IMPROVEMENTS IN OR RELATING TO ASSAY TIMING

Abstract

A storage and incubation device is provided. The device is configured to accommodate a plurality of assay chips, each assay chip including a unique identifier. The device comprises: a plurality of berths each sized to accommodate an assay chip; a communication module configured to receive information about the identifier of each assay chip; a clock timer configured to monitor the timing of the assay within each assay chip; a completion module to manage each assay chip when the assay is complete.

Claims

1. A storage and incubation device configured to accommodate a plurality of assay chips, each assay chip including an identifier, the device comprising: a plurality of berths each sized to accommodate an assay chip; a communication module configured to receive information about the identifier of each assay chip; a clock timer configured to monitor the timing of the assay within each assay chip; a completion module to manage each assay chip when the assay is complete.

2. The device according to claim 1, wherein the completion module includes a mechanism to eject the assay chip from the device.

3. The device according to claim 1 or claim 2, wherein the communication module is further configured to obtain clock data from the assay chip and provide this clock data to the clock timer.

4. The device according to any one of claims 1 to 3, further comprising a loading slot sized to accommodate an assay chip.

5. The device according to claim 4, wherein the loading slot is provided with a cover.

6. The device according to any one of claims 1 to 5, further comprising at least one sensor for monitoring the conditions within the device.

7. The device according to claim 6, wherein the sensor is a temperature sensor.

8. The device according to claim 6, wherein the sensor is a humidity sensor.

9. The device according to any claim 6 or claim 7, further comprising a temperature control device.

10. The device according to claim 8, further comprising humidity control device.

11. The device according to any one of claims 1 to 10, further comprising a protrusion that mechanically urges the chip into a configuration whereby the assay is initiated.

12. The device according to any one of claims 1 to 11, further comprising a mechanism for reordering the assay chips.

13. The device according to any one of claims 1 to 12, wherein the assay chip is an integrated assay chip.

14. A system for managing incubation and reading of assay chips, the system comprising a storage and incubation device according to any one of claims 1 to 12 and a reader.

15. The system according to claim 14, wherein the system is configured to take multiple readings from each chip.

16. The system according to claim 14, wherein the reader is provided in a light tight case.

17. The system according to claim 14 or claim 16, wherein the reader includes a communication module that enables transfer of data from the storage and incubation device.

18. The system according to any one of claims 14 to 17, further comprising a used chip collection zone.

19. The system according to claim 18, wherein the used chip collection zone has a sensor to indicate that it needs to be emptied.

20. The system according to any one of claims 14 to 19, wherein the storage and incubation device and the reader are contained within a common housing.

Description

[0051] The present invention will now be described, by way of example only, with reference to the accompanying figures in which:

[0052] FIG. 1 shows schematically part of an assay chip during provision of a saliva sample;

[0053] FIG. 2 shows the assay chip in a closed position;

[0054] FIG. 3 shows the assay chip inserted in a reader;

[0055] FIG. 4 shows the assay chip actuated and the assay initiated;

[0056] FIG. 5 shows an alternative assay chip;

[0057] FIG. 6 shows a further alternative assay chip;

[0058] FIG. 7 shows a system for chip management;

[0059] FIG. 8 shows an example of a stacker that may form part of the chip management system of FIG. 7;

[0060] FIG. 9; shows an alternative example of a stacker that may form part of the chip management system of FIG. 7;

[0061] FIG. 10 shows an alternative system for chip management;

[0062] FIG. 11A shows a further alternative system for chip management;

[0063] FIG. 11B shows an alternative embodiment of the system for chip management; and

[0064] FIG. 11C shows a cross-section view of the system for chip management.

[0065] FIG. 1 shows an assay chip 10, including a sample reception device 12 for receiving a liquid sample 14. The sample reception device 12 includes an opening 80 into which the liquid sample 14 is introduced. Including a sample reception device 12 within the assay chip 10 facilitates the input of a liquid sample 14 directly from the user providing an integrated chip. The sample reception device 12 also includes a lid 22 configured to cover the opening 80 once a liquid sample 14 has been provided. The lid 22 prevents the liquid sample 14 from exiting the chip 10. The lid 22 is attached to the assay chip 10 by a hinge 13. A hinged configuration is advantageous in that the lid 22 cannot be separated from the assay chip 10 and lost by the user.

[0066] The sample reception device 12 is provided with a flow pathway 16 that links the opening 80 to the location of the detection reagents 24 and capture components 22. The detection reagents 24 and capture components 22 are provided within the chip, facilitating an integrated assay chip 10. The fluid pathway 16 is provided with a flow controller or flow restrictor 19 that prevents the liquid sample 14 from moving along the fluid pathway 16. The flow restrictor 19 may be a hydrophobic filter or a capillary stop.

[0067] The detection reagent binds to the target component to form a detection reagent-target component complex. This complex then binds to the capture component to form a sandwich assay. The detection reagent can have inherent light emitting or scattering properties or the detection reagent may have applied to it a label. The detection reagent may be an antibody or an antibody fragment, protein or a peptide, or a nucleic acid.

[0068] The label may be one or more of the following: a luminescent entity; a fluorescent entity; a phosphorescent entity; a chemiluminescent entity; an entity that exhibits scattering, such as Rayleigh, Raman or Mie scattering; an entity that exhibits photon upconversion; an enzyme and its substrate that together produce an optical signal such as a luminescent signal and any entity providing a colorimetric signal regardless as to process but specifically exemplified by change to absorption cross section or extinction. In this context, the term upconversion is used to denote any emission following a multi-photon excitation process and this includes two photon fluorescence particles.

[0069] In this context, the term entity is used to refer to one or more of the following: a molecule; a cell or cell fragment such as a fragment of cell membrane; an ion; a particle which may be metallic, organic, inorganic or polymeric; a nanoparticle; a cluster, or a quantum dot.

[0070] In the illustrated embodiment, in addition to the flow restrictor 19 there is a sponge 82 and or a filter 83 provided in the opening 80 where the liquid sample 14 is collected. In some embodiments, the functionality of these three items may be provided by one or two layers, for example a PTFE layer which may provide some filtering as well as restricting the flow of the sample. In embodiments such as that shown in FIG. 1 where it is provided as a separate item, the sponge 82 helps to locate the sample 14 and also provides a coarse grade filter to remove any unwanted particulate matter from the liquid sample 14. The filter 83 is downstream of the sponge 82 and filters out finer unwanted particulates from the sample.

[0071] As shown in FIG. 2, the lid 22 is moved to a closed position by the user. This ensures that the liquid sample 14 cannot leave the assay chip 10. The lid 22 does not necessarily provide an air tight seal, but it does provide sufficient barrier to exit that, in combination with surface tension, the lid 22 prevents at least majority of the liquid sample 14 from leaking out of the assay chip 10.

[0072] Located within the lid 22 is a plunger 86 which is held in place in a recess in the lid 22 by an O-ring 85. The plunger 86 is accessible via one or more through holes 89 adjacent to the plunger 86. There may be a single, annular through hole 89 or there may be a plurality of individual through holes 89 provided.

[0073] FIG. 3 shows the assay chip 10 inserted into a reader 70. The reader 70 is provided with a key 90 which is configured to match the through holes 89. Once the assay chip 10 has been inserted into the reader 70, the assay is commenced by the deployment of the key 90 initiating the plunger 86 via the through hole or through holes 89.

[0074] A controller 100 is provided to initiate a reaction timer 110 when the fluid sample 14 and the reagent 24 are brought into contact. The reaction timer 110 is provided in the reader 70 as the reader 70 will monitor the timing of the assay from the initiation of the assay, through the timing of the incubation phase and then identifying the correct time to take the reading of the results.

[0075] The controller 100 is provided as part of the sample management module that forms part of the assay chip 10. The controller 100 provides feedback to the reader that the key has effectively actuated the plunger to commence the assay and therefore the reaction timer, located on the reader 70 should be started.

[0076] The controller 100 also includes a unique identifier 60, the content of which can also be communicated to the reader 70. The unique identifier 60 may be passive, such as a QR code or barcode. If the unique identifier 60 is passive, then it can only be read and not written to. It is unique and has, as its primary purpose, to identify the specific assay chip on which it is provided. The identity may be made up of multiple pieces of information including the biomarkers provided as detection reagents and capture components and also the batch from which it is drawn. This information may be common to a number of chips. Within each batch, each chip then has a unique identifier 60 so that the results can be allocated to a specific user. The presence of a unique identifier 60 also provides an element of quality control because each assay chip can be identified and therefore it is possible to check whether a particular assay chip 10 has been tampered with or used incorrectly in any way.

[0077] In some embodiments, the unique identifier 60 is active and can be updated to include information about the progress of the assay. In embodiments in which the unique identifier 60 is editable, it will include some form of memory enabling a data storage facility. The data storage may be in any suitable form of memory, either volatile or non-volatile, including but not limited to RAM, SRAM, ROM, EEPROM or Flash memory. For example, the unique identifier may be an RFID tag.

[0078] FIG. 5 shows schematically a further embodiment of the chip 10 shown in FIGS. 1 and 2. There is a considerable commonality of components between the embodiments. The key difference between the embodiments is the functionality of the controller 100 and the location of the reaction timer 110. In this embodiment, the lid 22 is provided with a one way latch or clip 23 so that, once closed, it cannot be reopened without the application of disproportionate force and the plunger 86 is provided in a recess in the lid 22. The plunger 86 and sponge 82 are sized such that, when the lid 22 is closed the plunger 86 compresses the sponge 82 providing sufficient pressure to overcome the flow restrictor 19 and introduce the fluid sample 14 into the fluid pathway 16 in which the detection reagents 24 and capture components 22 are provided. In this way, the closure of the lid 22 by the user, commences the assay.

[0079] The reaction timer 110 is included on the assay chip 10 and the controller 100 includes a circuit that is completed by the closure of the lid which thereby commences the reaction timer 110. The data relating to the timing of the assay is stored in the controller 100 or on the unique identifier, if it is editable, for communication to the reader 70. In this embodiment, the assay chip 10 does not need to be introduced to the reader 70 until the assay has been completed.

[0080] The fluid pathway 16 can be provided with a sensor (not shown) that identifies when the sample fluid reaches the detection reagents 24. The sensor can be capacitive or conductive. In some embodiments, the closure of the lid and the commencement of the assay occur effectively at the same time. This is the case where the assay time is quite long, for example 8 hours or 12 hours and therefore the seconds or minutes that it takes for the liquid sample to come into contact with the detection reagents and thereby to commence the assay is a negligibly small percentage of the assay time. In some embodiments, although the time taken for the liquid sample to reach the detection reagents and therefore commence the assay is a statistically significant proportion of the assay time, it is a known quantity which is reasonably repeatable between assays. In those embodiments where neither of the above applies, then the provision of an additional sensor in the fluid pathway provides additional certainty as to the exact timing of the commencement of the assay.

[0081] FIG. 6 shows a further embodiment of the assay chip 10 shown in FIGS. 1 and 2. Although there is a high degree of commonality of features between the embodiments of FIGS. 1, 2 and 6, the control of the initiation of the assay is different in the embodiment of FIG. 6. The flow controller 19 is a burstable layer such as a plastic film that, once burst allows a capillary channel to draw passively the fluid sample 14 past the detection reagents 24. The flow controller 19 is actuated by a key 90 which bursts the layer either through physical contact, such as the key 90 having a sharp protrusion or through the application of, for example, laser light.

[0082] This configuration allows the lid 22 to be closed and therefore the sample encapsulated from further contamination, but the assay not commenced. The chip 10 can therefore be stored in this configuration with the liquid sample 14 contained within the assay chip 10 for the assay to be run at a later time. The actuation of the assay would therefore occur only when the key 90 was activated, either on introduction of the assay chip 10 into a storage and incubation device or reader.

[0083] Whilst the liquid sample 14 is held in the assay chip 10 prior to the bursting open of the flow controller 19 to enable the commencement of the assay, the fluid sample 14 is retained in a reservoir 18 and the pressure within the reservoir 18 is managed by the provision of a vent 20.

[0084] FIG. 7 shows a system 200 for chip management. The system 200 includes a reader 70 which comprises an illumination device such as a laser 202 and a detection device such as a camera 204. The laser 202 and the camera 204 are both directed to a berth or location at which an assay chip 10 is provided to be read. The reader 70 may be configured to take an optical measurement, such as light scattering or fluorescence measurement. The excitation light may be provided in the form of total internal reflection (TIR). There is also a controller 210 that communicates with a storage and incubation device 220. The system 200 also includes a waste chip bin 212.

[0085] The storage and incubation device 220 includes a plurality of berths 222 each sized to accommodate an assay chip 10; a scanner 224 configured to read the unique identifier 60 of each assay chip 10; a clock timer 226 configured to monitor the timing of the assay within each assay chip 10; and a completion module 228 to manage each assay chip 10 when the assay is complete.

[0086] The scanner 224 is provided for reader data from the unique identifier 60. The information includes, at a minimum, the identity of the assay chip and an indication as to the timing regimen in use. For example, the data provided with the unique identifier may identify the batch from which the assay chip has been drawn, together with a unique identifier for the single assay chip. The data can then include the fact that the timing cannot be carried out on the assay chip because the assay chip in question does not have a reaction timer. This information can then be processed within the storage and incubation device 200 to ensure that the clock timer 226 is timing the entire assay as there is no provision on the assay chip 10 to time the assay locally.

[0087] The clock timer 226 times the incubation of the assay on each assay chip 10 that is introduced into the storage and incubation device 220. Depending on the initiation of the assay, the clock timer 226 may time the entire assay from start to finish or it may align itself with a reaction timer provided on the assay chip 10. In the later circumstance, it will time only the later part of the assay, commencing its monitoring at the point where the assay chip is introduced into the storage and incubation device 220.

[0088] A processor 225 is provided to write data to the unique identifier tag 60 where appropriate. Where the unique identifier is an editable tag with a writable memory, the processor 225 provides information about the incubation and storage of the assay chip to the unique identifier 60. This can include, but is not limited to timing information and identity information about the storage and incubation device. This information may then be accessed by the reader 70 directly from the assay chip 10 when the reader 70 obtains the results of the assay. The data stored may be pre-processed by the processor 225 within the storage and incubation device 220 in order to minimise the number of write operations required and also to reduce or eliminate the processing required on the assay chip 10 itself which may have very limited computational or battery capability. Therefore, where possible, the processor 225 within the storage and incubation device 220 processes the data such that only a summary, or meta-data, is written to the assay chip 10.

[0089] FIG. 8 shows an example of the storage and incubation device 220. In this embodiment the berths 222 are located in a linear stack that is held by gravity so that each assay chip 10 falls down by gravity onto the completion module 228. The berths 222 comprise one or more features, such as slots or grooves to match the shape or configuration of the assay chip and therefore to aid alignment. Alternatively or additionally, the movement of the chips 10 within the storage and incubation device 220 may be managed by a spring force against a latch 223 that can release a chip 10 to be transferred to the reader 70. The completion module 228 of this embodiment of the storage and incubation device 220 is a linear actuator or conveyor which is configured to make a linear translation of the chip 10 so that it exits the storage and incubation device 220 and moves into the reader 70.

[0090] The storage and incubation device 220 includes a loading slot 221. The loading slot 221 guides the assay chip 10 into position on one of the berths 222 provided within the storage and incubation device 220. Each of the berths is sized to accommodate an assay chip 10. The loading slot 221 is sized to compress the assay chip 10 thereby forcing the latch 23 to close the lid 22 of the assay chip 10 and the commencement of the assay. This may be achieved by the loading slot 221 being only just sufficiently large to accommodate the assay chip 10 and thereby to provide pressure around the circumference of the assay chip 10. Alternatively, the loading slot can include a projection at a key point on the circumference of the loading slot such that pressure is applied to a key part of the assay chip, adjacent to the latch 23 on the lid 22 of the assay chip 10.

[0091] The storage and incubation device 220 also includes a temperature sensor 230 and temperature controller 232. The rate at which assays progress is dependent on the temperature at which they are incubated. Some assays have a wide operating envelope with regard to temperature. In these circumstances it may be sufficient to monitor the temperature. Information about the temperature may be logged in the memory 62 associated with the controller 100 of the assay chip 10. This data can be used to identify when the assay will be complete. For example, if the assay proceeds more rapidly at an elevated temperature, then the assay will have progressed sufficiently to take a reading at an earlier time than would be the case at a lower temperature.

[0092] If the assay has a more narrow operating envelope, then the temperature controller 232 is used to modulate the temperature to ensure that the temperature remains within the required operating envelope of the assay.

[0093] The temperature controller 232 can also be used in circumstances where the operating envelope is wider, but the unique identifier 60 is not editable. In these embodiments, the temperature data cannot easily be stored on the assay chip 10 and therefore the rate at which the assay progresses has to be more actively controlled to ensure that it progresses at a predetermined rate by raising or lowering the temperature to a predetermined level.

[0094] A humidity sensor 234 and humidity controller 236 are provided. As with temperature sensing and control as outlined above, some assays are fairly resilient as to the humidity and a monitoring approach may be sufficient. In circumstances where the assay is more sensitive to the humidity, the humidity controller can be activated to maintain the humidity within a tighter acceptable operating window.

[0095] The completion module 228 may transfer the assay chips 10 to the waste chip bin 212. The waste chip bin 212 is a collection location for used chips. Depending on the chip contents, the chips may be removed from this location and disposed of in household waste by the user. However, the chips may be recycled and therefore the user may be expected to send them back to the service provider where they may be recommissioned or recycled in whole or in part. Alternatively, the waste chip bin 212 may store the chips securely for disposal via biohazard waste removal preventing the user from contacting the used chips. In order to alert the user to the need to empty the waste chip bin 212, there is a sensor 214 and an alarm 216 to communicate to the user that the waste chip bin needs to be emptied.

[0096] The completion module 228 includes a moving plate 229 that acts as a transferring element, linear actuator or conveyor configured to move the assay chip 10 from the storage and incubation device 220 and into the reader 70.

[0097] Movement of the assay chip 10 from the reader 70 into the waste chip bin 212 can either occur on a continuation of the moving plate 229 or by pressure in that the introduction of a subsequent assay chip 10 into the reader 70 displaces the incumbent assay chip 10 and ejects it into the waste chip bin 212.

[0098] FIG. 9 shows an alternative embodiment of the storage and incubation device 220 that is provided with a plurality of loading slots 221. Each loading slot 221 is provided adjacent to a corresponding berth 222 onto which an assay chip 10 can be delivered. The entire storage and incubation device 220 is then configured to move relative to the reader 70 so that the outlet of the reader 70 can be positioned adjacent to any one of the loading slots 221. The storage and incubation device 220 is provided with a mechanism that ejects an assay chip 10 from one of the berths 222 through the loading slot and directly into the reader 70. In this configuration the loading slot 221 is also effectively an unloading slot as the assay chip 10 both arrives and leaves the storage and incubation device 220 through the same slot 221.

[0099] FIG. 10 shows an alternative configuration in which the storage and incubation device 220 and the reader 70 are accommodated within a single housing 72. The housing 72 is substantially cylindrical and the berths 222 are configured on a planar circular surface 73 that can rotate around the axis 76 of the cylinder. The rotation of the berths 222 is indexed so that the berths 222 can stop in one of a predetermined number of positions around the circle. Each predetermined location at which a berth can stop has a defined function. One of the locations includes the loading slot 221 which may be an indentation in the housing 72 configured to expose the berth 222 indexed to the loading location. One of the locations includes the reader 70 so that the results of the assay on the assay chip 10 can be read when the assay chip 10 is indexed to the reading position. One of the locations includes a waste shoot 74 from which assay chips 10 may be sent to the waste chip bin, not shown in this embodiment as it is located beneath the berths 222. All of the other locations are used for incubation.

[0100] Although a total of six locations are shown in FIG. 10, the device 220 can be configured with any number of locations as appropriate. There must be at least three locations: loading, reading and ejection to waste. The scanner 224 can be positioned to interrogate the assay chip 10 in the loading or reading location. In most examples there will be at least four locations so that there is at least one dedicated incubation location. There may be one, two, three, four, five, ten or up to twenty incubation locations, but accommodating many more makes the design cumbersome as the required diameter increases to accommodate all of the incubation locations.

[0101] FIG. 11A shows an alternative configuration in which the storage and incubation device 220 is configured to move back and forth along a track 240. The storage and incubation device 220 can move into and out of a housing 244 through an entry/exit point 246. The housing 244 comprises a reader 70; a communication module which is a scanner 224 configured to read the unique identifier of each assay chip 10; and a clock timer 226 configured to monitor the timing of the assay within each assay chip 10.

[0102] The entry/exit point 246 within the housing 244 facilitates the loading and unloading of the storage and incubation device 220 by the user or by an ancillary device such as a completion module. Assay chips 10 are loaded into a plurality of berths in the storage and incubation device 220 simultaneously, and the storage and incubation device 220 is then moved along the track 240 into the housing 244 via the entry/exit point 246. The entry/exit point 246 in the housing 244 is provided with a cover 248 to prevent dirt, dust and light from entering the housing 244. In the illustrated embodiment, the assay chips 10 are held within the berths of the storage and incubation device 220 by gravity. In alternative embodiments, not illustrated, the assay chips 10 can be retained by a latch or clip.

[0103] The movement of the storage and incubation device 220 along the track 240 brings each assay chip 10 past a scanner 224 within the housing 244. The scanner 224 is configured to read the data from the unique identifier of each assay chip 10 which can provide, inter alia, an indication as to the timing regimen for each assay chip 10. The incubation of the assay on each assay chip 10 can be addressed accordingly and the order in which the assay chips 10 are entered into the reader 70 can be adjusted as required.

[0104] The storage and incubation device 220 is moved back and forth along the track 240, to align a berth of the storage and incubation device 220 with the reader 70 when it is determined that a reading is required to be taken from a particular assay chip 10. Each assay chip 10 can be read by the reader 70 as many times as is required thereby enabling sequential reads from the same chip and providing multiple different time points during the assays.

[0105] In the embodiment shown in FIG. 11A, the reader 70 is an integral part of the device. However, alternatively, the reader 70 may be located outside of the housing 244, in which case the alignment of the reader 70 must be known and either calibrated during assembly of the device or actively read during reading. This ensures correct alignment of the berths of the storage and incubation device 220 with respect to the reader 70.

[0106] When the assays are determined to be complete, the completion module moves the storage and incubation device 220 out of the housing 244 via the entry/exit point 246, and to an accessible position for attention of the user. The completion module can also be configured to alert the user that the assay is complete through an audible or visual alert, or by notification via SMS, phone alert or e-mail. It is also possible that the notification can be sent in conjunction with a result.

[0107] FIG. 11B shows a similar embodiment to FIG. 11A, with multiple storage and incubation devices 220 on the same track 240, each configured to move in one direction only. In this embodiment, assay chips 10 are loaded into the berths of multiple storage and incubation devices 220 simultaneously, enabling a greater number of assay chips 10 to be loaded into the system at once than in the embodiment shown FIG. 11A. In some configuration, not illustrated, multiple readers 70 can be located at different points along the track 240, so that each reader 70 can take a reading from an assay chip 10 as required, and sequential readings can be taken by sequential readers 70.

[0108] Each reader 70 is in communication with the others, either directly or via a central location such as the cloud, where the readings are aggregated, and the unique identity data of each assay chip 10 is used to assign each new reading to the intended user and add it to that user's data.

[0109] The track 240 may form a complete loop circuit, or can return the storage and incubation devices 220 to the start point via another track 240, enabling the storage and incubation devices 220 to be continuously re-used.

[0110] The completion module can be configured to load and remove assay chips 10 from the berths of the storage and incubation device 220 automatically after the desired number of readings have been taken or a predetermined time has elapsed.

[0111] FIG. 11C shows a cross section view of the device of FIGS. 11A and 11B, and shows how the storage and incubation device 220 can be configured to position the assay chips 10 adjacent to the track 240. Alternatively, the track 240 can be mounted in different orientations.

[0112] Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

[0113] “and/or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example “A and/or B” is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.

[0114] Unless context dictates otherwise, the descriptions and definitions of the features set out above are not limited to any particular aspect or embodiment of the invention and apply equally to all aspects and embodiments which are described.

[0115] It will further be appreciated by those skilled in the art that although the invention has been described by way of example with reference to several embodiments. It is not limited to the disclosed embodiments and that alternative embodiments could be constructed without departing from the scope of the invention as defined in the appended claims.