INTEGRATED DEVICES TO FACILITATE QUANTITATIVE ASSAYS AND DIAGNOSTICS

• US 20140001058A1
• Filed: 03/09/2012
• Published: 01/02/2014
• Est. Priority Date: 03/11/2011
• Status: Active Grant

• Current Assignee: Medidata Solutions Incorporated (Dassault Systemes SA)
• Original Assignee: MC10, Inc.
• Inventors: Ghaffari, Roozbeh, Lee, Stephen P., De Graff, Bassel
• Granted Patent: US 9,702,839 B2
• Time in Patent Office: Days
• US Class Current: 205/792
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: G01N 21/66 electrically excited, e.g. electroluminescence
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 27/02 by investigating impedance
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements

Abstract

Devices are described for providing quantitative information relating to a sample. Example devices include a flexible substrate, a sample receiver at least partially formed in or disposed on the flexible substrate, electronic circuitry and at least one indicator electrically coupled to the electronic circuitry. The flexible substrate includes at least one paper-based portion, at least one elastomeric portion, or at least one plastic portion. The electronic circuitry and the at least one indicator are at least partially formed in or disposed on the flexible substrate. The electronic circuitry generates an analysis result based on an output signal from the sample or a derivative of the sample. The at least one indicator provides an indication of the quantitative information relating to the sample based at least in part on the at least one analysis result.

Claims

1. A device to conduct an assay of an analyte in a biological sample and provide quantitative information relating to the biological sample, the device comprising:

a flexible substrate, wherein the flexible substrate comprises at least one paper-based portion, at least one elastomeric portion, or at least one plastic portion;

a container at least partially formed in or disposed on the flexible substrate to retain the biological sample;

a reagent disposed in the container to react with the biological sample, wherein an output optical signal comprising at least a color change or an electrochemical change is generated representing a degree to which the reagent reacts with the biological sample, when the biological sample is present;

electronic circuitry coupled to the flexible substrate to analyze the output signal and generate at least one analysis result, the electronic circuitry comprising;

at least one light source to illuminate the reagent and the biological sample, when present, to measure the color change or the electrochemical change and provide an output optical signal representing the color change or the electrochemical change; and

at least one photodetector to detect the output optical signal and generate an output electrical signal representing the color change,

wherein the at least one analysis result is based on the output electrical signal; and

at least one indicator coupled to the flexible substrate, and electrically coupled to the electronic circuitry, to provide an indication of the quantitative information relating to the biological sample based at least in part on the at least one analysis result.

2. The device of claim 1, further comprising a sample receiver at least partially formed in or disposed on the flexible substrate to receive the biological sample, wherein the sample receiver is coupled to the container.

3. The device of claim 2, further comprising a channel disposed between the sample receiver and the container to transfer the biological sample from the sample receiver to the container.

4. The device of claim 3, wherein the flexible substrate comprises at least one paper based portion, wherein the channel is formed at least partially in or disposed on the at least one paper-based portion of the flexible substrate, and wherein the at least one paper-based portion that forms the channel is configured to wick the biological sample from the sample receiver to the container by capillary action.

5. The device of claim 1, wherein the output electrical signal represents a value indicative of the quantitative information, the device further comprising:

a plurality of references coupled to the flexible substrate, the plurality of references having respective different reference values,

wherein the electronic circuitry includes at least one comparator to compare the value with the plurality of reference values so as to generate the quantitative information.

6. The device of claim 5, wherein the at least one indicator comprises a plurality of indicator light emitting diodes (LEDs), coupled to the at least one comparator, to display the indication of the quantitative information.

7. The device of claim 5, wherein the plurality of references each comprise a reference color, and wherein the electronic circuitry further comprises:

a plurality of reference light sources each to generate a reference optical signal based on the reference color; and

a plurality of reference photodetectors each to convert the reference optical signal into a reference electrical signal, wherein each respective different reference value is based on the respective reference electrical signal.

8. The device of claim 1, further comprising a power supply formed over the flexible substrate.

9. The device of claim 8, wherein the power supply comprises at least one of:

a primary battery;

a thin film battery;

a thermoelectric battery;

a solar cell; and

a radio frequency (RF) inductive coupler.

10. The device of claim 1, wherein the quantitative information comprises at least one of:

a glucose level;

a T-cell concentration;

a microorganism concentration;

a water-based pathogen concentration;

a bovine serum albumin (BVA) concentration;

a bacterial concentration;

a viral load;

an antigen level;

an antibody level;

a diagnosis of tuberculosis;

a diagnosis of dengue fever;

a cardiac enzyme concentration; and

a diagnosis of malaria.

11. A device for providing quantitative information relating to a sample, the device comprising:

a substrate comprising at least one paper-based portion;

a sample receiver to receive the sample, wherein the sample receiver is at least partially formed in or disposed on the at least one paper-based portion;

electronic circuitry at least partially formed in or disposed on the substrate, wherein the electronic circuitry generates at least one analysis result based on an output signal from the sample or a derivative of the sample; and

at least one indicator at least partially formed in or disposed on the substrate, and electrically coupled to the electronic circuitry, wherein the at least one indicator provides an indication of the quantitative information relating to the sample based at least in part on the at least one analysis result.

12. The device of claim 11, wherein the electronic circuitry analyzes the output signal from the sample or the derivative of the sample, and wherein the electronic circuitry generates the at least one analysis result based on the analysis of the output signal.

13. The device of claim 11, further comprising a container at least partially formed in or disposed on the substrate, wherein the container is coupled to the sample receiver to retain the sample or the derivative of the sample.

14. The device of claim 13, further comprising a channel disposed between the sample receiver and the container, and formed at least partially in or disposed on at least one paper-based portion, to transfer the sample or the derivative of the sample from the sample receiver to the container.

15. The device of claim 14, wherein the channel is formed in at least one paper-based portion of the substrate, and wherein at least one paper-based portion is configured to wick the sample or the derivative of the sample from the sample receiver to the container by capillary action.

16. The device of claim 13, further comprising a reagent disposed in the container to react with the sample or the derivative of the sample, when either is present, wherein the output signal comprises a reaction output of the reagent and the sample or the derivative of the sample.

17. The device of claim 16, wherein the substrate further comprises a water resistant material,

wherein a fluidic channel is formed between at least one paper-based portion and the water resistant material to transfer the sample or the derivative of the sample to the container to react with the reagent.

18. The device of claim 17, wherein the water resistant material comprises (poly)dimethylsiloxane.

19. The device of claim 13, further comprising a reagent disposed in the container to react with the sample or the derivative of the sample, when either is present, wherein the output signal represents a degree to which the reagent reacts with the sample or the derivative of the sample, and wherein the output signal comprises at least one of:

an optical signal representing the degree to which the reagent reacts with the sample or the derivative of the sample;

an electrochemical signal representing the degree to which the reagent reacts with the sample or the derivative of the sample;

an electrical signal representing the degree to which the reagent reacts with the sample or the derivative of the sample; and

an acoustic signal representing the degree to which the reagent reacts with the sample or the derivative of the sample.

20. The device of claim 19, wherein the optical signal is a color change, wherein the electrical signal is an impedance change, and wherein the acoustic signal is a pressure change.

21. The device of claim 20, wherein the output signal comprises an electrical signal, wherein the electrical signal is an impedance change representing the degree to which the reagent reacts with the sample or the derivative of the sample, and wherein the electrical circuitry comprises at least one pair of electrodes to generate the electrical signal representing the impedance change.

22. The device of claim 21, wherein the sample comprises blood, and wherein:

the device is configured to filter plasma from the blood;

the reagent comprises a glucose oxidase to react with glucose in the plasma to form gluconic acid; and

the electrical signal provides an indication of a concentration of glucose in the plasma.

23. The device of claim 11, wherein the quantitative information comprises at least one of:

a glucose level;

a T-cell concentration;

a microorganism concentration;

a water-based pathogen concentration;

a bovine serum albumin (BVA) concentration;

a bacterial concentration;

a viral load;

an antigen level;

an antibody level;

a diagnosis of tuberculosis;

a diagnosis of dengue fever;

a cardiac enzyme concentration; and

a diagnosis of malaria.

24. In a device comprising a paper-based substrate, at least one light source coupled to the paper-based substrate, at least one photodetector coupled to the paper-based substrate, and at least one indicator coupled to the paper-based substrate, a method for conducting an assay of an analyte in a biological sample so as to provide quantitative information relating to the biological sample, the method comprising:

applying the biological sample to the paper-based substrate, the paper-based substrate having a reagent disposed thereon to react with the biological sample, wherein an output signal including at least a color change is generated representing a degree to which the reagent reacts with the biological sample;

illuminating the reagent and the sample using the at least one light source to measure the color change and provide an optical signal representing the color change;

detecting the optical signal using the at least one photodetector and generating an output electrical signal representing the color change, and

providing the quantitative information relating to the sample, via the at least one indicator, based at least in part on the output electrical signal.