a, 12b, and the slide 16 dropped down vertically onto the platform as shown in Figure 6. Alternatively, as the slide 16 is loaded onto the platform 21, a first end of the cartridge 22 may be inside the casing and a second end of the cartridge may protrude from the casing, as shown in Figure 1. In this case, rather than being dropped down onto the platform 21 with the slide 16 remaining parallel with the platform 21, the first end of the slide 16 is loaded onto the platform 21 at an angle, and then the second end of the slide 16 is lowered down onto the platform 21 as the first end of the slide 16 is fed into the casing. The slots 14a, 14b must be sufficiently high to enable this loading method to be used without clashing with the casing.

[0093] In the loading methods described above, the slide 16 is loaded onto the platform 21 by lowering the slide 16 into contact with the platform 21. Equivalently the slide 16 may be loaded onto the platform 21 by raising the platform 21 into contact with the slide 16, although this would be a more cumbersome method. Also, the platform 21 may not be horizontal as the slide 16 is loaded onto the platform 21, although this is preferred.

[0094] The open structure of the cartridge 22 above the platform 21 provides a number of advantages. Firstly, it makes the cartridge 22 mechanically robust and less fragile than a cartridge designed to enable the sample carrier to be loaded onto the platform by sliding it through a slot of the cartridge. Secondly, it enables the slide 16 to be loaded easily and quickly onto the platform 21.

[0095] The cartridge 22 is inserted into the interior of the casing by inserting it through the aligned slots 14a, 14b. When fully inserted, the second end of the cartridge 22 may protrude from the casing, or the full length of the cartridge may be received in the casing.

[0096] The device 10 has a height, length and width which are labelled H, L and W respectively in Figure 1. The device 10 is sufficiently small and light to make it portable. By way of example the height H may be 10cm, the length may be L 20cm and the width W may be 15cm, giving a volume of approximately 1500 cm3. The weight of the device 10 (including the cartridge 22, the slide 16 and the camera 18) may be approximately 400gm. [0097] The camera 18 is part of an imaging system 18, 18a, 19, shown in detail in Figure 9. The camera 18 has an optical system with a lens or aperture 18a, and a sensor 32. A lens 19 in a lens mount 19a is fitted in the casing, with the lens 19 aligned with the lens or aperture 18a of the camera as shown in Figure 9. The lens 19 has a focal plane and a field of view.

[0098] The camera 18 (or other imaging system) is fitted to the casing - in this example it is fitted to the top part 12a of the casing. The camera 18 in this example is at least partially inside the casing, although it is not completely enclosed by the casing so its touch screen, ports and operating buttons are exposed. In other examples, the camera 18 (or other imaging system) may be fitted to the exterior of the casing so that no part of it is inside the casing.

[0099] When the cartridge 22 is fully inserted, the slide 16 is positioned at an imaging location with the lens 19 positioned above the slide 16 as shown in Figure 9. A small area of the slide 16 is in the field of view of the imaging system below the lens 19.

[0100] A lighting system shown in Figure 9 is arranged to illuminate the slide 16 (and the biological sample carried by the slide) at the imaging location. The camera 18 is configured to image the biological sample from a front side of the wafer (i.e. from the top of the view of Figure 9). The lighting system comprises a light source 41 which generates a beam of light 42 which is reflected by a pair of mirrors 46, 48 so that the transparent slide 16 is illuminated from its underside (i.e. from the bottom of the view of Figure 9). The beam of light 42 passes through the hole 6 in the shelf 5 on its way up. The light source 41 may be part of the camera 18, or it may be separate from the camera 18.

[0101] A drive system 50 shown in Figure 10 is housed in the lower part 12b of the casing. The drive system 50 comprises a lateral cartridge drive system 60, 61, and a focus drive system 70- 75.

[0102] The drive system 50 comprises a chassis 51 with a hole 52 shown in Figure 12 through which the beam of light 42 passes on its way up to the slide 16.

[0103] The lateral cartridge drive system comprises a pinion gear 60 shown in Figure 10 driven by a motor 61. As shown in Figures 12 and 13, the cartridge has a rack on its underside. The rack extends along a two-dimensional rack path - i.e. a rack path which does not consist only of a single straight line. In this case the two-dimensional rack path has a U-shape with a first straight segment 62, a second straight segment 63 parallel with the first straight segment 62, and a curved transition segment 64 joining the straight segments. [0104] Figures 1, 12, 14, 15 and 16A show the cartridge 22 in a first extended position with the first end of the cartridge inside the casing and the second end of the cartridge protruding from the casing. In this first extended position, the pinion gear 60 is coupled to the rack at one end of the first straight segment 62 as shown in Figure 15. Rotation of the pinion gear 60 by the motor 61 drives the cartridge 22 to a first intermediate position shown in Figure 16B, then to a first fully retracted position shown in Figure 13 and Figure 16C.

[0105] As the cartridge 22 is driven along a first drive path segment as shown in Figures 16A- 16C, it translates along a substantially straight path, roughly parallel with the side wall 30a of the chamber 33. During this phase of the drive path, all of the rail 29a is received in the groove 29c in the left-hand edge of the slide, and only part of the rail 29b is received in the groove 29c in the right-hand edge of the slide.

[0106] As the pinion gear 60 continues to rotate, it engages with the curved segment 64 of the rack path and drives the first end of the cartridge sideways. This causes the cartridge to pivot from the orientation of Figure 16C to the orientation of Figure 16D. As the pinion gear 60 continues to rotate further, it engages with the second straight segment 63 of the rack path and drives the cartridge 22 back to a second intermediate position shown in Figure 16E, then to a second extended position shown in Figure 16F.

[0107] As the cartridge 22 is driven along a second drive path segment as shown in Figures 16D-16F, it follows a substantially straight path, roughly parallel with the side wall 30b of the chamber 33. During this phase of the drive path, all or most of the rail 29b is received in the groove 29c in the right-hand edge of the slide, and only part of the rail 29a is received in the groove 29c in the left-hand edge of the slide.

[0108] Thus the lateral cartridge drive system 60-64 is configured to move the cartridge 22 along a two-dimensional drive path (i.e. a drive path which does not consist only of a translation in a single straight line) as described above and shown in Figures 16A-16F, with only a single motor 61.

[0109] The centre of the field of view traces a corresponding two-dimensional path (i.e. a path which does not consist only of a straight line) over the slide as shown in Figure 15. The two- dimensional path of the centre of the field of view has a first substantially straight segment 90 (corresponding with the first straight segment 62 of the rack path), a second substantially straight segment 91 (corresponding with the second straight segment 63 of the rack path) and a transition segment 92 (corresponding with the curved segment 64 of the rack path).

[0110] Other two-dimensional shapes are possible for the rack path, and the related path of the centre of the field of view. For instance either path may have a V-shape, a zig-zag shape, a sinuous shape (such as a sine wave) or any other shape which drives the cartridge in a two- dimensional back-and-forth motion.

[0111] The slide 16 is non-circular, with an elongate shape (i.e. a length which is greater than its width) and a rectangular periphery. This makes the slide 16 unsuitable for being driven by a pure rotation. Thus preferably the two-dimensional path of the centre of the field of view does not consist only of a circle or a portion of a circle.

[0112] A largely translational motion is preferred because of the elongate, non-circular, shape of the slide 16.

[0113] In other embodiments, an alternative lateral cartridge drive system may be used to move the cartridge by a pure rotation (i.e. a rotation about its centre with no translation). In this case the two-dimensional path of the centre of the field of view may be circular.

[0114] The lateral cartridge drive system 60-64 is configured to move the cartridge 22 in the chamber 33 within the casing 12a, 12b as described above, so that the cartridge 22 and the slide 16 move together between a series of lateral positions within the casing. Each lateral position brings a different area of the slide 16 into the field of view of the imaging system 18, 18a, 19, 32.

[0115] Returning to Figure 10, the other part of the drive system 50 is a focus drive system 70- 75 configured to lift the slide 16 off the platform 21 into the focal plane of the imaging system 18, 18a, 19, 32.

[0116] The focus drive system comprises a frame 70 which carries three drive members 71, 72, 73. The frame has a first shaft 74 coupled to a first axial drive motor 74a, and a second shaft 75 coupled to a second axial drive motor 75a. The axial drive motors 74a, 75a are configured to move the frame 70 up and down.

[0117] Each drive member 71-73 has a respective contact surface which is configured to contact an underside of the slide 16 in the casing. The contact surfaces lie in the same horizontal plane. As shown in Figure 11, each contact surface has a respective centre 7 la, 72a, 73a, and the centres of the contact surfaces are non-collinear. [0118] The centres 71a, 72a, 73a of the contact surfaces are also well spaced apart to provide a stable support for the slide 16 as it lifts off the platform.

[0119] The use of three drive members 71-73 provides a more stable support for the slide than only a single drive member. Also, a focus drive system with only a single drive member would require the drive member to be located precisely at the centre of the slide. The use of three drive members 71-73 enables the drive members to be offset from the centre of the slide by some distance.

[0120] In this example there are only three drive members 71-73, but in other embodiments the focus drive system may have more than three drive members.

[0121] As shown in Figure 2, the cartridge has a hole 29a in the platform 21. Two of the drive members 72, 73 are configured to move into contact with the underside of the slide 16 through this hole 29a.

[0122] The cartridge also has a recess 29b in a side of the platform 21. The other drive member 71 is configured to move into contact with the underside of the slide 16 through this recess 29b.

[0123] The device 10 is designed to use gravity to keep the slide 16 on the platform 21 before being engaged by the drive members 71-73. This requires the device 10 to be positioned parallel or at less than a 90 degree angle with respect to the floor. Another implementation uses one or more springs to hold the slide 16 in place. In such a case, the spring holds the slide in its place and is flexible enough for the focus drive system to move the slide.

[0124] The focus drive system 70-75 solves the problem of how to bring the sample into focus, without having to move the cartridge 22. Therefore a relatively large motor 61 can be used to move the cartridge 22 laterally, and relatively small axial drive motors 74a, 75a can be used to drive the sample axially and into focus.

[0125] A method of imaging a biological sample with the device 10 will now be described.

[0126] First the slide 16 is loaded with a biological sample 80 shown in Figure 6. The biological sample 80 may be carried on an upper surface of the slide 16, the slide 16 may comprise a cover slip which covers the biological sample 80, or the slide may have a chamber into which the biological sample 80 is loaded.

[0127] The biological sample 80 can be obtained from any biological source, animal or human. Typically, the biological sample 80 is obtained from a living organism. [0128] The biological sample 80 may be, for example: sputum/oral fluid, amniotic fluid, blood, a blood fraction, fine needle biopsy samples (e.g. surgical biopsy, fine needle biopsy, etc.), urine, semen, stool, vaginal fluid, peritoneal fluid, pleural fluid, tissue explant, organ culture, cell culture, and any other tissue or cell preparation, or fraction or derivative thereof or isolated therefrom.

[0129] A staining substance may be used to dye the sample 80 and the different molecular elements. In some implementations, the dye is a dry dye. In some implementations, the dry dye includes methylene blue and/or eosin, cresyl violet or some other staining product, including those related to fluorescence assays.

[0130] The application of the dye or other reagent(s) can be delivered in a various ways. In one example, a small quantity of dye (e.g., about 5 uL of the dye) is deposited in or on the slide 16. In another example, about 2 uL of the stain or other reagent is taken up by a tube or vial in a previous preparation step. In another example, the stain or other reagent is smeared across the slide by a traditional smearing mechanism.

[0131] In some implementations, an external test tube is configured with anticoagulant to prepare a stained biological sample as an intermediate step before loading the biological sample onto the slide 16.

[0132] Next, the slide 16 is loaded onto the platform 21, using one of the methods described above. Then the cartridge 22 is inserted into the casing, either manually or by rotating the pinion gear 60.

[0133] When the slide 16 is at a desired position, the focus drive system is operated to move the contact surfaces of the drive members 71-73 into contact with an underside of the slide 16 and then lift the slide 16 off the platform 21 to move the biological sample 80 into the focal plane of the imaging system. This focusing process is shown in Figures 17A-18B.

[0134] Figures 17A and 18A show the slide 16 in a lowered position, resting on the platform 21. Figures 17B and 18B show the slide 16 in a raised position, having been lifted off the platform 21 into the focal plane of the imaging system.

[0135] Figures 17B and 18B indicate the plane 27 at the level of the shoulder 26 and top wall 25 of the barrier. As shown in Figures 17B and 18B, the cartridge is configured to enable the focus drive system to lift the slide 16 higher than the barrier - i.e. higher than the shoulder 26 of the barrier and higher than the top 25 of the barrier. This enables a large range of axial motion if the focal plane is above the plane 27 at the top of the barrier.

[0136] Once the biological sample 80 is in the focal plane, the camera 18 is operated to image the biological sample 80. The device 10 may be operated to acquire only a single image, but more typically it is operated to generate a series of images or videos, each image or video capturing a different part of the biological sample 80.

[0137] Thus the lateral cartridge drive system is operated to move the cartridge 22 and the slide 16 together between a series of lateral positions within the casing, each lateral position bringing a different area of the biological sample 80 into the field of view of the imaging system. For each lateral position of the slide 16, the camera 18 is operated to image the area of the biological sample 80 in the field of view of the imaging system. The areas imaged by the camera 18 may be overlapping or non-overlapping.

[0138] The lateral cartridge drive system is configured to move the cartridge relative to the drive members 71-73 of the focus drive system, such that for each lateral position a different area of the underside of the slide is contacted by the contact surfaces of the drive members 71-73.

[0139] Typically for each lateral position of the slide 16, the following sequence of steps is performed in order: (a) the focus drive system is operated to lift the slide 16 off the platform to move the biological sample 80 into the focal plane of the imaging system; (b) the imaging system is operated to image the area of the biological sample 80 in the field of view of the imaging system; and (c) the focus drive system is operated to lower the slide 16 back onto the platform. After the slide 16 has landed back on the platform, the cartridge 22 is driven to the next lateral position and steps (a)-(c) repeated.

[0140] Optionally the contact surfaces of the drive members 71-73 remain in contact with the underside of the slide 16 as the cartridge 22 is moved by the lateral cartridge drive system. In this case each contact surface is configured to make a sliding contact with the underside of the slide, and the sliding contact is configured to enable the underside of the slide 16 to slide across the contact surface as the cartridge 22 is moved by the lateral cartridge drive system.

[0141] Alternatively the contact surfaces of the drive members 71-73 may disengage from the underside of the slide 16 at the end of step (c) above, and re-engage with a different area of the underside of the slide 16 at the beginning of the next step (a) above. In this case no sliding interface is required. [0142] Once sufficient images have been taken, the cartridge is fully or partially withdrawn from the casing 12a, 12b through the slots 14a, 14b; and the slide 16 is unloaded from the platform 21 by a reversal of one of the loading methods described above.

[0143] The camera 18 may take a series of still images, with the slide 16 held stationary as each image is taken. Alternatively, a video may be taken as the slide 16 moves continuously.

[0144] The image or video data acquired by the camera 18 may be stored and/or post processed by the device 10 and/or transmitted from the device 10 for remote storage or post processing.

[0145] In the post processing, the image or video data may be analysed to automatically classify sample features. If the post processing is performed by the device 10, then the device 10 comprises a processor configured to analyse the image or video data to automatically classify sample features.

[0146] An implementation moves the slide 16 up and down in order to avoid a feedback system to bring the biological sample 80 into focus. A video is taken by the camera 18 as the slide 16 moves up and down with a continuous sinusoidal movement. For certain frames of the video the sample will be in focus, and these frames can be selected a posteriori as part of image postprocessing. This implementation reduces the need for communication between a controller (not shown, however, may be part of the camera 18) and the focus drive system resulting in a significant reduction and device size minimisation from sampling area movement and reduction of the complexity of the device 1, and sampling method and mechanism.

[0147] The device 10 is battery powered, with one or more batteries for powering the camera 18, the drive system 50 and the lighting system 41. Optionally the camera 18 is a smartphone with a battery 17 shown schematically in Figure 9. The drive system 50 and the lighting system 41 may all be powered by the battery 17.

[0148] The device 10 may comprise a communication mechanism (either wired e.g. USB, or unwired, e.g. Bluetooth) for communicating data (such as video or image data) from the device 10 to another device, such as a server.

[0149] Figure 19 shows a device 110 for imaging a biological sample according to a further embodiment of the invention. Many of the elements of the device 110 are identical or equivalent to elements of the device 10 of Figure 1. Identical elements will not be described again, and equivalent elements are given the same reference number incremented by 100. [0150] Certain elements of the device 110 are shown in Figure 21, including a sample carrier (in this case a circular wafer 116) for carrying the biological sample; a cartridge 122 carrying the wafer 116; a camera 18 (identical to the camera 18 in the device of Figure 1); and a casing consisting of a top part 112a and a bottom part 112b.

[0151] The top part 112a of the casing has a slot 115 at one end, shown in Figure 25, and the camera 18 is inserted into the top part 112a of the casing via the slot 115. The top part 112a of the casing (carrying the camera 18) is then fitted into the lower part 112b. The two parts of the casing have respective slots 114a, 114b which line up when the casing is in its fully assembled state shown in Figure 19.

[0152] The casing is configured to enable the cartridge 122 to be inserted into the casing via the aligned slots 114a, 114b after the wafer 116 has been loaded onto the cartridge 122.

[0153] The top part 112a of the casing has a shelf 105 which provides the bottom boundary of the slot 114a. The shelf 105 has an opening 106 shown in Figure 24.

[0154] The top part 112a of the casing has V-shaped projecting rails which are received in V- shaped grooves 129 in the side of the cartridge, to guide the cartridge into the casing at the correct height. One of the grooves 129 is shown in Figure 22.

[0155] The cartridge 122 shown in Figures 22 and 23 has a recessed platform 121 which carries the wafer 116. A barrier is provided at a periphery of the platform 121. The barrier comprises a vertical cylindrical side wall 124 which extends away from the platform 121 to a convex circular shoulder or rim 126 where the side wall 124 meets the flat top of the cartridge. The barrier 124, 126 runs around a full circumference of the platform 121.

[0156] The shoulder or rim 126 defines a periphery of an opening above the platform 121, and the cartridge 122 is configured to enable the wafer 116 to be loaded onto the platform 121 via the opening and unloaded from the platform via the opening.

[0157] The cartridge 122 is free of obstructions above the platform 121, so that the wafer 116 can be loaded onto the platform from above the platform as shown in Figure 22. The side wall 124 of the barrier is configured to engage with an edge of the wafer 116 in order to inhibit sliding between the platform 121 and the wafer 116, after the wafer has been loaded as shown in Figure 20.

[0158] The wafer 116 can be loaded onto the platform 121 from above the platform in a variety of ways. For example, the cartridge 122 may be fully removed from the casing 112a, 112b, and the wafer 116 dropped down vertically onto the platform as shown in Figure 22. Alternatively, as the wafer 116 is loaded onto the platform 121, a first end of the cartridge 122 may be inside the casing and a second end of the cartridge 122 may protrude from the casing, as shown in Figure 19. In this case, rather than being dropped down onto the platform 121 with the wafer 116 remaining parallel with the platform 21, a first end of the wafer 116 is loaded onto the platform 121 at an angle, and then a second end of the wafer 116 is lowered down onto the platform 121 as the first end of the wafer 116 is fed into the casing. The slots 114a, 114b must be sufficiently high to enable this loading method to be used without clashing with the casing.

[0159] In the loading methods described above, the wafer 116 is loaded onto the platform 121 by lowering the wafer 116 into contact with the platform 121. Equivalently the wafer 116 may be loaded onto the platform 121 by raising the platform 121 into contact with the wafer 116, although this would be a more cumbersome method. Also, the platform 121 may not be horizontal as the wafer 116 is loaded onto the platform 121, although this is much preferred.

[0160] The cartridge 122 is inserted into the interior of the casing by inserting it through the aligned slots 114a, 114b. When fully inserted, the second end of the cartridge 122 may protrude from the casing, or the full length of the cartridge may be received in the casing.

[0161] The device 110 has the same overall dimensions and a similar weight to the device 1.

[0162] When the cartridge 122 is fully inserted, the slide 116 is positioned at an imaging location with the lens 19 positioned above the wafer as shown in Figure 30. A small area of the wafer 116 is in the field of view below the lens 19.

[0163] A wafer drive system shown in Figure 26 is housed in the casing 112a, 112b. The wafer drive system comprises a chassis 151 with a hole 152 shown in Figure 29 through which the beam of light 42 passes on its way up to the wafer 116 as shown in Figure 30.

[0164] The wafer drive system comprises a table with a table surface 170. Three rotary drive teeth 171, 172, 173 protrude from the table surface 170.

[0165] The wafer drive system also comprises a lateral drive system (in this case a rotary drive system) and a focus drive system.

[0166] The rotary drive system in this case provides a pure rotation of the wafer - in other it words it comprises a rotary drive system. The rotary drive system comprises a rotary drive motor 174 with a rotary output shaft which carries the table. The rotary drive motor 174 is mounted on a pair of pillars 176. [0167] The focus drive system comprises a pair of axial drive motors 174a, 174b connected to the rotary drive motor 174.

[0168] Operation of the axial drive motors 174a, 174b causes the rotary drive motor 174 to slide up and down on the pillars 176, and operation of the rotary drive motor 174 causes the table to rotate.

[0169] As shown in Figure 23, the cartridge has a hole 129a in the platform 121. The table is configured to move into contact with the wafer 116 through this hole 129a.

[0170] Figure 27 illustrates a disengaged state in which the table is not in contact with the wafer 116. The wafer drive system can be in this disengaged state when the cartridge 122 is being inserted and removed.

[0171] Figure 28 illustrates an engaged state in which the table is engaged with the wafer 116. The axial drive motors 174a, 174b can drive the rotary drive motor 174 up and down between the positions of Figure 27 and Figure 28. The axial drive motors 174a, 174b are also configured to lift the wafer 116 off the platform 121 into the focal plane of the imaging system.

[0172] The device 110 is designed to use gravity to keep the wafer 116 on the platform 121 before being engaged by the table. This requires the device 110 to be positioned parallel or at less than a 90 degree angle with respect to the floor. Another implementation uses one or more springs to hold the wafer 116 in place. In such a case, the spring holds the wafer 116 in its place and is flexible enough for the focus drive system to move the slide.

[0173] A method of imaging a biological sample with the device 110 will now be described.

[0174] First the wafer 116 is loaded with a biological sample 180 shown in Figure 22. The wafer 116 comprises a circular transparent cover which covers the biological sample 180.

[0175] Next, the wafer is loaded onto the platform 121, using one of the methods described above.

[0176] Next, the cartridge 122 is inserted manually into the casing.

[0177] Then when the wafer 116 is at a desired position, the axial drive motors 174a, 174b are operated to move the table into contact with the wafer 116 and then lift the wafer 116 off the platform 121 to move the biological sample 180 into the focal plane of the imaging system.

[0178] The cartridge 122 is configured to enable the table to lift the wafer 116 higher than the barrier - i.e. higher than the shoulder or rim 126 of the barrier and higher than the top of the cartridge. This enables a large range of axial motion if the focal plane is above the plane of the rim 126 at the top of the barrier.

[0179] Once the biological sample 180 is in the focal plane, the camera 18 is operated to image the biological sample. The device 110 may be operated to acquire only a single image, but more typically it is operated to generate a series of images or videos, each image or video capturing a different part of the biological sample 180.

[0180] The rotary drive motor 174 is operated to rotate the wafer 116 relative to the cartridge 122 between a series of orientations within the casing, each orientation bringing a different area of the biological sample 180 into the field of view of the imaging system. For each orientation of the wafer 116, the camera 18 is operated to image the area of the biological sample 180 in the field of view of the imaging system. The areas imaged by the camera 18 may be overlapping or non-overlapping .

[0181] Note that the cartridge 122 is configured to enable the wafer 116 to rotate relative to the cartridge 122 as the wafer 116 rotates at the imaging location. The cartridge 122 remains stationary during the rotation. The wafer 116 may or may not be in contact with the platform 121 as it rotates.

[0182] Once sufficient images have been taken, the cartridge 122 is fully or partially withdrawn from the casing 112a, 12b through the slots 114a, 114b; and the wafer 116 is unloaded from the platform 121 by a reversal of one of the loading methods described above.

[0183] Figures 31-34 show the wafer 116 in further detail. The wafer 116 comprises a transparent body, comprising a transparent circular base 190 and a transparent circular cover 191 shown most clearly in the enlarged view of Figure 33. The base 190 and cover 191 have circular peripheries 192, 193 which together form a circular periphery of the body. A chamber 194 is provided in the body of the wafer, in the form of a gap between the base 190 and the cover 191.

[0184] The cover 191 may be attached to the base 190 by adhesive, ultrasonic welding, or by surface tension of the biological sample 180. Alternatively the cover 191 and the base 190 may be integrally formed as a single piece, for example by injection moulding.

[0185] The chamber 194 is configured to be loaded with the biological sample 180. In this example the chamber 194 comprises an opening 195 at the circular periphery of the body, and the biological sample 180 is injected or otherwise loaded into the chamber 194 via the opening 195.

[0186] In one embodiment, the cover 191 may be attached to the base 190 at its centre by a thin adhesive patch which also acts as a spacer to maintain a small and precise gap distance between the cover 191 and the base 190. Patches of adhesive may also be distributed around the periphery of the wafer, or other locations, to keep the gap distance constant. The opening 195 in this case extends around the full periphery of the chamber 194 so the biological sample 180 can be loaded into the chamber 194 via the opening 195 from any direction.

[0187] In an alternative embodiment, the chamber 194 may have a closed circular periphery and the biological sample 180 may be injected into the chamber 194 via inlet ports, from the sides, top or bottom of the wafer.

[0188] Preferably the gap distance is in the range of 5-15 microns, or 1-20 microns, to enable the biological sample 180 to flow throughout the chamber 194 by capillary action.

[0189] In this example, both the base 190 and the cover 191 are transparent. The adhesive is not required to be transparent since it will not be in the field of view of the imaging system. In an alternative embodiment, in which the biological sample 180 does not need to be illuminated from below, then the base 190 may be opaque and only the cover 191 may be transparent.

[0190] Figure 31 and 32 show an underside 198 of the body, which is also the underside of the base 190. Three recesses 196 are provided in the underside 198 of the body. Each recess comprises a pair of end walls 197 shown in Figure 32. Each recess 196 extends along a circular arc, and each end wall 197 is positioned at a respective end of the circular arc.

[0191] In this example, each recess 196 passes through a full thickness of the base 190. In an alternative embodiment, each recess 196 may only pass through part of the thickness of the base 190.

[0192] As shown in Figure 27, the wafer drive system comprises a table with a table surface 170, and a rotary drive system (rotary drive motor 174, etc.) configured to rotate the table. Three rotary drive teeth 171-173 protrude from the table surface 170. A focus drive system (axial drive motors 174a, 174b, etc.) is configured to lift the table by lifting the rotary drive motor 174.

[0193] Each rotary drive tooth 171-173 is configured to be received in a respective recess 196 as shown in Figure 38 and 39. As the table is rotated by the rotary drive system, each rotary drive tooth 171-173 moves along the circular arc of its respective recess 196 until it comes into contact with one of the end walls 197. As the table is further rotated, each rotary drive tooth 171-173 pushes the end wall 197 of the recess 196 and drives the rotation of the wafer.

[0194] In this example, each end wall 197 is a continuous wall so that the recesses 196 are unconnected. In another embodiment, the recesses 196 may be joined up by cuts through the end walls 197. In this case, each end wall 197 can still act as a stop which is pushed by the rotary drive tooth.

[0195] Since the recesses 196 are elongate, the rotary drive teeth 171-173 can enter the recesses 196 at any point along the length of the recess 196, so the wafer does not need to be loaded onto the platform in a particular orientation. Figure 39 shows the rotary drive teeth 171-173 before they have come into contact with the end walls 197.

[0196] As shown in Figure 38, the table surface 170 is configured to contact the underside 198 of the wafer, so that as the table is lifted by the focus drive system, the table surface 170 lifts the wafer 116 off the platform 121.

[0197] Figures 40-43 show an alternative wafer 216 and associated wafer drive system which are similar to the wafer 116 and associated wafer drive system of Figures 31-39, so only the differences will be described. Equivalent features are given the same reference number, incremented by 100.

[0198] The wafer 216 has only two recesses 296 rather than three recesses 196, and the table has only two teeth 272, 273 on opposite sides of the table, rather than three teeth 171-173.

[0199] In a further embodiment (not shown) only a single recess may be provided (running around almost a full circle, or half a circle for example) along with only a single rotary drive tooth.

[0200] In the examples above, the (or each) rotary drive tooth is offset from an axis of rotation at the centre of the table. In another embodiment, the wafer may have a hexagonal recess which receives a hexagonal tooth protruding from the centre of the table. However this is less preferred because it requires the wafer to be loaded onto the platform in a particular orientation.

[0201] To sum up, the biological sample 180 is imaged by: loading the chamber 194 with a biological sample; loading the wafer 116 onto the platform; operating the focus drive system 174a, 174b to lift the table surface 170 into contact with the underside 198 of the wafer and insert each rotary drive tooth 171-173 into its respective recess 196; further operating the focus drive system 174a, 174b so that the table surface 170 lifts the wafer off the platform to move the biological sample 180 into the focal plane of the imaging system; operating the rotary drive system 174 to rotate the wafer 116 relative to the platform so that the wafer rotates between a series of orientations, each orientation bringing a different area of the wafer 116 into a field of view of the imaging system, wherein each rotary drive tooth 171-173 pushes one of the walls 197 of its respective recess and drives the rotation of the wafer; and for each orientation of the wafer, operating the imaging system to image the area of the biological sample 180 in the field of view of the imaging system.

Clauses

The following clauses set out further aspects of the present invention

1. A device for imaging a biological sample, the device comprising: a cartridge with a platform which is configured to enable a sample carrier with a biological sample to be loaded onto the platform; a casing configured to enable the cartridge to be inserted into the casing after the sample carrier has been loaded onto the platform; an imaging system with a focal plane; and a focus drive system configured to lift the sample carrier off the platform into the focal plane of the imaging system, wherein the focus drive system comprises three or more drive members, each drive member has a respective contact surface which is configured to contact an underside of the sample carrier in the casing, each contact surface has a respective centre, and the centres of the contact surfaces are non-collinear.

2. A device according to clause 1, wherein the focus drive system comprises a frame which carries the drive members; and one or more axial drive motors configured to lift the frame.

3. A device according to any preceding clause, wherein the cartridge further comprises an opening in the platform, and at least one of the drive members is configured to move into contact with an underside of the sample carrier through the opening in the platform.

4. A device according to clause 3, wherein the opening in the platform comprises a hole in the platform, or a recess in a side of the platform.

5. A device according to clause 3 or 4, wherein two or more of the drive members are configured to move into contact with an underside of the sample carrier through the opening in the platform.

6. A device according to any preceding clause, wherein the focus drive system has only three of said drive members.

7. A device according to any preceding clause, wherein the imaging system has a field of view, and the device further comprises a lateral cartridge drive system configured to move the cartridge within the casing so that the cartridge and the sample carrier move together between a series of lateral positions within the casing, each position bringing a different area of the sample carrier into the field of view of the imaging system, wherein the imaging system is configured to image an area of the biological sample in the field of view of the imaging system for each lateral position. A device according to clause 7, wherein the lateral cartridge drive system is configured to move the cartridge relative to the drive members, such that for each lateral position a different area of the underside of the sample carrier is contacted by the contact surfaces of the drive members. A device according to any preceding clause, wherein the cartridge further comprises a barrier at a periphery of the platform. A device according to clause 9, wherein the barrier extends away from the platform to a shoulder, and the cartridge is free of obstructions above the platform so that the sample carrier can be loaded onto the platform from above the platform. A device according to any preceding clause, wherein the cartridge is configured to enable a sample carrier with a non-circular periphery to be loaded onto the platform. A device according to any preceding clause, further comprising a sample carrier configured to be loaded with a biological sample and further configured to be loaded onto the platform. A device according to clause 12, wherein the sample carrier has a non-circular periphery. A device according to clause 12 or 13, wherein the sample carrier has an elongate shape and/or a rectangular periphery. A device according to any preceding clause, wherein the imaging system comprises a camera configured to acquire an image of the biological sample. A device according to any preceding clause, wherein the imaging system comprises a smartphone. A device according to any preceding clause, wherein the casing comprises a slot, and the casing is configured to enable the cartridge to be inserted into the casing via the slot. A device according to any preceding clause, further comprising a battery for powering the imaging system and/or the focus drive system. A device according to any preceding clause, wherein the device has a maximum dimension which is less than 50cm or less than 40cm or less than 30cm. A device according to any preceding clause, wherein the device has a weight less than 1kg, or less than 700g or less than 500g. 21. A device according to any preceding clause, further comprising a processor configured to analyse image or video data from the imaging system to automatically classify sample features.

22. A method of imaging a biological sample with the device of any preceding clause, the method comprising: loading a sample carrier with a biological sample; then loading the sample carrier onto the platform; then inserting the cartridge into the casing; operating the focus drive system to move the contact surfaces of the drive members into contact with an underside of the sample carrier and then lift the sample carrier off the platform to move the biological sample into the focal plane of the imaging system; operating the imaging system to image the biological sample; withdrawing the cartridge from the casing; and unloading the sample carrier from the platform.

23. A method according to clause 22, further comprising moving the cartridge and the sample carrier together between a series of lateral positions within the casing, each lateral position bringing a different area of the biological sample into a field of view of the imaging system; and for each lateral position of the sample carrier, operating the imaging system to image the area of the biological sample in the field of view of the imaging system.

24. A method according to clause 23, wherein for each lateral position of the sample carrier, the following sequence of steps is performed in order: (a) the focus drive system is operated to lift the sample carrier off the platform to move the biological sample into the focal plane of the imaging system; (b) the imaging system is operated to image the area of the biological sample in the field of view of the imaging system; and (c) the focus drive system is operated to lower the sample carrier back onto the platform.

25. A method according to any of clauses 22 to 24, wherein the imaging system generates image or video data, and the method further comprises analysing the image or video data to automatically classify features of the biological sample.

Clauses

The following clauses set out further aspects of the present invention

1. A wafer for holding a biological sample, the wafer comprising: a body with a circular periphery, an underside, and a recess in the underside of the body, wherein the recess comprises a pair of end walls, the recess extends along a circular arc, each end wall is positioned at a respective end of the circular arc, and at least part of the body is transparent; and a chamber in the body, wherein the chamber is configured to be loaded with a biological sample. A wafer according to clause 1, comprising two or more recesses in the underside of the body, wherein each recess comprises a pair of end walls, each recess extends along a circular arc, and each end wall is positioned at a respective end of the circular arc. A wafer according to any preceding clause, wherein the body of the wafer comprises a base and a transparent cover, the chamber is between the base and the cover, and the underside of the body is an underside of the base. A wafer according to clause 3, wherein the cover is attached to the base. A wafer according to clause 3, wherein the cover is attached to the base by adhesive, ultrasonic welding, or surface tension. A wafer according to any of clauses 3 to 5, wherein the cover and the base are integrally formed as a single piece. A wafer according to any preceding clause, wherein the chamber comprises an opening or inlet port at the circular periphery of the body. A device for imaging a biological sample, the device comprising: a wafer for holding a biological sample, the wafer comprising a body, an underside, and a recess in the underside of the body, wherein the recess comprises a pair of walls and at least part of the body is transparent; a platform configured to carry the wafer; an imaging system with a focal plane and a field of view; and a wafer drive system configured to rotate the wafer relative to the platform so that the wafer rotates between a series of orientations, each orientation bringing a different area of the wafer into a field of view of the imaging system, and further configured to lift the wafer off the platform into the focal plane of the imaging system, wherein the wafer drive system comprises: a table with a table surface; a rotary drive system configured to rotate the table; a rotary drive tooth protruding from the table surface; and a focus drive system configured to lift the table; wherein the rotary drive tooth is configured to be received in the recess, so that as the table is rotated by the rotary drive system, the rotary drive tooth pushes one of the walls of the recess and drives the rotation of the wafer; and wherein the table surface is configured to contact the underside of the wafer, so that as the table is lifted by the focus drive system, the table surface lifts the wafer off the platform. A device according to clause 8, wherein the wafer drive system comprises two or more rotary drive teeth protruding from the table surface; the wafer comprises two or more recesses in the underside of the wafer, wherein each recess comprises a pair of walls; and each rotary drive tooth is configured to be received in a respective one of the recesses, so that as the table is rotated by the rotary drive system, the rotary drive tooth pushes one of the walls of its respective recess and drives the rotation of the wafer. A device according to clause 8 or 9, wherein the (or each) recess extends along a circular arc; each wall of the (or each) recess is an end wall positioned at a respective end of the circular arc; and the (or each) rotary drive tooth is configured to move along the circular arc into contact with one of the end walls of the (or its respective) recess as the table is rotated by the rotary drive system. A device according to any of clauses 8 to 10, wherein the body of the wafer has a circular periphery. A device according to any of clauses 8 to 11, wherein the (or each) drive tooth is offset from an axis of rotation of the table. A device according to any of clauses 8 to 12, wherein the imaging system is configured to image an area of the biological sample in the field of view of the imaging system for each orientation of the wafer. A device according to any of clauses 8 to 13, wherein the device further comprises a casing, the platform is part of a cartridge in the casing, and the cartridge can be removed from the casing. A device according to any of clauses 8 to 14, further comprising a hole in the platform, wherein the table extends through the hole in the platform. A device according to any of clauses 8 to 15, wherein the imaging system comprises a camera configured to acquire an image of the biological sample. A device according to any of clauses 8 to 16, wherein the imaging system comprises a smartphone. A device according to any of clauses 8 to 17, wherein the device has a maximum dimension which is less than 50cm or less than 40cm or less than 30cm. A device according to any of clauses 8 to 18, wherein the device has a weight less than 1kg, or less than 700g or less than 500g. A device according to any of clauses 8 to 19, further comprising a processor configured to analyse image or video data from the imaging system to automatically classify sample features. A method of imaging a biological sample with the device of any of clauses 8 to 20, the method comprising: loading the wafer with a biological sample; loading the wafer onto the platform; operating the focus drive system to lift the table surface into contact with the underside of the wafer and insert the or each rotary drive tooth into its respective recess; further operating the focus drive system so that the table surface lifts the wafer off the platform to move the biological sample into the focal plane of the imaging system; operating the rotary drive system to rotate the wafer relative to the platform so that the wafer rotates between a series of orientations, each orientation bringing a different area of the wafer into a field of view of the imaging system, wherein each rotary drive tooth pushes one of the walls of its respective recess and drives the rotation of the wafer; and for each orientation of the wafer, operating the imaging system to image the area of the biological sample in the field of view of the imaging system. A method according to clause 21, wherein the imaging system generates image or video data, and the method further comprises analysing the image or video data to automatically classify features of the biological sample.

Claims

CLAIMS A device for imaging a biological sample, the device comprising: a sample carrier configured to be loaded with a biological sample; a cartridge comprising a platform and a barrier at a periphery of the platform, wherein the cartridge is free of obstructions above the platform so that the sample carrier can be loaded onto the platform from above the platform; a casing configured to enable the cartridge to be inserted into the casing after the sample carrier has been loaded onto the platform; an imaging system configured to image the biological sample in the casing, the imaging system having a focal plane; and a focus drive system configured to lift the sample carrier off the platform and into the focal plane of the imaging system. A device according to claim 1, wherein the barrier extends away from the platform to a shoulder. A device according to claim 2, wherein the shoulder defines a periphery of an opening above the platform, and the cartridge is configured to enable the sample carrier to be loaded onto the platform via the opening and unloaded from the platform via the opening. A device according to claim 2 or 3, wherein all or some of the shoulder lies in a plane which is parallel with the platform. A device according to any of claims 2 to 4, wherein the barrier comprises a side wall and a top wall, the side wall extends away from the platform to the shoulder, and the side wall meets the top wall at the shoulder. A device according to any preceding claim, wherein the barrier is configured to engage with an edge of the sample carrier in order to inhibit sliding between the platform and the sample carrier, A device according to any preceding claim, wherein the barrier comprises a plurality of barrier segments separated by openings. A device according to any preceding claim, wherein the barrier runs around a full circumference of the platform. A device according to any preceding claim, wherein the imaging system has a field of view, and the device further comprises a drive system configured to move the cartridge or the sample carrier within the casing so that the sample carrier moves between a series of positions or orientations, each position or orientation bringing a different area of the sample carrier into the field of view of the imaging system, and the imaging system is configured to image an area of the biological sample in the field of view of the imaging system for each position or orientation of the sample carrier. A device according to claim 9, wherein the sample carrier comprises a circular wafer, the barrier comprises a cylindrical wall, and the drive system comprises a rotary drive system configured to rotate the sample carrier relative to the cartridge so that the sample carrier rotates between a series of orientations, each orientation bringing a different area of the sample carrier into a field of view of the imaging system, and the imaging system is configured to image an area of the biological sample in the field of view of the imaging system for each orientation of the sample carrier. A device according to claim 9, wherein the drive system comprises a lateral cartridge drive system configured to move the cartridge within the casing so that the cartridge and the sample carrier move together between a series of lateral positions within the casing, each lateral position bringing a different area of the sample carrier into the field of view of the imaging system, and the imaging system is configured to image an area of the biological sample in the field of view of the imaging system for each lateral position. A device according to any preceding claim, wherein the imaging system comprises a camera configured to acquire an image of the biological sample. A device according to any preceding claim, wherein the imaging system comprises a smartphone. A device according to any preceding claim, wherein the cartridge is configured to enable the focus drive system to lift the sample carrier higher than the barrier. A device according to any preceding claim, wherein the cartridge further comprises an opening in the platform, and the focus drive system is configured to move into contact with an underside of the sample carrier through the opening in the platform. A device according to any preceding claim, wherein the casing comprises a slot, and the casing is configured to enable the cartridge to be inserted into the casing via the slot. A device according to any preceding claim, further comprising a battery for powering the imaging system. A device according to any preceding claim, wherein the device has a maximum dimension which is less than 50cm or less than 40cm or less than 30cm. A device according to any preceding claim, wherein the device has a weight less than 1kg, or less than 700g or less than 500g. A device according to any preceding claim, wherein the device comprises a processor configured to analyse image or video data to automatically classify sample features. A method of imaging a biological sample with the device of any preceding claim, the method comprising: loading the sample carrier with a biological sample; loading the sample carrier onto the platform from above the platform; inserting the cartridge into the casing; operating the focus drive system to lift the sample carrier off the platform and into the focal plane of the imaging system; operating the imaging system to image the biological sample; withdrawing the cartridge from the casing; and unloading the sample carrier from the platform. A method according to claim 21, wherein the sample carrier is loaded onto the platform by lowering the sample carrier into contact with the platform and/or by raising the platform into contact with the sample carrier. A method according to claim 21 or 22, wherein as the sample carrier is loaded onto the platform, a first end of the cartridge is inside the casing and a second end of the cartridge protrudes from the casing. A method according to any of claims 21 to 23, wherein the imaging system generates image or video data, and the method further comprises analysing the image or video data to automatically classify features of the biological sample. A method according to any of claims 21 to 24, wherein the focus drive system lifts the sample carrier higher than the barrier.