WO2014111721A1

WO2014111721A1 - Microfluidic platform

Info

Publication number: WO2014111721A1
Application number: PCT/GB2014/050128
Authority: WO
Inventors: Dominic BANKS
Original assignee: The University Of Liverpool
Priority date: 2013-01-18
Filing date: 2014-01-17
Publication date: 2014-07-24
Also published as: GB201300946D0

Abstract

Embodiments of the present invention provide a rotatable microfluidic platform (100), comprising a disc formed by first and second discs having, respectively, first and second planar surfaces in abutting contact, a microfluidic system (120) formed between the first and second discs (310, 320), comprising a separation chamber (230, 235) formed in at least the first surface, at least one measurement reservoir formed in at least the second surface, a valve inlet channel arranged between an intermediate portion of the separation reservoir and a heat-rupturable valve (250), the valve inlet channel being formed by a channel in the first surface and the planar second surface, and a valve outlet channel arranged between the valve and the at least one measurement chamber (251, 252), the valve outlet channel being formed by a channel in the second surface and the planar first surface, wherein the valve is arranged between the first and second surfaces at a junction between the valve inlet channel and the valve outlet channel.

Description

Microfluidic Platform

Embodiments of the present invention relate to a rotatable microfluidic platform for optically analysing a fluid.

Background

It is known to optically analyse one or more properties of a fluid, such as blood, following separation of the fluid into component parts. In order to allow for such analysis, a rotatable microfluidic platform may be used. The platform is typically disc shaped having a central aperture for receiving a spindle of an apparatus arranged to rotate the platform to cause separation of the component parts of the fluid.

It is an object of embodiments of the invention to at least mitigate one or more of the problems of the prior art.

Brief Description of the Drawings

Embodiments of the invention will now be described by way of example only, with reference to the accompanying figures, in which:

Figure 1 shows a microfluidic system according to an embodiment of the invention;

Figure 2 shows an enlarged portion of the microfluidic system according an embodiment of the invention;

Figure 3 shows first and second discs forming the microfluidic system according to the embodiment of the invention; Figure 4 shows a cross section through the microfluidic system according to an embodiment of the invention; and

Figure 5 shows a portion of a microfluidic system according to a further embodiment of the invention. Detailed Description of Embodiments of the Invention

Figure 1 illustrates a microfluidic platform 100 according to an embodiment of the invention. The microfluidic platform 100 is formed as a disc having a central aperture 110 for receiving a spindle of an apparatus arranged to rotate the platform 100. Whilst the aperture is shaped in Figure 1 as a circular hole it will be realised that the aperture may be shaped otherwise, such as a square or otherwise shaped to engage the platform 100 on the spindle with a known, fixed, orientation. For example, as shown in Figure 5, the aperture 510 may be generally circular and include a key feature for engaging with a corresponding feature on the spindle of the apparatus to ensure a specific orientation of the platform 100 on the spindle.

The microfluidic platform 100 comprises a microfluidic system formed in the disc 100 and generally denoted as 120. As will be explained, the microfluidic platform 100 is formed from first and second discs arranged in abutting planar contact. That is, the planar major surfaces of the first and second discs are brought substantially into contact and affixed to one another, such as by a suitable adhesive. Each of the first and second discs has a portion of the microfluidic system 120 formed therein, such that the microfluidic system 120 is formed by the combination of the components in both discs. The microfluidic system is formed by indented regions in the inwardly- facing surfaces of one or both discs. Microfluidic channels and reservoirs within the system 120 are formed as recesses in the inwardly-facing surfaces of one or both of the first and second discs. Figure 2 shows the microfluidic system 120 in close up view. Figure 3(a) is a view of the first disc 310 and Figure 3(b) is a view of the second disc 320 with the first and second discs separated. Figure 4 is a cross section through the first and second disc when arranged for use. The system 120 comprises an inlet 210 for receiving a fluid to be analysed. The fluid may be blood, although the usefulness of the present invention is not limited in this respect. In one embodiment, the inlet is formed as an aperture through the first disc i.e. an aperture formed into the first disc. However, in another embodiment as shown in Figure 5 the inlet 520 is formed as a protrusion upward from the surface of the first disc with the protrusion 520 having a vertically oriented channel therein. The channel may be arranged to taper so that a mouth of the channel is wider than the channel at a plane of the first disc. Advantageously, the wide mouth of the channel enables location of a needle, pipette or the like containing fluid within the inlet to receive fluid from the needle or pipette.

Fluid received in the aperture is directed into a fluid reservoir 215 which is formed as an elongate recess in the inward facing surface of the first disc. The second disc does not have a corresponding aperture to the inlet 210 such that the received fluid is directed into the reservoir 215. The reservoir is provided to store sufficient fluid to perform a separation process upon, as will be explained. The recesses forming channels and reservoirs in the first and second discs may be made by machining the disc surface or moulding the disc, for example. A portion of the reservoir 215 facing an outer edge of the disk i.e. away from the spindle aperture 110 has a fluid channel 220 leading there-from providing an outlet from the reservoir 215 as an inlet to subsequent components of the fluidic system. The portion of the reservoir 215 proximal to the channel 220 facing the outer edge of the disc is arranged to direct fluid toward the channel 220. Such arrangement may be achieved by curving or angling the lower side of the reservoir toward the channel i.e. in a V or U-shape such that fluid subjected to gyroscopic force from the platform 100 being rotated is directed toward the inlet channel 220.

The inlet channel 220 leads downward, i.e. toward the outer edge of the disc, to a first separation chamber 230. The inlet channel 220 is provided to an intermediate or upper portion of the first separation chamber 230. A region of the first chamber 230 above the inlet channel 220 has a separation channel 231 extending upward, i.e. toward the spindle aperture 110, to a second separation chamber 235. The second separation chamber 235 is arranged generally above or inward of the first separation chamber 230. Whilst in the embodiment shown in Figure 1 there are two separation chambers 230, 235 in other embodiments the chambers may be combined i.e. there may be only one chamber. The separation channel 231 acts as a pinch-point to reduce liquid flow between the first and second separation chambers 230, 235. It will be realised that the pinch-point may be included in an embodiment including only one separation chamber by forming a narrow portion within the chamber. Advantageously, the separation channel or pinch-point reduces remixing of the fluid within the separation chamber(s) after separation. At a top of the second separation chamber 235 i.e. directed toward the spindle aperture 110 there is provided an overflow outlet directed toward an overflow chamber 236. The overflow chamber 236 is provided to receive excess fluid from the separation chamber(s) 230, 235. That is, when fluid is drawn into the one or more separation chambers 230, 235 from the fluid reservoir 215 under the influence of gyroscopic force as the platform 100 rotates, should the separation chamber(s) 230, 235 become full then excess fluid is caused to flow into the overflow chamber 236. The platform 100 further comprises an outlet 238 for allowing gas within the system 120 to be expelled. The outlet is arranged above the separation chambers 230, 235 i.e. closer to the centre of the disc such that as fluid fills the separation chambers 230, 235 gas within the system 120, such as air, is expelled through the outlet 238 to prevent only partial filling of the separation chambers 230, 235. In the embodiment shown in Figure 2 the outlet 238 is arranged at a distal end of a channel 237 leading from the overflow chamber 236. At an intermediate location of the separation channel 231, there is arranged a valve inlet channel 241 leading to a burst valve 250. The valve inlet channel 241 provides an outlet capillary for the separation channel 231. In embodiments including only one separation chamber, the valve inlet channel 241 is arranged at an intermediate point of the chamber.

The location of the inlet channel 241 adjoining the separation channel 231 or separation chamber controls a volume of fluid drawn into the valve inlet channel 241 and subsequent portions of the system 120. The volume of fluid drawn into the valve inlet channel 241 is that within the separation channel 231 and chamber 235 between the valve inlet 241 and overflow. As can be appreciated from Figure 2 an overflow channel leading from a top of the second separation chamber 235 to the overflow chamber 236 includes an acute downward bend 239 such that a predetermined volume of fluid is present within the second separation chamber 235 between the valve inlet 241 and the bend 239. Excess fluid above the predetermined volume flows into the overflow chamber 236. For example the volume of the second separation chamber 235 between the valve inlet 241 and the bend 239 may be 20μ1, although it will be realised that this is merely exemplary. The valve inlet channel 241 is upwardly angled in relation to the separation channel 231 such that fluid within the separation channel 231 is discouraged from entering the valve inlet channel 241 under the influence of gyroscopic force during rotation of the disc. It will be realised that an increasingly acute angle of the valve inlet 241 may be utilised to discourage fluid entering the valve inlet, particularly when the fluid is blood and it is desired to discourage the red blood cells entering the inlet 241. The upward angle of the inlet channel 241 may also prevent all of the fluid in the second separation chamber 235 entering the inlet 241. Therefore the volume of fluid in the second separation chamber 235 may be increased accordingly. The valve inlet channel 241 is formed in the inward facing surface of the first disc 310. At a distal end of the valve inlet channel 241 the burst valve 250 is formed between the first and second discs 310, 320. The valve inlet channel 241 diverges or widens at the burst valve 250 such that the burst valve 250 has a larger cross section than the valve inlet channel 241. The valve 250 is arranged such that, in its unburst or closed state, flow of the fluid there-through is prevented. With the valve closed, fluid is retained within the first disc 310, at least in the region of the valve 250.

In the opposing second disc 320, a valve outlet channel 242 is formed. The valve outlet channel provides a capillary to one or more measurement chambers, as will be explained. With the valve 250 closed, fluid is prevented from entering the valve outlet channel 242. The valve outlet channel 242 is shaped the same as the valve inlet channel 241 proximal to the valve 250 i.e. the valve outlet channel has a wider cross section adjacent to the valve 250 than otherwise along its length. The valve outlet channel is angled toward the edge of the disc as it extends away from the valve 250 i.e. the valve outlet channel 242 slopes downward in the arrangement of Figure 3 away from the spindle aperture 110. When the valve 250 is opened or burst fluid is caused to flow along the valve outlet channel 242 under the influence of gyroscopic force from the disc 100 spinning. Figure 4 shows a cross-section of platform 100 through the valve 250. As can be appreciated, the valve 250 is formed in first and second discs 310, 320 which are substantially in planar contact affixed together by a layer of adhesive 360. The valve inlet 330 is recessed into the first disc 310. The valve outlet 340 is recessed into the second disc 320. The valve 250, is formed by a membrane 350 partially trapped, at least in the region of the valve 250, between the first and second discs 310, 320. The membrane may, in one embodiment, be arranged between the discs 310, 320 across substantially the entire interior surfaces of the discs 310, 320. However in another embodiment the membrane 350 may be confined generally to the region of the valve 250.

The membrane 350 may be manufactured from a material which may be caused to melt following impartation of energy thereto. In one embodiment the valve 250 may be manufactured from a polyester material, for example Mylar or other biaxially- oriented polyethylene terephthalate material. The membrane 350 may be selected to melt at a temperature which does not alter properties of the fluid in contact with the membrane 350 on the inlet 241 side. The valve may be formed by coating, for example, the first disc 310 interior surface with adhesive, placing the membrane over the inlet 241 and bringing the second disc into contact with first disc 310, adhesive 360 and membrane 350 such that the platform 100 is formed. It will be realised that the valve 250 may also be formed in the reverse process by applying adhesive 360 to second disc 320.

The membrane 350 may be formed from a dark coloured material, such as black, or from a material coated with a dark colour such that the membrane 350 absorbs as much energy from incident radiation as possible.

At a distal end of the outlet channel 242 from the valve 250, one or more measurement reservoirs 251, 252 are arranged. Each measurement reservoir 251, 252 is provided to allow optical measurement of received fluid. In the embodiment shown in Figures 1-3 the platform 100 comprises two measurement reservoirs 251, 252 although it will be realised that the platform may comprise one or more reservoirs. As can be appreciated from Figure 3, each reservoir 251, 252 is formed between the first and second discs 310, 320. That is, each of the first and second discs 310, 320 has a portion of each reservoir 251, 252 formed therein. The valve outlet 242 proximal to the reservoirs 251, 252 branches, such that a separate branch is directed to each reservoir 251, 252. In some embodiments, the membrane 350 may extend beyond the region of the valve 250 to surround the measurement reservoirs 251, 252 to improve optical measurement of the liquid within the reservoirs 251, 252. The membrane when dark in colour prevents light being transmitted through the disc at locations other than through the reservoirs 251, 252.

Each reservoir 251, 252 may be provided with an outlet 261, 262 for allowing gas to be expelled from the respective reservoir 251, 252 as fluid flows toward and into each reservoir from the outlet channel 242. The outlets 262, 262 are arranged upward or inward toward the centre of the disc from the respective reservoir 251, 252. The inward location of the outlets 261, 262 prevents or at least discourages fluid from escaping through the outlets 261, 262.

In use, the platform 100 is provided with a fluid sample via the inlet 210 to at least partially fill the fluid reservoir 215. The fluid is preferably a fluid which may be optically analysed following rotation of the platform 100. The fluid may be blood. When the platform 100 is rotated by a suitable apparatus via spindle aperture 110 the fluid is drawn by gyroscopic force via fluid inlet 220 into the first separation chamber 230 at a lower region thereof. Fluid eventually fills the first separation chamber 230, separation channel 231 and valve inlet channel 241. Fluid may also at least partially or completely fill the second separation chamber 242 235. Due to the gyroscopic force exerted on the fluid in the separation chamber(s) 230, 235 and channel 231 the fluid is caused into its component parts, such as white and red cells and plasma.

Following rotation of the platform 100 and separation of the fluid rotation of the platform 100 may be stopped. Properties of the fluid within the one or both of the measurement reservoirs 251, 252 may be determined by transmission or reflectance measurement.

The platform may be positioned so as to align the valve 250 with a means to impart energy to the membrane 350, such as a light emitter in the form of a laser or one or more LEDs which may be provided with a focussing lens. The light emitter may have a wavelength of 532nm (green) or longer, such as 635-660 nm (red) or 780-1980nm (Near infra-red).

The laser is operated to cause heating of the membrane 350 until the valve 250 opens. Once the valve 250 opens fluid is able to flow into the valve outlet channel 242 in the second disc 320 and into the measurement chambers. The fluid may then be analysed by transmitting radiation, such as light, through the measurement reservoirs 251, 252 to a suitable detector such as a CCD or other light detector arranged at an opposing side of the disc to the light source. However, in a reflectance mode of operation the light detector is arranged at the same side of the disc as the light source to receive light reflected from the fluid in the reservoir(s) 251, 252. In embodiments using reflectance measurement a geometry of the measurement reservoirs 251, 252 may be adapted to increase an amount of reflected light, such as by forming the reservoirs 251, 252 to have a greater surface area i.e. being wider. In some embodiments an opposing side of each reservoir from the light source may be coated or otherwise formed to have a reflective surface.

All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The claims should not be construed to cover merely the foregoing embodiments, but also any embodiments which fall within the scope of the claims.

Claims

1. A rotatable microfluidic platform, comprising: a disc formed by first and second discs having, respectively, first and second planar surfaces in abutting contact; a microfluidic system formed between the first and second discs, comprising: a separation chamber formed in at least the first surface; at least one measurement reservoir formed in at least the second surface; a valve inlet channel arranged between an intermediate portion of the separation reservoir and a heat-rupturable valve, the valve inlet channel being formed by a channel in the first surface and the planar second surface; and a valve outlet channel arranged between the valve and the at least one measurement chamber, the valve outlet channel being formed by a channel in the second surface and the planar first surface; wherein the valve is arranged between the first and second surfaces at a junction between the valve inlet channel and the valve outlet channel.

2. The platform of claim 1, wherein the valve comprises a membrane arranged between the first and second discs to separate the valve inlet and the valve outlet.

3. The platform of claim 2 wherein the membrane is formed from a polyester- based material.

4. The platform of claim 2 or 3, wherein the membrane is dark-coloured.

5. The platform of any of claims 1 to 4, wherein the separation chamber comprises first and second separation chambers separated by a separation channel.

6. The platform of claim 5, wherein the valve inlet adjoins the separation channel.

7. The platform of claim 5 or 6 wherein the valve inlet is arranged to intersect the separation channel at an acute angle with respect to a centre of the platform.

8. The platform of any preceding claim, wherein the separation chamber is arranged to store a predetermined volume of fluid between the valve inlet and a centre of the platform.

9. The platform of any preceding claim, wherein the valve outlet is arranged at an obtuse angle with respect to a centre of the platform.

10. The platform of any preceding claim wherein the microfluidic system comprises a fluid reservoir for holding a received fluid.

11. The platform of claim 10, wherein a channel is arranged between a region of the reservoir proximal to an outer circumference of the platform and a region of the separation chamber proximal to the outer circumference of the platform.

12. The platform of any preceding claim comprising a plurality of measurement reservoirs for storing fluid for optical measurement.

13. The platform of claim 12, wherein each measurement reservoirs is arranged in a respective branch from the valve outlet.

14. The platform of any preceding claim wherein the, or each, measurement reservoir is arranged to receive a separated portion of fluid for optical measurement.

15. The platform of any preceding claim wherein the, or each, measurement reservoir comprises an outlet for allowing gas to be expelled from the reservoir.

16. The platform of any preceding claim wherein the first and second discs are joined by an adhesive.

17. The platform of any preceding claim, comprising an overflow chamber arranged to receive excess fluid from the separation chamber.

18. The platform of claim 17 comprising a conduit arranged between an upper portion of the separation chamber and the overflow chamber, wherein the conduit comprises a bend having an obtuse angle with respect to a centre of the platform.

19. The platform of claim 18 wherein the separation chamber has a predetermined volume between the bend and the valve inlet.

20. The platform of claim 17, 18 or 19 wherein the overflow chamber comprises an outlet for allowing gas to be expelled from the separation chamber via the overflow chamber.

21. A method of analysing a fluid, comprising: receiving a portion of the fluid in a microfluidic system formed between the first and second discs having, respectively, first and second planar surfaces in abutting contact, of a fluid platform; rotating the fluid platform to at least partially separate components of the fluid within a separation chamber formed in at least the first surface; providing incident radiation to a heat-rupturable arranged at an end of an valve inlet channel extending from an intermediate portion of the separation chamber, the valve inlet channel being formed by a channel in the first surface and the planar second surface, such that the valve ruptures to cause fluid to flow into a valve outlet channel arranged between the valve and at least one measurement reservoir, the valve outlet channel being formed by a channel in the second surface and the planar first surface; optically measuring one or more properties of the fluid in the measurement reservoir.

22. The method of claim 21, wherein the providing incident radiation comprises directing a laser toward a portion of the platform comprising the valve.

23. The method of claim 20 or 21, comprising stopping rotation of the fluid platform so as to align the valve with a radiation source.

24. The method of claim 21, 22 or 23 comprising introducing fluid into a fluid reservoir of the microfluidic system.

25. The method of any of claims 21 to 24, wherein the rotation of the platform causes fluid to flow from a region of the fluid reservoir proximal to an edge of the platform into a region of the separation chamber proximal to an edge of the platform.

26. An apparatus substantially as described hereinbefore with reference to the accompanying drawings.

27. A method substantially as described hereinbefore with reference to the accompanying drawings.