Miniaturized fluid delivery and analysis system

• US 7,241,421 B2
• Filed: 05/14/2003
• Issued: 07/10/2007
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: AST Management Incorporated
• Original Assignee: AST Management Incorporated
• Inventors: Chen, Chi-Chen, Chang, Ping, Hong, Rong-I, Webster, James Russell, Wang, Shaw-Tzuv
• Primary Examiner(s): Wallenhorst; Maureen M.
• Application Number:
  US10/437,046
• Publication Number:
  US 20040063217A1
• Time in Patent Office: 1,518 Days
• Field of Search: 422/81, 422/100, 422/103, 436/46, 436/180, 436/518, 436/524, 435/6, 435/7.1, 435/287.1, 435/287.2, 435/287.3, 435/288.4, 435/288.5
• US Class Current: 422/503
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0605 check valves
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• 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: F04B 43/043 Micropumps
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention provides a method for combining a fluid delivery system with an analysis system for performing immunological, chemical, or biological assays. The method provides a miniature plastic fluidic cartridge containing a reaction chamber with a plurality of immobilized species, a capillary channel, and a pump structure along with an external linear actuator corresponding to the pump structure to provide force for the fluid delivery. The plastic fluidic cartridge can be configured in a variety of ways to affect the performance and complexity of the assay performed.

Claims

1. A fluid delivery and analysis system, comprising:

a fluidic cartridge including a first substrate, a second substrate and a flexible intermediate interlayer sealedly interfaced between said first substrate and said second substrate to form therein one or more channels of capillary dimensions within the first substrate and the second substrate on both sides of flexible intermediate interlayer;

a fluid reservoir, a pump chamber, a reaction chamber, and a port formed at least partially in said first substrate or said second substrate of said fluidic cartridge, and wherein the one or more channels connect the fluid reservoir to the pump chamber, the pump chamber to the reaction chamber, and the reaction chamber to the port;

a fluid flow controlling structure, formed in said fluidic cartridge, restricting a flow of a fluid in only a direction from said fluid reservoir to said reaction chamber via said one or more channels and said pump chamber; and

a linear actuator providing a pumping action in said pump chamber to push said fluid to flow from said fluid reservoir to said reaction chamber via said pump chamber and said one ore more channels.

2. The fluid delivery and analysis system, as recited in claim 1, wherein said pump chamber has a substrate chamber formed in said first substrate and a hole formed in said second substrate to free said flexible intermediate interlayer to act as a pump interlayer diaphragm, wherein said linear actuator moves in said hole to bend said pump interlayer diaphragm and therefore provides a necessary force to deform said pump interlayer diaphragm to provide said pumping action in said pump chamber to pump said fluid from said fluid reservoir to flow through said reaction chamber via said pump chamber and said one or more channels.

3. The fluid delivery and analysis system, as recited in claim 2, wherein said fluid flow controlling structure comprises a first passive check valve and a second passive check valve in said fluidic cartridge to restrict said fluid to flow from one of said one or more channels in said second substrate to another one of said one or more channels in said first substrate by bending of said pump interlayer diaphragm so as to control said fluid flowing from said fluid reservoir to said port, wherein any flow of said fluid from said port back to said fluid reservoir is controlled by restricting said bending of said pump interlayer diaphragm with said second substrate.

4. The fluid delivery and analysis system, as recited in claim 3, wherein each of said first and second passive check valves comprise a first substrate channel and a second substrate channel separated by said flexible intermediate interlayer wherein through holes formed in said flexible intermediate interlayer are contained within said first substrate channel but not within said second substrate channel.

5. The fluid delivery and analysis system, as recited in claim 1, wherein said fluid flow controlling structure comprises a first passive check valve positioned before said pump chamber and a second passive check valve positioned after said pump chamber in said fluidic cartridge to provide a lower resistance to said fluid to flow from said fluid reservoir to said reaction chamber via said pump chamber and said one or more channels and a higher resistance to said fluid to flow from said reaction chamber to said fluid reservoir via said pump chamber.

6. The fluid delivery and analysis system, as recited in claim 5, wherein each of said first and second passive check valves comprise a first substrate channel and a second substrate channel separated by said flexible intermediate interlayer wherein through holes formed in said flexible intermediate interlayer are contained within said first substrate channel but not within said second substrate channel.

7. The fluid delivery and analysis system, as recited in one of claims 1-3, wherein said reaction chamber contains a plurality of immobilized biomolecules for specific solid-phase reactions with said fluid, wherein after a predetermined period of reaction time, said fluid is pumped through said reaction chamber and out through said port.

8. The fluid delivery and analysis system, as recited in claim 7, wherein said plurality of immobilized bio-molecules is selected from the group consisting of immobilized antibodies and immobilized antigens.

9. The fluid delivery and analysis system, as recited in one of claims 1-3, wherein said first substrate and said second substrate of said fluidic cartridge are constructed from a plastic material selected from the group consisting of poly-methyl- methacrytate plastic, polystyrene plastic, polycarbonate plastic, polypropylene plastic, polyvinylchloride plastic, and ABS plastic.

10. The fluid delivery and analysis system, as recited in one of claims 1-3, wherein said first substrate is made of transparent plastic material and wherein said channels, said reaction chamber and said pump chamber are made by a method selected from the group consisting of injection molding, compression molding, hot embossing, and machining.

11. The fluid delivery and analysis system, as recited in claim 10, wherein each of said first and second substrates has a thickness of 1 mm to 3 mm.

12. The fluid delivery and analysis system, as recited in claim 10, wherein said flexible intermediate interlayer is made from a material selected from the group consisting of polymer, latex, silicone elastomer, polyvinylchloride, and fluoroelastomer.

13. The fluid delivery and analysis system, as recited in one of claims 1-3, wherein said flexible intermediate interlayer is made by a method selected from the group consisting of die cutting, rotary die cutting, laser etching, injection molding, and reaction injection molding.

14. The fluid delivery and analysis system, as recited in one of claims 1-3, wherein said linear actuator comprises a linear action source selected from the group consisting of electromagnetic solenoid, motor/cam/piston configuration, piezoelectric linear actuator, and motor/linear gear configuration.

15. A fluidic device for a fluid delivery and analysis system, comprising:

a first substrate, a second substrate and a flexible intermediate interlayer sealedly interfaced between said first substrate and said second substrate to form therein one or more channels of capillary dimensions, a pump chamber, an open reservoir and at least a reaction chamber, wherein said pump chamber, said open reservoir and said reaction chamber are connected to said one or more channels; and

means for restricting a fluid being pumped.

16. The fluidic device, as recited in claim 15, wherein said pump chamber has a substrate chamber formed in said first substrate and a hole formed in said second substrate to free said flexible intermediate interlayer to act as a pump interlayer diaphragm, whereby a linear actuator of the fluid delivery and analysis system is capable of moving in said hole to bend said pump interlayer diaphragm and therefore provide a necessary force to deform said pump interlayer diaphragm to provide a pumping action in said pump chamber to pump said fluid flow through said reaction chamber via said one or more channels.

17. The fluidic device, as recited in claim 16, wherein said means for restricting a fluid comprises a first passive check valve positioned before said pump chamber and a second passive check valve positioned after said pump chamber in said fluidic device to provide a lower resistance to said fluid to flow through said reaction chamber in one direction and a higher resistance to said fluid to flow through said reaction chamber in an opposing direction.

18. The fluidic device, as recited in claim 17, wherein said first passive check valve and said second passive check valve each comprise a first substrate channel and a second substrate channel separated by said flexible intermediate interlayer wherein through holes formed in said flexible intermediate interlayer are contained within said first substrate channel but not within said second substrate channel.

19. The fluidic device, as recited in claim 16, wherein said means for restricting a fluid comprises two passive check valves in said fluidic device to restrict said fluid to flow from one of said one or more channels in said second substrate to another one of said one or more channels in said first substrate by bending of said pump interlayer diaphragm, wherein any flow of said fluid in an opposite direction is controlled by restricting said bending of said pump interlayer diaphragm with said second substrate.

20. The fluidic device, as recited in claim 19, wherein each of said two passive check valves comprises a first substrate channel and a second substrate channel separated by said interlayer wherein through holes formed in said flexible intermediate interlayer are contained within said first substrate channel but not within said second substrate channel.

21. The fluidic device, as recited in one of claims 16-19, wherein said first substrate is made of transparent plastic material and wherein said one or more channels, said reaction chamber and said pump chamber are made by a method selected from the group consisting of injection molding, compression molding, hot embossing, and machining.

22. The fluidic device, as recited in claim 21, wherein each of said first and second substrates has a thickness of 1 mm to 3 mm.

23. The fluidic device, as recited in claim 21, wherein said intermediate interlayer is made from a material selected from the group consisting of polymer, latex, silicone elastomer, polyvinylchloride, and fluoroelastomer.

24. The fluidic device, as recited in one of claims 15-19, wherein said reaction chamber contains a plurality of immobilized bio-molecules for specific solid-phase reactions with said fluid, wherein after a predetermined period of reaction time, said fluid is pumped through said reaction chamber.

25. The fluidic device, as recited in claim 24, wherein said plurality of immobilized bio-molecules is selected from the group consisting of immobilized antibodies and immobilized antigens.

26. The fluidic device, as recited in one of claims 15-19, wherein said first and second substrates are constructed from a plastic material selected from the group consisting of poly-methyl-methacrylate plastic, polystyrene plastic, polycarbonate plastic, polypropylene plastic, polyvinylchloride plastic, and ABS plastic.

27. The fluidic device, as recited in one of claims 15-19, wherein said intermediate interlayer is made by a method selected from the group consisting of die cutting, rotary die cutting, laser etching, injection molding, and reaction injection molding.