Reducing optical interference in a fluidic device

• US 8,008,034 B2
• Filed: 03/13/2007
• Issued: 08/30/2011
• Est. Priority Date: 10/13/2006
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Gibbons, Ian, O'Connell, Michael
• Primary Examiner(s): YANG, NELSON C
• Application Number:
  US11/685,615
• Publication Number:
  US 20100291609A1
• Time in Patent Office: 1,631 Days
• Field of Search: None
• US Class Current: 435/7.91
• 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 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: G01N 33/5304 Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/536 with immune complex formed in liquid phase
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: Y10T 156/10 Methods of surface bonding and/or assembly therefor

Abstract

This invention is in the field of medical devices. Specifically, the present invention provides portable medical devices that allow real-time detection of analytes from a biological fluid. The methods and devices are particularly useful for providing point-of-care testing for a variety of medical applications. In particular, the medical device reduces interference with an optical signal which is indicative of the presence of an analyte in a bodily sample.

Claims

1. A method of detecting an analyte in a sample, comprising:

(a) allowing a sample suspected to contain the analyte to react with at least one reactant contained in a fluidic device, said device comprising;

(i) an assay assembly configured to yield an optical signal that is indicative of the presence of the analyte, said assay assembly comprising;

(1) a reagent chamber comprising at least one reagent used in said assay; and

(2) at least one reaction site comprising a reactant that binds said analyte,

wherein said assay assembly is adapted to yield an optical signal indicative of the presence of the analyte in the sample, and

wherein the at least one reagent reacts with a second reagent in said assay assembly to produce the optical signal; and

(ii) a quencher assembly in fluidic communication with but in a separate location from said assay assembly, wherein said quencher assembly comprises a quenching agent that inhibits an enzymatic reaction between the at least one reagent and the second reagent in said quencher assembly to reduce signals that interfere with the optical signals detected from said assay assembly; and

(b) channeling unreacted reactants to said quencher assembly where interfering signals from said unreacted reactants are quenched with said quenching agent; and

(c) detecting said optical signal thereby detecting the analyte in the sample.

2. The method of claim 1, wherein said at least one reagent comprises an enzyme conjugate or an enzyme substrate.

3. The method of claim 1, wherein said quenching agent is contained in a quenching site of the quencher assembly.

4. The method of claim 3, wherein said quencher assembly further comprises an absorbent material.

5. The method of claim 4, wherein said absorbent material is impregnated with said quenching agent.

6. The method of claim 4, wherein said absorbent material is selected from the group consisting of glass fiber, silica, paper, polyacylamide gel, agarose, and agar.

7. The method of claim 4, wherein said quenching agent is a denaturing agent.

8. The method of claim 7, wherein said quenching agent is 4-amino-1,11-azobenzene-3,41-disulfonic acid.

9. The method of claim 1, wherein said assay assembly is adapted to run a chemiluminescent assay.

10. The method of claim 1, wherein said quencher assembly is adapted to substantially eliminate optical interference from unreacted reagent.

11. The method of claim 3, further comprising a waste chamber, wherein said waste chamber comprises said quenching site.

12. The method of claim 1, wherein said sample of bodily fluid is blood.

13. The method of claim 1, wherein the optical signal is a luminescent signal.

14. The method of claim 13, wherein the luminescent signal is a chemiluminescent signal.

15. A method of detecting an analyte in a sample, comprising:

(a) allowing a sample suspected to contain the analyte to react with at least one reactant contained in a fluidic device, said device comprising;

(i) an assay assembly comprising at least one reaction site, said reaction site comprising a surface and immobilized thereon a reactant that forms a complex comprising the analyte;

(ii) a first reagent chamber comprising an enzyme conjugate;

(iii) a second reagent chamber comprising an enzyme substrate, wherein the enzyme substrate reacts with the enzyme conjugate to produce a chemiluminescent signal;

(iv) fluidic channels that connect the reagent chambers with the at least one reaction site;

(v) a quencher assembly at a separate location from the assay assembly, the quencher assembly comprising an absorbent material and a quenching agent, wherein the quenching agent inhibits the chemiluminescent reaction between the enzyme conjugate and the enzyme substrate to reduce signals that interfere with the chemiluminescent signal detected from said assay assembly; and

(vi) a plurality of fluidic channels that connect the sample collection unit and the quencher assembly with the assay assembly

(b) channeling unreacted reactants to said quencher assembly where interfering signals from said unreacted reactants are quenched with said quenching agent;

(c) detecting said chemiluminescent signal thereby detecting the analyte in the sample.

16. The method of claim 15, wherein said quencher assembly further comprises a waste chamber connected through a fluid channel with the assay assembly, wherein the waste chamber comprises the absorbent material.

17. The method of claim 15, wherein said absorbent material is selected from the group consisting of glass fiber, silica, paper, polyacylamide gel, agarose, or agar.

18. The method of claim 17, wherein said quenching agent is 4-amino-1,11-azobenzene-3,41-disulfonic acid and said enzyme conjugate is an alkaline phosphatase-labeled reagent.

19. The method of claim 15, wherein said assay assembly is adapted to run an immunoassay.