Miniaturized fluid delivery and analysis system

• US 20070031287A1
• Filed: 08/15/2006
• Published: 02/08/2007
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Agnitio Science & Technology
• Original Assignee: Agnitio Science & Technology
• Inventors: Chen, Chi-Chen, Chang, Ping, Hong, Rong-I, Wang, Shaw-Tzuv, Webster, James
• Granted Patent: US 7,666,687 B2
• Time in Patent Office: Days
• US Class Current: 422/68.100
• 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 or other chemical of biological assays. The method comprises 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

1-11. -11. (canceled)

12. A method of performing immunological assay of a fluid sample, wherein the method comprises the steps of:

(a) pumping said fluid sample from a fluid reservoir, where said fluid sample is placed therein, to a reaction chamber, wherein said fluid reservoir and said reaction chamber are defined in a fluidic cartridge and said reaction chamber comprises therein a plurality of immobilized species;

(b) allowing said fluid sample to react with said plurality of immobilized species for a predetermined reaction time; and

(c) excluding said fluid sample from said reaction chamber through an exit port.

13. The method, as recited in claim 12, further comprising the steps of:

(d) placing an antibody solution containing a specific secondary antibody conjugated with a detectable molecule into a fluid reservoir;

(e) pumping said antibody solution from said fluid reservoir to said reaction chamber;

(f) pumping said antibody solution out through an exit port after a predetermined reaction time; and

(g) providing a detectable signal.

14. The method as recited in claim 12, further comprising at least a washing step of pumping a wash buffer placed in a fluid reservoir through said reaction chamber and out an exit port.

15. The method as recited in claim 13, after step (c) and step (f), each further comprising a washing step of pumping a wash buffer placed in a fluid reservoir through said reaction chamber and out said exit port.

16. The method, as recited in claims 12 or 14, wherein said fluid sample contains a plurality of different antibodies.

17. The method, as recited in claims 12, 13 or 15, wherein said detectable molecule is selected from the group consisting of peroxidase enzyme, alkaline phosphatase enzyme and fluorescent tag.

18. The method, as recited in claim 17, after step (c), further comprising a step of pumping a substrate buffer placed in said fluid reservoir to said reaction chamber to allow a substrate in said substrate buffer to react with any enzyme captured in step (b) with said immobilized species providing a detectable signal.

19. The method, as recited in claim 17, after step (f), further comprising a step of pumping a substrate buffer placed in said fluid reservoir to said reaction chamber to allow a substrate in said substrate buffer to react with any enzyme captured in step (e).

20. The method, as recited in claims 12 or 14, wherein said fluid reservoir, said reaction chamber and said exit port are connected by one or more channels of capillary dimensions, wherein said fluidic cartridge includes a first substrate, a second substrate and an flexible intermediate interlayer sealedly interfaced between said first substrate and said second substrate to form therein said fluid reservoir, said one or more channels, said reaction chamber, and said exit port, and wherein said fluidic cartridge further provides a fluid flow controlling structure therein to restrict a flow of said fluid sample through said reaction chamber via said one or more channels in one direction only.

21. The method, as recited in claim 20, wherein in said pumping steps (a) and (c), a linear actuator provides a pumping action in a pump chamber defined in said fluidic cartridge so as to pump said fluid sample to flow from said fluid reservoir to said exit port through said reaction chamber and said one or more channels.

22. The method, as recited in claims 13 or 15, wherein said fluid reservoir, said reaction chamber and said exit port are connected by one or more channels of capillary dimensions, wherein said fluidic cartridge includes a first substrate, a second substrate and an flexible intermediate interlayer sealedly interfaced between said first substrate and said second substrate to form therein said fluid reservoir, said one or more channels, said reaction chamber, and said exit port, and wherein said fluidic cartridge further provides a fluid flow controlling structure therein to restrict a flow of said fluid sample and said antibody solution through said reaction chamber via said one or more channels in one direction only.

23. The method, as recited in claim 22, wherein in said pumping steps (a), (c), (e), and (f), at least one linear actuator provides a pumping action in at least a pump chamber defined in said fluidic cartridge so as to respectively pump said fluid sample and said antibody solution to flow from said fluid reservoir to said exit port through said reaction chamber and said one or more channels.

24. The method, as recited in claim 21, 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 sample from said fluid reservoir to flow through said reaction chamber and said one or more channels to said exit port.

25. The method, as recited in claim 23, 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 at least one 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 sample and said antibody solution from said fluid reservoir to flow through said reaction chamber and said one or more channels to said exit port.

26. The method, as recited in claim 21, 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 sample to flow from said fluid reservoir to said exit port through said reaction chamber via said one or more channels and a higher resistance to said fluid sample to flow from said exit port to said fluid reservoir.

27. The method, as recited in claim 23, 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 sample and said antibody solution to flow from said fluid reservoir to said exit port through said reaction chamber via said one or more channels and a higher resistance to said fluid sample and said antibody solution to flow from said exit port to said fluid reservoir.

28. The method, as recited in claim 21, wherein said fluid flow controlling structure comprises two passive check valves in said fluidic cartridge to restrict said fluid sample 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 said pump interlayer diaphragm so as to control said fluid sample to only flow from said fluid reservoir to said exit port.

29. The method, as recited in claim 23, wherein said fluid flow controlling structure comprises two passive check valves in said fluidic cartridge to restrict said fluid sample and said antibody solution 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 said pump interlayer diaphragm so as to control said fluid sample and said antibody solution to only flow from said fluid reservoir to said exit port.

30. The method as recited in claim 12, wherein said fluid sample comprises a plurality of bio-molecules at unknown concentrations or an analyte conjugated with a detectable molecule.

31. The method as recited in claim 12, wherein said immobilized species comprises a protein, an antibody, a nucleic acid, a DNA, a compound, or a combination thereof.