METHOD AND DEVICE FOR MICROSCOPY-BASED IMAGING OF SAMPLES

Abstract

A method for performing microscopy-based imaging of samples comprises: loading a sample holder (100) onto a support (50) configured to receive the sample holder (100); moving the sample holder (100) in a first direction, from a starting position on a first strip of the sample holder (100), to move the sample holder (100) relative to an imaging line of a line camera (10), to capture an image of the first strip of the sample holder (100); monitoring a focal plane using an autofocus system (15) as the sample holder (100) is moved in the first direction; in response to a signal from the autofocus system (15), moving an objective lens (25) along the optical axis to adjust the focal plane; and moving the sample holder (100) in a second direction, to align the imaging line of the line camera (10) with a position on a second strip of the sample holder (100).

Claims

1. An imaging device for microscopy-based imaging of samples comprising: a line camera; a support, configured to receive a sample holder; an objective lens received by a lens holder, wherein the lens holder is operable to move the objective lens along an optical axis; and an autofocus system, wherein the support is configured to move the sample holder in a first direction relative to an imaging line of the line camera to capture an image of a first strip of the sample holder, wherein the autofocus system is configured to determine a focal plane, and is configured to output a signal which causes the lens holder to translate the objective lens in order to adjust the focal plane, during movement of the sample holder in the first direction by the support, and wherein the support is configured to move the sample holder in a second direction to align the imaging line of the line camera with a position on a second strip of the sample holder, wherein the first direction is a straight line, and the second direction is a rotational direction.

2. The imaging device according to claim 1, wherein the device comprises a frame grabber configured to create an area image from a plurality of serially captured line images captured by the line camera.

3. The imaging device according to claim 1, wherein the autofocus system is a tracking autofocus system, and is configured to adjust the focal plane as the sample holder moves, and optionally, the autofocus system is configured to adjust the focal position at least every 0.5 ms.

4. The imaging device according to claim 1, wherein the autofocus system comprises an autofocus system light source, wherein the autofocus light source is an additional light source that is different from an illumination source and has a different wavelength from the wavelength of the illumination source.

5. The imaging device according to claim 1, wherein the light from the autofocus system light source is configured to pass through the objective lens, to be incident onto a bottom surface of the sample holder.

6. The imaging device according to claim 1, wherein a focal plane of the line camera is set at the same plane as the focal plane determined by the autofocus system.

7. An imaging device according to claim 1, wherein the line camera is mounted with a slight offset in the direction of the optical axis in order to place the focal plane of the line camera at a different level than the focal plane for the autofocus system, wherein optionally the line camera is offset by greater than 0 mm and less than 20 mm, for example by 15 mm, 10 mm, 5 mm, 2 mm or 1 mm.

8. An imaging device according to claim 1, wherein the device comprises a dichroic mirror, and optionally wherein the dichroic mirror is configured to be broadly transparent to light from an illumination source but to reflect light from the autofocus system, or is configured to be broadly transparent to light from the autofocus system but to reflect the light from an illumination source.

9. An imaging device according to claim 1, wherein the optical axis along which the lens holder is configured to move the objective lens is vertical and the objective lens is configured to be moved substantially vertically upwardly or downwardly.

10. An imaging device according to claim 1, wherein the line camera is configured to image the sample holder from below a plane at which the support is arranged to hold the sample holder.

11. An imaging device according to claim 1, wherein the line camera is mounted in a fixed position such that it does not move.

12. An imaging device according to claim 1, wherein the imaging device comprises an illumination source, wherein the illumination source is optionally monochromatic, or a narrow-band source, and/or wherein the illumination source is provided at a position above the support to illuminate the sample holder from above.

13. An imaging device according to claim 12, wherein the device comprises a condenser, for shaping the light beam emitted from the illumination source to provide substantially homogenous illumination at the position where the sample holder is imaged by the line camera.

14. An imaging device according to claim 1, wherein the device comprises a tube lens, for focusing a collimated beam coming out of the objective lens onto the line camera.

15. An imaging device according to claim 12, wherein the device comprises a narrow-band single band bandpass filter, wherein the central wavelength of the band is at approximately the central wavelength of the illumination source, and/or wherein the bandwidth of the bandpass filter is less than 200 nm, and is optionally approximately 100 nm, or less.

16. An imaging device according to claim 12, wherein the illumination source comprises a plurality of light sources; and/or wherein a diffuser is positioned between the illumination source and the sample holder.

17. An imaging device according to claim 1, wherein the support comprises a platform comprising a recessed region shaped to conform to the outer dimensions of the sample holder.

18. An imaging device according to claim 17, wherein the platform is provided on linear tracks attached to the support, allowing the platform to be linearly translated.

19. An imaging device according to claim 17, wherein the platform comprises a platform lid which is hingedly connected to the platform, and optionally wherein the platform lid is caused to move upwardly and downwardly, for example by engagement with a guide rail.

20. An imaging device according to claim 1, wherein the support comprises a drive wheel configured to rotate the sample holder about a vertical axis of the sample holder, wherein optionally, the drive wheel is located adjacent to the rim of the sample holder, to frictionally engage a rim of the sample holder, and/or wherein the drive wheel is configured so as to disengage from a rim of the sample holder to allow the sample holder to be removed from the support.

21. An imaging device according to claim 1, wherein the support comprises a detector, optionally a photodetector, configured to detect a single alignment structure which is present on the sample holder at a distance from the centre of the sample holder where no other structures are present, in order to determine an absolute rotational position of the sample holder, and optionally wherein the device is configured to carry out an adjustment to the rotational position by: positioning the imaging line in the outermost sample chamber of the first radial line; imaging the outermost sample chamber; carrying out image analysis, for example, comprising edge analysis to find the edges of the sample chamber; and rotating the sample holder until the midpoint of the imaged sample chamber is positioned on the optical axis.

22. A system for microscopy-based imaging of samples comprising the imaging device as claimed in claim 1, and a sample holder.

23. A system as claimed in claim 22, wherein the sample holder comprises a single sample chamber, or wherein the sample holder comprises a plurality of sample holders, for example up to 600 sample chambers, for example, 50 to 500 sample chambers, for example 80 to 400 sample chambers, for example 96 chambers, 336 chambers or 384 chambers.

24. A system as claimed in claim 22, wherein the sample holder comprises a plurality of sample chambers located along radial lines of the sample holder, wherein a single sample chamber is located along each radial line, or a plurality of sample chambers are located along each radial line.

25. A system as claimed in claim 22, wherein the sample holder comprises a plurality of sample chambers located along a plurality of concentric circles having different radii on the sample holder, wherein a single sample chamber is located along each coaxial circle, or a plurality of sample chambers are located along each coaxial circle.

26. A system as claimed in claim 22, wherein the sample holder comprises a plurality of sample chambers located along a plurality of parallel lines, wherein a single sample chamber is located along each parallel line, or a plurality of sample chambers are located along each parallel line.

27. A system as claimed in claim 22, wherein the sample holder comprises focus-checking structures, which are optionally pyramid-shaped or groove-shaped indentations, wherein optionally the focal structures are spaced to appear in every 10th line, every 50th line, or every 100th line, captured by the line camera.

28. A system as claimed in claim 22, wherein the sample chambers include a plurality of antimicrobial agents, each at a plurality of concentrations, for performing an AST analysis.

29. A system as claimed in claim 22, wherein the sample holder comprises samples, which include microscopic objects contained in a sample fluid.

30. A system as claimed in claim 29, wherein the samples include pathogens present in a microbiological growth medium for performing a broth microdilution assay.

Description

[0167] FIGS. 1A and 1B show systems for microscopy-based analysis of samples;

[0168] FIG. 2 shows a support for a sample holder which forms part of the system of FIG. 1A or FIG. 1B;

[0169] FIG. 3 shows a line camera, autofocus system, objective lens and tube lens, arranged as in the system of FIG. 1A;

[0170] FIG. 4 shows an exemplary sample holder which could be used in the system of FIG. 1A or FIG. 1B;

[0171] FIG. 5 illustrates a light beam directed at a focal structure (in this case, a pyramid indentation) on an exemplary sample holder and the resultant reflection and refraction of light rays;

[0172] FIG. 6A shows the light source incident on an optically active layer in a sample holder, and FIGS. 6B and 6C show modifications to the light source to counteract the effect of such an optically active layer;

[0173] FIG. 7 shows the movement of the sample holder where the sample holder comprises sample chambers following radial lines;

[0174] FIG. 8 shows the movement of the sample holder where the sample holder comprises sample chambers following concentric circles (each at a different radius); and

[0175] FIG. 9 shows the movement of the sample holder where the sample holder comprises sample chambers following parallel lines.

[0176] FIGS. 1A and 1B shows a system for microscopy-based analysis of samples. Each system comprises a device for microscopy-based analysis of samples comprising a line camera 10, a tracking autofocus system 15, a dichroic mirror 20, an objective lens 25, an illumination light source 30, a band-pass filter 31, a condenser 32, and a tube lens 40. The two systems in FIGS. 1A and 1B are very similar, the difference being that the locations of the line camera 10 (and tube lens 40) and autofocus system 15 are swapped.

[0177] In one example, the line camera 10 is a Linea LA-CM-16K05A (comprising a CMOS digital image sensor) manufactured by Teledyne DALSA, coupled with an XTIUM-CL MX4 frame grabber (not shown), also by Teledyne DALSA. The camera array size is 1×16,384 pixels, with each pixel being 3.5 μm×3.5 μm. The line width is therefore 3.5 μm, and its length is 57.7 mm. Only a portion of this length may be used, in practice (for example, fewer than half of the pixels may be used). The autofocus system 15 comprises a system from WDI WISE Device Inc., comprising the ATF6 SWIFT digital autofocus system (with laser wavelength of 785 nm) and an MCZ controller for controlling the position of the objective lens 25 in the z-direction. The objective lens 25 is a Nikon CFI Plan-fluor (10× magnification, NA 0.3). The dichroic mirror 20 is a 662 nm edge BrightLine single-edge imaging-flat dichroic beamsplitter manufactured by Semrock. The dichroic mirror 20 is held in a holder 21, which is shown in FIG. 3. The light source 30 comprises an LED light source Luxeon LXZ1-PX01 (with central wavelength of about 556-569 nm), a condenser 32, along with a 560/94 nm BrightLine® single-band bandpass filter 31, manufactured by Semrock. The tube lens 40 is an ITL200 tube lens, from Thorlabs, with a focal length of 200 mm. The condenser 32 produces an illuminated area in the plane of the bottom of the sample chamber at the imaging location of approximately 8×8 mm, with the central 5×5 mm area having an intensity variation less than approximately ±10%. The tube lens 40 focuses the collimated beam coming out of the objective lens 25 onto the line camera 10. The optical system comprising the tube lens 40 and the objective lens 25 in this example achieves a magnification of 10×.

[0178] The system further comprises a sample holder 100 comprising a plurality of sample chambers 116 (described in greater detail below, with reference to FIG. 4). As shown in FIG. 2, the sample holder 100 is received by a support 50 configured to receive the sample holder 100. The support 50 comprises a platform 52 comprising a recessed region 51 shaped to conform to the outer dimensions of the sample holder, such that, when placed within the recessed region, the sample holder cannot move laterally.

[0179] The platform 52 is provided on linear tracks 56a, 56b attached to the support, and a motor may be provided to drive the platform in either direction along the tracks. The motor (not shown) may drive movement of the platform along the tracks via a rack and pinion arrangement (not shown), for example.

[0180] The platform 52 comprises a platform lid 53 which, particularly during imaging, holds the sample holder 100 in a fixed position with respect to the vertical axis, i.e. such that the sample holder 100 does not move upwardly or downwardly.

[0181] The platform lid 53 is hingedly connected to the platform, so that it can pivot upwardly and away from the platform 52 about the hinged connection. In particular, the platform lid 53 is configured to move in this way when the platform 52 is translated to an extreme position at one end of the linear tracks 56a, 56b (to the far right, as shown in FIG. 2). This movement is the result of the platform lid 53 engaging with a guide rail (not shown), shaped so as to lift the platform lid 53 at the extreme position.

[0182] The sample holder 100 is loaded from above onto the support 50 (i.e. into the recessed region 51 of the platform 52) at the extreme position. In this position, the sample holder 100 rests within the recessed region 51 and is prevented from lateral movement by the recessed region 51. As the platform 52 moves from the extreme position, the platform lid 53 is guided down by the guide rail to press down on the sample holder 100, so that the sample holder 100 is prevented from movement upwardly by the downward force applied by the platform lid 53. That is, the platform lid 53 provides a vertical clamping function. The sample holder 100 is prevented from movement downwardly by being supported by the recessed region 51.

[0183] The support comprises a through-hole 54, below the plane at which the sample holder 100 is supported, which allows a portion of the sample holder 100 to be imaged by the line camera 10, from below.

[0184] In order to bring different radial lines of sample chambers 116 into line with the line camera 10 for imaging, the support 50 comprises a drive wheel 57 configured to rotate the sample holder 100 (about a vertical axis of the sample holder 100). When a sample holder 100 is held in the support 50, the drive wheel 57 is located adjacent to the rim of the sample holder 100, to frictionally engage the rim of the sample holder. The drive wheel 57 is pressed to the rim using a spring action. The drive wheel is driven by a second motor 55, via a drive belt (not shown).

[0185] The drive wheel 57 is configured to disengage from the rim of the sample holder 100 (i.e. the spring action pressing the drive wheel 57 to the rim of the sample holder 100 is relaxed) when the platform 52 is translated to the extreme position at the right-hand end (as shown in FIG. 2) of the linear tracks 56a, 56b. The drive wheel 57 is configured to engage with the rim of the sample holder 100 when the platform 52 is translated away from the extreme position. The drive wheel is configured to rotate the sample holder 100 at a speed of approximately 30° per second.

[0186] The support 50 is configured to align the sample holder 100 in a specific position such that the starting position for the imaging is known. The support 50 comprises a dedicated detector (for example, a photodetector, not shown) configured to detect a single alignment structure which is present on the sample holder 100 at a distance from the centre of the sample holder 100 where no other structures are present. This structure defines the absolute position, and then a predetermined offset gives the rotational position of the starting imaging position. The sets the rotational position of the sample holder to within ±500 μm, as measured at the outermost sample chamber. A fine positioning procedure is then done, by translating the platform 52 to position the imaging line in the outermost sample chamber of the first radial line, and imaging the sample chamber. Based on image analysis (for example, comprising edge analysis to find the edges of the sample chamber), the sample holder is rotated until the midpoint of the sample chamber is positioned on the optical axis. This sets the starting position for the imaging to within ±50 μm.

[0187] In the use of the device, the sample holder 100 is provided with appropriate samples in sample chambers 116 and images of the samples are gathered using the line camera 10.

[0188] Referring to FIG. 1A again, in use, light from the illumination source 30 is incident onto the sample holder 100 from above (via the band-pass filter 31 and condenser 32). The light passes through the sample chambers 116 of the sample holder 100, and is collected by the objective lens 25. After passing through the objective lens 25, the light reflects from the dichroic mirror 20, passes through the tube lens 40, and is then imaged by the line camera 10.

[0189] Similarly, in the system shown in FIG. 1B, in use, light from the illumination source 30 is incident onto the sample holder 100 from above (via the band-pass filter 31 and condenser 32). The light passes through the sample chambers 116 of the sample holder 100, and is collected by the objective lens 25. After passing through the objective lens 25, the light passes through the dichroic mirror 20, passes through the tube lens 40, and is then imaged by the line camera 10.

[0190] The sample holder 100 is moved in a first linear direction (by translating the platform 52) in the horizontal plane, such that the imaging line of the line camera 10 successively images different lines perpendicular to the radial line along which the sample chambers 116 are distributed.

[0191] The speed at which the sample holder is translated is, in this example, matched to the imaging rate (line rate) of the line camera, such that the resultant image is not distorted. The speed s of the linear movement of the sample holder is given by:

[00002]$s=\frac{\mathrm{pixel}\mathrm{width}\times \mathrm{line}\mathrm{camera}\mathrm{imaging}\mathrm{rate}}{\mathrm{magnification}}$

[0192] Here, the pixel width is 3.5 μm, the line camera imaging rate is 48 kHz and the magnification is 10×. This gives a speed s of 16.8 mm/s. This allows imaging of 50 radial lines, each of 50 mm length, within 6 minutes (including the time taken for rotation to each new radial line, and data transfers). A sample holder comprising 384 sample chambers can be fully scanned in 7 minutes. The total analysis time per sample chamber, including movement to the sample chamber, adjusting the focal plane during imaging, and acquiring images within the sample chamber is less than 2 seconds.

[0193] Following the completion of the translational movement of the sample holder 100, the sample holder is rotated by the support 50 (using the drive wheel 57) in order to bring another radial line of sample chambers 116 into alignment with the imaging line of the line camera 10. The sample holder 100 is then translated in a linear direction in the opposite direction to the first linear direction, to image the second radial line of sample chambers.

[0194] As mentioned, the system comprises an autofocus system 15. The relative positions of the line camera 10, autofocus system 15, objective lens 25, dichroic mirror 20 (not shown in FIG. 3, but its holder 21 is shown) and tube lens 40 (in a system similar to that shown in FIG. 1A) are shown in FIG. 3.

[0195] The autofocus system 15 comprises a laser light source (not shown) with wavelength of 785 nm. The laser light 15a passes through the dichroic mirror 20 and the objective lens 25 (in the opposite direction to the light gathered by the objective lens 25 from the sample chambers 116), to be incident onto a bottom surface of the sample holder 100. The autofocus system 15 sets the focal plane at the bottom surface of the sample chambers 116 in the sample holder. The focal plane of the line camera may be set at a predetermined upward offset therefrom (such that the focal plane lies at a plane within the sample chamber 116, above and parallel to the bottom surface of the sample chamber 116), by offsetting the line camera 10 along the optical axis (by between 0 mm and 20 mm).

[0196] The autofocus system 15 can adjust the focal position (if necessary) every 0.15 ms. This allows the autofocus system 15 to recheck the focal position approximately every 7 lines read by the line camera 10 (which has an imaging rate of 48 kHz). If the focal position needs to be adjusted, the autofocus system 15 outputs a signal which causes the lens holder 26 (see FIG. 3) to translate the objective lens 25 in order to adjust the focal plane. The lens holder 26 translates the objective lens 25 along an axis perpendicular to a plane of the support 50, with a precision of 1 μm. Movement of the lens holder 26 is driven by a linear actuator (not shown). To image a single sample chamber 116, the line camera 10 may capture thousands of lines (for example, between 10,000 and 15,000), and so the focal plane may be adjusted by the autofocus system 15 hundreds or thousands of times, across each sample chamber 116. Any non-uniformity in the base of the sample chamber 116 can therefore be accounted for in the imaging process.

[0197] As a radial line of sample chambers 116 is imaged by the line camera 10, a composite image comprising the plurality of imaged lines is built up. The composite image obtained by the line camera 10 includes all of the sample chambers 116 along the radial line. This composite image may be processed by an image processing algorithm to split the composite into separate image areas, each including one sample chamber 116, for example.

[0198] An image analysis system may receive the images taken by the system, and may carry out further image analysis, for example to determine the presence, absence, or amount of microscopic objects and/or to determine the type of microscopic objects (for example, as disclosed in Q-Linea AB's application PCT/EP2017/064713 (WO 2017/216312 A1)).

[0199] An exemplary sample holder 100 which is suitable for use with the device is now described in greater detail, with reference to FIG. 4. As seen in this figure, the exemplary sample holder 100 comprises three layers. A first, optically flat, layer 110 forms a base layer. A second layer 114 is placed on top of the first layer 110 and is formed with volumes (holes) forming sample chambers 116 for holding sample fluids. The sample chambers 116 are connected via channels 118. There are multiple channels 118 each with their own sample chambers 116. The first layer 110 closes the bottoms of the sample chambers 116. A third layer 120 covers the tops of the sample chambers 116 and the channels 118. The third layer 120 includes openings 122 at one end of each of the channels 118 to allow for dispensing of sample fluid(s) into each channel 118, and then along the channels 118 to fill all of the sample chambers 116. The third layer 120 also includes vents 124 at the other ends of each of the channels 118 to allow for gas to leave the channels 118 as they are filled with the sample fluid(s). The vents 124 and optionally also the openings 122 may be covered by a gas permeable membrane. At the end of each channel 118 is a reservoir 128 for any excess of the sample fluid.

[0200] All of the layers 110, 114, 120 have a central hole 126 that is used during loading of the sample holder 100 into the device for microscopy-based imaging of the samples.

[0201] The channels 118 extend outward from the centre of the sample holder 100 toward the outer circumference, and they are spaced about along radial lines.

[0202] The first layer 110 and the third layer 120 are transparent to light in the wavelengths used for imaging the samples and are typically transparent to visible light. The second layer 114 need not be transparent, although it may be.

[0203] In case of use in a fluorescent analysis, the first layer 110, second layer 114, and third layer 120 should be non-fluorescent in the relevant wavelength region (for example, 450-700 nm).

[0204] Focus-checking structures 112 (for example, pyramid-shaped indentations or grooves), may be provided in the first layer 110—such a focus-checking structure 112 is shown in FIG. 5. Such structures are described in Q-Linea AB's application PCT/EP2017/064715 (WO 2017/216314 A1)). The focus-checking structures may be provided in the bottom of each sample chamber 116, at the end of each channel 118, adjacent each sample chamber 116 or adjacent each channel 118. In another arrangement, each channel 118 may have a plurality of associated focal structures 112 spaced at set distances from the centre of the sample holder 110, such that the focal structures 112 lie along concentric circles centred on the centre of the sample holder 100. The focal structures 112 may be provided between adjacent sample chambers 116, spaced inwardly of the outer width of the sample chambers 116. The focal structures 112 may be spaced to appear in every 10th line, every 50th line, or every 100th line, captured by the line camera.

[0205] As shown in FIG. 5, a collimated light beam perpendicular to the flat surface of the first layer 110 gives rise to total internal reflection on the sidewalls of the focus checking structure 112. In the case of a less than perfectly collimated beam, the reflection may not be total, but it is still sufficient for contrast detection as detailed below. As a result of the (total) internal reflection, when viewed from the top, the majority of the area of the focus-checking structure 112 appears dark. If the line camera 10 is focused exactly on the base of the focus-checking structure 112, where the sidewalls meet and form the point of the pyramid indentation, then a bright spot appears. The contrast between this bright spot and the darker area of the surrounding part of the pyramid changes rapidly with changing focal plane.

[0206] As explained above, as the line of sample chambers 116 is imaged by the line camera 10, a composite image comprising the plurality of imaged lines is built up. The composite image obtained by the line camera 10 includes all of the sample chambers 116 and focal structures 112 along the channel 118. This composite image may be processed by an image processing algorithm to split the composite into separate image areas, each including a sample chamber and at least one focal structure 112. In one example, the focal structure 112 associated with a given sample chamber 116 comprises two pyramid indentations at each end of the sample chamber 116. In another example, there is a focal structure 112 comprising four pyramid indentations 30 at the end of each sample chamber 116. In each case the geometry (i.e. layout of the pyramid indentations) may be the same, but the subsequent association of a focal structure 112 with a sample chamber 116 in the imaging processing is different.

[0207] An image analysis system may check the images to determine if they are in focus by identifying the focal structures 112 and checking whether or not they are in focus (as described for example in Q-Linea AB's application PCT/EP2017/064711 (WO 2017/216310 A1)). If any of the images are not in focus then an indication can be given to the user and/or remedial action can be taken.

[0208] Referring to FIGS. 6A to 6C, in some embodiments, the third layer 120 of the sample holder 100 may be optically active, and causes non-uniformity in the light incident onto the sample chambers. In particular, the optically active layer may comprise structures that refract or block light so that the illumination intensity as perceived over the imaged areas is not even, but shows variations dependent on the shape of the third layer 120. Such variations may be detrimental to the image, and subsequent image processing. To counteract this, a diffuser 60 may be positioned between the illumination source 30 and the third layer 120 of the sample holder 100 (as shown in FIG. 6B). The diffuser may be an optical diffuser which diffuses the light evenly, or it may be an engineered diffuser comprising an engineered surface having structures designed to cancel out the light intensity variations caused by the optically active part of the sample holder. Alternatively, a plurality of light sources 30′ may be provided (as shown in FIG. 6C), positioned to provide different path lengths for illumination of the sample chambers. The diffuser 60 or plurality of light sources 30′ act to provide a more even illumination to the sample chambers.

[0209] In the foregoing description, the sample holder 100 comprises sample chambers aligned along radial lines. The movement of such a sample holder (in order to image the sample chambers) is shown in more detail in FIG. 7.

[0210] The sample chambers (not shown in FIG. 7) on the sample holder are distributed along strips S.sub.1, S.sub.2 and S.sub.3, broadly following radial lines L.sub.1, L.sub.2 and L.sub.3. The strips are defined by the line camera active line length W (number of pixels used×pixel length—the line camera active line length may be smaller than the maximum line length, because the number of pixels used may be fewer than the total number of pixels) divided by the magnification M, and the path the imaging line takes over the sample holder (as a result of movement of the sample holder relative to the imaging line). There may be a plurality of sample chambers along each strip S.sub.1, S.sub.2, S.sub.3 or there may be one long sample chamber per strip. Alternatively, there may be just one sample chamber, imaged in a plurality of strips S.sub.1, S.sub.2, S.sub.3. In FIG. 7, the strips are shown as not overlapping, but in other embodiments they may overlap (or abut, without significant overlap).

[0211] In FIG. 7, the support translates the sample holder linearly in a first direction T.sub.1 (by translating the platform 52), which moves the sample holder such that the first strip S.sub.1 moves across the imaging line from a radially outward position towards the centre of the sample holder. The first strip S.sub.1 is imaged as the strip is translated over the imaging line. When sample holder is positioned such that the imaging line is at the radially inward end of the first strip S.sub.1, the sample holder is rotated using the drive wheel 57 (in direction R.sub.1, which in this case is clockwise) to bring the radially inward imaging position of the second strip S.sub.2 into alignment with the imaging line of the line camera. The support then translates the sample holder linearly in a second direction T.sub.2, (the opposite direction from T.sub.1) by translating the platform 52 which in this case moves the second strip S.sub.2 across the imaging line from a radially inward position towards the outer edge of the sample holder. The second strip S.sub.2 is thus imaged. When the sample holder is positioned such that the imaging line is positioned at the radially outward end of the first strip S.sub.2, the sample holder is rotated (in direction R.sub.1, using the drive wheel 57) to bring the radially outward imaging position on the third strip S.sub.3 into position above the imaging line. The support then translates the sample holder linearly in the first direction T.sub.1 by translating the platform 52, for imaging of the third strip S.sub.3.

[0212] In alternative embodiments, the sample holder comprises sample chambers aligned along concentric circles (positioned at different radii). The movement of the sample holder in order to image the sample chambers is shown in more detail in FIG. 8.

[0213] The sample chambers (not shown in FIG. 8) on the sample holder are distributed along strips S.sub.1′ and S.sub.2′, broadly following concentric circles lines L.sub.1′ and L.sub.2′. The strips are defined by the line camera active line length W (number of pixels used×pixel length) divided by the magnification, and the path the imaging line takes over the sample holder (as a result of movement of the sample holder relative to the imaging line). There may be a plurality of sample chambers along each strip S.sub.1′, S.sub.2′ or there may be one long sample chamber per strip. Alternatively, there may be just one sample chamber on the sample holder, imaged in a plurality of strips S.sub.1′, S.sub.2. In FIG. 8, the strips are shown as not overlapping, but in other embodiments they may overlap (or abut, without any significant overlap).

[0214] In FIG. 8, the support rotates the sample holder in a first direction R.sub.1′ (which in this case is clockwise) using the drive wheel 57, which moves the sample holder such that the first strip S.sub.1′ moves across the imaging line. The first strip S.sub.1′ is imaged as the strip is moved over the imaging line. When the sample holder is positioned such that the imaging line returns to the initial position on the first strip S.sub.1′ (i.e. when the sample holder has been rotated by 360°), the sample holder is translated linearly in direction T.sub.1′ by translating the platform 52, which in this case causes the imaging line to be positioned at a radially outward position, such that a position of the second strip S.sub.2′ is brought into alignment with the imaging line of the line camera. The support then rotates the sample holder using the drive wheel in the first direction R.sub.1′ (although the support could instead rotate the sample holder in the opposite direction, i.e. anti-clockwise), which moves the sample holder such that the second strip S.sub.2′ moves across the imaging line. The first strip S.sub.2′ is imaged as the strip is moved over the imaging line.

[0215] In alternative embodiments, the sample holder comprises sample chambers aligned along parallel lines. The movement of the sample holder in order to image the sample chambers is shown in more detail in FIG. 9.

[0216] The sample chambers (not shown in FIG. 9) on the sample holder are distributed along strips S.sub.1″, S.sub.2″ and S.sub.3″, broadly following parallel lines L.sub.1″, L.sub.2″ and L.sub.3″. The strips are defined by the line camera active line length W (number of pixels used×pixel length) divided by the magnification M, and the path the imaging line takes over the sample holder (as a result of movement of the sample holder relative to the imaging line). There may be a plurality of sample chambers along each strip S.sub.1″, S.sub.2″, S.sub.3″ or there may be one long sample chamber per strip. Alternatively, there may be just one sample chamber on the sample holder, imaged in a plurality of strips S.sub.1″, S.sub.2″, S.sub.3″. In FIG. 9, the strips are shown as not overlapping, but in other embodiments they may overlap (or abut, without any significant overlap).

[0217] In FIG. 9, the support translates the sample holder linearly in a first direction T.sub.1 by translating the platform 52, which moves the sample holder such that the first strip S.sub.1 moves across the imaging line. The first strip S.sub.1 is imaged as the strip is translated over the imaging line. When the sample holder is positioned such that the imaging line is at a far end of the first strip S.sub.1, the support then translates the sample holder by translating the platform 52 linearly in a second direction T.sub.2″, (at an angle to T.sub.1″, and in this case perpendicular to T.sub.1″) to bring an end of the second strip S.sub.2″ into alignment with the imaging line of the line camera. The support translates the sample holder linearly in a third direction T.sub.3″ (opposite to T.sub.1″) by translating the platform 52, which moves the sample holder such that the first strip S.sub.2 moves across the imaging line. When the sample holder is positioned such that the imaging line is at a far end of the second strip S.sub.2″, the support then translates the sample holder linearly in the second direction T.sub.2 again (by translating the platform 52), to bring an end of the third strip S.sub.3″ into alignment with the imaging line of the line camera. The support then translates the sample holder linearly in the first direction T.sub.1″ again (by translating the platform 52), which moves the sample holder such that the third strip S.sub.3″ moves across the imaging line.

[0218] Where the sample holder comprises sample chambers aligned along parallel lines, there is no need for the drive wheel 57 in the system described in FIGS. 1A and 1B, 2 and 3. In that case, the platform 52 may be provided on additional linear tracks attached to the support, which are at an angle to, for example perpendicular to, the tracks 56a, 56b shown in FIG. 2. Movement along these tracks may be driven by the same motor which drives the motion along the first linear tracks 56a, 56b, or by a different motor.