WO2008036997A1 - Système et procédé de commande de fluides à l'intérieur d'un dispositif microfluidique - Google Patents
Système et procédé de commande de fluides à l'intérieur d'un dispositif microfluidique Download PDFInfo
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- WO2008036997A1 WO2008036997A1 PCT/AU2007/001387 AU2007001387W WO2008036997A1 WO 2008036997 A1 WO2008036997 A1 WO 2008036997A1 AU 2007001387 W AU2007001387 W AU 2007001387W WO 2008036997 A1 WO2008036997 A1 WO 2008036997A1
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- Prior art keywords
- magnetic
- fluid
- valve
- microfluidic device
- fluids
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Definitions
- the present invention relates to portable diagnostic systems utilized in molecular biology and medical science, and more specifically to a system and method providing control of fluids using channels and devices within a disposable cartridge referred to as a microfluidic cartridge device.
- test results are qualitative in that the presence of a particular infectious disease is provided on either a "Test Positive” or “Test Negative” basis as indicated by the presence (or not) of the visible stripe.
- LF rapid lateral flow
- these types of tests suffer from a lack of sensitivity, and are known to deliver a substantial number of false negative results, particularly when a patient is in the early stages of an infection, and when the amount of a particular antigen or virus in the patient may be low.
- it is in these early stages of detection that it is most important that diagnosis is correctly performed in order to administer an appropriate therapeutic to the patient, or to quarantine the patient to prevent the further spread of the infectious disease to the remainder of the community.
- these types of tests are often not suitable to accurate diagnosis of many diseases, since the interpretation of what may be a faint "test" line on the LF test may be subjectively interpreted as either "positive” or "negative” depending on the visual powers of observation of the user.
- Such equipment may include, for example, high throughput clinical chemistry analyzers, molecular diagnostic systems, clinical immunoassay systems, flow cytometry based systems for hematology, and many others.
- test result in the event that a test result is positive, the patient is generally required to return to the clinician's office for prescription of an appropriate therapeutic or for referral to a medical specialist. This second visit to the clinician generally results in additional costs to the patient, to health insurers and to government health systems. There are also some tests, for example for virulent infectious diseases where the clinician ideally requires immediate or very rapid test results to be obtained in order to prescribe the correct therapeutic course. In remote locations, there may not be a clinical pathology infrastructure near to the point of testing, and once again delays in obtaining test results in such circumstances could be life-threatening.
- POC point of care
- the present invention provides an apparatus for controlling fluids within a micro fluidic device comprising:
- an electromagnetic module operatively coupled to the magnetic fluid slug for inducing forces to control the movement of the magnetic fluid slug within the working fluid region for controlling fluids within the microfluidic device.
- an apparatus for controlling fluids within a microfluidic device comprising:
- valve sandwiched between an upper portion and a lower portion of the microfluidic device such that a channel being formed therethrough by the valve, the upper portion and the lower portion;
- an electromagnetic module operatively coupled to the valve for inducing forces for deforming the valve in order to provide a cavity channel for controlling fluids within the microfluidic device. Further the present invention provides a method of controlling fluids within a microfluidic device comprising:
- the present invention provides a method of controlling fluids within a microfluidic device comprising:
- the present invention provides a computer program product utilizing a method of controlling fluids within a microfluidic device, the computer program product comprising a computer readable medium configured with processor executable instructions, the computer program product comprising:
- the present invention provides a computer program product utilizing a method of controlling fluids within a microfluidic device, the computer program product comprising a computer readable medium configured with processor executable instructions, the computer program product comprising:
- FIGURE 1 illustrates an apparatus for controlling fluids within a microfluidic cartridge device according to the present invention.
- FIGURE 2 illustrates a transport mechanism of an apparatus in which fluids is displaced by operation of the magnetic field from the solenoid according to the present invention.
- FIGURE 3 illustrates a magnetic array having two coils for generating a desired magnetic field according to an embodiment of the present invention.
- FIGURE 4 illustrates an apparatus having an elastomeric valve for controlling fluids within a microfluidic cartridge device according to alternate embodiment of the present invention.
- FIGURE 5 illustrates a cross sectional view of an elastomeric valve according to an embodiment of the present invention.
- FIGURE 6 illustrates an isometric view of the elastomeric valve according to an embodiment of the present invention.
- FIGURE 7 illustrates an open condition of the valve under applied magnetic filed according to an embodiment of the present invention.
- FIGURE 8 illustrates a cross sectional view showing magnetic coils acting on a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 9 illustrates a top view of a magnetic coil array according to an embodiment of the present invention.
- FIGURE 10 illustrates a magnetic coil array constructed on a Printed Circuit Board (PCB) according to an embodiment of the present invention.
- PCB Printed Circuit Board
- FIGURE 11 illustrates a top view of a multi-channel pump assembly according to an embodiment of the present invention.
- FIGURE 12 illustrates a cross section view of a multi-channel pump assembly according to an embodiment of the present invention.
- FIGURE 13 illustrates an extended transport function within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 14 illustrates an embodiment of a microfluidic cartridge device for constructing a fluid valve, when the valve is closed.
- FIGURE 15 illustrates an embodiment of a microfluidic cartridge device for constructing a fluid valve, when the valve is open.
- FIGURE 16 illustrates a packaged valve element according to an embodiment of the present invention.
- FIGURE 17 illustrates a diagram of a four way, multi-port valve, resting position, all ports closed according to an embodiment of the present invention.
- FIGURE 18 illustrates a diagram of a four-way, multi-port valve, with external magnetic field applied to provide flow between two ports according to an embodiment of the present invention.
- FIGURE 19 illustrates a top view of a polymerase chain reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs according to an embodiment of the present invention.
- PCR polymerase chain reaction
- FIGURE 20 illustrates a polymerase chain reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs, cross section view XX, temperature controlled magnetic fluid in the resting position over the heater element according to an embodiment of the present invention.
- PCR polymerase chain reaction
- FIGURE 21 illustrates a Polymerase Chain Reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs, cross section view XX, magnetic fluid transported by external magnetic field to be in proximity and thermally coupled to the amplification chamber according to an embodiment of the present invention.
- FIGURE 22 illustrates a— stirring and heating through a fluid chamber within a micro fluidic cartridge device according to an embodiment of the present invention.
- PCR Polymerase Chain Reaction
- FIGURE 23 illustrates a transport function within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 24 illustrates a cross sectional view of a transport function within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 25 illustrates stirring and heating applications of a present invention.
- FIGURE 26 illustrates a top view of a pumping circuit within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 27 illustrates a cross section view of a pumping element within a microfluidic cartridge device, showing peristaltic pumping action, start of cycle according to an embodiment of the present invention.
- FIGURE 28 illustrates a cross section view of a pumping element within a microfluidic cartridge device, showing peristaltic pumping action, mid cycle according to an embodiment of the present invention.
- FIGURE 29 illustrates a cross section view of a pumping element within a microfluidic cartridge device, showing peristaltic pumping action, end of cycle according to an embodiment of the present invention.
- FIGURE 30 illustrates a packaged pumping element and its cross sectional view through section XX.
- FIGURE 31 illustrates a cross sectional view of a pumping application and pumping element according to an embodiment of the present invention.
- FIGURE 32 illustrates a top view of an inlet port sealing within a micro fluidic cartridge device according to an embodiment of the present invention.
- FIGURE 33 illustrates a top view of an inlet port sealing within a microfluidic cartridge device with sample probe inserted showing sealing around the probe according to an embodiment of the present invention.
- FIGURE 34 illustrates a top view of a use of magnetically releasable plugs for separating fluid regions within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 35 illustrates a cross section view of a microfluidic cartridge device showing a magnetic sheet according to an embodiment of the present invention.
- FIGURE 36 illustrates a chamber in a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 37 illustrates a cross sectional view of a pump element according to an embodiment of the present invention.
- FIGURE 38 illustrates a top view of multiple elements integrated within a single elastomer moulding according to an embodiment of the present invention.
- FIGURE 39 illustrates a flow diagram of a method for controlling fluids within a microfluidic cartridge device according to an embodiment of the present invention.
- FIGURE 40 illustrates a flow diagram of a method for controlling fluids within a microfluidic cartridge device according to another embodiment the present invention. Detailed Description of the Invention
- FIGURE 1 illustrates an apparatus for controlling fluids within a microfluidic cartridge device according to the present invention.
- the apparatus having a working fluid region that is generated between the lower section and the upper section of the microfluidic cartridge device such that a magnetic fluid slug 108 is retained at centre within the fluid region by a permanent magnet 114.
- the electromagnetic module 118 is coupled to the magnetic fluid slug 108 for inducing forces to control the movement of the magnetic fluid slug 108 within the working fluid region for controlling fluids within the microfluidic cartridge device.
- the magnetic fluid slug 108 is composed of magnetic particles carried within a base liquid such as water, hydrocarbon oils, perfluoropolyethers or silicon oil.
- the ferromagnetic materials used in the base liquid are typically magnetite and Mn-Zn complex ferrite.
- the magnetic fluid slug 108 is a liquid which becomes strongly polarised in the presence of a magnetic field.
- the particles used to manufacture a magnetic fluid are usually magnetite, hematite or some other compound containing Fe 2+ or Fe 3+ .
- the particles are typically of order lOnm diameter. This is small enough for thermal agitation to disperse them evenly within a carrier fluid, and for them to contribute to the overall magnetic response of the fluid.
- the magnetic fluid slug 108 is retained within a fluid channel 102 by the permanent magnet 114 such that the working fluid 104 and 110 are also static. These items are retained within a "cartridge" assembly 106, where the use of a small fluid channel and working fluid retained within the assembly is referred to as a microfluidic cartridge device.
- a microfluidic cartridge device where the use of a small fluid channel and working fluid retained within the assembly is referred to as a microfluidic cartridge device.
- the amount of movement can be controlled by the relative magnetic field strength of the permanent magnet 114 in relation to the field induced by the solenoid 116 and the offset location of the resulting field from the original permanent retaining magnetic field.
- the magnetic fluid slug 108 is moved by the magnetic field, the working fluid 104 is pushed ahead by this action and the working fluid 110 is drawn along by this action. In this way the device can provide transport action acting on the working fluid components 104 and 110.
- FIGURE 2 illustrates a transport mechanism of an apparatus in which fluids is displaced by operation of the magnetic field from the solenoid according to the present invention.
- the magnetic fluid slug 108 is now displaced to be over the solenoid 116 with the switch 120 is closed and current flows in the circuit 118.
- the transport action as illustrated can be utilized to move a working fluid 104 and 110, between activity areas or regions within a micro fluidic cartridge device, to draw fluid into the cartridge such as draw up a sample or reagent, to eject fluid from the cartridge and to cause and control mixing and reactions between reagents and samples.
- the working fluid as defined may be air, and thus an electromagnetic fluid transport system described above is able to be used as a pneumatic fluid delivery system. This is important as many conventional microfluidic cartridge devices rely on an externally provided pneumatic sources (for pumping and valving) which are relatively complex and expensive, and not suited to embodiment in a POC diagnostic system.
- FIGURE 4 illustrates an apparatus having an elastomeric valve for controlling fluids within a microfluidic cartridge device according to alternate embodiment of the present invention.
- the body of the microfluidic cartridge device can be manufactured from a layered construction where individually cut or stamped plastic sheets are laminated with adhesive and pressure to become bonded as a complete cartridge assembly with integrated fluid channels 416.
- the valve incorporates an elastic deformable valve element 420 with a magnetically susceptible inclusion 418.
- the inclusion 418 is iron or ferrite particles captured within the material of the deformable element.
- the fluid channels 416 within the device are obstructed by the valve element 420 in the resting state forming a normally closed valve assembly.
- the element shape is specifically designed to provide the required valve properties within a single flexible element including: Firstly, the required valve pre-load or spring force resulting from the elastic nature of the material and the geometry of the device to hold the valve in its normal resting position, (normally open or normally closed), and resist the operating fluid pressure when in this state. Secondly, a sealing surface that forms a reliable fluid seal against the geometry of the fluid ports provided by the microfluidic cartridge device. Thirdly, magnetic fluid inclusions, in specific areas of the valve, allow the element to be actuated by a magnetic field.
- valve element 420 which is manufactured by a separate process can be designed such that it can be compressed and inserted into the port 404 and allowed to release into the cavity 422 in the microfluidic cartridge device forming the required seal across the internal fluid ports.
- FIGURE 5 and FIGURE 6 illustrates a cross sectional view and an isometric view of the valve element 420 respectively.
- Features of its geometry include a thickened ring 502 that supports the structure of the element and provides a seal within the cavity 422 preventing escape of working fluids out of the overall valve assembly.
- the thinner section 420 of the valve element 420 provides increased flexibility for the valve to be lifted off its seat with the available external magnetic field. This approach allows the microfluidic cartridge device, and valve element 420 to be manufactured in separated processes, where the valve can be inserted into the microfluidic cartridge device at a later stage, typically after the working fluids have been introduced into the device. In this case the valve inserts complete the construction of the device, providing final sealing and separation of reagents within fluid channels separated by normally closed valves.
- a valve element of this geometry can be constructed in a mould of two or more parts, where the mould is filled with a reactive chemical fluid mix formulated to cure into a suitable flexible deformable plastic.
- suitable materials include silicone rubber or polydimethylsiloxane (PDMS) or flexible thermoplastic.
- the fluid mix introduced into the mould can also include magnetic particles such as iron powder or particles.
- a solid insert such as an iron core can be used, particles have advantages in that they can be mixed easily with the moulding compound at a specific concentration, will flow with the plastic prior to curing during the moulding process, and can be introduced into the mound along with the plastic material.
- FIGURE 5 illustrates a cross sectional view of the valve element according to an embodiment, where the magnetic particles have been retained in a specific region 418, within the overall elastomer material element. In this case the particles have been retained with reduced density at the face of the element forming the valve seat in contact with the working fluids.
- the device uses the optimum unfilled properties of the elastomer for the sealing surface in contact with the valve seat and the working fluids.
- This three dimensional localisation of the magnetic particles that can be achieved with the manufacture process described, also avoids contact between the magnetic particles that would otherwise be exposed at the sealing surface interface to the working fluid that may react chemically.
- This invention provides for the element itself and the magnetic regions within it to have a three dimensional form. This has important advantages over a simple flat sheet as it allows the device to be formed to be optimised its characteristics for fluid interaction, spring retaining force, and its actuation and detection by external magnetic fields.
- an electromagnetic solenoid coil 406 that forms part of a DC circuit made up of conductors and battery 410 and switch 408.
- a DC current will flow through the circuit and energises the coil, producing a magnetic field in the coil.
- a magnetically permeable ore may be used through the core of the coil to allow a concentration of the magnetic field at the poles of the coil.
- the magnetic field produced by the coil 406, will act on the magnetic susceptible particle region 418, in the valve element 420. This will cause the central region of the deformable elastic valve element to lift and create a fluid flow path connecting the fluid channels 416.
- FIGURE 7 illustrate an open condition of the valve under applied magnetic filed according to an embodiment of the present invention.
- the arrow represents fluid flow through the open valve assembly.
- the valve element 420 by nature of its elastic material properties will return to its stable position, re-sealing the valve assembly, blocking fluid flow, and returning the valve to the normally closed condition.
- the valve is shown in the open position with the external magnetic field applied.
- an alternating current (AC) signal represented by 414 is applied to the circuit and allowed to flow though the coil via the DC blocking capacitor 412, the AC component of the magnetic field created will inductively couple to the second coil 402 and allow an AC signal of the same frequency to be measured in the second coil 402.
- the inductive coupling of the AC signal onto the second coil 402 allows the coil 402 to be used as a sensing coil.
- the amplitude of the signal and its phase relationship to the original signal is related to the magnetic coupling between the coils. Where these coils are close to the each other and both in proximity to the magnetic region of the valve element, the magnitude of the received AC signal in the receiving coil can be used to sense the presence of the valve element and the relative position of the valve elements magnetic region.
- This sensing capability can be used as a sensing method to confirm the actuation and position of the valve and utilized as part of a feedback control loop.
- This feedback can be used to provide a level of assurance, self test and confirmation required in a typical clinical point of care microfluidic cartridge device reader system.
- the AC signal can be superimposed on the DC signal used to implement magnetic actuation and can be separately switched and sensed across the same coils used for the DC currents using electronic circuit methods to separate control of AC and DC signals including using inductors and DC blocking capacitors.
- the frequency of the AC signals can be much higher than any switch frequency used to modulate the DC currents in the coils. In this way the same set of coils including an array of coils can be used to both actuate and provide feedback sensing functions for magnetically operated components within the microfluidic cartridge device.
- valve element is configured such that its internal elastic strength, is smaller than the forces that can be applied by the fluids acting on its interface it will not act as a reliable valve, but can be used for its position sensing capability to provide flow indication or pressure sensing. In this case, when the fluid flow or pressure lifts the element from its seating position, the embedded magnetic particle region is also lifted. This change will alter the magnetic coupling between an excitation coil or coils and the receiver coil or coils in proximity, changing the amplitude of the AC signals measured across the receiver coils.
- An additional embodiment of the present invention is a programmable magnetic array where any number of electromagnetic microfluidic cartridge devices of different designs can be actuated and controlled.
- the array is suitable for control by a microprocessor and embedded software or firmware providing a flexible and adaptable construction for a general reader device that can accept and control a wide range of microfluidic cartridge devices utilising embodiments of this invention.
- FIGURE 3 and FIGURE 8 respectively for the two different embodiments.
- the magnetic field strength from each coil 306 and 312 can then be varied in proportion to the effective electrical current carried through each coil's windings. Where the two coils are in proximity the magnetic fields from the two coils can superimpose and, as a result, the position of the point of maximum magnetic field intensity can fall somewhere between the poles of the two coil assemblies. The position of this point is related to the ratio of the field intensity at each of the poles. In this way the electric current through both of the coils can be controlled to provide control of both the absolute magnetic field strength and the position of the maximum field point between the two solenoid poles.
- the current to each coil can be controlled either using analogue current control or by digital modulation of an electronic switch such as the switching transistors 302 and 308 shown in FIGURE 3 and FIGURE 8.
- modulation of the current provided to each coil provides a mechanism for control of the current and the resultant magnetic field provided by each coil.
- Changing the duty cycle of the square wave control signal will change the effective current through the coil. As examples a 0% duty cycle, resulting in the switch being off continuously will result in a zero current flow, while a higher duty cycle for example an 80% duty cycle would result in approximately 80% of the maximum current flow and magnetic field. In this way both the position of the maximum field strength location and the actual magnitude of the magnetic field can be varied under software control.
- This approach can be extended to an array of coils as illustrated in FIGURE 9.
- FIGURE 9 illustrates a top view of magnetic coil array according to the present invention.
- the magnetic coil array can have 4 row by 7 column array i.e. 28 coils.
- This array 906 is made of coils 902, each having a magnetic core 904.
- the maximum field strength location and the magnitude of the field strength can be directed to any location within the region bounded by the poles of the 4 coils.
- This approach can then be expanded to larger groups of coils beyond the basic set of 3 or 4 coils and used to provide control over the profile and overall diameter of the magnetic field.
- more than one magnetic field area can be established and controlled simultaneously, providing simultaneous control of more than one magnetic element within the microfluidic cartridge device placed in proximity to the array.
- a specific advantage of this arrangement is that the general control of magnetic field strength between a set of coils can be used dynamically to move this magnetic field smoothly, and it can be controlled to traverse the whole area of the array. This ability to define the location of the maximum field strength location, and to control its absolute field strength and diameter and to move this region across the array allows magnetic fluid components within the microfluidic cartridge device to be moved or pulled along through channels, in the microfluidic cartridge device as described in several of the embodiments of the present invention.
- each coil in the array can also act as either an AC exciter or receiver to provide feedback including position sensing of magnetic elements within the micro fluidic cartridge device in close proximity.
- a further embodiment of the invention is to build the magnetic array from a Printed Circuit Board (PCB) construction which does not require winding of individual coils.
- PCB Printed Circuit Board
- FIGURE 10 illustrates an embodiment of a multi-layer Printed Circuit Board henceforth referred to as a PCB.
- a spiral coil with a hole for a core 1006 is etched into the copper layer such that only the conductive spiral coil is retained as a conductive electrical element on the respective PCB layer.
- the coil can be connected to other spirals on layers above and below using inter layer connections or vias 1004 and 1008, such that the coils are connected in series or parallel electrical format.
- an assembly of ten layers can be used with the coils connected in series to form an array made of coils where each coil has 50 turns.
- a hole is provided in the PCB fiberglass composite construction into which magnetically permeable cores can be inserted.
- the magnetic cores provide preferential flow paths for the lines of magnetic field flux such that an effective solenoid action is provided at each coil.
- the cores can be inserted as discrete iron or ferrite type solid inserts or alternatively can be cast into an assembly such as a formed plastic with ferrite powder filler with cast in place posts that can accept the PCB assembly and provide a core through each coil assembly.
- a magnetically permeable material such as ferrite filled epoxy resin can be cast or poured over the PCB assembly forming a core in the hole provide in each coil assembly.
- a switching transistor and associated electronic components such as a flyback diode or control components are required to allow the current to each coil to be individually switched to provide digital modulated current control.
- the switching transistors and associated control components and passive components associated with each coil can be mounted on the same PCB assembly that forms the coils in close association to each coil within a regular array of coils. These components would typically be surface mounted components and be mounted on one layer such as the top layer of the assembly.
- This close association of the switching element to each coil also has the advantage that only power and switch logic control signals need to be routed to each coil, and the actual high frequency switching of the coil current is accomplished very close to each coil, minimizing circuit inductance and the enclose area of circuits with high rate of change of current. This approach minimizes the track lengths and potential for undesirable electromagnetic emissions from the coil assembly.
- fluid transport capabilities of the present invention can be used to transport any fluid including air.
- fluid components such as valves are typically actuated by positive or negative air pressure. This is provided by standard air pumps and valving within the reader unit.
- the invention is used to implement a multi-way air pump that can be used to actuate existing components within a microfluidic cartridge device.
- These air transport functions can be implemented within a microfluidic cartridge device and used to provide positive or negative air pressure to air activated components within the same microfluidic cartridge device.
- FIGURE 11 illustrates an alternate embodiment of the present invention in which the muti- way air pump assembly is implemented in a module 1106 similar to a micro fluidic cartridge device but intended for multiple uses and mounted within the instrument.
- the module 1106 can then supply positive or negative pressure through connection manifold 1102 to actuate air operated components within a microfluidic cartridge device inserted into the reader.
- the module 1106 can be integrated with its own magnetic array 1210 depicted in FIGURE 12 which illustrate the cross sectional view of the module 1106.
- a magnetic fluid slug 1112 or 1104 can provide fluid compression force on air within a channel such that negative or positive air pressure is delivered depending on the direction of travel of the magnetic fluid slug.
- This air pressure is applied at the port 1202 through the connection manifold 1204.
- the air-pressure can connect to tubes or a microfluidic cartridge device through air path 1202 and operate pressure actuated devices within the microfluidic cartridge.
- each of the magnetic fluid slugs 1112 in each channel are controllable via an array 1210 of solenoid coils embedded in a PCB, each of the magnetic fluid slugs may be programmably moved to any location within its operating channel. This allows for a programmable volume of air to be delivered to a secondary connected microfluidic cartridge device, enabling a wide range of chemistry protocols to be delivered to a secondary microfluidic cartridge device.
- a permanent magnet 1206 is placed between the air pump module 1106 and the magnetic array 1208.
- the permanent magnet 1206 ensures that the magnetic fluid slugs in each channel are retained in a central-channel location when the electromagnetic field 1210 is removed from the solenoids 1210 (that is, when the instrument is switched off). In this way, inadvertent loss or leakage of magnetic fluid is prevented.
- the magnetic field from the permanent magnet 1206 is annulled by the actuation of the magnetic field from the solenoid array 1210 when the device is in use.
- FIGURE 13 illustrates an extended Transport fiinction within a microfluidic cartridge device according to an embodiment of the present invention. The basic transport approach described previously can be extended to provide more complex transport capabilities within a microfluidic cartridge device.
- cavities 1302 and 1328 operate at each end of a microfluidic processing channel section.
- the magnetic fluid sections 1310 and 1326 form fluid seals at each end of the fluid channels that make up the cartridge assembly.
- the permanent magnets 1308 and 1324 hold the magnetic fluid region 1326 in place and by action of external atmospheric air pressure and surface tension all of the other fluid components of the system are also held in place during storage and transport.
- the fluid flow through the system mixes the sample with the working fluids in the device. This flow can further process the sample causing it to come in contact with other reagents and sections wittrin the device such as powders, dried reagents or fluid reagents in the chamber 1306 to further flow through the section where the sample and fluids under test can be heated or cooled.
- the process fluid can then enter a section such as the chamber 1322 where a test result can be read or sensed by such methods as a colour change or fluorescence emission.
- the magnetic field strength applied to one or both of the magnetic fluid regions can be used to control the internal pressure and rate of fluid flow within the device and to halt or reverse the flow at specific stages for particular process steps and analysis including reading of the final result. Relaxation of the magnetic field will allow the fluids to flow back towards the original holding condition with the magnetic fluid region 1326 fully retained by the permanent magnets 1308 and 1324. This effect may be used to enhance mixing or provide repeated temperature processing of the fluid reagents and samples.
- the permanent magnets can be deleted.
- the inherent viscosity and surface tension of the fluids can be utilized to hold the fluids in place during storage and transport.
- the application of magnetic fields to one or more of the magnetic fluid regions can be used to transport and process the working fluids through the device as described above.
- the magnetic fluid regions can also be separated from the working fluid by inclusion of a deformable or elastic membrane such as at the interface between the magnetic fluid region 1310 and the fluid within the cavity 1312.
- the magnetic fluid region can be enclosed within an envelope of flexible, deformable or elastomer material such as thin walled elastic thermoplastic or silicone rubber capsule.
- the packaged assembly can be filled with magnetic fluid and sealed as a manufacturing stage prior to assembly of the complete microfluidic cartridge device. A diagram of this type of packaged element is illustrated in FIGURE 16.
- the magnetic fluid is fully sealed within a packaged element in a separate manufacturing stage that simplifies handling of this fluid component at final assembly of the complete microfluidic cartridge device.
- the magnetic fluid region is separated from the working fluids and can not mix with or contaminate these fluids.
- the properties of the deformable capsule including its elasticity can be used to further enhance the capabilities of the device including providing a defined resting geometry for the fluid region when in operation without an external magnetic fluid present. This can remove the requirement for inclusion of permanent retaining magnets in the microfluidic cartridge device in some applications.
- this embodiment provides improved sealing characteristics between the capsule and the side wall of the cavity in the microfluidic cartridge device.
- FIGURE 14 and FIGURE 15 illustrates a cross sectional view of an embodiment of a microfluidic cartridge device for constructing a fluid valve, when the valve is closed or open.
- the use of a magnetic fluid within a microfluidic cartridge device can be used to construct a fluid valve.
- FIGURE 14 shows the valve in the normally closed position
- FIGURE 15 shows the valve in the open position under the operation of an external magnetic field.
- a fluid path is constructed with a fluid channel 1404.
- a magnetic fluid region 1406 is retained in place by a permanent magnet 1412. The retained magnetic fluid region forms a fluid plug in the cavity region and prevents flow of working fluid through the channel 1404. In this configuration, the valve is in the normally closed position.
- the magnetic field acts to pull the magnetic fluid region upwards into the cavity 1406 and opens a fluid flow path for the working fluid to flow through. This is the valve open position. Where a vent is provided in the cavity 1406, the magnetic fluid will continue to form a seal between the working fluid and the external vent.
- valve is in closed position due to the arrangement of the permanent magnet as shown. Where the positions of the permanent magnet and electromagnet are reversed, a normally open valve type can be constructed. Of note is that the valve design can operate within the same magnet array described previously. Using this approach the magnetic array could be used to operate several valves and provide fluid transport across a microfluidic cartridge device.
- the magnetic fluid region can be enclosed within an envelope of flexible, deformable or elastomeric material, such as thin walled elastic thermoplastic or a silicone rubber capsule.
- the packaged assembly can be filled with magnetic fluid and sealed as a manufacturing stage prior to assembly of the complete microfluidic cartridge device.
- a diagram of this type of packaged element is illustrated in FIGURE 16.
- the deformable body of the valve element 1502 forms the cavity shown as 1406 in the FIGURE 14 and the rim of the element 1406 can used to locate and secure the capsule in a microfluidic cartridge device.
- FIGURE 17 and FIGURE 18 illustrate a diagram of a four way, multi-port valve. The approach used to construct a basic valve using the elements of this invention can be extended to build multi-way valves.
- FIGURE 17 shows construction of a four way, multi-way valve where a permanent magnet 1708 under the assembly retains the magnetic fluid region 1712 such that it seals all four flow channels in its stable position with no external magnetic fields.
- a permanent magnet 1708 under the assembly retains the magnetic fluid region 1712 such that it seals all four flow channels in its stable position with no external magnetic fields.
- One flow channel 1702 is shown with the arrow.
- FIGURE 18 illustrates the device with an external magnetic field applied, offset to the position of the retaining magnet, such that the magnetic fluid region 1712 is displaced to one side of the valve cavity in the device to open a flow channel between two or more ports. In this case a flow channel is created between the ports 1702 and 1802.
- the magnetic fluid region can be enclosed within an envelope of flexible, deformable or elastomer material such as a thin walled elastic thermoplastic or a silicone rubber capsule.
- the packaged assembly can be filled with magnetic fluid and sealed as a manufacturing stage prior to the assembly of the complete microfluidic cartridge device.
- the elastic deformable nature of the pack construction can provide the retaining function providing a known fluid location without use of a permanent magnet.
- the package body then forms the sealing action against the fluid channels but can still be deformed into cavities and channel spaces under the action of an external magnetic field to provide valving functions.
- This embodiment provides a method for temperature control and implementation of thermo- cycling of a sample under test within a microfluidic cartridge device using the basic components of fluid transport and external variable magnetic fields acting on the device described previously.
- Thermo-cycling and temperature transitions are used in a number of biological and biomedical processes applicable to processing and testing samples within a microfluidic cartridge device.
- a specific example is Polymerase Chain Reaction amplification known as PCR, where a sample containing nucleic acid material is cycled between a set of temperatures in the presence of specific reagents to achieve an amplification in the quantity of starting nucleic acid prior to a subsequent test or analysis.
- An example of the PCR process requires cycling of the sample between three specific temperatures.
- a specific challenge in undertaking PCR in a microfluidic cartridge device is to either move fluids or change the temperature of a sample with accuracy and responsiveness using very small sample sizes but without excessive cost and complexity in either the reader/control assembly or in the microfluidic cartridge device itself.
- the microfluidic cartridge device should be low cost and disposable as it is typically contaminated by the test sample and would be prohibitively expensive and unsuitable to clean.
- FIGURE 19 illustrates a top view of a polymerase Chain Reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs according to an embodiment of the present invention.
- PCR polymerase Chain Reaction
- FIGURE 20 illustrates a Polymerase Chain Reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs, cross section view XX, temperature controlled magnetic fluid in the resting position over the heater element according to an embodiment of the present invention.
- PCR Polymerase Chain Reaction
- FIGURE 21 illustrates a Polymerase Chain Reaction (PCR) thermo-cycling implantation within a microfluidic cartridge device with three temperature reservoirs, cross section view XX, magnetic fluid transported by external magnetic field to be in proximity and thermally coupled to the amplification chamber according to an embodiment of the present invention.
- the microfluidic cartridge device 1910 contains a test sample cavity 1914 with fluid channel inlets and exits 1912 and 1920. Separate magnetic fluid regions 1904, 1906 and 1918 are each retained by a respective permanent magnet 1902, 1908 and 1916, such that each regions can be retained at different specific temperatures by an external heater 2004, brought into contact with the respective surface zone of the microfluidic cartridge device, when the cartridge is inserted in to reader unit.
- PCR Polymerase Chain Reaction
- the cartridge can be specifically designed to allow good thermal coupling between the external heater temperature control and the magnetic fluid region by use of a thin wall section or a cartridge construction with high thermal conductivity in this region. It is possible to manufacture the cartridge with a metallic wall or an embedded metallic insert over the magnetic fluid region.
- the heating or cooling element and temperature sensor and temperature control can then take place at the surface contact between this region of the microfluidic cartridge device and the external element established, when the microfluidic cartridge device is inserted into the reader assembly.
- the heating element and temperature sensor can be embedded within the microfluidic cartridge device and coupled such as by electrical connection when the microfluidic cartridge device is inserted into the reader.
- the magnetic fluid acts as a thermal reservoir and can be used to transport this temperature to be in close proximity or contact with the sample under test.
- FIGURE 21 where the magnetic fluid region 1904 is moved under the influence of an external magnetic field to be in close thermal coupling to the sample cavity 1914.
- the volume of the magnetic fluid is higher than that of the sample region such that the temperature effect of delivering heat to the sample is not significant for the process or is predictable and compensated for in the original magnetic fluid temperature.
- the externally applied field can be respectively deform each fluid region in turn and apply each different magnetic fluid temperature reservoir in turn to achieve thermal cycling or temperature processing of the sample under test.
- FIGURE 22 illustrates stirring and heating through a fluid chamber within a microfluidic cartridge device according to an embodiment of the present invention.
- the embodiment provides a method for stirring, heating and temperature control within a microfluidic cartridge device using the basic components of fluid transport and external variable magnetic fields acting on the device as described previously.
- a magnetic fluid region 2206 is included within a cavity 2204 filled with a working fluid such as test sample.
- a working fluid such as test sample.
- the working fluid is water based and the magnetic fluid is a type such as an oil based fluid that is immiscible in water.
- the chamber is provided with inlet and exit channels 2202 and 2208 such that fluid transport functions within the microfluidic cartridge device can introduce and remove sample fluids for mixing or heating or at completion of a mixing or heating function.
- the magnetic fluid region Under the action of an external magnetic field, the magnetic fluid region can be maintained as a cohesive region but moved within the fluid chamber, thus providing a stirring or mixing action. As the frequency and venousness of the stirring is increased, thermal energy can be introduced into the working fluid and used to heat the sample.
- the application of the varying external magnetic field can be adjusted so that it vibrates or excites the magnetic fluid region at high frequency such as there is little bulk movement of the region but useful heating action is provided. This has the advantage that stirring and heating, including a controlled mix of the two actions can be induced into a fluid sample within a microfluidic cartridge device using the embodiments of this invention including the magnetic array previously described.
- FIGURE 23 illustrates a top view of transport functions within a microfluidic cartridge device according to an embodiment of the present invention and its cross sectional view is illustrated in FIGURE 24.
- an elastomeric element with magnetic particle inclusions is constrained within a cavity such that some of the volume is available for the working fluid.
- the cavities 2306 and 2322 operate at each end of a microfluidic processing channel section.
- the flexible deformable elements 2402 and 2406 captured within the cavities act as diaphragms, and form fluid seals at each end of the fluid channels that make up the cartridge assembly.
- Working fluids can be retained within the microfluidic cartridge device and in the region 2306 over the deformable element 2402, such that when a magnetic field acting on the magnetic inclusion 2404 provides an upward force on the diagram structure of the element and asserts a fluid pressure in the working fluid captured within the region 2306 or similarly provides a displacement, moving this fluid out of the region.
- the cartridge can be inserted into a reader instrument where it can be exposed to the programmable magnetic fields of the magnetic array described previously.
- This element By applying an increasing magnetic field to the magnetically susceptible deformable element 2402, this element is lifted, pushing the working fluid through the fluid channel assembly.
- Displaced fluid can be received into the second cavity 2320 such that the fluid pressure deflects the flexible element retained within this cavity to increase the cavity volume.
- the magnetic field over the inclusion 2404 is decreased and an increasing field is applied to the second inclusion 2408, then fluid flow in the reverse direction, from the cavity 2320 back towards cavity 2306 can bde induced in the microfluidic cartridge device.
- a sample introduced into the port 2310 such as through a serf sealing elastomeric valve enters the cavity 2312.
- the fluid flow through the system from displacement of fluid within the cavity 2306 mixes the sample with the working fluids in the device.
- This flow can further process the sample causing it to come in contact with other reagents and sections witlrin the device such as powders, dried reagents or fluid reagents in the chamber 2304 to further flow through the section where the sample and fluids under test can be heated or cooled.
- the process fluid can then enter a section such as the chamber 2304 where a test result can then be read or sensed by such methods as a colour change or fluorescence emission when it reaches the cavity 2318.
- the magnetic field strength applied to one or both of the magnetic regions in the deformable elements can be used to control the internal pressure and rate of fluid flow within the device and to halt or reverse the flow at specific stages for particular process steps and analysis including reading of the final result.
- This embodiment provides a method for stirring, heating and temperature control within a microfluidic cartridge device using the flexible material insert with magnetic particle inclusions and the application of an external variable magnetic field acting on the device as described previously.
- a cavity 2504 within the microfluidic cartridge device can contain a working fluid, such as a test sample.
- the chamber can be provided with inlet and exit channels 2502 and 2506 such that fluid transport functions within the microfluidic cartridge device can introduce and remove sample fluids for mixing or heating or at completion of a mixing or stirring function.
- a flexible deformable element 2508 is fixed with a flexible projection 2510.
- This element contains a magnetically susceptible inclusion region 2512.
- the magnetic fluid region can be moved from side to side within the fluid chamber, thus providing a stirring or mixing action.
- thermal energy can be introduced into the working fluid and used to heat the sample.
- the application of the varying external magnetic field can be adjusted so that it vibrates or excites the flexible element projection 2510 at high frequency such as there is little bulk movement of the region but useful heating action is provided.
- This has the advantage that stirring and heating, including a controlled mix of the two actions can be induced into a fluid sample within a microfluidic cartridge device using the embodiments of the invention including the magnetic array previously described.
- FIGURE 26 illustrates a top view of a pumping circuit within a microfluidic cartridge device showing a fluid cycle with three serpentine sections that can be used to thermo- cycle a working fluid sample through three regions of different temperature according to an embodiment of the present invention.
- the embodiment of the invention provides controlling of a pumping component within the microfluidic cartridge device to provide a continuous pumping action rather than just a limited volume transport function.
- the pumping circuit where a pumping element 2616 provides circulation of the working fluid through a pumping circuit made up of fluid channels shown as 2602, 2604, 2610, and 2612 within a microfluidic assembly 2614.
- the pumping circuit includes tube paths designed to take the fluid through three serpentine regions 2602, 2604 and 2612, where these are maintained at different temperatures.
- the fluid, in circulating through areas of different temperature is exposed to a thermo-cycling action that can be used for the purposes PCR amplification of genetic material within the working fluid samples and reagent mix.
- FIGURE 27, FIGURE 28 and FIGURES 29 illustrate a cross section view of a pumping element within a microfluidic cartridge device according to an embodiment of the present invention.
- a magnetic fluid region 2712 is retained at one side of a flow channel 2708 of the working fluid.
- the magnetic fluid region 2712 can be retained by either a permanent magnet 2714 or a flexible membrane that encloses the magnetic fluid region.
- the external magnetic field shown as three electromagnet coil circuits 2702, 2704 and 2706 in these diagrams can be used to deform a section of the magnetic fluid region 2710 such that it will close off and obstruct the working fluid channel 2708.
- the obstruction point 2710 can then be moved along the magnetic fluid region 2712 such that obstruction of working fluid channel 2708 is maintained and any fluid within the channel is pushed ahead of the obstruction providing a pumping action shown in FIGURE 28.
- a second obstruction 2902 can be formed at the fluid entry by additional application of an external magnetic field, which is shown in FIGURE 29. In this way, as the initial obstruction lobe reaches its end of travel it can be released but the second obstruction is now in place preventing any backflow of working fluid and to maintain the pressure difference across the device. At this stage the device has returned to the initial state shown in FIGURE 27.
- the pump has a given displacement and can be used to meter or control the fluid flow rate in proportion to the speed of progress induced on the obstruction lobe providing the pumping action.
- This device is analogous to a peristaltic pump where rigid rollers act on a deformable tube to provide a pumping action.
- the magnetic field is contained within a deformable membrane package shown in FIGURE 30 (a) and a cross section view in FIGURE 30 (b).
- the package manufactured with walls 2712 and 2714 constructed from a deformable or elastomeric material such as thermoplastic or silicone rubber is filled with a region of magnetic fluid 2902.
- the external surface of the package material is selected to be inert in its interaction with the exposed working fluid reagents.
- the package can be manufactured from a hollow tube of elastomer material where a length is filled with magnetic fluid and the ends closed by adhesive or a welding process when the tube end is pinched closed.
- a blister cavity 2712 is formed and filled with magnetic fluid, where a second sheet or tape 2714 is then welded or adhered to the cavity material to form and enclosed capsule.
- an element of deformable, flexible elastic material such as silicone rubber or polydimethylsiloxane (PDMS) is moulded with as shape such as shown in FIGURE 31 (a) and also FIGURE 31 (b) in cross section with a region of magnetic particle inclusion.
- the deformable insert 3104 has a form that allows it to be retained within a microfluidic cartridge device. It incorporates a magnetic inclusion 31024 close to face of the insert exposed to the working fluid.
- the insert geometry and elasticity is configured such that an external magnetic field applied by a programmable magnetic array, can deform a section of the element surface shown as 2710 in FIGURE 27, such that it will close off and obstruct the working fluid channel 2708.
- the capsule can be manufactured separately prior to the assembly of the microfluidic cartridge device. It can then be supplied to the final assembly stage as a fully sealed component for assembly into the microfluidic cartridge device.
- the microfluidic cartridge device is manufactured with a cavity of given geometry and dimensions ready to accept the deformable pump element prior to bonding a final cover onto the microfluidic cartridge device that seals the device, retaining the package and forming the fluid channel and complete pump assembly within the microfluidic cartridge device.
- FIGURE 32 and FIGURE 33 illustrates a top view of an inlet port sealing within a microfluidic cartridge device according to an embodiment of the present invention.
- the invention can be implemented to provide an external air tight seal for an inlet port to the microfluidic cartridge device that will allow a test sample to be introduced under specific conditions.
- a typical microfluidic cartridge device contains fluids and solid reagents provided for the conduct of biological and chemical reactions as part of providing a diagnostic output or observable transformation indicative of a particular diagnostic trait. These reagents need to be protected from contaminants and atmospheric gasses during storage, transport and use including during the period from removal from any protective packaging up to and including introduction of a sample and execution of the intended testing.
- the microfluidic cartridge device has a sample entry port 3214 that will allow a probe 3302 carrying a sample to be inserted such that the sample can be introduced into the chamber 3206 and some of the sample material 3304 carried on the tip of the probe can be flushed from the probe through channels 3208 and 3210. This allows the sample within the microfluidic cartridge device working fluids to be transported to further reactions and testing.
- the fluid entry port 3214 is sealed by a magnetic fluid region 3202 that is held in place by magnetic attraction to a permanent magnet 3204 mounted under the entry cavity region 3212.
- the magnetic fluid in this case can be selected with enhanced magnetorheological properties such that the fluids viscosity increases significantly under the influence of the retaining magnetic field. This can be to the point that the magnetic fluid is effectively a solid plug under the influence of the permanent magnetic field.
- the sample probe 3302 is designed to be suitable for acquisition and retention on its tip of the required sample material that may include such typical test samples as water, dust, blood, urine, nasal discharge or saliva. These could be human, animal biological, food or environmental samples suitable for reaction analysis or testing within a microfluidic cartridge based device. Typically small cavities or an adsorptive region 3304, at the tip of the probe 3302, would be provided to assist with capture and retention of the sample material for transfer into the microfluidic cartridge device. Once the sample material is acquired, the probe can be pushed into the entry port to introduce the sample into the region of the internal chamber.
- the magnetic fluid will flow around the probe and under the influence of the retaining magnetic field will continue to provide a seal around the body of the probe and to the sides of the entry port maintaining an overall environmental seal 3202 as the probe is introduced.
- an external magnetic field can be introduced to oppose the retaining magnetic field such that the material can assume its fluid flow properties while the probe is introduced.
- Sufficient retaining magnetic field is used to retain the fluid in the inlet area such that a seal is maintained across the inlet port and around the probe body shown by the magnetic fluid region 3202 in FIGURE 33.
- the opposing magnetic field where it is required to fluidize in the inlet magnetic fluid plug can be provided by a secondary permanent magnet brought into proximity to that region of the microfluidic cartridge device during the probe insertion.
- This method may include the secondary magnet within the probe assembly or within a carrier or holder placed against the microfluidic cartridge device as part of the sample insertion stage.
- the secondary magnetic field can be provided by the magnetic array if the microfluidic cartridge device is first placed within the reader assembly prior to introduction of the sample. This can be arranged if the inlet port is at one end of the microfluidic cartridge device accessible externally when the microfluidic cartridge device is placed within the reader assembly but such that the required external magnetic field can still be applied in the required region by the programmable magnetic array.
- FIGURE 34 illustrates a top view of a use of magnetically releasable plugs for separating fluid regions within a microfluidic cartridge device according to an embodiment of the present invention.
- the embodiment describes a system of magnetic fluid plugs that can be used to provide seals or separation between reagent components of the microfluidic cartridge device during transport and storage and selective release of these separation barriers or seals during operation of the device.
- the microfluidic cartridge device contains a fluid channel.
- the channel has external vents 3402 and 3424, to allow atmospheric equalization, where it is necessary to force movement of fluids within the device and introduce external (atmospheric pressure) samples.
- Each of the shaded regions 3404, 3410, 3414, 3418 and 3422 are magnetic fluid regions retained by permanent magnets in proximity to each magnetic fluid region to hold and position the respective region.
- FIGURE 35 illustrates a cross section view of a microfluidic cartridge device showing a magnetic sheet, such a flexible plasticized sheet of magnetic particles on one side of a microfluidic cartridge device to provide retention of magnetic fluid components, according to an embodiment of the present invention.
- the microfluidic cartridge device 3502 is shown in cross section.
- the permanent magnet is a sheet of flexible magnetic material 3504 (such as magnetised ferrite powder) carried in a plasticised carrier, such as the flexible magnetic sheet often used as printed refrigerator magnets. This sheet can be magnetized such that it will retain all of the magnetic fluid regions within the microfluidic cartridge device and can be used as the permanent magnet implementation applicable to many of the embodiments described according to the present invention.
- the flexible magnetic sheet can be removed by the user by peeling it off or as part of the packaging removal process.
- the sheet 3504 can remain in place when the microfluidic cartridge device comprising 3502 and 3504 is inserted into the reader and the secondary magnetic field of the magnetic array applied to oppose and substantially reduce the field strength at the locations of the magnetic fluid regions.
- the magnetic fluid is a magnetorheo logical type
- the viscosity of the plug will be substantially reduced and this plug will become fluid such that the fluids within the channel are free to move and will mix when the transport properties previously described are applied and the fluids are moved to the mixing chamber 3420 in the microfluidic cartridge device as shown in FIGURE 34.
- the magnetic fluid can be use to move and mix the fluids and then be extracted from the working fluids by pulling the magnetic fluid to one side or into an intended recess or extraction channel provided in the microfluidic cartridge device design.
- FIGURE 36 illustrates a chamber in a microfluidic cartridge device where a magnetic fluid is used to form separated fluid cavities to separate working fluid reagents, such that the magnetic fluid forms the walls of the cavities according to an embodiment of the present invention.
- Multiple chambers such as 3604, 3606, 3608 and 3610, can be created within a working cavity in a microfluidic cartridge device using magnetically induced displacement of a magnetic fluid 3602.
- the magnetic fluid region is effectively used to create walls that can be used to separate the working fluid regions 3604, 3606, 3608 and 3610, where the walls of the chambers are formed by the magnetic fluid itself. Magnetic manipulation of the magnetic fluid region can then be used to move or join rejoins of working fluids or to conduct controlled or sequenced mixing and reaction of sample and reagent regions.
- the magnetic fluid itself can be used to construct fluid channels or reaction regions that can be controlled or changed through the conduct of a test or analysis under software control of a programmable magnetic array in proximity to the micro fluidic cartridge device.
- the walls and internal chambers of the cavities can be formed at manufacturing stage by a strong magnetic field biased to pull the fluid into walled regions with internal cavities.
- the structure can then be maintained by permanent magnets incorporated into the microfluidic cartridge device or its packaging including a flexible magnetic sheet fixed to the surface of the microfluidic cartridge device as illustrated in FIGURE 35.
- the retaining magnetic field is removed such as by removing the magnetic sheet, or substantially reducing by application of an opposing external magnetic field, the magnetic fluid barriers separating the chambers will collapse and the working fluids and reagents carried within the chambers is free to mix.
- the action of array on the magnetic fluid can then be utilized to provide mixing, transport, separation and heating functions as previously described.
- FIGURE 37 illustrates a cross sectional view of a pump element according to an embodiment of the present invention.
- FIGURE 38 illustrates a top view of a pump element having multiple elements integrated within a single elastomeric moulding.
- the embodiment provides a method for a number of flexible element, magnetically actuated devices to be integrated within a single moulding.
- a flexible element sheet integrating several devices is as shown.
- a microfluidic cartridge device is typically constructed partly or fully from layers of cut sheet bonded together in a stack.
- the element set shown in FIGURE 37 is designed to be captured or retained within a microfluidic cartridge device layered construction, where it contains flat sections 3710, and cutouts such as 3708 and 3712 that allow the sheet to accurately located and captured within a suitably designed microfluidic cartridge device construction.
- the embodiment provides within a single moulding, three of the devices previously described, which are a peristaltic pump element 3702, a valve element 3704, and a fluid displacement diaphragm 3706.
- Each device contains its own magnetic particle inclusions where these were added to the moulding material mix and held in place by separate magnetic fields while the deformable carrier material, such as silicone rubber or PDMS cured as part of the moulding process.
- each element component is moulded with it corresponding three dimensional form in sections where this provides optimized fluid and magnetic control.
- FIGURE 39 illustrates a flow diagram of a method of controlling fluids within a microfluidic device according to the present invention.
- a working fluid region is generated between a lower section and an upper section of the microfluidic device such that a magnetic fluid slug is retained at centre within the fluid region by a permanent magnet.
- electromagnetic forces are induced to control the movement of the magnetic fluid slug within the working fluid region for controlling fluids within the microfluidic device.
- FIGURE 40 illustrates a flow diagram of a method of controlling fluids within a microfluidic device according to the present invention.
- a valve is positioned between an upper portion and a lower portion of the microfluidic device such that a channel being formed therethrough by the valve, the upper portion and the lower portion
- electromagnetic forces are induced for deforming the valve in order to provide a cavity channel for controlling fluids within the microfluidic device.
- the present invention provides a methodology and an apparatus for controlling fluids within a microfluidic cartridge device offers various advantages. Firstly, the present invention is able to rapidly and cheaply deliver a quantifiable test result having the same accuracy as central clinical pathology laboratory based testing but which do not require expensive equipment, clinical laboratories, or skilled personnel to perform such tests. Secondly, the fluid transport system can be manufactured with no moving parts using solid state components. Thirdly, the magnetic field actuation system can be manufactured with no moving parts using solid state components. Fourthly, diagnostic instruments designed using the methods described herein are cost effective.
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Abstract
La présente invention concerne un appareil permettant d'assurer la commande de fluides au moyen de canaux et d'instruments à l'intérieur d'un dispositif microfluidique jetable. Cet appareil est utilisé pour un système de diagnostic rapide et rentable pour diverses maladies. L'appareil comprend un moyen de générer une zone de fluide de travail entre une section inférieure et une section supérieure du dispositif microfluidique de façon qu'une masse de fluide magnétique soit retenue au centre dans la zone de fluide par un aimant permanent et que la masse de fluide magnétique puisse être déplacée en conséquence dans la zone de fluide de travail par des forces électromagnétiques induites. Cet appareil comprend également un moyen de positionner une soupape entre une partie supérieure et une partie inférieure du dispositif microfluidique de façon qu'un canal soit formé entre elles, la soupape pouvant ensuite être déformée sous l'action de forces électromagnétiques afin qu'on obtienne une cavité permettant de commander des fluides à l'intérieur du dispositif microfluidique.
Applications Claiming Priority (2)
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AU2006905373 | 2006-09-28 | ||
AU2006905373A AU2006905373A0 (en) | 2006-09-28 | System and method for valving and pumping of fluids within a microfluidic cartridge |
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WO2008036997A1 true WO2008036997A1 (fr) | 2008-04-03 |
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EP2308589A1 (fr) * | 2009-10-06 | 2011-04-13 | INSTITUT FÜR MIKROTECHNIK MAINZ GmbH | Structure micro-fluidique |
WO2011113563A1 (fr) * | 2010-03-15 | 2011-09-22 | Boehringer Ingelheim International Gmbh | Dispositif et procédé permettant d'agir sur un liquide |
KR101199980B1 (ko) | 2010-08-26 | 2012-11-12 | 중앙대학교 산학협력단 | 자기 유변 탄성체를 제조하는 방법 및 자기 유변 탄성체를 이용한 마이크로 유체 제어 장치 |
WO2016174230A1 (fr) * | 2015-04-30 | 2016-11-03 | Orphidia Limited | Valves et dispositifs microfluidiques |
CN110242533A (zh) * | 2019-05-17 | 2019-09-17 | 杭州电子科技大学 | 一种电磁微泵装置及其泵液方法 |
WO2021081103A1 (fr) | 2019-10-22 | 2021-04-29 | The Regents Of The University Of California | Dispositif ferrofluide numérique à commande électronique et procédé destiné à des opérations bio-analytiques évolutives et localisables |
CN113234591A (zh) * | 2021-05-28 | 2021-08-10 | 宁波康程德诺生物医药有限公司 | 一种一体化核酸快提试管、快提检测装置和方法 |
CN114405561A (zh) * | 2015-07-24 | 2022-04-29 | 新型微装置有限责任公司(Dba 新型装置) | 微流体样品处理设备和制备生物样品的方法 |
USD1069156S1 (en) | 2023-04-10 | 2025-04-01 | Becton, Dickinson And Company | Dispensing device |
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EP2308589A1 (fr) * | 2009-10-06 | 2011-04-13 | INSTITUT FÜR MIKROTECHNIK MAINZ GmbH | Structure micro-fluidique |
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CN114405561A (zh) * | 2015-07-24 | 2022-04-29 | 新型微装置有限责任公司(Dba 新型装置) | 微流体样品处理设备和制备生物样品的方法 |
CN114405561B (zh) * | 2015-07-24 | 2024-03-15 | 新型微装置有限责任公司(Dba 新型装置) | 微流体样品处理设备和制备生物样品的方法 |
CN110242533A (zh) * | 2019-05-17 | 2019-09-17 | 杭州电子科技大学 | 一种电磁微泵装置及其泵液方法 |
WO2021081103A1 (fr) | 2019-10-22 | 2021-04-29 | The Regents Of The University Of California | Dispositif ferrofluide numérique à commande électronique et procédé destiné à des opérations bio-analytiques évolutives et localisables |
EP4049018A4 (fr) * | 2019-10-22 | 2023-03-08 | The Regents of the University of California | Dispositif ferrofluide numérique à commande électronique et procédé destiné à des opérations bio-analytiques évolutives et localisables |
CN113234591A (zh) * | 2021-05-28 | 2021-08-10 | 宁波康程德诺生物医药有限公司 | 一种一体化核酸快提试管、快提检测装置和方法 |
CN113234591B (zh) * | 2021-05-28 | 2024-03-22 | 宁波康程德诺生物医药有限公司 | 一种一体化核酸快提试管、快提检测装置和方法 |
USD1069156S1 (en) | 2023-04-10 | 2025-04-01 | Becton, Dickinson And Company | Dispensing device |
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