Assay Cartridge and Support Housing

Abstract

An assay cartridge (31) for use in a molecular diagnostics assay comprising: an assay region (32), possibly containing a plurality of reagent wells (34); a first end comprising a first engagement member (35), such as a lip or protrusion, for engaging with a support housing; and a second end comprising a second engagement member (36) for engaging with a support housing; wherein the second engagement member comprises a clip, the clip being formed by a resilient element extending from the second end of the cartridge and a fastening element extending from said resilient element; wherein the clip comprises a release element extending from the resilient element actuatable to release the clip from a caddy or support housing in use.

Claims

1. An assay cartridge for use in a molecular diagnostics assay, the assay cartridge comprising: an assay region; a first end comprising a first engagement member for engaging with a support housing; and a second end comprising a second engagement member for engaging with a support housing; wherein the second engagement member comprises a clip, the clip being formed by a resilient element extending from the second end of the assay cartridge and a fastening element extending from said resilient element, and wherein the clip comprises a release element extending from the resilient element actuatable to release the clip from a support housing in use.

2. The assay cartridge according to claim 1, wherein the first engagement member comprises a lip, the lip being formed by a protrusion at the first end of the assay cartridge.

3. The assay cartridge according to claim 1, wherein the assay region comprises one or more biochip regions.

4. The assay cartridge according to claim 3, wherein the assay cartridge comprises one or more slideable caps that may be positioned over the one or more biochip regions.

5. The assay cartridge according to claim 1, wherein the assay region comprises one or more reagent wells.

6. The assay cartridge according to claim 5, wherein at least one of the reagent wells includes a wash fluid.

7. The assay cartridge according to claim 1, wherein the assay region comprises one or more sample regions.

8. (canceled)

9. (canceled)

10. (canceled)

11. (canceled)

12. (canceled)

13. (canceled)

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. A cartridge-housing system, comprising: an assay cartridge for use in a molecular diagnostics assay, the assay cartridge comprising: an assay region; a first end comprising a first engagement member for engaging with a support housing; and a second end comprising a second engagement member for engaging with a support housing; wherein the second engagement member comprises a clip, the clip being formed by a resilient element extending from the second end of the assay cartridge and a fastening element extending from said resilient element, and wherein the clip comprises a release element extending from the resilient element actuatable to release the clip from a support housing in use; and the support housing for holding the assay cartridge, the support housing comprising: a first cooperating member configured to engage with the first engagement member; and a second cooperating member configured to engage with the second engagement member; wherein the support housing comprises a channel for receiving the assay cartridge, and wherein the first cooperating member is provided at one end of the channel and the second cooperating member is provided at the other end of the channel.

20. The cartridge-housing system according to claim 19, wherein the first cooperating member of the support housing comprises a first recess for receiving the first engagement member of the assay cartridge.

21. The cartridge-housing system according to claim 19, wherein the second cooperating member of the support housing comprises an abutment element and a second recess.

22. The cartridge-housing system according to claim 19, wherein the support housing comprises handles.

23. The cartridge-housing system according to claim 19, wherein each side of the channel of the support housing comprises a protruding rail, each rail extending at least partially along its respective side of the channel.

24. The cartridge-housing system according to claim 19, wherein the support housing comprises a notch on its lower side configured to align with a corresponding protrusion in an assay machine.

25. A method of loading an assay cartridge into a support housing, the method comprising: engaging a first engagement member of the assay cartridge with a first cooperating member of the support housing, wherein the assay cartridge comprises an assay region and a first end comprising the first engagement member, and wherein the support housing comprises a first cooperating member configured to engage with the first engagement member and a channel for receiving the assay cartridge, wherein the first cooperating member is provided at one end of the channel; and engaging a second engagement member of the assay cartridge with a second cooperating member of the support housing, wherein the assay cartridge further comprises a second end comprising the second engagement member, wherein the second engagement member comprises a clip being formed by a resilient element extending from the second end of the assay cartridge and a fastening element extending from said resilient element, wherein the clip comprises a release element extending from the resilient element actuatable to release the clip from the support housing in use, and wherein the support housing further comprises the second cooperating member, wherein the second cooperating member is provided at the other end of the channel.

26. The method of claim 25, further comprising unloading the assay cartridge from the support housing by: orienting the assay cartridge and support housing such that the assay cartridge is below the support housing; and disengaging the second engagement member from the second cooperating member, the weight of the assay cartridge thereby causing disengagement of the first engagement member from the first cooperating member.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Embodiments of the invention are described herein with reference to the accompanying drawings, of which:

[0048] FIG. 1A shows an isometric view of a machine that may be used in a molecular diagnostics assay;

[0049] FIG. 1B shows plan view of the machine of FIG. 1A but with its upper cover removed;

[0050] FIG. 2 shows a prior art array of biochips for use in molecular diagnostics assays;

[0051] FIG. 3 shows an isometric view of a cartridge according to embodiments of the invention;

[0052] FIG. 4 shows a close up view of the clip of the cartridge provided according to embodiments of the invention;

[0053] FIG. 5 shows an isometric view of a support housing provided according to embodiments of the invention;

[0054] FIG. 6 shows a plan view of the support housing of FIG. 5;

[0055] FIG. 7 shows an elevation view of the support housing of FIG. 5;

[0056] FIG. 8 shows a front-on view of the support housing of FIG. 5;

[0057] FIG. 9 shows an isometric view of a support housing according to embodiments of the invention in which are provided cartridges according to embodiments of the invention;

[0058] FIG. 10 shows a cross-sectional view of the cartridge-support housing system of FIG. 9;

[0059] FIG. 11 shows a different cross-sectional view of the cartridge-support housing system of FIG. 9;

[0060] FIG. 12 shows a plan view of the cartridge-support housing system of FIG. 9;

[0061] FIG. 13 shows a plan view of the underside of the cartridge-support housing system of FIG. 9;

[0062] FIG. 14 shows a cartridge-support housing system according to embodiments of the invention in use in an assay machine; and

[0063] FIGS. 15A and 15B show the removal of a cartridge from a cartridge support housing system according to embodiments of the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0064] FIG. 1A shows an example of a machine 11 that may be used in a molecular diagnostics assay. The machine 11 may be configured to carry out one or more of the steps of an assay, including extraction of DNA/RNA from a sample, amplification of the sample, and/or analysis of the amplified sample. Typically, the extraction is carried out by a lysis process, the amplification of the sample by a polymerase chain reaction (PCR) process, and the analysis of the sample by detecting biochemical reactions occurring on a biochip.

[0065] FIG. 1B shows a plan view of the interior of the assay machine 11. This particular example shows an analyser 11 that is separated into different sections 111, 112, and 113 where each of the extraction and purification (section 111), amplification (section 112), and detection (section 113) steps is carried out. A cartridge-caddy system 12 as described herein is shown in section 111 of the analyser.

[0066] The biochip 21 may itself be provided as part of an array of biochips 22, and FIG. 2 shows an example of a prior art array 22 that comprises several biochips 21 in separate biochip wells 23. In conventional assay machines suitable for use with the biochip 21, reagents are typically stored in large bottles inside the assay machine. In order to supply a reagent to the biochip 21, a robotic pipettor travels to the relevant bottle, collects a volume of the reagent and then travels to the biochip onto which it dispenses the reagent. The use of an array 22 of biochips 21 simplifies the assay process, but there are nevertheless problems associated with the use of these arrays 22.

[0067] Firstly, in order to provide reagents and samples onto the biochips 21 it is necessary for the machine to be able to determine the location of these biochip wells 23. This is especially important when different samples and/or reagents are to be provided in separate regions of a single biochip 21, as this requires precise spotting of samples and reagents. These prior art arrays 22 must therefore be provided on mechanical assemblies that allow for accurate positioning of the biochips. These mechanical assemblies have introduced additional complexity into the machines used for carrying out assays.

[0068] The second problem associated with the arrays 22 used up until now is that these arrays 22 are difficult to load into a machine for assay processing, a problem that is particularly acute when several such arrays 22 must be loaded for processing at once. Similarly, the unloading of arrays 22 is less simple than might be desired. The processing of samples is therefore slowed down by the reduced speed of loading and unloading.

[0069] Thirdly, reagents stored in large bottles for long periods of time are susceptible to loss by evaporation and instability due factors such as variations in the ambient conditions (e.g. temperature and humidity). While it is possible to incorporate additional apparatus to control these factors, doing so adds complexity to the assay machine. It is often not practical to achieve the desired degree of control without impinging severely on other considerations (e.g. the size of the machine, maintenance requirements, and ease of operation).

[0070] Therefore, what is needed is a means of providing biochips, reagents, and samples to a machine for assay processing that is more convenient and efficient, and which is less prone to contamination of samples.

[0071] FIG. 3 shows a cartridge 31 according to an embodiment of the invention that solves these and other problems. This particular example of the invention provides an elongate cartridge 31 that comprises, in an assay region 32 of the cartridge 31, a biochip region 33 and a plurality of reagent wells 34. The specifics of the biochip do not affect the functioning of the cartridge 31, which can be adapted to be used with different types of biochip. At one end of the cartridge there is provided a protrusion 35, or lip, as a first engagement member that allows for engagement with a corresponding portion of a support housing. The support housing will be described later. At the other end of the cartridge there is provided a clip 36 as a second engagement member for engaging with a different portion of the support housing.

[0072] The protrusion 35 that forms the lip 35 of the cartridge 31 extends outwardly from the upper surface of the cartridge 31. The protrusion 35 extends by an extent that provides a balance between ensuring sufficient engagement with the support housing to hold the cartridge 31 in place while allowing the cartridge 31 to be easily removed. In particular, the quick release of the cartridge 31 that is described later benefits from a lip 35 that does not stick when the support housing is upturned and the clip 36 is disengaged. The protrusion 35 preferably extends by a distance from 1 mm to 3 mm from the upper surface of cartridge 31, and more preferably extends by 2 mm from the upper surface of the cartridge 31.

[0073] The clip 36 at the other end of the cartridge 31 is shown in more detail in FIG. 4. The clip 36 comprises a resilient element 41 that is configured to abut with a support housing and a pawl 42 as a fastening element that extends from the resilient element 41. The pawl 42 serves to constrain the vertical movement of the cartridge 31, such that when the lip 35 and the clip 36 are both engaged the cartridge 31 is held within the support housing. The clip 36 also comprises a release element 43. The release element 43 extends from the resilient element 41 in a direction opposite to the pawl 42, such that when a user presses on the release element 43 the clip 36 is disengaged. By pressing on the release element 43, a moment is created about the point where the resilient element 41 is attached to the cartridge and the clip 36 rotates about this point. The pawl 42 exits the recess and the clip 36 is disengaged. When looking from the direction shown in FIG. 4, the rotation is in an anticlockwise sense.

[0074] The assay region 32 of the cartridge 31 can be modified depending on the intended use of the cartridge 31. The biochip region 33 can be removed and replaced with further reagent wells 34, or conversely the cartridge 31 could comprise more than one biochip region 33, possibly absent any reagent wells 34. Alternatively, the cartridge 31 could comprise one or more sample regions so that the cartridge 31 could be used to provide samples for testing. The cartridge 31 could also comprise any combination of biochip regions 33, reagent wells 34, and sample regions. The individual reagent wells 34 may differ in volume from one another. In this example, the two reagent wells 34 nearest the clip 36 are of a greater volume than the others (as is clearly visible in FIG. 3). In general, the number, volumes and arrangement of the reagent wells 34 can be chosen to suit the particular assay for which the cartridge 31 is intended for use in.

[0075] The cartridge 31 may also comprise a slide cap. This is not shown in FIG. 3 but may be seen in the cartridges illustrated in FIGS. 9 to 12. The cap finds utility in some embodiments of the invention in which the cartridge 31 comprises one or more biochip regions 33. The assay may require incubation of the biochip, in which case the slide cap can be positioned over the biochip during incubation to prevent evaporation of the sample or of any reagents.

[0076] The cartridge 31 is typically made of medical grade polypropylene, for example H350, which is a particular medical grade polypropylene manufactured by Total S.A. Medical grade polypropylenes are particularly suitable since they typically do not react with biological materials and are easily moulded into the required shapes. The softness of the material used is selected so as to ensure the desired level of rigidity. If the material is too soft the rigidity will be low, in which case the cartridge 31 might bow outwards from a support housing or the clip 36 might not fasten securely to a support housing. Conversely, if the material is too hard the rigidity will be high and it will be difficult to engage and disengage the clip 36.

[0077] In some examples to prepare a cartridge 31 for use, a user manually dispenses sample fluid (e.g. liquid), reagents and/or wash into respective wells 34 in a predetermined dispensing plan that identifies which well each substance should be dispensed into. Each well is only able to be filled to a particular volume. This gives the user confidence that by filling the well, they have provided the correct amount of substance into the respective well, and that the environment the sample is exposed to is controlled to the level expected by the user up to the point when testing is carried out. This is in contrast to large bottles (such as those used in conventional analysers), being provided that have the associated detrimental factors outlined above.

[0078] An example of a support housing 51 configured to hold cartridges according to the invention is shown in isometric view in FIG. 5, in which the support housing 51 takes the form of a caddy 51. The caddy 51 comprises regions 52 for receiving cartridges that are spaced regularly along the caddy 51. The caddy 51 can be configured to receive different numbers of cartridges. At either end of the caddy 51 there is provided a handle 53 for carrying the caddy 51. An assay machine suitable for use with the caddy 51 could be provided with features adapted to cooperate with the handles 53 so as to improve the ease and accuracy with which the caddy 51 can be aligned inside the assay machine. The caddy 51 also comprises a notch 54 in its base to aid in positioning of the caddy 51 in an assay machine. The notch 54 aligns with a corresponding protrusion in the assay machine to ensure that the caddy 51 will be correctly positioned. As the cartridges all have fixed positions within the caddy 51, this in turn means that the assay machine can determine the locations of the biochips, reagent wells, and/or sample regions. The notch can be seen more clearly in FIG. 7. The notch 54 is preferably provided off-centre so that the caddy 51 can only be loaded into the assay machine with one orientation.

[0079] The regions 52 for receiving the cartridges can be seen more clearly in FIGS. 6 and 8. Each region comprises a channel providing side walls 61 between each cartridge that serve to separate the cartridges. The rearmost section of each channel comprises protruding rails 62, which preferably extend along a third of the length of each channel. These rails 62 provide support to the cartridge so as to ensure the upper surface of each cartridge is flat when held in the caddy 51.

[0080] At the rear of each channel there is provided a first recess 55 as a first cooperating member for receiving the end of the cartridge having the lip. The lip engages with the first recess 55 to hold this end of the cartridge in place. At the other end of the channel there is an abutment element 56 for abutting with the first element of the clip, and below the abutment element there is provided a second recess 57 for receiving the second element of the clip. The abutment element 56 and recess 57 together function as a second cooperating member.

[0081] The caddy 51 is typically reusable and is accordingly made of a material that is resistant to wear and tear. For example, the caddy 51 may be made of metal, preferably aluminium.

[0082] FIG. 9 shows an example of a support housing 90, again in the form of a caddy 90, holding cartridges 100. The lip 101 of each cartridge 100 is engaged with the corresponding first recess 91 (shown most clearly in FIGS. 11 and 13) in its respective channel 92 in the caddy 90, and each clip 102 is also engaged with the corresponding second recess 93 and abutment member 94 of the caddy 90. The two ends of each cartridge 100 are held by the lip 101 and the clip 102 such that the movement of the cartridge 100 is inhibited. The rails 95, in combination with the engagement of the clips 102 and the lips 101, provide sufficient support for each cartridge 100 that the upper surface of each cartridge 100 is substantially flat when held in the caddy 90.

[0083] Viewing a cross section of the cartridge-caddy system of FIG. 9 taken along the length of the caddy 90, as shown in FIG. 10, the engagement of the lip 101 and the clip 102 of the cartridge 100 with the corresponding recesses 91, 93 of the caddy 90 may be seen. The engagement of the lip 101 constrains the horizontal and vertical movement of the cartridge 100, while the clip 102 constrains the vertical movement of the cartridge 100. When both the lip 101 and the clip 102 are engaged, the cartridge 100 is prevented from falling out of the caddy 90.

[0084] As noted above, FIGS. 9 and 12 also show a slide cap 103 as part of the cartridge 100. The slide cap 103 is configured such that it does not interfere with the positioning of the cartridge 100 in the channel 92. The position of the slide cap 103 may be changed while the cartridge 100 is held in the caddy 90 so that a sample and/or reagents may be provided on the biochip and the lid repositioned over the biochip region, i.e. closed, to prevent evaporation. As shown in the figures, the slide cap 103 comprises a protrusion 104. The protrusion 104 is shaped to allow enable repositioning of the cap 103 by an element of an assay machine, such that the cap 103 may be closed after reagents and/or samples have been provided by the assay machine on the biochip.

[0085] The engagement of the lip 101 can be seen particularly well in FIGS. 11 to 13. Comparing the cross section of FIG. 11 and the plan view of FIG. 12, it is possible to see that the lip 101 extends beyond the end of the channel 92 and into a recess 91 in the caddy. In this example an elongate hole is formed in the caddy 90 at the position of the recess 91, which allows a user to easily determine by sight whether the lip 101 is correctly positioned in the recess 91 (and accordingly confirm whether the cartridge 100 is correctly mounted in the caddy 90).

[0086] FIG. 14 shows a cartridge-caddy system positioned in an assay machine. Each cartridge 100 is accurately located in its respective channel 92 by means of the clip 102 and the lip 101 and the caddy 90 is itself correctly positioned owing to the alignment of the notch 54 with the corresponding protrusion in the machine. A camera can then be correctly positioned over each biochip to detect reactions, for example bioluminescence or chemiluminescence.

[0087] Similarly, an aspirator, not shown, can be correctly positioned over each reagent well, and samples and reagents can be precisely located on different regions of the biochip. The assay machine may also comprise one or more elements for repositioning the slide cap using the protrusion. The aspirator may comprise an element to position the slide cap over the biochip after samples and reagents have been provided, while the camera may comprise an element for moving the slide cap away from the biochip region to allow for detection of reactions.

[0088] Once the relevant steps of the assay have been completed, the cartridge-caddy system is removed from the assay machine and the cartridges 100 removed from the caddy as illustrated in FIGS. 15A and 15B. The cartridge-caddy system is inverted so that the cartridges 100 are below the caddy 90 and the user presses the release element of the clip 102 of each cartridge 100 in turn.

[0089] FIG. 15A shows the cartridge-caddy system prior to the release element of the clip being pressed. Pressing on the release element along the direction indicated by the arrow 1501 causes disengagement of the clip 102 from the recess 93 in the caddy. As a result, this end of the cartridge 100 falls from the caddy 90. The weight of the cartridge 100 is then supported only by the engagement of the lip 101 with its respective recess 91. The lip 101 and the recess 91 are configured such that the engagement of the lip 101 with its respective recess 91 is not itself sufficient to support the weight of the cartridge 100 when the caddy 90 is inverted, so once the clip 102 of the cartridge 100 is disengaged the weight of the cartridge 100 causes disengagement of the lip 101. Thus, the user can eject the cartridges 100 from the caddy 90 by pressing each release element in turn.

[0090] Typically, the process shown in FIG. 15 is carried out with the cartridge-caddy system positioned over a bin so that the spent cartridges 100 may be easily collected.

[0091] Once the cartridges 100 have been ejected the caddy 90 can be loaded with new cartridges 100 for use in another assay process.