WO2010084190A1

WO2010084190A1 - Fluidic single use valve and microfluidic systems incorporating said valve

Info

Publication number: WO2010084190A1
Application number: PCT/EP2010/050801
Authority: WO
Inventors: Antonio Ricco; Jose L Garcia Cordero; Jens Ducree; Luke Lee; Fernando Benito Lopez
Original assignee: Dublin City University
Priority date: 2009-01-23
Filing date: 2010-01-25
Publication date: 2010-07-29

Abstract

A fluidic device (100) comprising first (120) and second (130) formations separated from one another by one or more localised photoactuable separators (140) (141), the photoactuable separators (140) (141) being responsive to photoactuation to transform from a first closed state to a second open state, adoption of the open state defining a fluid path between each of the first (120) and second (130) formations. The device is desirably rotatable, rotation of the device effecting a biasing of the fluid from a first formation into a second formation.

Description

Title

Fluidic single use valve and microfluidic systems incorporating said valve

Field of the Invention The present invention relates to valves for controlling the flow of a fluid through a flow path within a microfluidic device. Desirably the flow path is from one formation to another formation. The formations may be channels or reservoirs or other defined volumes within the microfluidic device for operably accommodating a fluid. The invention more particularly relates to a single use valve for use in microfluidic systems, actuation of the valve enabling fluid flow from one formation of the microfluidic system to another formation of the system. The invention further relates to a microfluidic reagent storage device comprising at least one single use valve. The invention further relates to point of care (POC) diagnostic devices comprising two or more microfluidic formations separated from one another by single use valves.

Background

Point-of-care (POC) diagnostic devices are known. Such devices are intended for use at or near the patient being tested. It is envisaged that such devices will revolutionize and improve global public health by diagnosing diseases in a timely manner, preventing epidemics, controlling chronic health conditions, tailoring treatments, and decreasing national health system costs. As it is intended that such POC devices will be used outside controlled laboratory conditions and may be used in deprived- resource settings it is important that the devices have the capacity to be portable, possible disposable, are available at low cost, can be used simply and are sufficiently rugged for their intended environment of use. They also need to deliver assay results with similar sensitivity, reproducibility, and selectivity to centralized laboratory tests. Finally, it is desirable that POC devices should operate with minimal, non-expert operator attention. Of the different technologies that currently exist to address this issue, microfluidic and lab-on-a-chip technologies are being used to provide such POC diagnostic systems. The lab-on-a-chip vision is to miniaturize clinical laboratory processes, integrating them onto disposable units the size of a credit card using minute amounts of complex samples and precious reagents. These autonomous and integrated chips would consist of different modules or components that would handle a complex sample such as blood, preparing it and mixing it with the necessary reagents to produce a signal that can be read by a miniaturized, even an on-chip, detection system. Microfluidic valves and pumps are ubiquitous in integrated microfluidic systems, but fluid actuation and control can greatly add to the fabrication costs of integrated microsystems: external actuators may be needed to drive them or their implementation into manufacturing processes may be a costly engineering challenge. There is therefore a number of problems with the practical use of microfluidic systems within POC devices.

It is understood that on-chip long-term reagent storage will be necessary for market success of many microfluidic point-of-care devices. Although both wet and dry reagent storage in microfluidic compartments has been reported, a key issue remains: delivering the reagents after an extended storage time, in a well-controlled fashion. There are problems in existing arrangements of providing a sealed environment for the long term storage of the reagents within the POC device. Furthermore, known approaches do not lend themselves for use in complex, integrated microfluidic systems comprising a plurality of formations within a single device. There are therefore a number of problems with existing arrangements.

Summary

These and other problems are addressed in accordance with the present teaching by a microfluidic device comprising a first and second formations separated from one another by a single use valve. In a first arrangement, the microfluidic device is a multilayer system with the first and second formations are desirably provided in first and second layers of the fluidic device and a valve is provided to control fluid passage therebetween. The valve provides a separating membrane between the two formations and on photo-actuation is configured to rupture to provide a fluid path between the two formations. In a first arrangement the valve is provided in a third layer separating the first and second layers. The third layer may optimally be a film such as a plastic film having a structural integrity defining a continuous sheet. The sheet may be provided as a discrete leaf which may be stored in a stack or roll prior to use. In fabrication of the microfluidic device, the third layer is desirably laid down onto the first or second layers as a single solid element for example by unrolling it from its stored configuration.

The valve is desirably formed by providing at a predefined location within or on the third layer an absorber which on exposure to a provided electromagnetic radiation signal will heat and effect a localised melting of the third layer to provide fluid communication between the first and second formations.

Desirably, a plurality of valves are provided by patterning the third layer at predefined locations with an absorbing material. The one or more valves are desirably provided on the third layer. In a first arrangement the valves are provided by printing the absorber material onto the third layer. In such an arrangement laser printing is a particularly effective means of depositing an absorber material at predefined locations on the third layer, and can be used for depositing one or more dots of absorber material at predefined locations on the third layer. The absorber may be provided on an upper or lower surface of the third layer.

Desirably the absorber is provided on a lower surface such that any effect of the material properties of the absorber material on the reagents is minimised. It will however be appreciated that it is not intended to limit the present teaching to the exact placement of the absorbing materials relative to the stored fluid within the device. The dot can either be proximal or distal relative to the stored fluid. In the event that there were reasons for concern about interaction between the fluid or components of the fluid and the material comprising the dot, then it would be advantageous to have the dot on the distal side of the third layer relative to the stored fluid. Whether this is necessary depends on the details of the fluid's components, and the particular material chosen for the dot as well. In another configuration where there is a desire to separate the absorbing material from each of the two formations which it will ultimately provide fluid communication between, the absorbing material could be encapsulated or sandwiched between first and second films. For example, if the dots were printed or otherwise deposited on a first plastic film, a second plastic film could be laminated onto the first film (using for example thermal means), thereby sandwiching and effectively encapsulating the dots. Such an arrangement is particularly advantageous in applications where two different liquids require separation by a valve layer and there is a requirement to minimise the exposure of either of the two liquids to the material providing the dots. The absorber is desirably formed from a material having a greater or higher absorption characteristic to the material forming the third layer or in other arrangements to the surrounding areas of the device. In this way, on exposure to the electromagnetic radiation signal, the absorber will preferentially heat relative to its environment. In this way selective and controlled melting at predefined locations may be effected. This localised preferential heating provides for a highly controlled generation of a fluid path between first and second formations.

The first formation may be segmented having first and second individual segments separated from one another by the second formation. In such an arrangement first and second valves are provided between each of the first segment and the second formation, and the second formation and the second segment respectively. By effecting an actuation of the absorber at the location of each of the first and second valves, controlled flow of a fluid from the first segment through the second formation and into the second segment may be effected. The actuation could be achieved concurrently or a first valve could be actuated prior to actuation of a second valve.

The first formation may define a reservoir. In such an arrangement the first formation is fabricated to have a volume sufficient to contain a predefined volume of a fluid. The first formation comprises an entry port and an exit port, control of fluid egress from the exit port being effected by a valve coincident with the exit port, and wherein on introduction of a fluid into the reservoir the entry port is sealed to prevent evaporation of the fluid from the reservoir. In another arrangement a point of care device is provided comprising: a multilayer microfluidic device comprising first and second formations provided in first and second layers of the microfluidic device and separated from one another by a single use valve provided in a third layer separating the first and second layers, the valve comprising an absorber material provided on a localised region of the third layer; a source of electromagnetic radiation for directing an electromagnetic signal onto the absorber and wherein on exposure of the absorber to a provided electromagnetic signal, the absorber material heats and effects a localised melting of the third layer to provide fluid communication between each of the first and second formations. These and other features of the present invention will now be described with reference to an exemplary arrangement thereof which is provided to assist in an understanding of the teaching of the invention but is not intended to be construed as limiting the invention to the exemplary arrangements which follow.

Brief Description Of The Drawings

The present invention will now be described with reference to the accompanying drawings in which:

Figure 1A is a schematic representation of single use valves provided in accordance with the present teaching showing how segments of a formation provided in a first layer may be connected with one another by formations provided in a second layer.

Figure 1 B is a sectional view showing the separation of the first and second segments of Figure 1A. Figure 1 C is a side cross sectional view of details of Figures 1 A in use. Figure 2 is a schematic showing operation of the device of Figure 1 with Figure 2A showing the loading of liquid into a first segment, Figure 2B showing the opening of a first valve and the flow of the liquid into the second formation, Figure 2C showing the opening of the second valve to allow for fluid communication between the second formation and the second segment.

Figure 3 shows in schematic form the fabrication or formation of a microfluidic reservoir in accordance with the present teaching.

Figure 4 shows in schematic form a centrifugal microfluidic system comprising first and second formations separated by a valve with Figure

4A showing the system prior to opening the valve and Figure 4B showing the same arrangement on opening the valve and effecting a rotation of the system to induce the flow of fluid from the first formation to the second.

Figure 5 shows in schematic form the use of a valve in accordance with the present teaching to enable the on-board storage of two solutions.

Figure 6 shows various arrangements for provision of outlets from a reservoir or formation in accordance with the present teaching.

Detailed Description Of The Drawings

Exemplary arrangements of a valve arrangement for use in microfluidic systems will now be described to assist in an understanding of the present teaching. In these exemplary arrangements the fabrication of a single-use valve based on laser printing technology will be described. Such valves are provided in a normally closed state and may be opened with a single laser shot or pulse, to allow for the flow of a fluid within the microfluidic system. As an application of the same technology, a system for the storage of liquid reagents in sealed reservoirs for up to 30 days with no significant evaporation will also be described. While the exemplary arrangements are described with reference to polymers and fabrication techniques such as hot embossing and multilayer plastic lamination, it will be appreciated that these specifics are provided to assist in an understanding of the present teaching and are not intended to limit the scope of the present invention to the specifics described.

Figure 1 shows in schematic form an example of a multilayer microfluidic device 100 incorporating first 110A and second 110B microfluidic single- use valves. First 120 and second 130 formations are provided in first 125 and second 135 layers of the device. The first formation 120 is, in this arrangement, segmented into first 121 and second 122 segments. The second formation 130 overlaps at least partially with each of the first and second segments and is separated from each of the first 121 and second segments by a third layer 140. In this arrangement the third layer 140 is formed from a plastic polymer foil with laser-printed dots 141 and is sandwiched between each of the first 125 and second 135 layers. The valves 110A, 110B are formed by the provision of the laser printed dots 141 on the third layer 140 and are defined at the respective overlap between each of the first segment and the second formation, and the second formation and the second segment. In this way, on opening the valves, the second formation provides a fluid interconnect between the first and second segments. While the dots 141 are described as being laser printed on the third layer 140, it should be appreciated that it is not intended to limit the teaching of the present application to laser printing. The applicant envisages that the dots 141 may be deposited using any suitable means. Furthermore it will be appreciated that dots are an exemplary arrangement of discrete high absorption actuators, and that the teaching is not to be considered as being limited to the geometry of a dot. The purpose of each laser-printed dot 141 is to absorb optical energy from an actuating light source such as a laser diode, rapidly heat and effect a perforation of the plastic foil 140 by melting it within a localised region coincident with the location of the dots 141 to form an outlet 112 between the two formations. It should therefore be appreciated that the laser printer dots 141 operate as actuators for opening the valves. As the absorption properties of the dots 141 are such that it will preferentially absorb the incident radiation relative to the surrounding areas of the plastic foil or film that forms the third layer 140, the integrity of the remaining areas of the third layer 140 are unaffected. By providing such a valve structure, localised perforation of the third layer may be effected and this reduces the required accuracy of aiming the laser, provided it is scanned over an area that encompasses the valve spot.

Operation of the valves of Figure 1 is illustrated in Figure 2. In Figure 2A, step 200, a fluid is provided into the first segment 121. A source of electromagnetic radiation, desirably a controlled pulse signal of predefined duration and intensity, is provided in this arrangement by a laser diode 250. The laser diode 250 is positioned to point at the first valve 110A. The absorption of a short pulse of light 255 by the valve 110A effects a localised heating of the third layer and melts the plastic polymer foil that forms that layer in that localised region to form an outlet 112. This outlet provides a fluid path between the first segment 121 and the second formation 130.

In Step 210, the laser diode 250 is then moved to the second valve 110B and the operation repeated. Liquid then can be moved through the second formation 130 into the second segment 122. Once the fluid path between the first and second segments through the second formation is generated the laser diode may be turned off (Step 220)- this does not require the flow of the actual fluid, simply that a path is fabricated. It will be appreciated that as the strength of the applied signal needs only to be sufficient to effect a heating of the absorber material the laser can be left on while moving it from the first valve 110A to the second valve 110B without effecting any damage to the intervening structure- the strength of the laser diode being insufficient to effect a melting of the third layer in the absence of the absorber materials. In this arrangement fluid communication between first and second segments provided within the same layer is provided through a fluid interconnect within a second layer. To provide such interconnect in a controlled fashion first and second valves are described. The need for two valves may not be obvious: one of the two could be perforated before assembly, reducing the complexities of positioning and control of the laser, but adding an additional step to the fabrication process. Pre-perforation of one dot would also eliminate the redundancy against leakage or slow permeation of water vapour afforded by two dots/valve. It will however be appreciated that it is not intended to limit the application of the present teaching to an arrangement that requires sequential opening of first and second valves to enable fluid communication between first and second segments within the same layer.

While the arrangement of Figures 1 and 2 is effectively of longitudinal formations in the configuration of channels having a length greater than their width, it is not intended to limit the present teaching to such geometries. As shown in Figure 3 the first formation may be dimensioned to define a reservoir 300. In such an arrangement the formation is fabricated to have a volume sufficient to contain a predefined volume of a fluid. The formation comprises an entry port 310 and an exit port 320 with control of fluid egress from the exit port 320 being effected by a valve 330 coincident with the exit port. The valve is provided- similarly to that described above, by a localised well-defined region of a high absorbing actuator (printed dot) which on exposure to incident EM radiation will heat and effect a localised melting of the third layer 340 on which it is disposed. Fluid communication between the reservoir 300 and a connecting formation 350 provided below the valve is thereby enabled and the fluid within the reservoir may flow out of the reservoir to other regions of the device.

When fabricating such a device, the structure of the reservoir is first defined within the first layer. This reservoir is defined in the upper layer and can be designed to hold any fluid volume. The valve for this storage reservoir is laser-printed at its peripheral end and at the intersection with a microfluidic formation 350 that connects it to the rest of the microfluidic system. The barrier properties of the foil to store liquid reagents as was described above are exploited. After assembly of the device, reagents 360 are loaded into the reservoir and encapsulated using pressure-sensitive adhesive (PSA) film 370 or other suitable sealing means. This film seals tightly the storage reservoir and prevents evaporation. Liquid from the container 300 can be cleanly released into the formation by centrifugal or capillary actuation.

Experimental arrangement

To demonstrate the laser valve concept, a centrifugal microfluidic "lab-on- a-disc" cartridge with two chambers 400, 410 connected by a microfluidic channel 420 such as that schematically shown in Figure 4 was fabricated. Flow through the channel was controlled by provision of a valve 430 between the first chamber 400 and the channel 420. The first and second chambers were fabricated on a substrate 440 that was configured to be rotated on a spindle 441. In this exemplary arrangement the substrate 440 is a planar disc structure. The first and second chambers were radially arranged relative to one another with the first chamber being provided proximal to the spindle and the second chamber 410 distally provided. A fluid solution 450 is initially loaded into the first chamber- Figure 4A. The substrate 440 was rotated at different speeds and no leakage was observed through the valve even while spinning at 5000 rpm. The disc was then stopped and light from a laser diode was aimed at the laser- printed area- i.e. the valve 430, creating a communication port between the first chamber 400 and the channel 420 in less than 1 second. The disc was spun again and the fluid solution was fully transferred to the second chamber 410 under the influence of the biasing centrifugal forces resultant from rotation of the substrate 440- Figure 4B.

The device of Figure 4 was fabricated using multi-layer lamination. A CO2 laser (Laser Micromachining LightDeck, Optec, Belgium) system was used to cut the various polymer layers to form the necessary formations or chambers therein. To laminate the plastic layers, a thermal roller laminator (Titan-110, GBC Films, USA) was used. A laser-printer (resolution:

600dpi, LaserJet 4050 Series, HP, USA) was used to print dots onto a transparency film which was used as the intermediary third layer.

Connecting channels were cut from an 80-μm thick layer of PSA (AR9808, Adhesives Research, Ireland) and laminated onto a 250-μm poly(methylmethacrylate), PMMA, support layer (GoodFellow, UK). The width of the connecting microfluidic channel was measured to be approximately 400 μm. This assembly of channels constituted the connecting layer in both devices. The upper chambers shown in Figure 4 were laser-cut from a 250-μm PMMA sheet. These layers were then laminated onto the connecting layer. Finally, a layer of PSA with laser-cut holes that function as vents was laminated on top of the chambers. It will be appreciate that the provision of vent holes is particularly useful in the filling of chambers or channels that were originally empty. It will be understood that to fill a sealed chamber requires a displacement of the existing volume- be that liquid or gas and that by providing such vents in a downstream chamber that once the fluid is introduced into the initially empty chamber, the pressure within the chamber will not increase. If left within the chamber any fluid could over an extended time period evaporate through these one or more holes. It will also be understood that the provision of vent holes is not critical in that one can also construct such a pair of chambers with no holes in either of them. In such a scenario, the rotation velocity may need to be higher in order to generate enough pressure that the fluid flows into the empty chamber through the valve, and air bubbles backwards through the hole (just like pouring water from a bottle with a narrow mouth). Figure 5 illustrates the system design for the on-board reagent-storage device 500. In this system, two reservoirs 505, 510 are defined on a rotatable substrate 515 and located near the centre of the substrate 515. It will be appreciated that as the radial motion of the substrate 515 induces movement from a chamber proximally located to the centre of rotation of the substrate towards a chamber distally located from that centre of rotation that it is important in such an arrangement that the reservoirs are arranged relative to one another such that on rotation of the substrate 515 that the fluid has an outward path of flow. As shown in Figure 5A, two solutions 506, 511 were loaded into the reservoirs 505, 511 respectively and sealed with PSA-coated film. The first and second reservoirs were coupled to a mixing chamber 520 via first 507 and second 512 channels respectively. Flow of liquid from the chambers to the channels is controlled by first 508 and second 513 valves.

In operation, the fluid solutions were provided into each of the reservoirs. The valves are then opened and the disc spun to displace the liquids into a mixing chamber, as shown in Figure 5B, to form a mixed volume 550. It was noted that when in the reservoirs that the stored solutions did not evaporate for a period of 30 days, and suitable polymers could extend this significantly. The valves prevent fluid leakage at rotation rates of at least 5000 rpm (corresponding to 840xg).

It will be appreciated that heretofore where two or more regions of higher absorption have been described that absorption properties of each of the two or more regions have not been discussed. It will be understood that different materials have different absorption characteristics such that exposure of a first material to a first level of incident radiation will affect that material differently to exposure of a second material having different absorption characteristics to that same level of radiation. Using such knowledge it is possible to provide within the context of the present teaching selective photo-thermal activations of microfluidic valve arrays. In order to accomplish efficient and precise photo-thermal activations of microfluidic valve array it is possible to provide for colour-selective activations by using different materials (i.e. with different absorption characteristics), which absorb different wavelength of laser beam selectively. In another arrangement it is possible to apply light-absorbing micro- and nanoparticles, which allow controlling the photo-thermal activations of microfluidic valves selectively upon exposure to a specific wavelength of laser pulses. By matching selective resonant frequency of nanoparticles, we can also multiplex light activations of microfluidic valves. The resonant frequency-based photo-thermal activation can deposit energy selectively and the thermal confinement particular to nanoplasmonic physics allows a minimization of the heat transfer (i.e. flow) from the plasmonic nanoparticles to the surrounding areas so as to provide for the localised perforation for generation of a fluid path.

By providing highly localised and definable regions between two formations, such as channels, that can be easily perforated in response to photothermal activation, it is possible to use a plurality of individual outlets within the same channel or reservoir and by selective actuation of each of the outlets within the channel it is possible to provide a number of beneficial applications. For example as shown in Figure 6 such localized outlets 600 defined within the same reservoir 610 can be used for aliquoting or volume splitting of smaller volumes of a fluid from a larger volume, the routing of fluid from the same reservoir to different channels by addressing of spatially separated outlets or the sequential release of liquid from a reservoir by the sequential addressing of individual ones of the outlets. Figure 6A shows an arrangement whereby a plurality of outlets 600 are provided on the same axis which is substantially perpendicular to the axis of the induced centrifugal force 605. As a result of the action of the centrifugal force the liquid within that reservoir and along that axis of the outlets 605 will be experiencing the same force. By selective addressing of individual ones of the outlets, one of a plurality of available channels 615 can be opened, and a portion of the volume of liquid within the reservoir 610 will exit the reservoir and follow that path. Each of the channels 615 can be directed to the same or different destination such that routing of fluid within the microti iridic device can be achieved. It will be appreciated that the liquid that is in a lower region 620 of the reservoir is biased there by the applied centrifugal force and will therefore not escape from an opened outlet. The level of the outlets relative to the length of the reservoir can therefore be used to redirect specific portions of the fluid.

A further example of this is shown in Figure 6B where a number of outlets are provided along the longitudinal axis of the reservoir. In such an arrangement, selective opening of individual ones of these outlets will release specific volumes from the reservoir. For example if outlet 600A is opened only fluid above that outlet will escape. The controlled opening of a plurality of provided outlets can therefore provide for a controlled release of a specific portion of the fluid from the reservoir. This is particularly useful in the context of a feedback system where an initial separation of the fluid is effected through centrifugal rotation and based on feedback optical analysis to determine the transition points within the reservoir, a decision can be made as to which outlet should be opened to separate the constituents. The ability to spatially distinguish between highly localised outlets and to selectively actuate these allows for such separation. This readout of the phase interface can be done dynamically during the rotation of the device and the same or different optical device that is used for the ultimate laser ablation step to generate the outlet can be used for the optical analysis. Such dynamic control of the fluid paths within a microfluidic system is a particularly advantageous aspect of a device provided in accordance with the present teaching. It will be appreciated that a plurality of individual target outlets can be provided radially along the same axis, such as shown in Figure 6C. In this arrangement selective movement of the device used for the laser ablation can be used to controllably define which of the plurality of outlets could be opened. The use of a controller in conjunction with the laser diode (or other source of the necessary radiation to provide the photothermal actuation of the device) can be used to selectively redirect specific volumes from specific locations within the reservoir out of the reservoir to predefined destinations. The location of these outlets can be precisely defined and as such the ultimate volume that is redirected can be also known to a high degree of precision.

The example of Figure 6C has particular application where the reservoir 610 provides a buffer solution that is needed in sequential steps of a test. By addressing the outlets in strict order and the buffer solution can be released sequentially to a separate chamber- not shown- where it can be mixed with or otherwise used with different reagents in strictly controlled volumes. In this arrangement the release of the fluid is defined in time (i.e. the ultimate destination is the same), whereas the arrangement of Figures 6A and 6B allow for the routing to be defined in both a time sequence and/or a destination address.

While the schematics shown illustrate the provision of each of the outlets in the same plane, i.e. they are provided at the same horizontal level within the microfluidic device, it will be understood that one of the advantages of having highly defined outlets within a structure that individual outlets could be provided in different layers of the microfluidic device such that they are vertically spaced apart from one another. By selectively activating individual ones of the outlets it is possible to induce a fluid within the reservoir to pass through multiple layers of the device. The individual spatial addressing of the outlets by the actuating source provides for highly controlled and localised photoactuation of individual portions of the device. This localised ablation can be therefore considered as being available in both the horizontal and vertical dimensions of the device. Figure 6D shows a further arrangement where the outlet is provided having an extended dimension to the highly localised pattern that has heretofore been described. In this arrangement a stripe 650 of material defines the outlet. This stripe of material is defined in this arrangement along a radial path within the reservoir 610 that is parallel with the axis of the induced centrifugal force 605. By selectively targeting the individual portions of this stripe it is possible to increase the dimensions of the outlet. It will be appreciated that this stripe pattern is just a further example of the type of geometry that can be achieved by the highly localised positioning of regions of higher absorption within the context of the present teaching.

It will be appreciated that exemplary arrangements of a fluidic device comprising first and second formations separated from one another by one or more localised photoactuable separators has been described. These separators are distinct elements that define a region of high absorption within the device which on exposure to radiation are responsive to the photoactuation to transform from a first closed state to a second open state, adoption of the open state defining a fluid path between each of the first and second formations. The highly defined geometry of such separators allows for highly controlled generation of fluid passages within the device which can be used to generate one or more independently controllable fluid paths within the fluidic devices. Using a combination of a plurality of such separators, which may be individually addressed and ablated, it is possible to provide for a controlled linking between individual fluid paths within the microfluidic device it is possible to provide a highly controlled movement of fluid within the device. This can be used to provide for the storage and or mixing of fluids. It can also be used to effect movement of fluids in both vertical and horizontal directions through the device. The separators have been described with reference to a single use valve or a dot of an absorber material that is provided onto a substrate. It will be appreciated that such separators provide a rupturable membrane between each of the two channels that are initially separated and are exemplary of a surface having a discrete high absorption actuator provided thereon. By rupturing the membrane, achieved desirably through a preferential heating of the membrane relative to its immediate surroundings and a subsequent perforation of the membrane through that heating, it is possible to generate an aperture or fluid communication path between each of the first and second channels (formations). Such perforation results in a destruction of the integrity of the membrane at that location and in this way the separator can be considered a single use valve. As has been described herein the fluidic device is desirably provided on a rotatable substrate, rotation of which generates a centrifugal force which biases the flow of a fluid from one portion of the device to another portion. The rupturing of the membrane may be achieved concurrently with the rotation of the device or could be effected while the substrate is stationary.

While the arrangements described heretofore have been with reference to an exemplary multilayer device with a film or third layer provided between formations on separate layers, it will be understood that it is not essential to form the region of high absorption on a distinct layer. In an arrangement of a first and second formation arranged one above the other, by suitably patterning a lower surface of the first formation or an upper surface of the second formation with one or more regions of high absorption it is possible to effect a preferential rupturing of that portion of the surface to provide a fluid path. Furthermore where the first and second formations are co- planar it is possible to simply separate them within the same plane by a region of high absorption which on photoactuation will ablate and allow fluid from a first formation to pass into a second formation. This ablation may result in a melting or evaporation of the region separating the first and second formations.

While preferred arrangements have been described in an effort to assist in an understanding of the teaching of the present invention it will be appreciated that it is not intended to limit the present teaching to that described and modifications can be made without departing from the scope of the invention. It will be understood that devices and systems provided in accordance with the present teaching require lower laser powers than systems heretofore available. By the use of localised patterning of the intermediary layer between the first and second layers of the multilayer microfluidic device it is possible to provide valves on multiple layers that can be individually addressed. The electronics and software- control algorithms to operate the valves are simpler and the precision of positioning the laser spot less demanding since a general raster of the laser beam in the vicinity of the valve opens it. The use of the exemplary described printed valve technology facilitates the design and fabrication of fully integrated and automated lab-on-a-chip cartridges that require pressure-resistant valves or long-term reagent storage. One key advantage is the absence of mechanical components in the valve and its actuation, facilitating its manufacture and use. Using the teaching of the present invention it is possible to fabricate multilevel microfluidic systems where layers of microfluidic formations are separated by valving layers. As long as the laser-printed spots do not overlap, the appropriate valve can be selected on demand and formations on different layers connected at will.

It will therefore be appreciated that modifications can be made to that described herein without departing from the spirit and or scope of the present teaching which is to be construed as limited only insofar as is deemed necessary in the light of the claims which follow.

The words comprises/comprising when used in this specification are to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers , steps, components or groups thereof.

Claims

1. A microfluidic device comprising a flow path, the flow path having a valve provided at a predefined location within the flow path, the valve operable for controlling a flow of fluid through the flow path, the valve comprising: a surface having a discrete high absorption actuator deposited thereon which on operable exposure to incident radiation is responsive to the radiation to rupture the surface and transform the valve from a first closed state to a second open state to allow the passage of fluid through the flow path.

2. The device of claim 1 wherein the valve surface is provided as a film, the high absorption actuator being selectively deposited on the film, the actuator being operably responsive to the incident radiation to cause the film to heat and rupture for facilitating a transition of the valve from the closed state to the open state.

3. The device of claim 2, wherein the high absorption actuator is deposited at a predefined location or distinct region on the surface of the film such that the film has regions of low absorption and at least one region of high absorption.

4. The device of claim 2 or 3, wherein the high absorption actuator is patterned on the surface of the film.

5. The device of any one of claims 2 to 4, wherein the high absorption actuator is printed on the surface of the film.

6. The device of any one of claims 2 to 5 wherein the high absorption actuator is integrally formed within the flow path.

7. The device of any one of claims 2 to 5 wherein the high absorption actuator is deposited within the flow path.

8. The device of claim 1 wherein the flow path and the valve surface are formed within a substrate material.

9. The device of any preceding claim wherein the flow path operably provides fluid communication between a first and second formation of the microfluidic device.

10. The device of claim 9 wherein the first and second formations are co- planar.

11. The device of claim 9 wherein the device is a multilayer structure, the first and second formations being provided in different layers of the multilayer structure and wherein the valve is provided in a region of overlap between the first and second formations.

12. The device of claim 11 wherein the valve is provided between the layers of the multilayer structure.

13. The device of claim 2 wherein the film is patterned to comprise a plurality of regions of high absorption and regions of lower absorption, the regions of high absorption being provided to effect, on exposure of the film to incident radiation, a localised melting of a portion of the film coincident with the location of the regions of high absorption.

14. The device of claim 13 wherein the film defines a separating membrane between a first and second formation of the device, the film being configured to locally melt in regions coincident with the regions of high absorption to form a fluid communication path between each of the two formations.

15. The device of claim 14 wherein the regions of high absorption are provided by a plurality of discrete deposits of absorption material on upper and/or lower surfaces of the film, each discrete deposit of absorption material defines a corresponding high absorption actuator.

16. The device of claim 15 wherein at least one of the formations comprises a fluid stored therein, the discrete deposits being provided on a distal surface of the film to the formation storing the fluid.

17. The device of claim 15 comprising a second film, the plurality of deposits being encapsulated by the first and second films.

18. The device of any preceding claim wherein the valve is configured to operate as a single use valve.

19. The device of claim 2 wherein the high absorption actuator operably causes a discrete region of the film coincident with the high absorption actuator to melt.

20. The device of claim 2 wherein the film comprises a plurality of discrete high absorption actuators, the high absorption actuators being formed by printing high absorption material at discrete locations on the surface of the film.

21.The device of claim 20 wherein the high absorption actuators are provided in the form of printed dots.

22. The device of claim 20 wherein at least one of the high absorption actuators is provided in the form of a stripe.

23. The device of claim 9 when dependent on claims 2 to 8, wherein the first formation is segmented into first and second segments which are separated from one another by the second formation, an operable rupturing of the film in the region of the high absorption actuator providing for the first and second formations to be in fluid communication via the second formation.

24. The device of claim 23 wherein each of the first segment and the second formation and the second formation and the second segment are separated by first and second regions of high absorption material respectively.

25. The device of claim 11 wherein the film forms a third layer between the first and second layers.

26. The device of any preceding claim wherein the valve operably provides for a selective and controlled opening of a fluid communication path between first and second formations within the device.

27. The device of claim 26 wherein the first formation defines a reservoir comprising an entry port and an exit port, control of fluid egress from the exit port being effected by rupturing a localised region of the film coincident with the exit port, and wherein on introduction of a fluid into the reservoir the entry port is sealed to prevent evaporation of the fluid from the reservoir.

28. The device of claim 26 wherein the first formation comprises a plurality of exits through which a fluid may exit, individual ones of the exits being coincident with a corresponding high absorption actuator and wherein controlled opening of one or more of the exits is effected by controlled heating of specific ones of the high absorption actuators.

29. The device of claim 28 wherein a controlled opening of a specific exit provides for aliquoting of specific volumes of a fluid from the first formation.

30. The device of claim 28 or 29 wherein the plurality of exits are arranged longitudinally within the first formation parallel with an axis corresponding with an induced centrifugal force.

31.The device of claim 28 or 29 wherein individual exits provide fluid paths to different second formations.

32. The device of claim 28 or 29 wherein a controlled opening of specific exits provides for selective release of a fluid from the first formation.

33. The device of claim 32 wherein each of the exits are coupled to the same second formation, the selective release providing for the sequential flow of fluid from the first formation to the second formation.

34. The device of claim 2, wherein the deposited high absorption material forms a pattern of dots; each dot defining an actuator on the film which is responsive to electromagnetic radiation for perforating the film in regions coincident with the dots.

35. The device of claim 34, wherein each actuator is independently controllable.

36. A point of care device comprising the microfluidic device as claimed in any of claims 1 to 35.

37.A multilayer microfluidic device comprising a first and second formations provided in first and second layers, the first and second layers being separated from one another by a film having a distinct actuator deposited on a surface thereof, the actuator being responsive to electromagnetic radiation to effect a thermal heating of a localised region of the film so that the film perforates for facilitating the first and second formations being in fluid communication.

38. The device of claim 37 comprising a plurality of single use valve elements, individual ones of the valve elements being independently actuatable relative to others.

39. A fluidic device comprising first and second formations separated from one another by a film having one or more actuators deposited at predefined locations on a surface thereof, the actuators being responsive to photoactuation to transform one or more regions of the film from a first closed state to a second open state, adoption of the open state defining a fluid path between each of the first and second formations.

40. The device of claim 39 comprising a plurality of actuators, individual ones of the actuators differing from others in their absorption characteristics.

41.The device of claim 39 or 40 comprising a plurality of individual flow paths defined by individual formations and separated from one another by a plurality of actuators, individual ones of the actuators being individually addressable to effect photoactuation and provide for a controlled linking between individual fluid paths within the microfluidic device.

42. The device of claim 41 wherein the device is a multilayer microfluidic device and the plurality of flow paths are provided in different layers of the device, the actuators being provided in intermediary layers between individual flow paths and wherein the actuators are arranged within the device such that individual actuators on individual intermediary layers may be individually addressed.

43. The device of claim 41 or 42 being configured such that sequential photoactuation of a plurality of actuators provides for a routing of a fluid through the device.

44. The device of claim 43 wherein the routing effects movement of the fluid in both vertical and horizontal directions through the device.

45. The device of claim 41 wherein the plurality of actuators are arranged along a longitudinal axis of the first formation for facilitating a release of specific volumes from the first formation.

46. The device of claim 45 wherein the plurality of actuators are addressable sequentially in time to allow for a time differentiated release of fluid from the first formation.

47. The device of claim 41 comprising a third formation, the first and third formations being separated from one another by one or more localised actuators, the actuators being responsive to photoactuation to transform one or more regions of the film from a first closed state to a second open state, adoption of the open state defining a fluid path between each of the first and third formations.

48.An analysis system comprising a. a microfluidic device comprising first and second formations separated from one another by a continuous film carrying a plurality of discrete actuators, the actuators being responsive to photoactuation for perforating one or more regions of the film such that the first and second formations are in fluid communication, b. a photoactuator configured to effect photoactuation of individual ones of the actuators; c. drive means for effecting rotation of the device; d. control means configured to control the photoactuator for facilitating a controlled release of a specific portion of the fluid from the first formation.

49. The system of claim 48 wherein the control means is configured to provide a feedback arrangement responsive to an initial separation of fluid within the first formation resultant from a rotation of the device, to determine which of the plurality of actuators should be operated so as to effect separation of constituents of the fluid.

50. The system of claim 48 or 49 being configured to spatially distinguish between the actuators and to selectively actuate the actuators during a rotation of the device.