Microfluidic valve and integrated microfluidic system

• US 6,068,751 A
• Filed: 12/17/1996
• Issued: 05/30/2000
• Est. Priority Date: 12/18/1995
• Status: Expired due to Fees

• Current Assignee: Neukermans, Armand P.
• Original Assignee: Neukermans, Armand P.
• Inventors: Neukermans, Armand P.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US08/768,303
• Time in Patent Office: 1,260 Days
• Field of Search: 137/606, 251/129.06, 251/7, 251/213, 204/601, 204/604
• US Class Current: 204/601
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/505 flexible containers not provided for above
• CPC Class Codes: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: F15C 5/00 Manufacture of fluid circuit elements; Manufacture of assemblages of such elements integrated circuits
• CPC Class Codes: Y10T 137/87684 Valve in each inlet

Abstract

A microfluidic delivery system (20) and microfluidic system (100) control flows of a liquid or a gas through elongated capillaries (62, 126) that are enclosed along at least one surface by a layer (42, 114) of a malleable material. An electrically-powered actuator included in the systems (20, 100) extends toward or retracts a blade from the layer (42, 114) of a malleable material to either occlude or open capillaries. Reservoirs (46, 124) included in a pouch (22, 108) together with the capillaries (62, 126) supply fluids whose flow is controlled by movement of the blades. The microfluidic system (100) permits dispensing at will, under microprocessor control at predetermined flow rates, liquids, samples, chemicals, reagents and body fluids, and mixing them together and/or reacting for diagnostic medical or analytical tests, DNA sequencing etc. The microfluidic delivery system (20) and microfluidic system (100) may be used for clinical testing, environmental or forensic testing, analytical chemistry, fine chemistry, biological sciences, combinatorial synthesis, etc.

Claims

1. A first microfluidic valve for controlling a flow of a fluid through an elongated capillary that is enclosed along at least one surface by a layer of a malleable material, the capillary having an inlet port and an outlet port, the microfluidic valve comprising:

a valve housing adapted to be pressed firmly against the layer of malleable material;

an actuator secured within said valve housing for producing movement toward or away from the layer of malleable material upon application of a control signal to the actuator; and

a blade coupled to the actuator and shaped so that movement produced by the actuator toward the layer of malleable material presses the blade against the layer of malleable material thereby occluding the capillary and barring fluid from flowing from the inlet port to the outlet port, and whereby, upon retracting the blade away from the layer of malleable material, fluid introduced into the inlet port of the capillary may flow through the capillary to exit the capillary through the outlet port.

2. The microfluidic valve of claim 1 wherein the actuator includes a piezo-electric device arranged in an orientation in which increasing or decreasing an electric potential applied to the piezo-electric device produces the movement toward or away from the layer of malleable material.

3. The microfluidic valve of claim 1 further comprising a pouch that includes the capillary;

at least a portion of the pouch, in addition to the surface of the capillary, being provided by a layer of malleable material that is shaped to provide a reservoir adapted for holding a quantity of fluid;

the reservoir being in communication with the inlet port of the capillary so that upon application of pressure to the layer of malleable material of the reservoir fluid may flow from the reservoir into the capillary.

4. The microfluidic valve of claim 3 wherein the capillary includes:

a first segment of the capillary adjacent to the inlet port that has a small cross-sectional area; and

a second segment of the capillary adjacent to the outlet port that has a cross-sectional area that is larger than the cross-sectional area of the first segment.

5. The microfluidic valve of claim 1 further comprising:

a base plate having a planar anvil surface and base-plate registration means; and

a substantially planar, elongated, paddle-shaped nozzle that includes the capillary, said nozzle being adapted to be juxtaposed with the anvil surface of said base plate and interposed between the blade of said valve housing and the anvil surface, said nozzle including a nozzle registration means that mates with and engages the base-plate registration means, a short segment of the capillary intermediate the inlet port and the outlet port being disposed accurately between the blade and the anvil surface when the nozzle registration means mates with and engages the base-plate registration means.

6. The microfluidic valve of claim 5 further comprising a pouch that includes the nozzle;

at least a portion of the pouch, in addition to the surface of the capillary, being provided by a layer of malleable material that is shaped to provide a reservoir adapted for holding a quantity of fluid;

the reservoir being in communication with the inlet port of the capillary so that upon application of pressure to the layer of malleable material of the reservoir fluid may flow from the reservoir into the capillary.

7. A pouch adapted for use with a microfluidic valve that is adapted for controllably releasing a flow of a fluid from the pouch, the microfluidic valve including:

a base plate having a planar anvil surface and base-plate registration means; and

a valve housing adapted to be mated with and urged toward the anvil surface of said base plate, said valve housing including an actuator that producing movement toward or away from the layer of malleable material upon application of a control signal to the actuator, said valve housing also including a blade coupled to the actuator and shaped so that movement of the actuator juxtaposes the blade with the anvil surface;

the pouch comprising;

a layer of malleable material having formed therein a reservoir that is adapted for holding a quantity of the fluid, said pouch including a substantially planar, elongated, paddle-shaped nozzle that projects outward from the reservoir and is adapted to be juxtaposed with the anvil surface of said base plate interposed between the blade of said valve housing and the anvil surface, the nozzle including a nozzle registration means that mates with and engages the base-plate registration means of said base plate, the nozzle also having an elongated capillary formed within the nozzle that communicates directly with the reservoir, the capillary being disposed accurately between the blade and the anvil surface when the nozzle registration means mates with and engages the base-plate registration means of said base plate, the capillary also including a outlet port opening distal from the reservoir, whereby, upon retracting the blade away from the anvil surface of said base plate, pressure applied to said pouch about the reservoir urges fluid in the reservoir to flow out of said pouch along the capillary and through the outlet port, and whereby extending the blade toward the anvil surface presses the malleable material of the nozzle together thereby occluding the capillary and barring fluid from flowing from said pouch along the capillary.

8. The pouch of claim 7 wherein the capillary includes:

a first segment of the capillary that extends outward from and that communicates directly with the reservoir, and that has a small cross-sectional area; and

a short segment of the capillary that extends outward from and that communicates directly with the first segment, and that has a cross-sectional area that is larger than the cross-sectional area of the first segment.

9. A microfluidic system for controlling a flow of a fluid comprising:

a pouch having a capillary that is enclosed along at least one surface by a layer of a malleable material, the capillary having an inlet port and an outlet port, the layer of malleable material also being shaped to provide a processing chamber that is located along the capillary intermediate the inlet port and the outlet port;

a pair of valve housings adapted to be pressed firmly against the layer of malleable material, a first one of said valve housings being located intermediate said processing chamber and the inlet port of the capillary, a second one of said valve housings being located intermediate said processing chamber and the outlet port of the capillary;

a pair of actuators, one actuator being secured within each of said valve housings producing movement toward or away from the layer of malleable material upon application of a control signal to the actuator;

a pair of blades, each blade being coupled to one of said actuators, and each of said blades being shaped so movement of the actuator to which the blade is coupled toward the layer of malleable material juxtaposes such blade with the capillary and presses the blade against the layer of malleable material thereby occluding the capillary and barring the fluid from flowing through the capillary, and whereby, upon retracting the blade away from the layer of malleable material, fluid introduced into the capillary may flow through the capillary; and

a piston having a face that is adapted for controllably depressing the malleable material of said pouch about said processing chamber, the face of said piston being juxtaposed with said processing chamber.

10. The microfluidic system of claim 9 wherein the face of said piston is knurled.

11. A microfluidic system for controlling flows of a fluid through a plurality of interconnected, elongated capillaries that are all enclosed along at least one surface by a layer of a malleable material, each capillary having an inlet port and an outlet port, the microfluidic system comprising:

a plurality of valve housings adapted to be pressed firmly against the layer of malleable material;

a plurality of actuators equal in number to the plurality of valve housings, each actuator being secured within one of said valve housings; and

each of said actuators producing movement toward or away from the layer of malleable material upon application of a control signal to said actuator; and

a plurality of blades equal in number to the plurality of valve housings and actuators, each blade being coupled to one of said actuators, and each of said blades being shaped so movement of the actuator to which the blade is coupled toward the layer of malleable material juxtaposes such blade with one of the capillaries and presses the blade against the layer of malleable material thereby occluding the capillary and barring the fluid from flowing from the inlet port to the outlet port, and whereby, upon retracting the blade away from the layer of malleable material, fluid introduced into the inlet port of the capillary may flow through the capillary to exit the capillary through the outlet port of the capillary.

12. The microfluidic system of claim 11 wherein at least one of the actuators includes a piezo-electric device arranged in an orientation in which increasing or decreasing an electric potential applied to the piezo-electric device produces the movement toward or away from the layer of malleable material.

13. The microfluidic system of claim 11 wherein said valve housings have profiles and at least one of said actuators includes a leaf spring coupled to said actuator, the leaf spring supporting said blade outside of the profile of the valve housing within which said actuator is secured.

14. The microfluidic system of claim 11 further comprising a pouch that includes the capillaries;

at least a portion of the pouch, in addition to the surface of the capillaries, being provided by a layer of malleable material that is shaped to provide reservoirs each of which is adapted for holding a quantity of fluid;

each reservoir being in communication with the inlet port of one of the capillaries so that upon application of pressure to the layer of malleable material of such reservoir fluid may flow from the reservoir into the capillary.

15. The microfluidic system of claim 14 wherein at least one of the capillaries includes:

a first segment of the capillary adjacent to the inlet port that has a small cross-sectional area; and

a second segment of the capillary adjacent to the outlet port that has a cross-sectional area that is larger than the cross-sectional area of the first segment.

16. The microfluidic system of claim 14 wherein said pouch further comprises a reaction chamber.

17. The microfluidic system of claim 16 wherein said reaction chamber is an electrophoretic cell.

18. The microfluidic system of claim 14 wherein said pouch further comprises a heater.

19. The microfluidic system of claim 14 further comprising a valve plate to which said valve housings together with the associated actuators and blades are secured.

20. The microfluidic system of claim 19 further comprising a base plate having an anvil surface against which said pouch is juxtaposed, said base plate further comprising base-plate registration means, said pouch and said valve plate respectively having pouch registration means and valve-plate registration means that respectively mate with and engage the base-plate registration means.

21. The microfluidic system of claim 20 wherein ridges protrude outward from the anvil surface said base plate for limiting contact between the pouch and said valve plate and the valve housings carried by said valve plate to small areas about the valve housings.

22. The microfluidic system of claim 20 further comprising a heater secured within said base plate for heating a region of said pouch immediately adjacent to said heater.

23. The microfluidic system of claim 20 further comprising a cooler secured within said base plate for cooling a region of said pouch immediately adjacent to said heater.

24. The microfluidic system of claim 14 wherein:

a processing chamber is formed in the malleable material of said pouch along one of the capillaries intermediate the inlet port and the outlet port of that capillary; and

a pair of said valve housings together with the associated actuators and blades are respectively located along the capillary on opposite sides of said processing chamber;

a first one of said valve housings together with the associated actuator and blade being located intermediate said processing chamber and the inlet port of the capillary, and a second one of said valve housings together with the associated actuator and blade being located intermediate said processing chamber and the outlet port of the capillary; and

the microfluidic system further comprising a piston having a face that is adapted for controllably depressing the malleable material of said pouch about said processing chamber, the face of said piston being juxtaposed with said processing chamber.

25. The microfluidic system of claim 24 wherein the face of said piston is knurled.

26. The microfluidic system of claim 14 wherein:

a pair of processing chamber are formed in the malleable material of said pouch along one of the capillaries intermediate the inlet port and the outlet port of that capillary; and

a pair of said valve housings together with the associated actuators and blades are respectively located along the capillary on opposite sides of said pair of processing chamber;

a first one of said valve housings together with the associated actuator and blade being located intermediate the inlet port of the capillary and said processing chamber nearest to the inlet port, and a second one of said valve housings together with the associated actuator and blade being located intermediate the outlet port of the capillary and said processing chamber nearest to the outlet port.

27. The microfluidic system of claim 26 further comprising a pair of pistons each having a face that is adapted for controllably depressing the malleable material of said pouch about one of said processing chambers, the face of said piston being juxtaposed with said processing chamber.

28. The microfluidic system of claim 26 wherein a third valve housing together with the associated actuator and blade are respectively located along the capillary between said pair of processing chambers.

29. The microfluidic system of claim 26 wherein said pouch further comprises a heater.

30. The microfluidic system of claim 14 wherein one of the capillaries has an ultraviolet ("UV") window formed in the malleable material.

31. The microfluidic system of claim 14 wherein the pouch includes a Total Internal Reflection ("TIR") detector disposed along one of the capillaries.

32. The microfluidic system of claim 14 further comprising means for applying pressure to at least one of the reservoirs.