Apparatus and method of extracting and optically analyzing an analyte from a fluid-based sample

• US 20060246501A1
• Filed: 06/29/2006
• Published: 11/02/2006
• Est. Priority Date: 09/09/2004
• Status: Active Grant

• Current Assignee: MicroFluidic Systems, Inc.
• Original Assignee: MicroFluidic Systems, Inc.
• Inventors: Northrup, Allen
• Granted Patent: US 8,053,214 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 3/0217 of the plunger pump type medical syringes A61M
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 1/14 Suction devices, e.g. pumps; Ejector devices
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 1/405 by adsorption or absorption

Abstract

An extraction and analysis device includes a microfluidic based collection system that extracts one or more different analytes from a fluid-based sample and an optical analysis system directly coupled to the collection system to perform optical analysis on the one or more collected analytes. The microfluidic based collection system includes microfluidic circuitry for directing a fluid based sample to a purification chip. Analytes collected within the purification chip can be either subsequently removed and analyzed or the analytes can be analyzed directly, while still within the purification chip, using the optical analysis system. The purification chip is preferably comprised of a plurality of pillars, the surface area of each pillar is coated with a specific capture chemistry. The specific capture chemistry is applied by derivitizing the pillars such that a ligand, such as a nucleic acid, an amptimer, or an antibody is attached to each pillar.

Claims

1. A device to extract and analyze one or more different analytes from a fluid-based sample, the device comprising:

a. a purification apparatus to extract the one or more different analytes from the fluid-based sample and to prepare the extracted one or more different analytes for detection; and

b. a detection apparatus coupled to the purification apparatus, wherein the detection apparatus detects one or more characteristics associated with the one or more extracted analytes in the purification apparatus, and classifies the one or more different analytes based on the detected one or more characteristics.

2. The device of claim 1 wherein the purification apparatus comprises a plurality of raised structures, each raised structure is coated with a capture moiety to bind with the one or more different analytes.

3. The device of claim 2 wherein the purification apparatus further comprises one or more solution containers, each solution container stores a solution, and microfluidic circuitry coupled to the one or more solution containers and the plurality of raised structures to transport the solutions, wherein the solutions are used to prepare the extracted one or more different analytes for detection.

4. The device of claim 1 wherein the purification apparatus further comprises a detection signal generated in-solution within the purification apparatus.

5. The device of claim 1 wherein an analyte comprises a ligand, a nucleic acid, an antibody, an antigen, an amplifier, an amptimer, or any substance capable of binding with the capture moiety and having characteristics measurable by the detection system.

6. The device of claim 1 wherein the purification apparatus further comprises a temperature control device to thermally control the purification apparatus.

7. The device of claim 1 further comprising a self-contained power source.

8. The device of claim 7 wherein the self-contained power source comprises a battery.

9. The device of claim 1 wherein the detection apparatus comprises an optical detection apparatus that detects one or more optical characteristics associated with the one or more extracted analytes.

10. The device of claim 9 wherein the optical detection apparatus comprises an optical source and an optical detector.

11. The device of claim 9 wherein the optical detection apparatus is configured to perform one or more of a fluorescence method, a chi-luminescence method, or a time resolved fluorescence method to detect the one or more optical characteristics.

12. The device of claim 1 wherein the device is a portable device.

13. The device of claim 1 further comprising an intake apparatus coupled to the purification apparatus to draw the fluid-based sample into the device.

14. An extraction and detection system to extract and analyze one or more different analytes from one or more fluid-based samples, the extraction and detection system comprising:

a. a fluid delivery system to deliver one or more fluid-based samples; and

b. an extraction and detection system coupled to the fluid delivery system, wherein the extraction and detection system comprises a plurality of purification chips, each purification chip comprising a plurality of raised structures coated with a capture moiety to bind with one or more different analytes, and a detection apparatus coupled to each of the plurality of purification chips to detect one or more characteristics associated with the one or more different analytes bound to the plurality of raised structures and to classify the one or more different analytes based on the detected one or more characteristics.

15. The extraction and detection system of claim 14 wherein the fluid delivery system further comprises one or more solution containers, each solution container stores a solution used for detection of an analyte, and microfluidic circuitry coupled to the one or more solution containers to transport the solutions to each of the plurality of purification chips.

16. The extraction and detection system of claim 14 wherein each purification chip further comprises a detection signal generated in-solution surrounding the plurality of raised structures.

17. The extraction and detection system of claim 14 wherein an analyte comprises a ligand, a nucleic acid, an antibody, an antigen, an amplifier, an amptimer, or any substance capable of binding with the capture moiety and having characteristics measurable by the detection system.

18. The extraction and detection system of claim 14 wherein each purification chip further comprises a temperature control device coupled to the plurality of raised structures to thermally control the plurality of raised structures.

19. The extraction and detection system of claim 14 wherein the detection apparatus comprises an optical detection apparatus that detects one or more optical characteristics associated with the one or more extracted analytes.

20. The extraction and detection system of claim 19 wherein the optical detection apparatus comprises one or more optical sources and one or more optical detectors.

21. The extraction and detection system of claim 19 wherein the optical detection apparatus is configured to perform one or more of a fluorescence method, a chi-luminescence method, or a time resolved fluorescence method to detect the one or more optical characteristics.

23. The apparatus of claim 21 wherein the temperature control device comprises a heating means coupled to the base.

22. A thermally controlled apparatus comprising:

a. a purification chip including a base layer and a plurality of raised structures connected to the base layer, each raised structure is coated with a capture moiety to bind with one or more different analytes; and

b. a temperature control device coupled to the base layer to thermally control the plurality of raised structures, thereby controlling a temperature of an analyte bound to the capture moiety, a substance coupled to the analyte, or a solution surrounding the plurality of raised structures.

24. A thermally controlled apparatus comprising:

a. a purification chip including a plurality of raised structures, wherein a plurality of groups of nucleic acid probes are attached to the plurality of raised structures, further wherein each group of nucleic acid probes includes a unique sequence of nucleic acids and each group of nucleic acid probes bind to a specific type of nucleic acid to form a bound-pair group; and

b. a temperature control device coupled to thermally control the plurality of raised structures such that a temperature of the plurality of nucleic acid probes and any bound nucleic acids are systematically adjusted to independently melt each bound-pair group at a bound-pair group melting point temperature.

25. The thermally controlled apparatus of claim 24 further comprising a collection apparatus to individually collect the nucleic acid from each melted bound-pair group.

26. An apparatus to perform a PCR reaction, the apparatus comprising:

a. a purification chip including a plurality of raised structures, each raised structure is coated with a capture moiety to bind with one or more different nucleic acids; and

b. a temperature control device coupled to the plurality of raised structures to thermally control the plurality of raised structures such that a temperature of the one or more different nucleic acids attached to the plurality of raised structures is thermally cycled for a PCR reaction.

27. The apparatus of claim 26 wherein the plurality of raised structures are connected to a base, and the temperature control device is coupled to the base.

28. The apparatus of claim 26 wherein the plurality of raised structures are connected to a base, and the temperature control device comprises a heating means coupled to the base.

29. An apparatus to perform a PCR reaction, the apparatus comprising:

a. a purification chip including a plurality of raised structures; and

b. a temperature control device coupled to the plurality of raised structures to thermally control the plurality of raised structures such that a temperature of a nucleic acid is thermally cycled for a PCR reaction.

30. The apparatus of claim 29 wherein the plurality of raised structures are connected to a base, and the temperature control device is coupled to the base.

31. The apparatus of claim 29 wherein the plurality of raised structures are connected to a base, and the temperature control device comprises a heating means coupled to the base.

32. A method of performing a PCR reaction comprising:

a. providing a PCR apparatus comprising a purification chip including a plurality of raised structures, each raised structure is coated with a capture moiety to bind with one or more different nucleic acids, and a thermally controlled device coupled to the plurality of raised structures to thermally control the plurality of raised structures; and

b. performing thermal cycling by alternatively raising and lowering a temperature of the plurality of raised structures, thereby alternatively raising and lowering a temperature of one or more substances either attached to plurality of raised structures or in-solution surrounding the plurality of raised structures.