WO2008117031A1

WO2008117031A1 - Test plate reader

Info

Publication number: WO2008117031A1
Application number: PCT/GB2008/001001
Authority: WO
Inventors: Darren Peter Frost; Allin David Winter
Original assignee: Trek Diagnostic Systems Limited
Priority date: 2007-03-23
Filing date: 2008-03-20
Publication date: 2008-10-02
Also published as: GB0705652D0; WO2008117031A8

Abstract

A microorganism test plate reader (10) comprising a light source (40) arranged to provide diffuse illumination of a test plate (20), and a camera (70) arranged to capture an image of the test plate (20) under diffuse illumination.

Description

TEST PLATE READER

Field of the Invention

The present invention relates generally to a test plate reader and in particular a microorganism test plate reader.

Background of the Invention

Microorganisms may be grown in the laboratory on a test plate for clinical, research or other purposes.

EP0454784 describes such test plates and their use. A typical test plate may comprise 96 wells and standard dimensions of such test plates are 137 mm x 106 mm for large plates or 127 mm x 86 mm for small plates. Typically, a technician will inoculate each test well, incubate the test plate and determine which particular test wells react in a pre-specified manner within a particular time window. After visual analysis the plate is usually discarded. GB2390155 describes a system for measuring fluorescence and luminescence from a microtitre well plate. Instead of a visual assessment the luminescence of each test well is measured. However, such a system only works for tests which exhibit a fluorescence or luminescence response. As each test plate must be analysed by an experienced technician there is a limit to rate at which tests may be carried out by a particular laboratory. Furthermore, the experience of each individual technician may contribute to the accuracy of individual test results with less experienced technicians making more mistakes. In a clinical environment this may lead to diagnostic or other errors. Furthermore, the conditions under which each test plate are analysed may vary between technicians, test plates and/or laboratories leading to even more inconsistent results.

Therefore, there is required a way of reading microorganism test plates that overcomes the above drawbacks .

Summary of the Invention

The present invention provides an apparatus for capturing an image of a micro-organism test plate under diffuse light conditions. A camera captures the image, which may be stored for later retrieval . The camera captures an image of substantially all of the cells at once. The illumination conditions may be adjusted depending on the test plate type and particular test carried out. Also the illumination conditions may be repeatable so that each similar test plate has its image captured under substantially similar conditions, therefore, reducing variability and improving the repeatability of the tests. The image may be viewed in real time or stored for later retrieval or verification of a test result. The camera capture technique is suitable for tests that do not exhibit a fluorescence response.

Preferably the illumination may be from the side of a test plate providing indirect illumination.

Optionally, the illumination may be from above a test plate.

Optionally the test plates, which are typically transparent or translucent, may be illuminated from behind, i.e. backlit, thereby improving contrast when an image is captured by the camera. A combination of the two illumination techniques may also be used with each type of illumination being variable and adjustable in discrete steps. The illumination conditions may be set in advance for a particular type of test plate or test such the accuracy of the results may be maximised. The backlit illumination option allows improved image capture for samples not suitable for diffuse illumination only.

Optionally, a combination of the two types of illumination may provide further improved image capture for still other sample types .

The apparatus may be enclosed within an enclosure to keep out stray light that may otherwise interfere with the image capture. The enclosure may also include openings or panels to enable the interior of the enclosure to be accessed or cleaned.

Optionally, the camera may be located such that debris from the test plate does not fall on to it. In use the test plate may have a mirror placed underneath it, which directs the image onto the camera located in a separate part of the enclosure, preferably above and/or to the side of the test plate under investigation. The mirror also has the advantage of extending the working distant of the camera, which minimises distortion including parallax aberrations.

Preferably the microorganism test plate reader further comprises an interface for interfacing with a computer. The computer may capture an image of a test plate recorded by the camera via this interface.

Optionally, the computer may process the image to highlight each test well within the test plate. This allows a technician to more easily identify each test well within the test plate. More preferably, a grid may be applied to the image to separate the test wells.

Optionally, characters such as letters or numbers, for instance, may be applied to the test plate image to further assist in identifying each test well. The image may be stored with or without the additional highlighting features .

Advantageously, image manipulation may be carried out using software within the computer, which may be a desktop or laptop computer such as a PC or Apple Mclntosh, for instance.

According to a further aspect of the present invention there is provided a method of analysing a microorganism test plate comprising the steps of capturing an image of the microorganism test plate, and highlighting within the image test wells within the microorganism test plate. Either all or a subset of the wells may be highlighted. The highlighting may be by applying an overlay to the test plate image or applying characters to test wells within the test plate image. The highlighting may be carried out within a computer system and the image may be stored on a permanent storage.

Brief description of the Figures

The present invention may be put into practice in a number of ways and an embodiment will now be described by way of example only and with reference to the accompanying drawings, in which:

Fig. 1 shows a side view of a microorganism test plate reader according to an embodiment of the invention, given by way of example;

Fig. 2 shows a perspective view of the microorganism test plate reading of Fig. 1; and Fig. 3 shows a schematic diagram of a system including the microorganism test plate reader of Figs . 1 and 2 further including a personal computer.

It should be noted that the figures are illustrated for simplicity and are not necessarily drawn to scale.

Detailed description of an embodiment

Fig. 1 shows a side view of a microorganism test plate reader 10 according to an embodiment of the present invention. The components of the microorganism test plate reader 10 are housed within enclosure 80, which provides a substantially light tight environment. Furthermore, the enclosure may be made from a material suitable to be easily cleaned by wiping down. Such a feature is important in the laboratory environment when spills often occur.

The microorganism test plate reader 10 is shown together with a test plate 20 mounted on a test plate holder 30. The test plates 20 themselves may be single use disposable test plates such as the Trek H511A plate. Test plate holder 30 is removable from the interior of the enclosure 80 and acts as a light tight drawer moving in a direction indicated by arrow 100 to introduce the test plate 20 into the enclosure 80. Fig. 1 shows the test plate holder 30 in the exposed or open position. The test plate holder 30 slides on runners acting on wheels 110. The test plate holder may be manually moved or alternative electrically driven, the controls of which are not shown in the figures.

The test plate holder 30 supports the test plate 20 around its periphery such that the test wells are exposed from below as shown in Fig. 1. Locator pins 35 on the test plate holder 30 locate the test plate 20 in a repeatable position and stop the test plate 20 from moving relative to the test plate holder 30. The test plate 20 may be made from transparent or translucent plastics material. Therefore, the contents of each test well may be viewed from below even when supported within the enclosure 80 by the test plate holder 30.

The test plate holder 30 may be easily modified to accommodate other test plates. For instance, the locator pins 35 may be moved for different sized plates.

Fig. 2 shows a perspective view of the microorganism test plate reader 10 in which individual test wells 200 are shown on test plate 20.

Within the enclosure 80 the test plate 20 may be illuminated by four flat edge-illuminated side panels 40. The side panels 40 are located above the test plate holder 30 and around the periphery of the test plate 20 when located within the test plate holder 30. The side panels 40 provide a diffuse, indirect or surround type lighting of the test plate 20. The side panels 40 may also direct light into the edge of the test plate 20, which due to the translucent or transparent nature of the test plate provides further diffuse or even illumination of each test well by scattering the light or by internal reflections. As the side panels 40 provide indirect lighting the background of the test plate 20, when viewed from below appears dark thereby improving contrast. This side illumination reduces glare and further improves readability of the test plate 20. Furthermore, side illumination is particularly useful for low density samples where greater visual contrast is required.

A second, backlight source 50 is provided across the top of the test plate 20 when located within the enclosure 80. Again, this backlight 50 may be a flat, edge- illuminated panel such as those used to illuminate PDA displays. This backlight 50 provides an even, near-white field which acts both as a source of illumination and as a white background. A neutral density filter may be applied to the underside (or side facing the test plate) of the backlight 50 in order to improve contrast when the test plate 20 is illuminated by the side panels 40 in isolation. Controls 90 independently control the light produced by side panels 40 and the backlight 50. Illumination may be provide by either light source or a combination of both. Controls 90 may be graduated in discreet steps (for instance 0 to 10) to facilitate repeatability of the light setting. Controls 90 may be rotary type controls, for instance. Power for each light may be provided by an external supply connected through the enclosure 80 or by an internal power supply. The power supply may be a low voltage supply such as 12 VDC.

Because the lighting can be accurately and repeatably controlled, eye strain of a laboratory technician reading the test plate 20 may be reduced. Furthermore, as the technician does not need to hold the test plate 20 when viewing the results other physical strains such as shoulder repetitive strain injuries may be minimised. This is particularly important when a high rate of testing is carried out as typical in a clinical environment.

Mirror 60 directs an image of the underside of the test plate 20 onto camera 70. As the camera is not located directly under the test plate contamination or debris entering the camera is minimised. Furthermore, the inclusion of mirror 60 allows an increase in the working distance of the camera 70 (without requiring a larger enclosure 80) reducing parallax type distortions in the captured images especially at the extremities of the test plate 20 under investigation. Such distortions may be further reduced by introducing a lens in front of the camera 70. Port or openings 210, 220 in the enclosure 80 may be provided to clean or replace the mirror 60. The mirror 60 may be flat or curved (concave or convex or aspheric) to assist in focussing the image or for compensating for distortions .

The camera 70 may be a web-cam type 1.3 Mega pixel (or higher) CCD camera, with a pinhole or lens focussing element, for instance. The camera may be secured to the enclosure 80 by a suitable bracket. The CCD may be for instance, a 1/3" or 2/3" with an 18mm focal length and may include a "C" or "CS" lens mount. The working distance of the camera 70 may be about 300mm.

Fig. 2 shows various access panels or ports 210, 220 used to access the interior of the microorganism plate reader 10 for cleaning or other maintenance.

Fig. 3 shows a schematic diagram of a system comprising the microorganism plate reader 10 and a personal computer

300. The personal computer 300 may be an IBM compatible x86 PC running Windows 2000, XP, Vista (RTM) or later. The camera 70 may be interfaced to the personal computer 300 by a universal serial bus (USB) 305 in a way familiar to those skilled in the art. USB 2.0 may be used to allow a higher bandwidth interface decreasing image capture time. Either a cable 307 or wireless connection may be used to interface the microorganism plate reader 10 with the personal computer 300. The camera driver software may include an API to interface with image manipulation software on the personal computer 300. Once the personal computer 300 captures an image of the test plate 20 it may displayed on display 310. The personal computer 300 includes software to manipulate the image. In particular, the individual test wells (or a subset of them) may be highlighted on the image. For example, a grid 330 may be overlaid on top of the test plate image 320 or alphanumeric characters may be placed next to each test well or both as shown in Pig. 3. A further benefit of the personal computer 300 is that the camera image 320 may be stored for later retrieval on a disk drive or other suitable medium. This is important considering the limited window within that a test plate 20 is valid for. If for instance, a hospital doctor or laboratory supervisor disputed a result he may retrieve the stored image at any later time even after the test plate 20 had been destroyed. Furthermore, he may view the test plate under more optimal lighting conditions .

As will be appreciated by the skilled person, details of the above embodiment may be varied without departing from the scope of the present invention, as defined by the appended claims .

For example, the personal computer 300 may be interfaced to the microorganism plate reader 10 and as well as controlling the camera, also controls the illumination 40, 50 rather than the manual controls 90. Furthermore, the personal computer 300 may also control the electrically operable test plate holder 30 if present. In this way, an entire test analysis may be controlled by the personal computer 300 facilitating automated or semi-automated control.

In an alternative embodiment the camera 70 may view the test plate 20 from above or from the side of the test plate having open test wells 200. This embodiment may or may not require a mirror.

Other side-illumination configurations may be used. Although four side illuminating panels 40 are shown any number may be used, for instance two panels or a single panel. Furthermore, the four panels may be combined to form a single surrounding light source. The side-illumination may also be provided in the plane of the test plate 20 or simply as a strip around the periphery of the test plate. A subset of cells of a test plate may be imaged rather than substantially the entire test plate.

Claims

CLAIMS :

1. A microorganism test plate reader comprising: a light source arranged to provide diffuse illumination of a test plate; and a camera arranged to capture an image of the test plate.

2. The microorganism test plate reader of claim 1, wherein the light source provides side illumination of the test plate.

3. The microorganism test plate reader of claim 1 or claim 2, wherein the intensity of the light source may be varied.

4. The microorganism test plate reader according to any previous claim, wherein the intensity of the light source is variable in discreet steps.

5. The microorganism test plate reader according to any previous claim further comprising: a backlight arranged to transmit light through a test plate and into the camera.

6. The microorganism test plate reader of claim 5, wherein the intensity of the backlight is variable.

7. The microorganism test plate reader according claim 5 or claim 6, wherein the intensities of the backlight and the light source are independently variable.

8. The microorganism test plate reader according to any of claims 5-7, wherein the intensity of the backlight is variable in discreet steps.

9. The microorganism test plate reader according to any previous claim, wherein the light source is an edge- illuminated panel.

10. The microorganism test plate reader according to any previous claim, wherein the light source is an LED.

11. The microorganism test plate reader according to any previous claim, wherein the camera is a CCD.

12. The microorganism test plate reader according to any previous claim further comprising an enclosure.

13. The microorganism test plate reader of claim 12, wherein the enclosure is light tight.

14. The microorganism test plate reader according to any previous claim, wherein the camera is arranged to capture an image of the underside of a test plate.

15. The microorganism test plate reader according to any previous claim further comprising a mirror arranged to direct an image of the test plate onto the camera.

16. The microorganism test plate reader according to any previous claim, wherein the camera is located remote from the test plate such that debris from the test plate does not fall on the camera.

17. The microorganism test plate reader according to any- previous claim further comprising a test plate support.

18. The microorganism test plate reader of claim 17, wherein the test plate support is removable.

19. The microorganism test plate reader according to any previous claim, wherein the camera further comprises a parallax compensating lens.

20. The microorganism test plate reader according to any previous claim, further comprising an interface for connecting the camera to a computer.

21. The microorganism test plate reader of claim 20, wherein the interface is a Universal Serial Bus, USB.

22. The microorganism test plate reader according to any previous claim, further comprising a computer arranged to capture an image from the camera.

23. The microorganism test plate reader of claim 22, wherein the computer is arranged to highlight individual test wells of the test plate within the image of the test plate.

24. The microorganism test plate reader of claim 22, wherein the individual test wells are highlighted with a grid overlaid on the image .

25. The microorganism test plate reader according to any of claims 22-24, wherein the computer is arranged to apply to the image a character reference for test wells of the test plate within the image of the test plate.

26. The microorganism test plate reader according to any of claims 22-25 further comprising a computer display arranged to display the image.

27. A method of analysing a microorganism test plate comprising the steps of: capturing an image of the microorganism test plate; and highlighting within the image each test well within the microorganism test plate.

28. A method of analysing a microorganism test plate comprising the steps of: adjusting the illumination of a test plate; and capturing an image of the test plate under the adjusted i1lumination .

29. The method of claim 28, wherein the illumination adjusted is a side illumination.