Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
MICROPUMP
Document Type and Number:
WIPO Patent Application WO/2008/150210
Kind Code:
A1
Abstract:
The present invention provides a displacement micropump (1) and a method for manufacturing such. The displacement micropump (1) comprises a pumping chamber (12), an inlet valve (4), an outlet valve (5), and a first flexible diaphragm (14) arranged to be able to vary the volume of the pumping chamber (12), and integrated means for moving the flexible diaphragm (18). The micropump (1) 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 such as stainless steel. The plurality of layers comprises a micro structured microfluidic layer (24) which at least partly forms the pumping chamber (12). Preferably paraffin is used for moving the diaphragm. The multilayer structure may be sealed using clamping and/or a conformal coating on the plurality of layers forming an intermediate sealing layer (31).

Inventors:
BODEN ROGER (SE)
HJORT KLAS (SE)
LEHTO MARCUS (SE)
SCHWEITZ JAN-AAKE (SE)
SIMU URBAN (SE)
THORNELL GREGER (SE)
Application Number:
PCT/SE2008/000379
Publication Date:
December 11, 2008
Filing Date:
June 04, 2008
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
GE HEALTHCARE BIO SCIENCES AB (SE)
BODEN ROGER (SE)
HJORT KLAS (SE)
LEHTO MARCUS (SE)
SCHWEITZ JAN-AAKE (SE)
SIMU URBAN (SE)
THORNELL GREGER (SE)
International Classes:
F04B19/00; F04B43/04; F04B43/14
Domestic Patent References:
WO2007024829A22007-03-01
Foreign References:
US20060076068A12006-04-13
US20040217279A12004-11-04
US20040146409A12004-07-29
US6565331B12003-05-20
Other References:
BODEN R. ET AL.: "A polymeric paraffin actuated high-pressure micropump", SENSORS AND ACTUATORS A: PHYSICAL, vol. 127, no. 1, 28 February 2006 (2006-02-28), pages 88 - 93, XP005296912
TAKESHI KOBAYASHI ET AL.: "An easy fabrication technique for micro paraffin actuator and application to microvalve", ELECTROCHEMICAL SOCIETY PROCEEDINGS, vol. 2004-09, 2004, pages 330 - 335
BODEN R. ET AL.: "Metallic High-Pressure Microfluidic Pump with Active Valves", SOLID-STATE SENSORS, ACTUATORS AND MICROSYSTEMS CONFERENCE, 2007. TRANSDUCER 2007. INTERNATIONAL, 10 June 2007 (2007-06-10) - 14 June 2007 (2007-06-14), pages 2429 - 2432, XP031133721
Attorney, Agent or Firm:
GE HEALTHCARE BIO-SCIENCES AB et al. (Björkgatan 30, Uppsala, SE)
Download PDF:
Claims:

CLAIMS

1. A displacement micropump (1) comprising a pumping chamber (12), an inlet valve (4) and an outlet valve (5) on each side of the pumping chamber (12) and connected thereto, a first flexible diaphragm (14) arranged to be able to vary the volume of the pumping chamber (12), and integrated means for moving the flexible diaphragm (14), characterized in that the micropump (1) 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 comprising a micro structured microfluidic layer (24) which at least partly forms the pumping chamber (12).

2. A displacement micropump (1) according to claim 1, wherein at least one of the microstructured layers of a metal or metal alloy is the microfluidic layer (24). 3. A displacement micropump (1) according to claim 1 or 2, wherein an intermediate sealing layer (31) is located between at least two adjacent layers of the plurality of layers.

4. A displacement micropump (1) according to claim 3, wherein the sealing layer (31) is fixedly joined to at least one of the plurality of layers. 5. A displacement micropump (1) according to claim 3 or 4, wherein the sealing layer (31) is made of a polymer.

6. A displacement micropump (1) according to claim 5, wherein the sealing layer (31) is a conformal coating on at least one of the plurality of layers.

7. A displacement micropump (1) according to claim 6, wherein the conformal coating is made of parylene.

8. A displacement micropump (1) according to any of the claims 3-7, wherein at least two adjacent layers of the plurality of layers are fixedly joined to each other.

9. A displacement micropump (1) according to any of the claims 3-8, wherein the multilayer structure is clamped together.

10. A displacement micropump (1) according to claim 1 or 2, wherein the plurality of layers further comprises an intermediate diaphragm layer (25),

and the first flexible diaphragm (14) is formed in the intermediate diaphragm layer (25).

11. A displacement micropump (1) according to claim 10, wherein the intermediate diaphragm layer (25) is made of a polymer. 12. A displacement micropump (1) according to claim 1, wherein the inlet valve (4) and the outlet valve (5) are active valves.

13. A displacement micropump according to any of the preceding claims, wherein the inlet valve (4) comprises a second flexible diaphragm (13) arranged to be moved against an adjacent inlet valve seat (6) with a vertical inlet hole (2), the outlet valve (5) comprises a third flexible diaphragm (15) arranged to be moved against an adjacent outlet valve seat (7) with a vertical outlet hole (3), the second and third diaphragm (13, 15) being formed in the intermediate diaphragm layer (25), and the inlet valve seat (6) and the outlet valve seat (7) being formed in the microfluidic layer (24). 14. A displacement micropump (1) according to any of the preceding claims, wherein the inlet valve (4) has a horizontal inlet (2) and the outlet valve (5) has a horizontal outlet (3), the inlet valve (4) is adapted to be an inlet pumping chamber, the outlet valve (5) is adapted to be an outlet pumping chamber, and the inlet pumping chamber, the outlet pumping chamber and the pumping chamber (12) are adapted to work with a peristaltic pumping principle.

15. A displacement micropump (1) according to any of the claims 1-2 and 12- 14, wherein the plurality of layers further comprises at least a first cavity layer (26) and a backing layer (30), the means for moving the first, the second, and the third diaphragm (13, 14, 15) comprises an actuator material (19), which reversibly changes volume due to a temperature change, the actuator material (19) being enclosed by at least the diaphragm layer (25), the first cavity layer (26) and the backing layer (30).

16. A displacement micropump (1) according to claim 15, wherein the actuator material (19) is a phase-change actuator material.

17. A displacement micropump (1) according to claim 16, wherein the actuator material (19) is paraffin.

18. A displacement micropump (1) according to any of the claims 15-17, wherein the temperature change is provided by at least one individually addressable heater element (16) placed within the actuator material (19).

19. A displacement micropump (1) according to claim 18, wherein the heater element (16) is located in a heater layer (29).

20. A displacement micropump (1) according to claim 19, wherein the heater layer (29) and the heater element (16) are made of a flexible printed circuit.

21. A displacement micropump (1) according to claim 19 or 20, wherein the heater layer (29) is perforated to allow for the actuator material (19) to pass through the heater layer (29).

22. A displacement micropump (1) according to claim 20, wherein the flexible printed circuit comprises a copper clad layer, the copper clad layer being patterned by making narrow trenches to define the heater elements (16).

23. A displacement micropump (1) according to claim 1, wherein the inlet valve (4) and the outlet valve (5) are passive valves, such as check valves or diffuser valves.

24. A displacement micropump (1) according to claim 1, wherein channels (9) connecting the inlet valve (4) and the pumping chamber (12) and the pumping chamber (12) and the outlet valve (5) each comprises at least one ridge (10) with the same height as the depth of the channel (9).

25. A displacement micropump (1) according to claim 24, wherein the ridge (10) is formed in the microfluidic layer (24).

26. A displacement micropump (1) according to any of the preceding claims, wherein a plurality of pumping chambers (12) are connected in series. 27. A displacement micropump (1) according to any of the preceding claims, wherein a plurality of pumping chambers (12) are connected in parallel.

28. A displacement micropump (1) according to claim 1, wherein the metal or metal alloy is stainless steel.

29. A displacement micropump (1) according to claim 1, wherein the metal or metal alloy is titanium or titanium alloy.

30. A displacement micropump (1) according to claim 1, wherein the micro structured layer of metal or metal alloy is coated with a biocompatible material such as TiN, AI2O3 or glass.

31. A method for manufacturing a displacement micropump having an inlet valve (4), a pumping chamber (12) and an outlet valve (5), the displacement micropump being a multilayer structure with a plurality of layers, comprising 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; - stacking the 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 and one of the layers is a flexible diaphragm layer (25), to form the multilayer structure; and

- sealing mating surfaces of the micro structured layer and said at least one further layer to form a microfluidic path leading through the multilayer structure.

32. A method according to claim 31, wherein, the micro structured microfluidic layer is formed in the step of etching of a layer of metal or metal alloy.

33. A method according to claim 32, wherein supporting ridges (10) are formed in the microstructured microfluidic layer of metal or metal alloy.

34. A method according to any of the claims 31-33, wherein the step of sealing further comprises the step of arranging an intermediate sealing layer (31) in between the mating surfaces of the micro structured layer and said at least one adjacent layer. 35. A method according to claim 34, wherein the step of arranging the intermediate sealing layer (31) further comprises the step of depositing the sealing layer (31) using a vapour deposition process.

36. A method according to claim 34 or 35, wherein the step of arranging the intermediate sealing layer (31) further comprises patterning of the sealing layer.

37. A method according to claim 31, further comprising filling at least one cavity formed in the multilayer structure with an actuator material (19), which reversibly changes volume due to a temperature change.

38. A method accroding to claim 37, wherein the step of sealing further comprises sealing the cavity, which is filled with the actuator material (19).

39. A method according to any of the claims 31-38, wherein the step of sealing further comprises the step of clamping the multilayer structure.

40. A method according to claim 39, wherein the step of clamping is performed at an elevated temperature to fixedly join the individual layers.

Description:

MICROPUMP

Technical field of the invention

The present invention relates to micropumps, particularly displacement micropumps, suitable for microfluidic systems and particularly for handling high back pressures.

Background of the invention

Since the first piezoelectric micropumps were presented more than two decades ago micropumps made of silicon and actuated by piezoceramics have been dominating the field. 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 deterπiining 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 (μTAS), lab-on-a-chip (LOC), etc. 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.

Currently most microfluidic systems, although a high level of miniaturisation and integration, have external pumps for controlling the fluid motion in the system. Reasons for this are that current micropumps are not readily integrated in the microfluidic systems due to their size, process compatibility, fabrication cost, biocompatϊbility issues, performance or driving issues. For example, processing of piezoceramics is performed at very high temperatures which neither the common silicon microfluidic systems nor the emerging polymer microfluidic systems can withstand. Hence, 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. Furthermore, piezoceramics have to be driven with a high voltage.

The reduction of reagent and sample volume also calls for micropumps that can handle low flow rates (below 1 μl/min) accurately. In some applications, like liquid chromatography, and for systems comprising e.g. flow restricting features like filters and mixers there is also a need for micropumps that can work against high back pressures, i.e. in the range of 100 kPa up to 30 MPa.

Except for 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). Generally 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. Ib. 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.

Recently a polymeric paraffin actuated micropump was disclosed (Roger Boden et al, "A polymeric paraffin micropump with active valves for high-pressure microfluidics", Sensors and Actuators A 127, pp. 88-93, 2006). 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. In addition 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.

In principle, 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. However, the cost for this is high mainly since costly clean room facilities and machines, apart from the more expensive raw material, are required. Moreover, although having a high 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. There is a vast knowledge in micromachining of polymers and in the development of chemistry for specific polymers. Furthermore polymers can be processed at low cost. However, as for the epoxy, which is a polymer, the structural rigidity and the thermal conductivity may be limited.

Other issues when designing micropumps for microfluidics systems like biochemical or biological systems is the 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. For many polymers 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.

Summary of the invention

Obviously the prior art has drawbacks with regards to being able to provide an affordable displacement micropump being able to work against high back pressures.

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.

Preferably the microfluidic layer is made of a metal or metal alloy.

Preferably 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. Preferably 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.

Preferably 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

5

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.

Preferably a sealing layer is provided at least between two of the mating surfaces. The sealing layer may be deposited using a vapour deposition process.

O

The multilayer structure is preferably clamped together to obtain a reliable sealing.

Thanks to the invention it is possible to provide a 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.

It is a further advantage of the invention to provide a cost-effective industrial batch process for manufacturing displacement micropumps. O

Obviously the prior art has drawbacks with regards to being able to provide a biocompatible low-cost micropump that has low dead volume, easy driving, and enables high back pressures and accurate handling of small flow rates. Embodiments of the invention are defined in the dependent claims. Other objects, 5 advantages and novel features of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings and claims.

Brief description of the drawings 0 Preferred embodiments of the invention will now be described with reference to the accompanying drawings, wherein

Fig. Ia is a schematic cross sectional view of a displacement micropump comprising passive check-valves and a piezoelectric actuator according to prior art.

5 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. 0

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.

Detailed description of embodiments

None of the commonly used actuation principles for displacement micropumps are perfectly suited for displacement micropumps intended for working at high back pressures. It would be favourable to make the diaphragms as stiff as possible, while maximizing their strokes. This is contradictory with conventional pump designs and actuation principles. However, phase-change actuators, such as paraffin actuators, exhibit a large volume change in the solid to liquid transition. One obvious advantage of this 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. Hence the 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. In particular 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. In addition, 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. 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. In particular 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. Many metal or metal alloys have the mechanical and thermal properties required, but are usually not easily micromachined to form microfluidic systems and are hardly used as substrate materials in the field of microelectromechanical systems and microfluidics. In particular 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. One reason for this is that 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. Yet another alternative is to use 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. Although 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. However, 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.

A displacement pump according to one embodiment of the invention is schematically illustrated in Fig. 2a. 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

13, 14, 15 and means for moving the diaphragm 18. 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. Further, 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. In this embodiment 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. In operation 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. However 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.

As shown in 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. With this kind of design 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.

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. Furthermore 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.

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. Furthermore, 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.

In one embodiment of the present invention 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. Otherwise, if a single wide channel 9 is used, there is no support for the diaphragm layer 25 in the channel area. Hence there is a significant risk that the diaphragm layer 25 may be pushed up from the first cavity layer 26 by the expanding paraffin. Once the diaphragm layer 25 is released from the first cavity layer 26 there will flow paraffin in between the diaphragm layer 25 and the first cavity layer 26, whereupon some paraffin is lost leading to reduced stroke of the actuator and eventually a risk that the paraffin leaks out from the multilayer structure. Accordingly a reinforcement of the channel 9, with ridges, pillars or other structures 10, ensures a high reliability of the micropump 1 of the present invention. As shown in Fig. 6b, an alternative design uses the inlet/ outlet layer 23 to complete the channels 9.

As shown in Fig. 7, another embodiment of the present invention is 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 . However, the micropump only occupies an area of less than 9x3 mm 2 in the middle of the chip. In the following each layer is described with reference to Fig. 7.

1. Inlet/ outlet layer 23: 200 μm thick micro structured stainless steel sheet, two through holes with a diameter of 0.6 mm forming an inlet and an outlet respectively.

2. 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 μm.

3. Diaphragm layer 25: a polymer film, such as polyimide, with a thickness of about 50 μm.

4. First cavity layer 26: 200 μm 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.

5. Third cavity layer 28: identical to the first cavity layer. 6. 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.

7. Second cavity layer 27: identical to the first cavity layer.

8. Backing layer 30: 200 μm thick micro structured stainless steel sheet.

In this embodiment the cavities are filled with paraffin. Preferably 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.

Although the 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

13 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 layers of the embodiments described above are joined either by clamping and/ or using an intermediate sealing layer 31.

In one embodiment 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.

In another embodiment 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. Either the sealing layers 31 are dismountable or fixedly joined to at least one of the surfaces in contact with the sealing layer 31. Preferably 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. Another alternative is to use adhesives. 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.

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. In fact 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.

In the embodiments described above 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.

In another embodiment the heater layer 29 has heater elements 16 on both sides, i.e. a double-sided flexible printed circuit.

In the disclosed embodiments the paraffin is heated by resistive heater elements 16.

Alternatively 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. Usually the flexible printed circuits are made of a polyimide layer with a copper clad, either single-sided or double-sided. As described above, 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

) bonding pads in this area where 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.

In one embodiment of the present invention 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.

Using a metal or a metal alloy, such as stainless steel or titanium, in 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. If 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. In fact, the force exerted by the actuator may 0 permanently deform different parts of the micropump, such as the valve seats. For example titanium and stainless steel meet the requirements on the rigidity.

To increase a flow rate through a micropump of a given size the frequency of the actuator has to be increased. The paraffin of the paraffin actuator is cyclically melted 5 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. On the other hand

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. In addition the polymers, with a typical Young's modulus of 1-5 GPa, 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. aluminium (69 GPa, 238 Wm- 1 K- 1 ) and copper (120 GPa, 400 Wm- 1 K- 1 ), although without the advantageous biocompatibility of stainless steel and titanium. The biocompatibility properties are particularly interesting for the layers that are in contact with the fluid to be pumped. Silicon also has a high thermal conductivity (170 Wm- 1 K" 1 ) and a high Young's modulus (100). Accordingly a metal or metal alloy with a thermal conductivity in the range of about 5 to 400 Wm- 1 K" 1 and a Young's modulus of about 50 to 200 GPa can be chosen for any layer of the micropump.

In one embodiment of the present invention 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 μl giving a theoretical stroke volume of 0.19 μl. 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). For evaluation of the back pressure capability 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 μl/min and a maximum back pressure of 5 MPa were obtained, Le. much higher back pressure than obtained by other micropumps. A comparison with state-of-the-art micropumps is shown in Fig. 8. The piezoelectric (PE) and the 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. Moreover 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.

In one embodiment of the present invention 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.

In another embodiment of the present invention 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.

In yet another embodiment of the present invention 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. Commonly 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. For example, in some applications it may be necessary to have a certain polymer in contact with the fluid to be pumped since the chemistry is developed for that certain polymer. Moreover, it may in different applications be necessary to have a transparent window to at least a part of the microfluidic structures inside the multilayer structure. Then e.g. 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;

- stacking the 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; and

- sealing mating surfaces of the micro structured layer and said at least one further layer to form a microfluidic path, which comprises the inlet valve 4, the pumping chamber 12 and the outlet valve 5, leading through 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 of metal or metal alloy such as stainless steel to form at least one micro structured microfluidic layer 24 of metal or metal alloy;

- 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;

- stacking the microfluidic layer 24 and the cavity layer 26 and a flexible diaphragm layer 25 made of e.g. a polymer, to form the multilayer structure;

- sealing mating surfaces of the micro structured layer and said at least one further layer to form a microfluidic path, which comprises the inlet valve 4, the pumping chamber 12 and the outlet valve 5, leading through the multilayer structure;

- filling the cavities of the first cavity layer 26 with an actuator material 19 such as paraffin;

- sealing the cavities that are filled with an actuator material 19 by arranging a backing layer 30 on the cavity layer 26.

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. Typically the aperture sizes can be smaller than 100 μm and controlled within tens of micrometers. The thickness of the stencils is commonly in the range of 0.1 up to 0.4 mm. Moreover 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.

Preferably 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.

In another embodiment of the method for manufacturing a displacement micropump according to the invention a micro structured inlet/ outlet layer 23 of stainless steel is provided. The inlet/outlet layer 23 is stacked together with the other layers.

In yet another embodiment of the method of the present invention a second micro structured cavity layer 27 and micro structured heater layer 29 is provided. In the step of stacking 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.

Preferably 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-. When 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. Alternatively, the step of sealing the layers comprises the step of providing an intermediate sealing layer 31. With a sealing layer 31 the requirements on the roughness of the surfaces to be stacked are less demanding. Furthermore 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. By stacking the multilayer structure with one sealing layer 31 in between each layer, or at least the layers requiring a sealing layer 31, and clamping the multilayer structure together the micropump is more efficiently sealed. Different sealing materials can be used, e.g. parylene, photoresist, PDMS, polyethylene terephthalate (PET), etc.

) In another embodiment according to the present invention, the method comprises the step of depositing a sealing layer 31 of e.g. parylene onto the layers of the multilayer structure before stacking. Hence 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. In particular, parylene can be bonded to parylene under certain conditions.

Preferably, 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.

One example of a method of making a micropump according to the invention is schematically illustrated in Fig. 10a-e. 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. Thus a plurality of micropumps can be manufactured in a batch process. As schematically illustrated in Fig. 10b, 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. In the etching step all

features of the layers are formed, e.g. the microfluidic channels 9, the supporting ridges 10 (according to Fig. 5 and 6), the alignment holes, etc. Further, 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. Preferably, 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. Accordingly, 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. As schematically illustrated in Fig. 10c, 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. As schematically illustrated in Fig. 1Od, 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. Subsequently the three cavities formed under the flexible diaphragms 13, 14, 15 are filled abundantly with melted paraffin 19. After cooling and solidification of the paraffin the excessive paraffin is scraped off on a level with the surface of the second cavity layer 27. A sealing layer 31, e.g. in the form of an adhesive, is coated on the side of the backing layer 30 to be arranged on the second cavity layer 27. As schematically illustrated in Fig. 1Oe, 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.

While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, on the contrary, is intended to cover various modifications and equivalent arrangements within the appended claims.