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WO2008150210A1 - Micropompe - Google Patents

Micropompe Download PDF

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Publication number
WO2008150210A1
WO2008150210A1 PCT/SE2008/000379 SE2008000379W WO2008150210A1 WO 2008150210 A1 WO2008150210 A1 WO 2008150210A1 SE 2008000379 W SE2008000379 W SE 2008000379W WO 2008150210 A1 WO2008150210 A1 WO 2008150210A1
Authority
WO
WIPO (PCT)
Prior art keywords
layer
micropump
layers
displacement
displacement micropump
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/SE2008/000379
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English (en)
Inventor
Roger BODÉN
Klas Hjort
Marcus Lehto
Jan-Åke SCHWEITZ
Urban Simu
Greger Thornell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Global Life Sciences Solutions USA LLC
Original Assignee
GE Healthcare Bio Sciences Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GE Healthcare Bio Sciences Corp filed Critical GE Healthcare Bio Sciences Corp
Publication of WO2008150210A1 publication Critical patent/WO2008150210A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F04B43/14—Machines, pumps, or pumping installations having flexible working members having peristaltic action having plate-like flexible members

Definitions

  • the present invention relates to micropumps, particularly displacement micropumps, suitable for microfluidic systems and particularly for handling high back pressures.
  • micropumps are commonly reciprocating displacement pumps comprising two passive check-valves and a single pumping chamber.
  • Other designs like valve-less pumps with nozzle and diffuser valves for deter ⁇ iining the flow direction have been disclosed as well.
  • Micropumps are primarily needed in microfluidics technology where there is a rapid development in terms of miniaturization and integration.
  • Microfluidics technology is advantageously used to develop new, and to improve existing biomedical, biochemical, and biological systems, such as drug delivery systems, micro total analysis systems ( ⁇ TAS), lab-on-a-chip (LOC), etc.
  • ⁇ TAS micro total analysis systems
  • LOC lab-on-a-chip
  • One driving force for making such miniaturised systems is to minimize the dead volume of the systems, and hence reagent and sample volumes.
  • Another driving force is to integrate more functionality into a device to be able to make smaller, more efficient, more accurate and/ or more affordable systems.
  • microfluidic systems Although a high level of miniaturisation and integration, have external pumps for controlling the fluid motion in the system.
  • current micropumps are not readily integrated in the microfluidic systems due to their size, process compatibility, fabrication cost, biocompat ⁇ bility issues, performance or driving issues.
  • processing of piezoceramics is performed at very high temperatures which neither the common silicon microfluidic systems nor the emerging polymer microfluidic systems can withstand.
  • the piezoceramic actuators used for actuation of the micropumps have to be assembled onto the microfluidic device, which is a costly operation and it also results in an uncertainty in the performance.
  • piezoceramics have to be driven with a high voltage.
  • micropumps that can handle low flow rates (below 1 ⁇ l/min) accurately.
  • flow restricting features like filters and mixers
  • micropumps that can work against high back pressures, i.e. in the range of 100 kPa up to 30 MPa.
  • piezoelectric micropumps pneumatic, thermopneumatic and electroosmotic micropumps are common, which can be understood from a review article on micropumps (D.J. Laser, "A review of micropumps", J. Micromech. Microeng. 14, pp. 34-64, 2004).
  • piezoelectric, pneumatic and thermopneumatic micropumps exhibit relatively high maximum flow rates (up to about 1 ml/min), but are modest in terms of back pressure (below 100 kPa).
  • Electroosmotic micropumps exhibit much wider back pressure range (up to about 1 OMPa), but have the disadvantage that ionic currents in the fluid to be pumped and very high drive voltages, i.e. typically 100-1000 V are required.
  • a prior art reciprocating displacement pump is schematically illustrated in Fig. Ia and comprises a pumping chamber, a passive inlet valve and a passive outlet valve.
  • the fluid to be moved enters the pump from the inlet side and is trapped by the inlet valve 4 and the outlet valve in the pumping chamber.
  • a flexible diaphragm in the pumping chamber is moved by an actuator, typically a piezoelectric actuator assembled on the diaphragm, so that the fluid is pressurised and thereby forced out through the outlet valve.
  • the passive valves are typically check-valves, as shown in Fig. Ia, but nozzle and diffuser valves with different flow restriction on inlet side and outlet side are also used for determining the flow direction.
  • Another example of a prior art displacement micropump is schematically illustrated in Fig.
  • This micropump has active inlet and outlet valves, each comprising a flexible diaphragm which is deflected against a valve seat e.g. by piezoelectric actuators.
  • Other actuation principles or means for moving the diaphragms of the pumping chamber and the valves in a displacement pump are known, such as pneumatic, thermopneumatic, and shape memory actuators.
  • the sub-cm 3 paraffin micropump comprises two active valves and a pumping chamber operated by three identical paraffin actuators utilizing the powerful expansion of paraffin - when melting - for actuation.
  • a maximum flow rate of 74 nl/min was obtained and the valves were subjected to pressures of about 1 MPa without showing any leakage.
  • the disclosed paraffin micropump was made by a rapid prototyping process in epoxy.
  • Epoxy as most other polymeric materials, has a low thermal conductivity and hence the operation speed for the actuator is limited due to the relatively slow thermal cooling of the actuator.
  • the polymeric material does not give structural rigidity, which was found to limit the back pressure capability and the reliability of the micropump.
  • the powerful expansion of the paraffin requires a pump structure that can withstand the pressure.
  • a similar paraffin actuated micropump can be built using silicon micromachining, i.e. using manufacturing methods comprising dry or wet etching of silicon wafers and silicon fusion bonding.
  • Many microfluidic systems are readily made using such manufacturing methods.
  • the cost for this is high mainly since costly clean room facilities and machines, apart from the more expensive raw material, are required.
  • Young's modulus of 100 GPa silicon is a brittle material, which limits the robustness of devices built in this material.
  • Different polymers e.g. polystyrene and PDMS, are also widely used for making microfluidic systems.
  • polymers can be processed at low cost.
  • the epoxy which is a polymer, the structural rigidity and the thermal conductivity may be limited.
  • micropumps for microfluidics systems like biochemical or biological systems
  • biocompatibility or the chemical inertness of the materials used in the micropump Neither the silicon nor the epoxy mentioned above is materials that normally are used in conventional biotechnical systems, and hence not generally accepted by the industry as biocompatible.
  • suitable chemistry have been developed to prevent for example binding of elements in the fluid to be pumped on the walls of the microfluidic channels. In many cases the requirement on such chemistry is costly.
  • the object of the present invention is to overcome the drawbacks of the prior art. This is achieved by the device as defined in claim 1 and the method as defined in claim 31.
  • the device according to the invention is a displacement micropump comprising a pumping chamber, an inlet valve and an outlet valve on each side of the pumping chamber and connected thereto, a first flexible diaphragm arranged to be able to vary the volume of the pumping chamber, and integrated means for moving the flexible diaphragm.
  • the micropump is a multilayer structure having a plurality of layers, wherein at least one layer is a micro structured layer of a metal or a metal alloy.
  • the plurality of layers comprises a micro structured microfluidic layer which at least partly forms the pumping chamber.
  • the microfluidic layer is made of a metal or metal alloy.
  • an intermediate sealing layer is located between at least two adjacent layers of the plurality of layers.
  • the sealing layer can be fixedly joined to at least one of the plurality of layers.
  • a polymer which may be applied as a conformal coating on at least one of the plurality of layers, is used.
  • a parylene coating may be used as sealing layer. Irrespective of if a sealing layer is used the sealing of the multilayer structure may be obtained using clamping.
  • a displacement micropump according to the invention comprises active valves, wherein each valve is operated by flexible diaphragms.
  • Actuator materials such as paraffin, which reversibly changes volume due to a temperature change may be enclosed in the multilayer structure and used for moving the flexible diaphragms.
  • Supporting structures or ridges are preferably used in the microfluidic layer to give enhanced rigidity of the multilayer structure.
  • the metal or metal alloy is preferably stainless steel or titanium. 8 000379
  • a method for manufacturing a displacement micropump according to the present invention comprises the steps of: etching a layer of metal or metal alloy to form the micro structured layer of metal or metal alloy; providing the plurality of layers comprising at least a micro structured layer of a metal or metal alloy and a flexible diaphragm layer; stacking the plurality of layers to form the multilayer structure; and sealing the mating surfaces of the layers.
  • a sealing layer is provided at least between two of the mating surfaces.
  • the sealing layer may be deposited using a vapour deposition process.
  • the multilayer structure is preferably clamped together to obtain a reliable sealing.
  • micropump which simultaneously is 5 biocompatible, has a low dead volume, accurately handles low flow rates, enables easy driving at low voltage and works at high back pressures.
  • Fig. Ia is a schematic cross sectional view of a displacement micropump comprising passive check-valves and a piezoelectric actuator according to prior art.
  • Fig. Ib is a schematic cross sectional view of a displacement micropump comprising active valves and piezoelectric actuators according to prior art.
  • Fig. 2a is a schematic cross sectional view of a displacement micropump with vertical inlet and outlet according to the invention. .0
  • Fig. 2b is a cross sectional view of a peristaltic displacement micropump with horizontal inlet and outlet according to the invention.
  • Fig. 2c is a cross sectional view of a displacement micropump with paraffin actuators L 5 according to the invention.
  • Fig. 3a is a perspective view of the displacement micropump shown in Fig. 2a..
  • Fig. 3b is a front view of the microfluidic layer of the micropump shown in Fig. 3a. 0
  • Fig. 3c is a perspective view of the microfluidic layer shown in Fig. 3b.
  • Fig. 4 is a cross sectional view of a micropump comprising heater elements integrated in the bottom of the actuator cavity and a front view of a microfluidic layer with open 5 channels.
  • Fig. 5 is a cross sectional view of micropump comprising heater elements integrated in the middle of the actuator cavity and a front view of a microfluidic layer with supporting ridges within the channel.
  • Fig. 6a is a cross sectional view of a displacement micropump according to the invention and a front view of the microfluidic layer having supporting ridges to be placed against the diaphragm layer.
  • Pig. 6b is a cross sectional view of a displacement micropump according to the invention and a front view of the microfluidic layer having supporting ridges to be placed against the inlet/ outlet layer.
  • Fig. 7 is a perspective view of a displacement micropump according to the invention, an exploded view of the layers of the multilayer structure and a close up showing the microfluidic layer.
  • Pig. 8 is a cross sectional view of a displacement micropump comprising a sealing layer.
  • Fig. 9 is showing a schematic comparison of different micropumps.
  • Fig. 10a-e is a schematic illustration of a process scheme for manufacturing a displacement micropump according to the invention.
  • phase-change actuators such as paraffin actuators
  • phase transition compared with the commonly used liquid to gas transition, which often gives a much greater volume expansion, is that the liquid is much less compressible than the gas.
  • solid to liquid transition gives a much more powerful actuator, which of course is advantageous when a displacement pump for high back pressures is desired.
  • paraffin is an interesting actuator material since it exhibits a very large volume expansion even at high back pressures, has a melting temperature that can be tailored from -100 to 150 0 C, is biocompatible and is cheap. Moreover, the thermal actuation of the paraffin is easily accomplished using simple low voltage driving of resistive heaters.
  • Paraffin consists of hydrocarbon chains with the composition C n H2n+2. The maximum temperature of the paraffin during operation can be chosen so that it is well below any limit that is set for the fluid to be pumped.
  • the energy density of paraffin is among the highest for actuation principles, which ensures low power consumption. Therefore paraffin has been chosen as actuator material for the displacement micropump of the present invention in the following description, although it should be understood that other phase-change actuator materials and completely other actuation principles can be used as well.
  • Microfluidic systems currently comprise microstructured materials, such as glass, silicon and different polymers, often selected due to the vast micro fabrication knowledge accumulated in the fields of electronics, micro electromechanical systems (MEMS) and microfluidics.
  • MEMS micro electromechanical systems
  • microfluidics As mentioned above silicon and polymers are commonly used for microfluidics and micropumps in particular. However, other materials would be at least or better suited for making displacement micropumps.
  • a paraffin micropump would benefit from a material that has a higher thermal conductivity than e.g. polymers, and that gives the structural rigidity required to handle high back pressures and the powerful expansion of the paraffin.
  • stainless steel is an attractive material since it is already widely used in biotechnology applications, for example in fittings, reservoirs, heads for high pressure liquid chromatography, etc.
  • stainless steel is biocompatible, chemically resistant and solvent inert. This is not the case for most polymers that currently are used in microfluidics.
  • Another attractive material is titanium or titanium alloys, which are widely used due to the inertness.
  • any suitable construction material with the desired mechanical properties that can be coated with a biocompatible material such as TiN, AI2O3, glass etc.
  • Materials such as stainless steel and titanium are more ductile than e.g. silicon that has excellent mechanical properties but is brittle.
  • stainless steel commonly is used in microfluidics it is not used for making the micro fabricated microfluidic structures. Stainless steel is not easily machined using for example milling or other conventional processing techniques, and the high precision that often is required is not easily obtained.
  • a convenient process for machining stainless steel is found in a high precision wet etch process (chemical milling) which currently is used for manufacturing stencils for printing solder paste. According to the present invention this process may be used for manufacturing micro structured layers to be used in a micropump.
  • the displacement micropump 1 comprises a pumping chamber 12, an active inlet valve 4 and an active outlet valve 5, each having a flexible diaphragm
  • a microfluidic path extends from an inlet 2 via the inlet valve 4, the pumping chamber 12 and the outlet valve 5 to an outlet 3.
  • the displacement micropump 1 according to the invention is a multilayer structure comprising a plurality of layers, wherein at least on layer is a micro structured metal or metal alloy layer 24, such as a micro structured stainless steel stencil or sheet.
  • the microfluidic path extends in such a micro structured metal or metal alloy layer, which is arranged on a diaphragm layer 25 that comprises the flexible diaphragms 13, 14, 15.
  • the micro structured layer 24 comprising the microfluidic structures or channels, which partly form the valves and the pumping chamber, is hereinafter referred to as a microfluidic layer 24.
  • the relative thickness of the layers is throughout all cross sectional views of the figures exaggerated for the sake of clarity.
  • Valve seats 6, 7 with central vertical inlet/ outlet holes 2, 3 in the microfluidic layer 24 are positioned above the diaphragms 13, 14, 15.
  • the pumping chamber 12 is an open cavity to be filled with a fluid to be pumped.
  • the fluid enters the open inlet hole 2, gets trapped in the pumping chamber 12 by closed inlet/ outlet valves 4, 5, is pressurised by the pumping diaphragm 14 that is deflected inwards in the pumping chamber 12, and is finally forced out through the outlet 5.
  • the active valves 4, 5 enable reversal of the pump direction if desired.
  • the pumping sequence can be described as a peristaltic pump sequence, wherein the diaphragms 13, 14, 15 are sequentially phased to transfer a momentum from the diaphragms to the fluid in a travelling wave manner.
  • a pure peristaltic pump does not comprise any flow rectifying elements, but the pump can even though the active valves are flow rectifying elements be regarded as peristaltic since the valve diaphragms contribute to the fluid motion themselves.
  • FIG. 2b another embodiment according to the present invention has a horizontal inlet 2 and a horizontal outlet 3 with three identical pumping chambers 12 in between formed by a micro structured microfluidic layer of a metal or a metal alloy and a diaphragm layer comprising the flexible diaphragms 13, 14, 15.
  • a peristaltic pumping principle is possible.
  • the displacement micropump 1 according the embodiment shown in Fig. 2a is shown in a perspective view in Fig. 3a.
  • a front view and a perspective view of the microfluidic layer are shown in Fig. 3b and 3c respectively.
  • the microfluidic structures, i.e. the valve seats 6, 7, the pumping chamber 12 and the connecting channels 9, are formed by a lowered region.
  • FIG. 4 One embodiment of the present invention is shown in Fig. 4.
  • This design of the displacement pump 1 comprises a pumping chamber 12, a normally open inlet valve 4, and a normally open outlet valve 5, each operated by a phase-change actuator 19, such as a paraffin actuator.
  • the micropump 1 is a multilayer structure comprising a microfluidic layer 24 made, a diaphragm layer 25, a first cavity layer 26 and a backing layer 30.
  • Inlet/ outlet holes 2, 3, valve seats 6, 7, a pumping chamber 12, and channels 9 connecting the valves 4, 5 and the pumping chamber 12 are formed by the microfluidic layer 24 made of metal or metal alloy such as stainless steel.
  • the microfluidic layer 24 is arranged on the diaphragm layer 25, which in this embodiment is a thin film of a polymer, e.g. polyirnide, polyeten, or polystyrene.
  • the cavity layer 26 of a metal or metal alloy, such as stainless steel, is micro structured and placed so that a cavity is formed under each diaphragm 13, 14, 15.
  • the cavities are filled with a phase-change actuator material 19, such as paraffin, and sealed with the backing layer 30.
  • means for heating the actuator material 19 are arranged on or within the backing layer 30, e.g. by applying individually addressable resistive heater elements 16 on the backing layer 30 in connection with each cavity, either on the outside or on the inside of the cavities.
  • FIG. 5 Another embodiment of the present invention is shown in Fig. 5.
  • This design of the displacement pump 1 comprises a pumping chamber 12, a normally open inlet valve 4, and a normally open outlet valve 5, each operated by a phase-change actuator 19, such as a paraffin actuator.
  • the micropump is a multilayer structure comprising a microfluidic layer 24, a diaphragm layer 25, a first cavity layer 26, a heater layer 29, a second cavity layer 27 and a backing layer 30.
  • Inlet/ outlet holes 2, 3, valve seats 6, 7, a pumping chamber 12, and channels 9 connecting the valves 4, 5 and the pumping chamber 12 are formed by the microfluidic layer 24 made of metal or metal alloy such as stainless steel.
  • at least one supporting ridge 10 is arranged in each channel 9.
  • the microfluidic layer 24 is arranged on the diaphragm layer 25.
  • the cavity layers 26, 27 of a metal or metal alloy, such as stainless steel, are micro structured and placed so that a cavity is formed under each diaphragm 13, 14, 15 with an intermediate heater layer 29.
  • Heater elements 16 are formed within the cavities to heat the phase- change actuator material 19, such as paraffin, which is filling the cavities.
  • the cavities are sealed with a backing layer 30.
  • the microfluidic layer 24 made of a metal or a metal alloy layer see Fig. 6a and 6b, comprises a plurality of ridges 10 in the microfluidic channel 9 connecting the inlet/ outlet valve structures 4, 5 with the pumping chamber 12.
  • the ridges 10 are monolithically integrated with the microfluidic layer 24. Furthermore the surface of the lowered region described above is decreased to minimize the dead volume of the micropump 1. As observed in Fig. 6a the lowered regions around the inlet 4, the outlet 5 and the pumping chamber 12 are only narrow circular segments.
  • the plurality of ridges 10 extends along the channel 9 and the height of the ridges 10 is the same as the depth of the channel 9.
  • the channels 9 in between the ridges 10 are placed so that the channel 9 formed in the microfluidic layer 24 is completed using the diaphragm layer 25.
  • These ridges 10 give additional support and, if the microfluidic layer 24 is fixedly joined to the diaphragm layer 25, an additional bonding surface.
  • a displacement micropump 1 that comprises a pumping chamber 12, a normally open inlet valve 4 and a normally open outlet valve 5, each operated by a paraffin actuator 19.
  • the micropump 1 is a multilayer structure comprising, from the top, an inlet/ outlet layer 23, a microfluidic layer 24, a diaphragm layer 25, a first cavity layer 26, a third cavity layer 28, a heater layer 29, a second cavity layer 27 and a backing layer 30. All layers are rectangular with rounded corners and an equally sized (2 mm diameter) through hole adjacent to each corner for alignment of the layers to each other. In this particular case the overall multilayer structure or the chip is 35x15x1.3 mm 3 .
  • Inlet/ outlet layer 23 200 ⁇ m thick micro structured stainless steel sheet, two through holes with a diameter of 0.6 mm forming an inlet and an outlet respectively.
  • Microfiuidic layer 24 two through holes with a diameter of 0.6 mm in the same positions as the inlet and outlet holes in the inlet/ outlet layer forming a continuation of the inlet and outlet, two circular valve seats with an outer diameter of 1,2 mm giving a width of the valve seat of 0.3 mm, the valve seats being formed by two circular lowered regions with an outer diameter of about 2 mm, each valve seat enclosing the inlet/ outlet through hole, a third circular lowered region with an outer diameter of about 2 mm in between the other two circular lowered regions defining the pumping chamber, two lowered regions (channels) connecting the circular lowered regions to each other, the lowered regions having a depth of about 100 ⁇ m.
  • Diaphragm layer 25 a polymer film, such as polyimide, with a thickness of about 50 ⁇ m.
  • First cavity layer 26 200 ⁇ m thick micro structured stainless steel sheet, three through holes with essentially the same diameter as the circular lowered regions of the microfiuidic layer, and in corresponding positions.
  • Heater layer 29 made of a flexible printed circuit comprising polyimide film with a copper clad, the copper clad patterned to form individually addressable resistive heaters in the position of each cavity, the heater layer being perforated in the area of each cavity to make an open connection between the cavities within the first cavity layer and the second cavity layer, the heater layer having a slightly larger size than the other layers to enable electrical connection of leads from the resistive heaters outside the multilayer structure.
  • Second cavity layer 27 identical to the first cavity layer.
  • Backing layer 30 200 ⁇ m thick micro structured stainless steel sheet.
  • the cavities are filled with paraffin.
  • the paraffin is filled so that the diaphragms 13, 14, 15 are concave, i.e. deflected into the cavities. In such way the microfiuidic path is open from the inlet 4 to the outlet 5.
  • microfiuidic layer is made of a metal or a metal alloy in the embodiments described above, the microfiuidic layer 24 or other layers may be made in a more conventional manner, i.e. made of micro structured silicon or polymer. For example, 79
  • the microfluidic layer 24 may be a relatively thin polymer layer supported by a metal or metal alloy inlet/ outlet layer. Thereby a decent structural rigidity is obtained.
  • the multilayer structure disclosed above with reference to Fig. 4 is clamped without intermediate sealing layers 31. This requires accurate fitting of the mating surfaces of all of the layers of the multilayer structure, Le. the mating surfaces are typically planar.
  • One embodiment of a displacement micropump according to present invention comprises a sealing layer 31 as illustrated in Fig. 8.
  • the multilayer structure is essentially the same as the embodiment disclosed above with reference to Fig. 5. All layers of the multilayer structure, except from the backing layer, have a thin intermediate sealing layer 31 of e.g. parylene that covers all surfaces of the layers in a conformal way, i.e. all surfaces are covered with a parylene layer of uniform thickness.
  • the parylene layer has been used to fixedly join the layers of the multilayer structure.
  • the backing layer is joined using an adhesive. If the micropump has to work with really high back pressures the multilayer can be clamped as well.
  • the multilayer structure disclosed above with reference to Fig. 7 has intermediate sealing layers 31 arranged between all of the plurality of layers.
  • the sealing layers 31 are patterned at least to provide openings for the inlet 2 and outlet 3 and also for the cavities adjacent to the heater layer 29.
  • the sealing layers 31 are dismountable or fixedly joined to at least one of the surfaces in contact with the sealing layer 31.
  • the sealing layer 31 is essentially thinner than the other layers of the multilayer structure, while still being flexible to provide a good sealing when clamped. If all sealing layers 31 are fixedly joined to both surfaces in contact, the micropump 1 is functional without clamping. However, if really high back pressures are desired clamping is required.
  • Preferred sealing materials are different kinds of polymers, such as polyimide, polyester, photo resists and parylene.
  • Parylene is suitable for micropumps since it exhibits chemical inertness, has low permeability, low heat capacity, enables stress free conformal deposition, is patternable, etc.
  • the conformal coating is a result of a vapour deposition process.
  • the vapour deposition process used in parylene deposition can be regarded as a chemical vapour deposition process. In such processes a conformal coating, irrespective of the surface roughness of the substrate, can be obtained.
  • Other polymers than parylene can be used according to the present invention. Spinning, spraying, physical vapour deposition can be used as well, but conformal coatings are not easily obtained on rough substrates, e.g. micro structured layers, using such methods.
  • a sealing layer 31 of e.g. parylene In another embodiment of the present invention according to the embodiment presented with reference to Fig. 7, all layers are coated with a sealing layer 31 of e.g. parylene.
  • a lower part of the multilayer structure from the diaphragm layer 25 to the backing layer 30 is fixedly joined together and an upper part comprising the microfluidic layer 24 and the inlet/ outlet layer 23 fixedly joined together. Consequently the lower and the upper part are dismountable and can for example be inspected or cleaned.
  • the parylene layer on the mating surfaces of the microfluidic layer 24 and the diaphragm layer 25 then works as a gasket.
  • the micropump 1 of the present invention allows for designs wherein any layer of the multilayer structure can be dismountable. However, if the structure has loosely arranged layers the structure has to be clamped during operation. In particular, the cavities for the actuator material 19 are advantageously permanently sealed.
  • the heater element 16 is placed in the middle of the cavity, between two cavity layers 26, 27, 28. This placement is advantageous from a thermal transport point of view. Paraffin has a rather low thermal conductivity and if the heater is placed in the bottom of the cavity, or within or on the opposite side of the backing layer, the distance over which the thermal transport will be made is doubled.
  • the heater 16 can also be integrated in the upper part of the cavity, or even in the diaphragm layer 25, to quicker have a deflection of the diaphragm 13, 14, 15. However, this would lead to increased heating of the fluid to be pumped. In many applications within biotechnology the temperature must be kept below a critical level. Obviously paraffin that does not have to be heated above this critical level can be chosen, which is an advantage of the paraffin actuator material, but the heater elements will have a temperature higher than this to enable higher flow rates.
  • the heater layer 29 has heater elements 16 on both sides, i.e. a double-sided flexible printed circuit.
  • the paraffin is heated by resistive heater elements 16.
  • the paraffin can be heated by other means, e.g. using irradiation through a transparent backing layer 30.
  • the heater layer 29 is preferably made of a flexible printed circuit.
  • the flexible printed circuits are made of a polyimide layer with a copper clad, either single-sided or double-sided.
  • the flexible printed circuit has resistive heaters 16 within the cavities. These resistive heaters 16 have leads leading to an area of the flexible printed circuit protruding outside the multilayer structure. Either there are
  • the resistive heaters can be connected to a driver, or the area of the flexible printed circuit comprises electronic circuitry, e.g. driver, battery, etc.
  • the heater layer is made of a flexible 5 printed circuit comprising a polyimide film and a copper clad, which has been perforated and patterned to form the resistive heaters, leads and bonding pads.
  • These features are formed in the copper clad layer by making narrow trenches isolating them from the rest of the copper clad. This kind of design is advantageous compared with a design where the excessive copper clad is removed since the surface becomes !0 essentially planar and easier to seal.
  • a metal or a metal alloy such as stainless steel or titanium
  • the micropump 1 gives a structural rigidity and heat conduction properties that are advantageous when e.g. paraffin actuation is used.
  • the paraffin is a very powerful actuator and 5 consequently the actuator exerts a great force on the surrounding structures.
  • the micropump 1 or at least the pressurised parts of the micropump is constructed using material, e.g. a polymer, which has a low Young's modulus the structural rigidity of the device may not be good enough to keep the paraffin within the cavities or the fluid to be pumped within the microfluidic channels.
  • the force exerted by the actuator may0 permanently deform different parts of the micropump, such as the valve seats.
  • titanium and stainless steel meet the requirements on the rigidity.
  • the frequency of the actuator has to be increased.
  • the paraffin of the paraffin actuator is cyclically melted5 and solidified.
  • the melting is obtained by heating the paraffin.
  • the time for the paraffin to melt is mainly dependent on the power supplied to the heater.
  • the time for the paraffin to solidify is dependent on the ability to transport the heat away from the paraffin. Since the power supplied to the paraffin easily can be increased the cycle time is highly dependent on the cooling time.
  • Polymers typically have a thermal conductivity in the range of 0.1 to 1 Wm 4 K- 1 and hence a polymer tnicropump will have a long cooling time.
  • the polymers do not give the structural rigidity required.
  • Stainless steel having a Young's modulus of about 200 GPa, is commonly used as a construction material and has a fairly high thermal conductivity of about 8 to 15 Wm- 1 K- 1 .
  • Titanium has similar properties with a Young's modulus of about 110 GPa and a thermal conductivity of about 13-19 Wm- 1 K" 1 . Both materials are superior to the polymers.
  • Other metal or metal alloys with high Young's modulus and a significantly higher thermal conductivity can be chosen, e.g.
  • At least one cavity layer is made of copper to improve the cooling rate of the paraffin actuator.
  • the pumping performance of a micropump according to the present invention has i.a. been tested with a fixedly joined micropump comprising deposited sealing layers of parylene (Parylene C).
  • the design of the micropump was according to Fig. 7. Paraffin (Sigma- Aldrich 76228) with a melting point of 44-48 °C and a volume expansion of about 10% was used in the cavities. Each cavity has a volume of 1.9 ⁇ l giving a theoretical stroke volume of 0.19 ⁇ l.
  • the actuators 19 were driven by different voltage drive signals with an amplitude of 1.8 V, a period time of 14 s and an average input power to each actuator of about 0.6 W.
  • the backing layer 30 was in this particular micropump 1 adhesively bonded to the second cavity layer using an adhesive (Loctite 407).
  • an adhesive Loctite 407
  • the micropump was clamped between 4 mm thick aluminium blocks and tightly screwed together by four screws extending through the through holes in the layers, as shown in Fig. 6.
  • Ferrule fittings were used for the fluid connection and the flow rate was measured by observing meniscus propagation in a capillary connected to the outlet in one end and closed in the other end. The generated pressure was measured using a pressure sensor connected to the closed volume defined by the capillary.
  • a constant flow rate of 0.75 ⁇ l/min and a maximum back pressure of 5 MPa were obtained, Le. much higher back pressure than obtained by other micropumps.
  • thermopneumatic/pneumatic (TP/P) displacement micropumps generally provides higher flow rates, but cannot handle nearly as high back pressures.
  • the paraffin micropump according to the present invention can handle high back pressures as good as the electroosmotic (E) micropumps, although without the disadvantage of requiring high electrical fields and ionic currents in the fluid.
  • AU dimensions in the disclosed embodiments are only by way of example. Purthermore the thickness of the layers in the cross sectional views of the figures have been exaggerated relatively the horizontal dimensions to improve the clarity.
  • the design can be optimised in many ways depending on the desired performance. For example the valve seat 6, 7 width can be changed e.g. to increase the back pressure capability, the depth of the lowered regions can be decreased or the channel 9 width can be decreased to minimized the dead volume. Further the thickness of the diaphragm layer 25, the cavity layers 26, 27, 28 and heater layer 29 and the cavity width along with other parameters can be adjusted to obtain an appropriate actuator performance. It is also possible to add additional cavity layers to increase the stroke of the actuator.
  • the diameter of the pumping chamber and the corresponding diaphragm 13, 14, 15 and actuator cavity can be varied to adjust the stroke volume.
  • the diameter of the valve diaphragms 13, 15 and the corresponding actuator cavity can also be varied e.g. to adjust the force of the valve actuator.
  • a plurality of pumping chambers 12 are arranged in parallel between the inlet and the outlet. This is e.g. an alternative way of increasing the flow rate of the pump.
  • a plurality of micropumps are arranged in parallel, connected to a common inlet 2 and a common outlet 3. For example, by running the different pumps out of phase a more stable flow can be obtained. Moreover the response time of many small pumps in parallel is faster than for a single larger micropump.
  • a plurality of pumping chambers and corresponding actuators are arranged in series. On example of such micropump arrangement comprises an active inlet valve, three pumping chambers, and an active outlet valve, wherein the pumping chambers are driven in a peristaltic pumping action.
  • the multilayer structure of the micropump of the present invention allows for integration of other microfluidic structures such as filters, reactors, etc. within the stainless steel layers.
  • Selected layers which previously in this description have been of stainless steel, can be exchanged with other layers made of e.g. polymer, ceramics, glass or silicon.
  • microfluidics are made in polymer materials and silicon and for different reasons it may be necessary to use such materials in at least one layer of the multilayer structure instead of a metal or metal alloy, such as stainless steel.
  • a metal or metal alloy such as stainless steel.
  • an inlet/ outlet layer of glass is an alternative. If a stainless steel layer is exchanged this may be at the expense of deteriorated heat conduction and hence a reduced flow rate, and also limited back pressure capability.
  • a method for manufacturing a displacement micropump according to the invention comprises the steps of: - etching of a layer of metal or metal alloy to form at least one micro structured layer of metal or metal alloy;
  • micro structured layer of metal or metal alloy with at least one further layer, wherein one of the layers is a micro structured microfludic layer 24 and one of the layers is a flexible diaphragm layer 25, to form the multilayer structure;
  • Another embodiment of the method for manufacturing a displacement micropump 1 according to the invention, wherein the micropump 1 comprises paraffin actuators 19 for moving the diaphragms 13, 14, 15, comprises the steps of:
  • etching of a layer or a metal alloy such as stainless steel to form at least a first microstructured cavity layer 26 of a metal or metal alloy comprising a cavity each for the inlet valve 4, the pumping chamber 12, and the outlet valve 5;
  • microfluidic path which comprises the inlet valve 4, the pumping chamber 12 and the outlet valve 5, leading through the multilayer structure
  • the micro structured metal or metal alloy layers are provided preferably using etching methods.
  • One example of such a process is the process commonly used to manufacture stencils for printing solder paste in the electronics industry, wherein stainless steel sheets are high precision wet etched (chemical milling) to form stainless steel stencils. Since electronics systems continuously are miniaturised, the requirement on precision is high.
  • the aperture sizes can be smaller than 100 ⁇ m and controlled within tens of micrometers.
  • the thickness of the stencils is commonly in the range of 0.1 up to 0.4 mm.
  • the stencils are manufactured in large sheets (580x700 mm 2 ). In comparison, silicon micromachining for
  • MEMS/microfluidics is performed on much smaller 6 to 12 inch wafers, with higher precision, but at much higher cost since costly cleanroom facilities and machines, apart form the more expensive raw material, are required.
  • the mating surfaces of the cavity layer 26 and the diaphragm layer 25 are sealed before filling the paraffin.
  • the paraffin is filled into the cavities using for example pouring or dispensing of melted paraffin. Excessive paraffin is after solidification removed or scraped off and the backing layer is arranged on the cavity layer to seal the cavities. Since the paraffin shrinks during solidification the originally planar diaphragms are drawn into the cavities after the first solidification. This results in a concave shape of the diaphragms.
  • a micro structured inlet/ outlet layer 23 of stainless steel is provided.
  • the inlet/outlet layer 23 is stacked together with the other layers.
  • a second micro structured cavity layer 27 and micro structured heater layer 29 is provided.
  • the heater layer 29 is arranged in between the first and the second cavity layers 26, 27 to obtain a heater element 16 centrally placed in the cavity.
  • the heater layer 29 is made of a flexible printed circuit, which is processed in accordance with conventional processes known in the art, i.e. the copper is etched using a wet etch process and the flexible polymer is patterned using wet or dry etch processes. If only the circuits formed in the copper clad of the flexible printed circuits are left after processing the surface of the heater becomes rather rough-.
  • the cavity layer is arranged on the heater layer 29 it will come in contact with the copper structures, and a gap is formed in between the cavity layer and the flexible polymer. This will make the sealing complicated. On the other hand, if only a narrow isolation trench is removed adjacent to the circuits, the sealing is simplified.
  • the step of sealing is for example performed by clamping the layers of the multilayer structure together.
  • the step of sealing the layers comprises the step of providing an intermediate sealing layer 31.
  • a sealing layer 31 the requirements on the roughness of the surfaces to be stacked are less demanding.
  • the sealing layer 31 may allow for permanent joining of the layers, or at least some of the layers of the multilayer structure.
  • the step of providing a sealing layer 31 is in one embodiment accomplished by patterning a polymer film using e.g. wet or dry etching processes. Alternatively e.g. laser machining, water jet, punching or other machining techniques can be used.
  • the sealing layer 31 is patterned at least to have openings corresponding to the inlet and outlet through holes 2, 3, the cavities, and the diaphragms 13, 14, 15, i.e. the design of the sealing layers 31 differ depending on which layer the sealing layer 31 is aimed for.
  • Different sealing materials can be used, e.g. parylene, photoresist, PDMS, polyethylene terephthalate (PET), etc.
  • the method comprises the step of depositing a sealing layer 31 of e.g. parylene onto the layers of the multilayer structure before stacking.
  • a sealing layer 31 of e.g. parylene onto the layers of the multilayer structure before stacking.
  • the sealing layer 31 is conveniently fixedly joined to the layers of the multilayer structure.
  • the coated layers are stacked and clamped together to provide a sealing.
  • the stacking irrespective if the sealing layer is a separate layer or if the sealing layer is deposited, is preferably performed at elevated temperature.
  • parylene can be bonded to parylene under certain conditions.
  • the step of stacking layers comprises the step of aligning the layers using passive alignment means such as alignment holes 33 and/or the circumferential edges of the layers, the holes and/ or the circumferential edges being provided with high accuracy using micro fabrication methods such as etching, laser machining, drilling, etc.
  • passive alignment means such as alignment holes 33 and/or the circumferential edges of the layers, the holes and/ or the circumferential edges being provided with high accuracy using micro fabrication methods such as etching, laser machining, drilling, etc.
  • a method of making a micropump according to the invention is schematically illustrated in Fig. 10a-e.
  • Fig. 10a As schematically illustrated in Fig. 10a, four stainless steel sheets 24, 26, 27, 30, one flexible printed circuit sheet 29, i.e. a polyimide film with a double sided copper clad, and one polymer film 25 are substrates for making the individual layers of the multilayer structure. All substrates are preferably larger than the size of the micropump.
  • the four stainless steel sheets are high precision wet etched (chemically milled) to form the microfluidic layer 24, the first cavity layer 26, the second cavity layer 27 and the backing layer 30.
  • the flexible printed circuit sheet 29 is patterned according to methods known in the field of printed circuits, e.g. the copper clad on one side is patterned and used as a mask to shape the flexible printed circuit 29, and the heater elements 16 and the leads are formed in the copper clad on the other side.
  • the heater elements 16 and the leads are formed by etching only narrow trenches in the copper clad.
  • the polymer film 25 is patterned using e.g. photolithography and dry etching.
  • all layers 24, 25, 26 ,27 ,29, 30 are patterned using etching processes to form the microfluidic layer 24, the diaphragm layer 25, the first cavity layer 26, the heater layer 29, the second cavity layer 27 and the backing layer 30.
  • the outline of a micropump chip and alignment holes 33 are preferably formed in the same process step.
  • the microfluidic layer 24, the diaphragm layer 25, the first cavity layer 26, the heater layer 29, and the second cavity layer 27 are coated with a conformal sealing layer 31, such as a parylene layer, which covers all surfaces of the layers.
  • a conformal sealing layer 31 such as a parylene layer
  • the microfluidic layer 24, the diaphragm layer 25, the first cavity layer 26, the heater layer 29, and the second cavity layer 27 are arranged on each other and aligned using the alignment holes 33 to form a multilayer structure.
  • This multilayer structure is clamped together by applying a force to the multilayer structure, e.g. using a fixture and screws extending through the alignment holes 33, heated to 200 0 C for 30 minutes in a N2 atmosphere at a vacuum pressure of 100 mbar to give a fixedly joined multilayer structure.
  • the three cavities formed under the flexible diaphragms 13, 14, 15 are filled abundantly with melted paraffin 19.
  • the paraffin shrinks during the transition from liquid to solid and therefore the flexible diaphragms are deflected inwards, opening the fluidic path through the microfluidic layer.
  • the backing layer 30 is bonded to the second cavity layer to enclose the paraffin.

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  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Reciprocating Pumps (AREA)

Abstract

L'invention concerne une micropompe volumétrique (1) et son procédé de fabrication. La micropompe volumétrique (1) comprend une chambre de pompage (12), une soupape d'entrée (4), une soupape de sortie (5), et une première membrane souple (14) agencée pour pouvoir modifier le volume de la chambre de pompage (12), et des moyens intégrés pour déplacer la membrane souple (18). La micropompe (1) a une structure multicouche ayant une pluralité de couches, dans lesquelles au moins une couche est une microcouche structurée d'un métal ou d'un alliage métallique tel que de l'acier inoxydable. La pluralité de couches comprend une couche microfluidique microstructurée (24) qui forme au moins partiellement la chambre de pompage (12). De préférence, de la paraffine est utilisée pour déplacer la membrane. La structure multicouche peut être étanchéifiée en utilisant un serrage et/ou un revêtement conforme sur la pluralité de couches, formant une couche d'étanchéification intermédiaire (31).
PCT/SE2008/000379 2007-06-07 2008-06-04 Micropompe Ceased WO2008150210A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0701402 2007-06-07
SE0701402-0 2007-06-07

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JP2012102710A (ja) * 2010-11-12 2012-05-31 Fujitsu Ltd マイクロポンプ及びこれを用いた半導体装置
FR3015310A1 (fr) * 2013-12-24 2015-06-26 Espci Innov Dispositif de manipulation, de tri, de generation et de stockage d'un element d'un fluide non miscible et dispositif de fusion de deux tels elements
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CN107939634A (zh) * 2017-12-20 2018-04-20 爱科赛智能科技（台州）有限公司 一种无源加热式微型气动泵
WO2018169842A1 (fr) * 2017-03-13 2018-09-20 Marsh Stephen Alan Systèmes de micro-pompe et techniques de traitement
CN108855260A (zh) * 2018-06-16 2018-11-23 南京大学 一种石蜡微阀成型及其封装方法
WO2020104996A1 (fr) * 2018-11-23 2020-05-28 Hnp Mikrosysteme Gmbh Dispositif de transport comprenant un actionneur et une couche de séparation

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Cited By (10)

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Publication number Priority date Publication date Assignee Title
JP2012102710A (ja) * 2010-11-12 2012-05-31 Fujitsu Ltd マイクロポンプ及びこれを用いた半導体装置
US9103331B2 (en) 2011-12-15 2015-08-11 General Electric Company Electro-osmotic pump
FR3015310A1 (fr) * 2013-12-24 2015-06-26 Espci Innov Dispositif de manipulation, de tri, de generation et de stockage d'un element d'un fluide non miscible et dispositif de fusion de deux tels elements
WO2015097300A1 (fr) 2013-12-24 2015-07-02 Espci Innov Dispositif microfluidique de manipulation des fluides non miscible
WO2018169842A1 (fr) * 2017-03-13 2018-09-20 Marsh Stephen Alan Systèmes de micro-pompe et techniques de traitement
CN107939634A (zh) * 2017-12-20 2018-04-20 爱科赛智能科技（台州）有限公司 一种无源加热式微型气动泵
CN108855260A (zh) * 2018-06-16 2018-11-23 南京大学 一种石蜡微阀成型及其封装方法
WO2020104996A1 (fr) * 2018-11-23 2020-05-28 Hnp Mikrosysteme Gmbh Dispositif de transport comprenant un actionneur et une couche de séparation
CN113272980A (zh) * 2018-11-23 2021-08-17 Hnp微系统有限责任公司 具有执行器和分离层的运输设备
US12228121B2 (en) 2018-11-23 2025-02-18 Hnp Mikrosysteme Gmbh Transport device having an actuator and separating layer

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