GB2467298A - Multilayer microfluidic device - Google Patents

Multilayer microfluidic device Download PDF

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Publication number
GB2467298A
GB2467298A GB0901115A GB0901115A GB2467298A GB 2467298 A GB2467298 A GB 2467298A GB 0901115 A GB0901115 A GB 0901115A GB 0901115 A GB0901115 A GB 0901115A GB 2467298 A GB2467298 A GB 2467298A
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Prior art keywords
channels
absorption
regions
layer
fluid
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GB0901115A
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GB0901115D0 (en
Inventor
Antonio Ricco
Jose L Garcia Cordero
Jens Ducree
Luke Lee
Fernando Benito Lopez
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Dublin City University
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Dublin City University
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Priority to GB0901115A priority Critical patent/GB2467298A/en
Publication of GB0901115D0 publication Critical patent/GB0901115D0/en
Priority to PCT/EP2010/050801 priority patent/WO2010084190A1/en
Publication of GB2467298A publication Critical patent/GB2467298A/en
Withdrawn legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0034Operating means specially adapted for microvalves
    • F16K99/0042Electric operating means therefor
    • F16K99/0044Electric operating means therefor using thermo-electric means
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874Three dimensional network
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1861Means for temperature control using radiation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0677Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0073Fabrication methods specifically adapted for microvalves
    • F16K2099/008Multi-layer fabrications

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Micromachines (AREA)

Abstract

A multilayer microfluidic device comprises first 120 and second 130 channels provided in first 125 and second 135 layers separated from one another by a plastic film 140 disposed therebetween. The film has regions of high and low absorption (formed by energy-absorbing laser printed dots) such that on exposure to incident radiation (e.g. from a laser diode), the regions of higher absorption will preferentially melt and provide a fluid communication path between each of the two channels.

Description

Microfluidic 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 from one channel to another channel. The invention more particularly relates to a single use valve for use in microfluidic systems, actuation of the valve enabling fluid flow from one channel of the microfluidic system to another channel 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 (P00) diagnostic devices comprising two or more microfludic channels 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 P00 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 P00 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 P00 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 rnicrofluidic 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 P00 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 P00 device. Furthermore, known approaches do not lend themselves for use in complex, integrated microfluidic systems comprising a plurality of channels within a single device. There are therefore a number of problems with existing arrangements.
Sum mary These and other problems are addressed in accordance with the present teaching by a microfluidic system comprising a first and second channel separated from one another by a single use valve. The first and second channels are desirably provided in first and second layers of the microfludic device and the valve is provided in a third layer separating the first and second layers. 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 each of the first and second channels.
Desirably a plurality of valves are provided by patterning the third layer at predefined locations coincident. 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 absorber 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 film relative to the stored fluid. Whether this is necessary depends on the details of the fluid its components, and the particular material chosen for the dot as well. In another configuration where there is a desire to separate the absorber material from each of the two channels which it will ultimately provide fluid communication between, the absorber 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 sandwich ing 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 absorption characteristic to the material forming the third layer. In this way, on exposure to the electromagnetic radiation signal, the absorber will preferentially heat relative to the third layer. In this way selective and controlled melting of the third layer at predefined locations may be effected.
The first channel may be segmented having first and second individual segments separated from one another by the second channel. In such an arrangement first and second valves are provided between each of the first segment and the second channel, and the second channel and the second segment respectively. By effecting a melting of the third layer at each of the first and second valves, controlled flow of a fluid from the first segment through the second channel and into the second segment may be effected.
The first channel may define a reservoir. In such an arrangement the channel is fabricated to have a volume sufficient to contain a predefined volume of a fluid. The channel 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 channels provided in first and second layers of the microfludic 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 within or 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 channels.
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 channel provided in a first layer may be connected with one another by channels 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 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 channel, Figure 2C showing the opening of the second valve to allow for fluid communication between the second channel and the second segment.
Figure 3 shows in schematic form the fabrication of a microfluidic reservoir in accordance with the present teaching.
Figure 4 shows in schematic form a centrifugal microfluidic system comprising first and second channels 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 channel 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 channel 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 microfludic 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 a microfluidic device 100 incorporating first 11 OA and second 11 OB microfluidic single-use valves. First 120 and second channels are provided in first 125 and second 135 layers of the device. The first channel 120 is, in this arrangement, segmented into first 121 and second 122 segments. The second channel 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 foil with laser-printed dots and is sandwiched between each of the first 125 and second 135 layers. The valves 11 OA, 11 OB are formed the provision on the third layer of the laser printed dots and are defined at the respective overlap between each of the first segment and the second channel, and the second channel and the second segment. In this way, on opening the valves, the second channel provides a fluid interconnect between the first and second segments.
The absorber material that is used to fabricate the valves is provided in this exemplary arrangement by a laser printed dot. The purpose of each laser-printed dot is to absorb optical energy from 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 to form an outlet 112 between the two channels. As the absorption properties of the dots are such that it will preferentially absorb the incident radiation relative to the surrounding areas of the plastic foil that forms the third layer, 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 11 OA. The absorption of a short pulse of light 255 by the valve 11 OA effects a localised heating of the third layer and melts the plastic 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 channel 130.
In Step 210, the laser diode 250 is then moved to the second valve 11 OB and the operation repeated. Liquid then can be moved through the second channel 130 into the second segment 122.
Once the fluid path between the first and second segments through the second channel 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 that forms the valve that the laser can be left on while moving it from the first valve 11 OA to the second valve 11 OB 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 vapor 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 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 may be dimensioned to define a reservoir 300. In such an arrangement the channel is fabricated to have a volume sufficient to contain a predefined volume of a fluid.
The channel 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 region of an absorber 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 channel 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 channel 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 channel 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 firts 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 was a planar disc structure.
The first and second channels 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 sec. 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 002 laser (Laser Micromachining LightDeck, Optec, Belgium) system was used to cut the various polymer layers to form the necessary channels or chambers therein. To laminate the plastic layers, a thermal roller laminator (Titan-i 10, 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-pm thick layer of PSA (AR9808, Adhesives Research, Ireland) and laminated onto a 250-pm poly(methylmethacrylate), PMMA, support layer (GoodFellow, UK). The width of the connecting microfluidic channel was measured to be approximately 400 pm. This assembly of channels constituted the connecting layer in both devices.
The upper chambers shown in Figure 4 were laser-cut from a 250-pm 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 center of the substrate 51 SIt will be appreciated that as the radial motion of the substrate induces movement from a chamber proximally located to the center of rotation of the substrate towards a chamber distally located from that center 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 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 provided within the context of the present teaching selective photothermal activations of microfluidic valve arrays.
In order to accomplish efficient and precise photothermal activations of microfluidic valve array it is possible to provide for colour-selective activationsby 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 photothermal 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 photothermal 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 plasrnonic 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 channels that can be easily perforated as a 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 thel 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 microfluidic 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 rnicrofluidic 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 60. 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 60 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 (ie 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 microfluidic device comprising first and second channels separated from one another by one or more localised photoactuable seperators has been described. These seperators 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 channels. The highly defined geometry of such seperators 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 seperators, 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.
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 local ised 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 channels are separated by valving layers. As long as the laser-printed spots do not overlap, the appropriate valve can be selected on demand and channels 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 (20)

  1. Claims 1. A multilayer microfluidic device comprising a first and second channels provided in first and second layers of the microfluidic device and separated from one another by a film disposed therebetween, the film having regions of high absorption and regions of lower absorption such that on exposure to incident radiation the regions of higher absorption will preferentially melt and provide a fluid communication path between each of the two channels.
  2. 2. The device of claim 1 wherein the film is patterned to provide the regions of higher absorption.
  3. 3. The device of claim 1 or 2 wherein the regions of high absorption are provided by a plurality of individual deposits of absorption material on upper or lower surfaces of the film.
  4. 4. The device of claim 3 wherein at least one of the channels comprises a fluid stored therein, the individual deposits being provided on a distal surface of the film to that channel.
  5. 5. The device of claim 3 wherein comprising a second film, the plurality of deposits being encapsulated by the first and second films.
  6. 6. The device of any preceding claim wherein regions of high absorption are provided by absorption material separate to the film material but located in or on the film material.
  7. 7. The device of claim 6 wherein the film includes regions proximal to the absorption material and regions distal to the absorption material, the regions proximal to the absorption material defining single valves between each of the first and second channels, the valves being actuated by the absorption and subsequent heating of the absorption material to effect a corresponding melting of the valve.
  8. 8. The device of any preceding claim wherein the third layer is configured such that any melting of the third layer is restricted to a localised melting of the third layer at the regions of higher absorption so as to provide fluid communication between each of the first and second channels.
  9. 9. The device of any preceding claim wherein the regions of higher absorption are coincident with the overlap between the first and second channels.
  10. 1O.The device of any preceding claim wherein the regions of higher absorption are provided by a plurality of printed depositions provided onthefilm.
  11. 11.The device of claim 10 wherein the printed depositions are provided in the form of dots printed on at least one of the upper or lower surfaces of the film.
  12. 12.The device of any preceding claim wherein the first channel is segmented into first and second segments which are separated from one another by the second channel, a melting of the film effecting generation of a fluid communication path from the first segment through the second channel and into the second segment.
  13. 13. The device of claim 12 wherein each of the first segment and the second channel and the second channel and the second segment are separated by first and second regions of higher absorption respectively.
  14. 14.The device of any preceding claim wherein the absorber is formed from a material having a greater absorption characteristic to the material forming the third layer such that on exposure to an electromagnetic radiation signal, the absorber will preferentially heat relative to the third layer.
  15. 15. The device of any preceding claim wherein the valve provides for selective and controlled melting of the third layer at predefined locations.
  16. 16.The device of any preceding claim wherein the first channel defines a reservoir comprising 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.
  17. 1 7.A point of care device is provided comprising: a. a multilayer microfluidic device comprising first and second channels provided in first and second layers of the microfludic 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 within or on a localised region of the third layer; b. 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 channels.
  18. 18.A multilayer microfluidic device comprising a first and second channels provided in first and second layers of the microfludic device and separated from one another by a distinct photoactuable element, the element being responsive to exposure to electromagnetic radiation to effect a local thermal heating of a localised definable region between the first and second channels so as to degrade and provide a fluid communication path between each of the two channels.
  19. 19.The device of claim 1 comprising a plurality of elements, individual ones of the elements being independently actuatable relative to others.
  20. 20.A microfluidic device comprising first and second channels separated from one another by one or more localised photoactuable seperators, the photoactuable seperators 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 and second channels.
GB0901115A 2009-01-23 2009-01-23 Multilayer microfluidic device Withdrawn GB2467298A (en)

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PCT/EP2010/050801 WO2010084190A1 (en) 2009-01-23 2010-01-25 Fluidic single use valve and microfluidic systems incorporating said valve

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013075871A1 (en) * 2011-11-22 2013-05-30 Robert Bosch Gmbh Microfluidic membrane-valve device, and a corresponding production method
GB2553100A (en) * 2016-08-19 2018-02-28 Univ Dublin City A microfluidic device
EP3293239A1 (en) * 2016-09-09 2018-03-14 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Adhesive element and valve assembly

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7152616B2 (en) * 2002-12-04 2006-12-26 Spinx, Inc. Devices and methods for programmable microscale manipulation of fluids

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7152616B2 (en) * 2002-12-04 2006-12-26 Spinx, Inc. Devices and methods for programmable microscale manipulation of fluids

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013075871A1 (en) * 2011-11-22 2013-05-30 Robert Bosch Gmbh Microfluidic membrane-valve device, and a corresponding production method
GB2553100A (en) * 2016-08-19 2018-02-28 Univ Dublin City A microfluidic device
EP3293239A1 (en) * 2016-09-09 2018-03-14 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Adhesive element and valve assembly

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