APPARATUS FOR CONDUCTING AN ASSAY

Abstract

The present invention provides an apparatus for conducting an assay in a microfluidic system comprising magnetic beads, said apparatus comprising: a platform upon which a microfluidic system can be mounted, one or more actuators having a magnet, configured to directly influence movement of magnetic beads housed within a microfluidic system when a microfluidic system is mounted on said platform, and a control means configured to control relative movement of the one or more magnets, and a microfluidic system when mounted, to enable the magnet to trace a desired path across a mounted microfluidic system, said magnet being positionable at any x- and y-coordinates of a mounted microfluidic system, wherein said apparatus further comprises: a) at least one rotary actuator configured to enable magnet movement in an x-axis, and/or b) a means for moving a mounted microfluidic system in a stepwise fashion.

Claims

1. An apparatus for conducting an assay in a microfluidic system comprising magnetic beads, said apparatus comprising: a platform upon which a microfluidic system can be mounted, one or more actuators having a magnet, configured to directly influence movement of magnetic beads housed within a microfluidic system when a microfluidic system is mounted on said platform, and a control means configured to control relative movement of the one or more magnets, and a microfluidic system when mounted, to enable the magnet to trace a desired path across a mounted microfluidic system, said magnet being positionable at any x- and y-coordinates of a mounted microfluidic system, wherein said apparatus further comprises: a) at least one rotary actuator configured to enable magnet movement in an x-axis, and/or b) a means for moving a mounted microfluidic system in a stepwise fashion.

2. An apparatus according to claim 1, wherein, when the apparatus comprises a means for moving a mounted microfluidic system, the system is rotatable.

3. An apparatus according to claim 1, wherein the stepwise motion of a mounted microfluidic system may be achieved by non-continuous rotation.

4. An apparatus according to any preceding claim, wherein, when the apparatus comprises a means for moving a mounted microfluidic system in a stepwise fashion, the actuator comprises a rotary actuator.

5. An apparatus according to any preceding claim, wherein the actuator comprises a linear actuator

6. An apparatus according to any preceding claim, wherein the apparatus comprises a rotary actuator and a linear actuator on a single driveshaft.

7. An apparatus according to any preceding claim, wherein the apparatus comprises a magnet positionable above a mounted microfluidic system and/or a magnet positionable below a mounted microfluidic system.

8. An apparatus according to any preceding claim 7, wherein the apparatus comprises a means to move magnet clear of the microfluidic device.

9. An apparatus according to claim 8, wherein the means to move a magnet clear of the microfluidic device comprises a rotary actuator configured to allow rotation of the magnetic drive-shaft about an x-axis.

10. An apparatus according to any preceding claim, wherein the magnet may contact or be held at a fixed distance from the surface of a mounted microfluidic system.

11. An apparatus according to any preceding claim, wherein the magnet is mounted on a spring assembly.

12. An apparatus according to any one of claims 1 to 10, wherein the magnet is mounted on an adjustable mounting assembly.

13. An apparatus according to claim 12, wherein the adjustable mounting assembly comprises an adjustable magnet holder and a through plate located on a portion of the rotary and/or linear actuator.

14. An apparatus according to any one of claim 12 or 13, wherein the through plate comprises a first engagement portion; and wherein the adjustable magnet holder comprises a second engagement portion configured to engage with the first engagement portion of the through plate.

15. An apparatus according to any one of claims 12 to 14, wherein the first engagement portion of the through plate comprises a threaded portion and the second engagement portion of the adjustable magnet holder comprises a corresponding threaded portion.

16. An apparatus according to any one of claims 11 to 15, wherein the adjustable mounting assembly is configured to allow positioning of the magnet in a position along a Z-axis.

17. An apparatus according to any one of claims 11 to 16, wherein the magnet is in contact with the surface of the microfluidic device.

18. An apparatus according to any preceding claim, wherein the platform comprises a turntable configured to receive and controllably rotate an assay disc comprising a microfluidic system.

19. An apparatus according to claim 18, wherein the control means controls one or more actuators and the turntable to enable the magnet to trace a desired path across a mounted microfluidic system.

20. An apparatus according to any of claim 18 or 19, wherein the turntable comprises one or more heater modules to apply heat to one or more specific parts of a mounted microfluidic system during rotation.

21. An apparatus according to any of claims 18 to 20, wherein said turntable further comprises: a heater controller to select a required heater and to control the temperature thereof, and an IR transceiver to allow instructions and/or heating parameters to be transferred to the heater controller wirelessly.

22. An apparatus according to any of claims 18 to 22, wherein said turntable further comprises a means to facilitate the correct positioning of the assay disc relative to the turntable.

23. An apparatus according to claim 22, wherein said means comprise a central spindle on the turntable corresponding to a spindle hole in the assay disc, and wherein said spindle has a longitudinal groove to correspond with a longitudinal projection on the hub of the assay disc.

24. An apparatus according to claim 23, wherein the horizontal dimension of the groove of the spindle decreases in a longitudinally downward direction.

25. An apparatus according to claim 22, wherein said means comprise a locating projection on the turntable to mate with a corresponding locating recess on an assay disc, optionally at, adjacent to, or near the periphery of the assay disc.

26. An apparatus according to claim 22, wherein means of locating the assay disc relative to the turntable is as claimed in claim 23 or claim 24, and also as claimed in claim 25.

27. An apparatus according to any of claims 18 to 26, wherein said turntable further comprises clamping means to secure the assay disc to the turntable.

28. An apparatus according to claim 27, wherein said clamping means comprise a mechanical ball bearing clamping mechanism to hold the assay disc to the turntable.

29. An apparatus according to claim 27 or claim 28, wherein clamping means comprise magnetic means for holding the assay disc in a fixed position relative to the turntable and/or for aligning and/or guiding the disc to the correct position.

30. An apparatus according to claim 29, wherein said magnetic means comprise disc magnets arranged in opposite pole directions in the turntable corresponding to disc magnets arranged in opposite pole directions in the assay disc.

31. An apparatus according to any of claims 18 to 30, wherein said turntable comprises a power transfer assembly comprising a wireless power transfer means to transfer power to heater modules in the turntable and/or to the heater controller.

32. An apparatus according to any of claims 21 to 30, wherein the IR transceiver comprises one or more IR emitters and one IR receiver.

33. An apparatus according to claim 32, wherein the IR transceiver comprises four IR emitters.

34. An apparatus according to claim 33, wherein the four emitters are arranged in equidistance surrounding the central hub of the timetable.

35. An apparatus according to any of claims 21 to 34, wherein there are one or more heater modules.

36. An apparatus according to claim 35, wherein the heater modules are independently controlled.

37. An apparatus according to claim 35 or claim 36, wherein the power supplied to the heater can be shared and distributed among the heaters on demand.

38. An apparatus according to any of claims 18 to 37, wherein the turntable comprises a power transfer assembly comprising a stationary coil assembly and a rotational coil assembly with the stationary coil assembly mounted axially coincident below.

39. Assay unit comprising an apparatus as claimed in any preceding claim.

40. Assay unit as claimed in claim 39, further comprising means for heating and/or cooling the ambient temperature of the chamber within which the assay disc is located during the assay.

41. Assay unit as claimed in claim 40, wherein said means is a fan heater or cooler.

42. The combination of an apparatus as claimed in any of claims 1 to 28 or an assay unit as claimed in any of claims 39 to 41, and an assay disc configured to be mounted on the apparatus.

43. Use of an apparatus as claimed in any preceding claim to conduct an assay.

44. A method for carrying out an assay comprising the steps of: i) mounting an assay disc comprising a microfluidic system on a turntable, wherein said microfluidic system comprises a plurality of magnetic beads; and ii) providing a magnet on an actuator such that the magnet made be positioned at any x- and y-coordinates of the assay disc.

45. A method according to claim 44, further comprising the step of moving a plurality of magnetic beads through a portion of the microfluidic system by moving said magnet whilst rotating said assay disc such that said magnet traces a desired locus in an x-, y-plane of the assay disc.

46. An apparatus as substantially described herein with reference to the figures.

Description

[0097] The present invention will now be described in further, non-limiting, detail, with reference to the following Figures in which:

[0098] FIG. 1 shows a schematic representation of one example of an apparatus according to the present invention, with a microfluidic disc mounted thereupon, the apparatus comprising a magnet mounted on a linear actuator;

[0099] FIG. 2 shows a schematic representation of an alternative example of an apparatus according to the present invention, with a microfluidic disc mounted thereupon, the apparatus comprising a magnet mounted on a rotary actuator;

[0100] FIG. 3 shows a side view schematic representation of a mounted microfluidic disc mounted on apparatus according to the present invention, comprising a magnet mounted on linear actuator;

[0101] FIG. 4 shows a side view schematic representation of a mounted microfluidic disc mounted on an apparatus according to the present invention, comprising a linear and rotatory actuator mounted on a single drive shaft;

[0102] FIG. 5 shows a front view schematic representation of the apparatus of FIG. 4;

[0103] FIG. 6 shows one example of a turntable platter in accordance with the present invention;

[0104] FIG. 7 shows how magnetic locating and clamping means may be used in the present invention;

[0105] FIG. 8 shows a side view of a turntable in accordance with the present invention;

[0106] FIG. 9 shows a perspective view of a turntable in accordance with the present invention;

[0107] FIG. 10 shows, in exploded schematic view, some possible elements of a turntable power transfer assembly in accordance with the present invention; and

[0108] FIGS. 11 to 16 show some components of a turntable in accordance with the present invention.

[0109] FIGS. 17 and 18 show schematic views of an adjustable mounting assembly according to certain embodiments of the present invention.

[0110] With reference to FIG. 1, the apparatus 1 comprises a linear actuator 2a, having a magnet 3 mounted thereupon, wherein the magnet may be made to traverse a path 4 which may extend across a surface of a microfluidic disc 5, which may be mounted on the apparatus. The apparatus 1 further comprises a controller for controlling the rotation of the assay disc 5, with disc rotation shown by arrow 6, and movement of the magnet 3, as depicted by arrow 7, enabling the magnet 3 to traverse any desired path across the surface of the microfluidic system.

[0111] The range of movement of the magnet 3 may be limited such that the magnet may only be positioned along a portion of the radius of a mounted microfluidic disc corresponding to regions where a microfluidic channel or chamber may be present. Alternatively, the range of movement of the magnet may extend across the entire radius of a mounted microfluidic disc.

[0112] In particular, the controller controls the rotation of the mounted assay disc 5 in a clockwise and/or anticlockwise direction, as required, while simultaneously controlling the movement of the linear actuator in order that the magnet may trace a path between chambers 8 via the channels 9. Magnetic beads housed within a chamber 8 or channel 9 are attracted to the localised magnetic field caused by the proximity of the magnet and are directed through the chambers and/or channels, mirroring the path of the magnet 3.

[0113] The channels may be angled such that they run parallel to the circumference of the assay disc, or are angled thereto. The channels may also comprise curves and bends 9a.

[0114] In an alternative embodiment, depicted in FIG. 2, the magnet may be mounted on a rotary actuator 2b. The range of movement of the magnet 3 may be limited such that the magnet may only be positioned along an arc which is predominantly in line with at least a portion of the radius of the assay disc.

[0115] As depicted in FIG. 3, in some embodiments, multiple magnets 3 may be mounted on actuators 2a which are positioned above and below a mounted assay disc. Alternatively, magnets may be positioned only above a mounted microfluidic disc, or only below mounted microfluidic disc.

[0116] As shown in FIGS. 4 and 5, in some embodiments a linear actuator 2a and rotary actuator 2c are mounted on a single driveshaft 10 which positions the magnet beneath the assay disc. Alternatively, the magnet may be positioned above assay disc. Rotation of the rotary actuator 2c in one direction brings the magnet 3 into contact with the assay disc 5, while rotation of the rotary actuator 2c in the opposite direction moves the magnet away from the assay disc, as shown by rotation arrow 11.

[0117] The linear actuator 2a enables the magnet to be moved along a desired x-axis along the radius of a mounted microfluidic disc.

[0118] A leaf spring, 12, may apply a suitable force to keep the magnet 3 contact with the assay disc 5.

[0119] As shown in FIGS. 17 and 18 in some embodiments and adjustable mounting assembly 2 may be used for mounting the magnet 3 and positioning the magnet in the Z-axis in relation to the assay disc 5. The adjustable mounting assembly may be used in combination with a leaf spring 12 as shown in FIG. 5 or without a leaf spring. In certain embodiments the adjustable mount assembly may comprise a spring in order to provide a suitable force to keep the magnet 3 in contact with the assay disc 5.

[0120] The adjustable mounting assembly comprises a through plate 22 and a magnet holder 25. The through plate may be mounted onto the drive shaft 10 of one or more linear 2a and/or rotary actuators 2b/2c. The through plate 22 may be located so as to be positioned above the assay disc 5. The through plate 22 comprises a first engagement portion 24 which is configured to engage with a second engagement portion 26 of the adjustable magnet holder 25. The adjustable magnet holder comprises a holding portion 27 where the magnet 3 is engaged and held in place.

[0121] The holding portion 27 may be a recess where the magnet 3 is inserted. The magnet 3 may be held in the holding portion 27 by magnetic force. In some embodiments the magnet 3 may be held in the holding portion 27 by one or more clips or engagement members. In some embodiments the holding portion may have the spring located above the magnet 3 within the recess so as to provide a suitable force to keep the magnet 3 in contact with the assay disc 5.

[0122] In some embodiments the first engagement portion 24 may be a threaded though hole and the second engagement 26 may be a correspondingly threaded protrusion, as shown in FIGS. 17 and 18 extending from the holding portion 27. In some embodiments, the first engagement 24 portion may comprise a female threaded through hole and the second engagement portion 26 may comprise a correspondingly male threaded portion. In some embodiments, the first engagement 24 portion may comprise a male threaded through hole and the second engagement portion 26 may comprise a correspondingly female threaded portion.

[0123] When the male treaded portion is inserted into the female threaded portion or vice versa, the threads engage with each other. This allows for the adjustable magnet holder 21 and the magnet 3 held therein to be maintained in a fixed position above the assay disc 5. The adjustable magnet holder comprises an actuator portion 35 that allows for the adjustable magnet holder 25 to be rotated as shown by arrow 34. Rotation may be clockwise or anti-clockwise and depending on the arrangement of the threaded portions allows the second engagement portion to travel in the Z-axis relative to the assay disc 5 along the first threaded portion 24 leading to movement of the magnet 3 according to arrow 36 as shown in FIG. 18. This allows the adjustable magnet holder 25 and the magnet 3 held therein to be positioned at a location in the Z-axis above or below the assay plate and maintained in this position. The actuation portion may be a slot, grove or depression that is able to receive a corresponding protrusion for example a protrusion of a screwdriver, allen key, hex key or other actuating device.

[0124] With reference to FIG. 6, turntable platter 112 comprises heaters 14 and insulators 16. The insulators 16 are inserted in between the heaters 14 and the turntable and reduce the heat loss due to conduction. As a result, they improve heat efficiency and heat rate.

[0125] The turntable platter 112 comprises a central spindle 18 which itself comprises a longitudinal groove 110 which functions as an inner guide feature to allow coarse alignment of an assay disc 5 onto the spindle 18. Turntable platter 112 comprises boss 1112 which acts as a finer alignment feature.

[0126] The magnetic means of locating and securing the assay disc 5 to the turntable platter 12 are shown most clearly in FIG. 7. Most of the features of the turntable platter 112 and the assay disc 5 are omitted from this Figure for clarity. Assay disc 5 comprises spindle hole 1102 for locating on spindle 18 of turntable platter 112. The turntable comprises disc magnet assembly 114 with north pole 116 and south pole 118. Assay disc 5 comprises corresponding disc magnetic assembly 1104 consists of a north pole disc magnet 1108 and a south pole disc magnet 1110, which for clarity is shown separate from assay disc 5 in FIG. 7, though in use it is fixed to the assay disc 5, for example by using a neoprene sheet. The neoprene sheet may be pre-cut to a shape as shown in FIG. 7 that only allows the assay disc 5 to be sited on the turntable in a specific orientation. The neoprene sheet also provides a frictional grip that prevents the assay disc 5 from skidding when it is spun to high speed.

[0127] The magnet assemblies 114 and 1104 are conveniently positioned at the hub of the apparatus, and accordingly in the embodiment shown, this magnet assembly 1104 has hole 1106 corresponding to spindle hole 1102 of the assay disc.

[0128] A side view and a perspective view of a turntable in accordance with the present invention are shown in FIGS. 8 and 9 respectively.

[0129] With reference to FIG. 10, the turntable power transfer assembly may comprise stationary infrared transceiver 130, stationary coil lower holder 132, ferrite sheet 134, stationary coil 136, stationary coil upper holder 138, rotational coil lower holder 140, rotational coil 142, ferrite sheet 144, rotational coil upper holder 146 and assembly 148 comprising a heater controller and a rotational infrared transceiver. The lower and upper holders for both the stationary coil and the rotational coil act as clamps and may conveniently be made from plastic material.

[0130] Some of the components of the turntable are shown in FIGS. 11 to 16. A schematic perspective view of the stationary coil assembly 150 is shown in exploded view in relation to some of the components in FIG. 12, and FIG. 13 shows the rotational coil assembly 152 positioned on top of the stationary coil assembly 150. IR transceiver stationary and rotational components 130, 155 are shown in FIGS. 14 and 15 respectively. A side view showing the full construction of a turntable assembly is shown in FIG. 16. It starts with the BLDC motor mount component 13 as the base. The first component sitting on top of the BLDC mount is the stationary IR transceiver component 130. It is followed by the stationary coil component 150. Beneath turntable assembly component 112 are rotational IR transceiver component 155 and heater controller circuitry component 154. Components 155 and 154 share the same PCB board.