CENTRIFUGE APPARATUS

Abstract

Provided is a centrifuge apparatus for a processing cartridge, including a rotary plate and at least one cartridge holder, and the cartridge holder is rotatable around its centre axis and arranged off-centre the centre axis of the rotary plate and comprises an inner side wall surrounding a through-going passage, wherein the through-going passage is able to accommodate the processing cartridge; and the inner side wall includes a resilient locking assembly for interaction with at least one cooperating first abutting surface on the processing cartridge, such that the processing cartridge may be inserted into the through-going passage and releasably secured by the locking assembly; and at least one stopping element for interaction with at least one cooperating second abutting surface on the processing cartridge, the at least one stopping element being arranged to retain the processing cartridge at a desired vertical level when the cartridge is releasably secured.

Claims

1. A centrifuge apparatus for a processing cartridge comprising: a rotary plate configured to rotate around its centre axis and comprising at least one cartridge holder, wherein the rotary plate has an upper face and a lower face, the at least one cartridge holder is configured to rotate around its centre axis, is arranged off-centre the centre axis of the rotary plate and comprises an inner side wall surrounding a through-going passage, wherein the through-going passage is configured to accommodate the processing cartridge and extends from the upper face to the lower face of the rotary plate, and at least one stopping element configured to interact with at least one cooperating second abutting surface on the processing cartridge, the at least one stopping element being arranged to retain the processing cartridge at a desired vertical level when the cartridge is releasably secured, wherein the inner side wall comprises a resilient locking assembly for interaction with at least one cooperating first abutting surface on the processing cartridge, such that the processing cartridge is configured to be inserted into the through-going passage and releasably secured by the locking assembly.

2. The centrifuge apparatus of claim 1, wherein the resilient locking assembly is arranged to push the at least one second abutting surface of an accommodated processing cartridge against the at least one stopping element.

3. The centrifuge apparatus of claim 1, wherein the inner side wall comprises at least one of a vertical rib or a recess for interaction with a cooperating recess or vertical rib, respectively, arranged at a circumferential side wall of the processing cartridge, such that the cartridge may only be introduced into the cartridge holder at a specific rotational direction relative a centre axis of the cartridge holder.

4. The centrifuge apparatus of claim 1, wherein the resilient locking assembly is for interaction with the first abutting surface when the first abutting surface is arranged on a circumferential side wall of the processing cartridge.

5. The centrifuge apparatus of claim 1, wherein the stopping element is for interaction with the second abutting surface when the second abutting surface is arranged on a circumferential side wall of the processing cartridge.

6. The centrifuge of claim 1, wherein the resilient locking assembly is biased towards a locking position, in which position an accommodated processing cartridge may be releasably secured.

7. The centrifuge of claim 1, wherein the resilient locking assembly comprises multiple resilient elements spaced around the inner side wall, each of the resilient elements is preferably a pretensioned ball arranged in the inner side wall.

8. The centrifuge of claim 1, wherein the at least one stopping element comprises a recess in the inner side wall of the cartridge holder, wherein the recess extends from an edge portion of the side wall and one end of the recess being distal from the edge portion is for interaction with the second abutting surface, preferably the at least one stopping element comprises at least two of said recesses spaced around the inner side wall.

9. The centrifuge apparatus of claim 3, wherein the inner side wall comprises a vertical rib, for interaction with a cooperating recess arranged at the circumferential side wall of the processing cartridge, and the at least one stopping element comprises a recess in the vertical rib for interaction with the second abutting surface.

10. The centrifuge of claim 1, wherein a cartridge holder element comprises the inner wall of the cartridge holder.

11. The centrifuge of claim 1, wherein the cartridge holder is arranged such that the processing cartridge may enter the through-going passage from the lower face of the rotary plate, during use.

12. A processing cartridge for a centrifuge apparatus comprising: an upper face, a lower face and a circumferential side wall, the circumferential side wall comprising at least one first abutting surface facing away from the upper face and at least one second abutting surface facing away from the lower face, the first abutting surface is part of a section of the circumferential side wall being inclined relative to the centre axis of the cartridge and the at least one second abutting surface is arranged on at least one rib/protrusion at the circumferential side wall.

13. The processing cartridge of claim 12, wherein the circumferential side wall comprises a recess extending from the lower face to the upper face.

14. The processing cartridge of claim 12, wherein the upper face, the lower face, and the circumferential side wall defines a disc-shaped body.

15. The processing cartridge of claim 12, wherein an internal volume of the cartridge comprises a microfluidic processing circuit.

16. (canceled)

17. A method of loading a processing cartridge into a centrifuge apparatus comprising a cartridge loading tray and a cartridge loading piston, the method comprising: loading a processing cartridge onto the cartridge loading tray; moving the cartridge loading tray, such that the centreline of the processing cartridge is in line with the centreline of the cartridge holder; and moving the cartridge loading piston in a vertical direction, such that the processing cartridge is pushed into the at least one cartridge holder, such that the processing cartridge is releasably secured in the cartridge holder.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0046] Embodiments of the invention will now be described in greater detail by way of example only and with reference to the following drawings:

[0047] FIG. 1 is a perspective view of some embodiments of the centrifuge apparatus, according to some embodiments;

[0048] FIG. 2 is a perspective view of the centrifuge apparatus in FIG. 1, wherein the light and optics assembly is removed, according to some embodiments;

[0049] FIG. 3 is a perspective view of the rotary assembly of the centrifuge apparatus in FIGS. 1 and 2, according to some embodiments;

[0050] FIG. 4 is a top view of the cartridge holder of the centrifugal apparatus in FIGS. 1 and 2, comprising a releasably secured processing cartridge, according to some embodiments;

[0051] FIG. 5 is a side view of the cartridge holder in FIG. 4, according to some embodiments;

[0052] FIG. 6 is a bottom view of the cartridge holder in FIG. 4, according to some embodiments;

[0053] FIG. 7 is a cross-sectional side view of the cartridge holder in FIG. 4, according to some embodiments; and

[0054] FIG. 8 is an exploded view of the cartridge holder in FIG. 4, according to some embodiments.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0055] A perspective view of an exemplary centrifuge apparatus 1 according to the disclosure is shown in FIG. 1. Further views of the centrifuge apparatus, wherein certain elements have been removed for illustrative purposes, are shown in FIGS. 2 and 3.

[0056] The centrifuge apparatus 1 may be used for liquid processing and flow control within microchips or cartridges used for analytical assays, chemical processing etc. The microchips or cartridges are in the present specification commonly termed as processing cartridges. By use of the present centrifuge apparatus, controlled processing of fluidic elements in at least two dimensions may be performed.

[0057] With reference to FIGS. 1-3, the centrifuge apparatus 1 comprises a horizontally arranged rotary plate 3. The rotary plate 3 has an upper face 4 and a lower face 5 and is adapted to be rotated about a first vertical axis C1 which intersects through the centre of the plate 3 (i.e. the centre axis of the plate).

[0058] The centrifuge apparatus 1 further comprises two cartridge holders 15,15. The cartridge holders are arranged in the rotary plate 3 and are symmetrically placed on opposite sides of the first axis C1, as viewed in FIG. 3. Each cartridge holder is arranged to rotate about a respective vertical second axis C2, C2 (i.e. the centre axis of each cartridge holder) and may be rotated both clockwise and counter clockwise about its second axis. Each cartridge holder is adapted to accommodate and releasably secure a processing cartridge 2. When secured in the cartridge holder, the processing cartridges will corotate with the respective cartridge holder about the second axis C2, C2 (and also rotate about the first axis C1 when the rotary plate 3 is turned). Details of the cartridge holder and the external design of the processing cartridge are shown in FIGS. 4-8 and further described below.

[0059] The centrifuge apparatus 1 further comprises a first servo-mechanical motor 17a and a second servo-mechanical motor 17b. Generally, servo-mechanical motors (or servo motors) are representative of motors where exact rotational speed and rotational position may be defined and monitored at any time.

[0060] The servo-mechanical motors 17a,17b at opposite sides/faces of the rotary plate 3. The first motor 17a is positioned below the rotary plate 3, while the second motor 17b is placed above.

[0061] The first motor 17a is arranged to rotate the rotary plate 3 about the first axis C1. To this end, the first motor 17a may be fixed or rigidly coupled to the rotary plate 3 via a first drive shaft (not shown). The first drive shaft may be a separate shaft or the output shaft of the first motor 17a. The first drive shaft is co-axial with the first axis C1. The rotational ratio of the first motor 17a to the first drive shaft is here 1:1, i.e. one turn of the motor corresponds to one turn of the shaft.

[0062] The second motor 17b is adapted to drive or rotate the two cartridge holders 15, 15. The second motor 17b is mechanically connected or coupled to each of the cartridge holders 15, 15, as illustrated in more detail in FIG. 3.

[0063] With reference to FIG. 3, the second motor 17b has a second drive shaft 18 co-axial with the first axis C1 (and aligned with the first drive shaft). The rotational ratio of the second motor 17b to the second drive shaft 18 is here 1:1. The second drive shaft 18 terminates at the rotary plate 3 with a gear or gear wheel 19. The gear 19 is rigidly coupled to the second drive shaft 18, but not rigidly coupled to the rotary plate 3. The gear 19 is further engaged with two sets of intermediate gear assemblies 20, 20, one set for each cartridge holder. Each of the intermediate gear assemblies 20, 20 is further engaged with a gear 21 or set of teeth (see FIGS. 5-7) arranged on an outer circumference of a respective cartridge holder 15, 15. The gear ratio between the second motor 17b and the gear 21 (or consequently the cartridge holder) may for instance be 72:1, but any suitable ratio is possible.

[0064] The centrifuge apparatus may further comprise suitable control means (not shown) for controlling the rotation of the rotary plate 3 and the cartridge holder(s) 15, 15.

[0065] In some embodiments, the centrifuge apparatus comprises a first optical analysis and control system 22 comprising a strobe light source and a camera directed at the rotary plate 3 and the cartridge 2. This is used for monitoring and controlling the centrifugal process for directing various reagents, samples, analytical beads, solvents etc. in the fluid circuit of a cartridge 2.

[0066] The centrifuge apparatus also comprises a second optical analysis and control system 23. This system produces a light beam which is directed at the cartridge 2 and is used for analysing a processing result obtained in the fluid circuit of the cartridge. The processing result may for instance be the final product of a chemical reaction, or a set of analytical beads obtained in an assay of a sample, performed in the fluid circuit 16. The optical analysis and control system 23 may further comprise a camera for visualising the geometry of the cartridge 2 for monitoring where on the cartridge 2 the light beam is hitting. This is used for fine tuning the rotation of the rotary plate 3 and the cartridge holder 15 for precise positioning of the cartridge 2 relative to the light beam. Reflected light from the light beam, or light emitted from the processing result in response to the light beam, is examined for determining properties of the processing result.

[0067] Alternative and/or additional analysis and control systems are described in for instance WO 2011/081531 (p. 8 line 31-p. 10 line 23), which is incorporated by reference.

[0068] The principle solution of obtaining the required rotational movement of the rotary plate and the cartridge holders by use of two coaxial drive shafts, each connected to a separate motor, is disclosed in for instance WO 2011/081521 and U.S. Pat. No. 6,593,143. Although the inventive centrifuge apparatus is described by reference to a specific and preferred design for obtaining the required rotational movement of the rotary plate and the cartridge holder (i.e. two motors having coaxial drive shafts), other solutions would be obvious for the skilled person based on the present disclosure. Such alternative solutions may for instance comprise the use of a first motor for rotating the rotary plate and a separate second motor for each of the cartridge holders. The second motors may for instance be arranged on or inside the rotary plate, preferably symmetrically arranged in relation to the centre axis of the rotary plate.

[0069] Details of an advantageous cartridge holder, and a suitable processing cartridge 2, arranged in the rotary plate 3 of the centrifuge apparatus 1 are shown in FIGS. 4-8.

[0070] The cartridge holder comprises an inner side wall 7 surrounding a through-going passage 6 extending from the upper face 4 to the lower face 5 of the rotary plate 3. The through-going passage, or at least the end of the passage through which the cartridge is inserted, has a cross-section substantially corresponding to an outer circumference of the processing cartridge 2, such that the passage 6 is able to accommodate the processing cartridge 2.

[0071] The processing cartridge 2, see FIGS. 6-8, comprises an upper face 27, a lower face 28 and a circumferential side wall 29 defining a disc-shaped body. The circumferential side wall comprises a locking surface 9 (i.e. at least one first abutting surface) and multiple stopping surfaces 11 (i.e. at least one second abutting surface). The locking surface 9 face away from the upper face 27 of the processing cartridge. In some embodiments, the locking surface is part of a lower section of the circumferential side wall 29 being angled relative to the centre axis (C3) of the cartridge. The multiple stopping surfaces face away from the lower face 28 and are arranged on top of two protrusions/ribs 30 in the circumferential side wall 29 and on a shoulder element 31 within the vertical recess 13. In some embodiments, the circumferential wall of the processing cartridge, as well as the inner wall of the cartridge holder, have a substantially circular cross-section. However, the circumferential wall of processing cartridge and the corresponding inner wall of the cartridge holder, may in some embodiments have any suitable cross-section, such as rectangular, square or elliptic.

[0072] The inner side wall 7 comprises multiple balls 8 pretensioned by springs 25 (i.e. a resilient locking assembly comprising multiple resilient elements) for interaction with the cooperating locking surface 9 (i.e. the at least one first abutting surface) on the processing cartridge 2. The balls 8 are positioned at the same vertical level along the inner wall and extend through multiple corresponding openings 26 in the inner wall 7. Thus, when the processing cartridge is inserted into the passage 7, the balls 8 are initially pushed against their respective springs 25 allowing an upper section of the cartridge to pass (i.e. the cartridge is pushed with a force sufficient to overcome the elastic force provided by the springs). After passage of the upper section of the processing cartridge, the balls are forced by the respective springs to push against the locking surface 9 at the lower section. In order to hold the processing cartridge at a predetermined vertical level when accommodated in the cartridge holder, the cartridge holder comprises two recesses 10 arranged in the inner wall 7 and one recess (not shown) arranged in a vertical rib 12 (i.e. stopping elements). Each of the two recesses 10 in the inner wall interact with a respective stopping surface 11 arranged on one of the two ribs/protrusions 30 of the processing cartridge, while the recess in the vertical rib 12 interacts with the shoulder element 31 in the recess 13 of the processing cartridge. In this manner, the processing cartridge may be inserted into the cartridge holder and releasably secured at a predetermined level. During processing of a processing cartridge in a dual axis centrifuge apparatus, the processing cartridge is subjected to high G-forces and fast changes in rotation around its centre axis C2. To obtain reproducible results of high accuracy, the vertical level of the processing cartridge should be kept at a predetermined level at all times. An advantage of the present cartridge holder comprising a resilient locking assembly and stopping elements is that the processing cartridge is securely and releasably held at a predetermined vertical level throughout the processing. A further advantage of having the locking surface 9 and the stopping surfaces 11 arranged on the circumferential side wall of the processing cartridge is that the whole upper and lower face of the cartridge is visible to optical readout analysis and control systems 22, 23, allowing maximum utilization of the cartridge volume and a superior flexibility when designing a required fluid circuit 16.

[0073] The cartridge holder 15 of FIGS. 4-8 comprises three main ring-shaped elements, a first element 35 (i.e. a first cartridge holder element) comprising the inner wall 7, a second element 36 comprising a ball bearing 37, and a third element 38 comprising the gear 21. The second element have an outer section 39 rigidly connected to, or embedded in, the rotary plate 3 and an inner section 40 rigidly connected to the first element and the third element. Thus, when the third element is rotated by interaction between the gear 21 and the intermediate gear assembly 20, the first element rotates relative the rotary plate 3.

[0074] The cartridge holder and the processing cartridge according to the disclosure is described by reference to some embodiments as disclosed in FIGS. 4-8. However, other types of resilient locking assemblies and stopping elements suitable for use in a cartridge holder having a through-going passage 6, as well as corresponding locking surfaces and stopping surfaces on a processing cartridge, would be obvious to the skilled person based on the teachings of the present specification. Alternative locking assemblies may for instance comprise any type of suitable resilient clip fasteners etc. arranged in or on the inner wall for direct interaction with locking surfaces on the processing cartridge. Further, in some embodiments, the cartridge holder may comprise a locking assembly and stopping element suitable for interaction with a processing cartridge, wherein the locking and stopping surfaces are a section of the lower and upper face of the processing cartridge, respectively.

[0075] The design of the cartridge holder, in particular the combination of a through-going passage and the resilient locking assembly, allows for a highly advantageous automatic loading and/or ejection of a processing cartridge into/out of the cartridge holder.

[0076] During use, the processing cartridge is inserted into the centrifuge apparatus via a cartridge loading tray 24 (shown in FIG. 1 in the closed position). The cartridge loading tray is substantially similar to a common CD loading tray. The tray is arranged to accommodate a processing cartridge 2 and comprises a central opening (not shown) arranged below the processing cartridge arranged on the tray. When the cartridge loading tray is in the open position (not shown), an operator may place a processing cartridge 2 upon the cartridge loading tray 24 for subsequent insertion into the centrifuge apparatus (i.e. by moving the cartridge loading tray into the closed position). In the closed position, the processing cartridge may be arranged directly below one of the cartridge holders 15,15. The centrifuge apparatus features a cartridge loading piston 32 for loading the processing cartridge into one of the cartridge holders 15, 15 and a cartridge ejection piston 33 for ejecting the processing cartridge out of one of the cartridge holders. The loading and ejection pistons are coaxially arranged on opposite sides of the cartridge loading tray and the rotary plate 3, and are controlled by a camshaft assembly 34. During loading of the processing cartridge, the loading piston 32 is moved vertically upwards to engage the lower face 28 of the processing cartridge and push the cartridge 2 into the passage 6 of the cartridge holder 15 from below. The loading piston 32 applies a force to the cartridge which is sufficient to overcome the elastic force of the resilient locking assembly. After processing, the processing cartridge is ejected from the cartridge holder 15 to the cartridge loading tray 24. To eject the cartridge, the ejection piston 33 is moved vertically downwards to engage the upper face 27 of the processing cartridge and pushes the cartridge into the tray. The ejection piston 33 applies a force to the cartridge 2 which is sufficient to overcome the elastic force of the resilient locking assembly 8, 25.

[0077] The present disclosure is described by reference to a specific mechanical camshaft assembly 34 for automatic loading/ejection of the cartridge 2 to/from the cartridge holder from a cartridge loading tray arranged below the cartridge holder. However, other solutions for obtaining an automatized loading/ejection of the cartridge 2 to/from the cartridge holder would be obvious for the skilled person based on the present disclosure.

[0078] The processing cartridge 2 comprises an internal fluidic or microfluidic circuit. A schematic fluidic circuit 16 is shown in the cartridges of FIGS. 1-3 for illustrative purposes. The fluidic circuit of the processing cartridge may be designed for processing a sample, for instance performing various types of analytical assays on a whole blood sample, or for processing various chemical reactions including polymerase chain reaction (PCR) and synthetic chemistry reactions. The cartridge may for instance include micro channels and a variety of fluidic cavities for handling, processing and transporting nL-quantities, L-quantities and mL-quantities of various liquids. Further, the cartridge may be optically transparent or translucent. This allows studying of transportation of liquids, colour development, separations, etc. throughout the cartridge. The sample may be a fluidic sample (or a fluidized solid sample), a liquid, a blood sample, etc. Also, the cartridge may contain one or more reagents. Exemplary fluidic circuits that may be used in a processing cartridge suitable for the present centrifuge apparatus 1 is disclosed in for instance WO 2011/081530 A1, the content of which herein is incorporated by reference. Further, various methods that may be performed in such fluid circuits, as well as suitable fluid circuits, are disclosed in PCT/EP2015/063811, PCT/EP2015/063817 and PCT/EP2015/063824. Further, the processing cartridge will commonly comprise a port for introduction of a sample. However, in some instances, for instance if the processing cartridge is used for the manufacture of small quantities of chemicals/drugs having a short shelf life, the required reagents may be introduced during manufacture of the processing cartridge.