Integration of fluids and reagents into self-contained cartridges containing sensor elements and reagent delivery systems

• US 8,101,431 B2
• Filed: 12/22/2004
• Issued: 01/24/2012
• Est. Priority Date: 02/27/2004
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: McDevitt, John T., Ballard, Karri L., Floriano, Pierre N., Christodoulides, Nick J., Neikirk, Dean, Anslyn, Eric, Shear, Jason
• Primary Examiner(s): Yu, Melanie J
• Application Number:
  US11/020,443
• Publication Number:
  US 20060257992A1
• Time in Patent Office: 2,589 Days
• Field of Search: 422/68.1, 422/81, 422/82.01, 422 8205- 8209, 435/287.1, 435/287.2, 435/288.4, 435/288.7, 435/808, 436/501, 436/518, 436/524, 436/164, 436/523, 436/800, 436/805, 436/809, 356/38
• US Class Current: 436/809
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/251 : Colorimeters; Construction thereof
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

Abstract

Described herein is an analyte detection device and method related to a portable instrument suitable for point-of-care analyses. In some embodiments, a portable instrument may include a disposable cartridge, an optical detector, a sample collection device and/or sample reservoir, reagent delivery systems, fluid delivery systems, one or more channels, and/or waste reservoirs. Use of a portable instrument may reduce the hazard to an operator by reducing an operator'"'"'s contact with a sample for analysis. The device is capable of obtaining diagnostic information using cellular- and/or particle-based analyses and may be used in conjunction with membrane- and/or particle-based analysis cartridges. Analytes, including proteins and cells and/or microbes may be detected using the membrane and/or particle based analysis system.

Claims

1. A system for detecting analytes in a sample comprising:

(a) a cartridge, comprising a particle-based detection system and a membrane-based detection system, wherein;

(i) the particle detection system is configured to produce a signal, when in the presence of an analyte, from an individual particle positioned in an individual cavity at an individually addressable position in the particle detection system and the membrane detection system is configured for analysis of microbes or cells captured on a membrane,

(ii) an integrated waste reservoir that collects reagent and/or sample during use,

(iii) a trap coupled to a fluid delivery system and configured to at least partially remove air from the sample, thereby reducing air bubbles within the sample, and

(iv) a reagent delivery system disposed in or on the cartridge, the reagent delivery system comprising one or more reagents in a substantially sealed reservoir, and wherein the reagent delivery system is configured to deliver one or more reagents to the sample during use; and

(b) an optical platform, wherein the optical platform is configured to detect a signal produced by the interaction of the sample and/or analyte with the particle detection system or the membrane detection system during use.

2. The system of claim 1, wherein the reagent delivery system comprises a reagent capsule.

3. The system of claim 2, wherein the reagent capsule comprises one or more dried reagents.

4. The system of claim 2, wherein the reagent capsule comprises a reagent pad positioned in the reagent capsule.

5. The system of claim 1, wherein the reagent delivery system comprises one or more reagents dried in or on a reagent pad.

6. The system of claim 5, wherein the reagent delivery system further comprises a buffer, and wherein the reagent delivery system is configured such that the buffer flows through or over the reagent pad, and wherein flowing the buffer through or over the reagent pad at least partially reconstitutes at least one of the reagents in or on the reagent pad, and wherein the buffer and the at least partially reconstituted reagent is delivered to the sample.

7. The system of claim 1, wherein the reagent delivery system comprises a reagent pack comprising one or more reagents, wherein the reagent pack is a sealed reservoir configured to release at least one of the reagents upon application of pressure to the reagent pack.

8. The system of claim 7, wherein the reagent delivery system further comprises an actuator configured to apply pressure to the reagent pack.

9. The system of claim 1, further comprising:

a sample collection device in, on, or coupled to the cartridge, wherein the sample collection device is configured to receive and/or collect a sample; and

a fluid delivery system coupled to the sample collection device and the cartridge, wherein the fluid delivery system is configured to deliver a sample from the sample collection device to the cartridge during use.

10. The system of claim 1, wherein the membrane-based detection system comprises a membrane coupled to a body.

11. The system of claim 10, further comprising a membrane support in contact with the membrane, wherein the membrane support is configured to maintain the membrane in a substantially planar orientation during use.

12. The system of claim 10, further comprising a top member positioned above the membrane, wherein the top member comprises a fluid inlet configured to allow fluid to be introduced to the membrane by or through the top member.

13. The system of claim 10, further comprising a top member positioned above the membrane, wherein the top member comprises a wash fluid outlet configured to allow fluid to pass across the membrane and out of the membrane-based detection system during a washing operation.

14. The system of claim 10, further comprising a bottom member positioned below the membrane, wherein the bottom member comprises a fluid outlet configured to allow fluid to pass from the membrane and out of the membrane-based detection system.

15. The system of claim 1, wherein the particle-based detection system is configured to simultaneously detect a plurality of analytes in the fluid.

16. The system of claim 1, wherein the particle-based detection system further comprises a cover layer positioned over at least one of the cavities, wherein the cover layer is configured to inhibit dislodgment of at least one of the particles during use, and wherein the cover layer is positioned such that a channel is formed between an upper surface of the supporting member and the cover layer such that the fluid passes through the channel during use.

17. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin.

18. The system of claim 1, wherein a diameter of at least one of the particles ranges from about 0.05 microns to about 500 microns.

19. The system of claim 1, wherein at least one of the particles comprises a polymeric resin and a biopolymer coupled to the polymeric resin, and wherein the biopolymer undergoes a chemical reaction in the presence of the analyte to produce a signal.

20. The system of claim 1, wherein at least one of the particles is configured to entrap microbes.

21. The system of claim 1, wherein the particle-based detection system is coupled to the membrane-based detection system via one or more channels.

22. The system of claim 1, further comprising a cartridge positioning system coupled to the cartridge.

23. The system of claim 9, wherein the fluid delivery system delivers fluids to and/or from the cartridge.