Smart glass slide for microarrays

• US 9,810,688 B2
• Filed: 03/15/2013
• Issued: 11/07/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Robert Bosch GmbH
• Original Assignee: Robert Bosch GmbH
• Inventors: Fomina, Nadezda, Johnson, Christopher, Kavusi, Sam, Ahmad, Habib
• Primary Examiner(s): Bunker, Amy M
• Application Number:
  US13/834,126
• Publication Number:
  US 20140274760A1
• Time in Patent Office: 1,698 Days
• Field of Search: 506 9
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

Device for use in a biosensor comprising a multisite array of test sites, the device being useful for modulating the binding interactions between a (biomolecular) probe or detection agent and an analyte of interest from a biological by modulating the pH or ionic gradient near the electrodes in such biosensor. The device provides a biosensor which is more accurate, reliable and the results of which are more reproducible. Analytic methods for more accurately measuring an analyte of interest in a biological sample are also provided.

Claims

1. A device for use in a biosensor, the device comprising a multisite array of test sites, the multisite array of test sites including:

(1) a support substrate, wherein the support substrate is glass or plastic; and

(2) a biomolecular interface layer that includes;

(i) a layer of immobilized polyethylene glycol (PEG) that covers the support substrate;

(ii) a plurality of Green Fluorescent Protein spots that are immobilized by attachment directly to the layer of immobilized PEG; and

(iii) a plurality of immobilized probes immobilized by attachment directly to the layer of immobilized PEG, wherein the plurality of immobilized probes are selected from the group consisting of a protein, a peptide, an antibody, an antigen, a nucleic acid, and a cell;

wherein;

(a) each test site of the multisite array of test sites comprises;

(i) a single Green Fluorescent Protein spot of the plurality of Green Fluorescent Protein spots;

(ii) at least one working electrode that includes one or more counter-electrodes;

(iii) a first area of the support substrate that supports, and is covered by, the at least one working electrode, wherein the device is configured to repeatedly modulate a pH of the first area of the support substrate with the at least one working electrode; and

(iv) a second area of the support substrate;

(b) the biomolecular interface layer is arranged such that, with respect to each test site of the multisite array of test sites;

(i) a first portion of the single Green Fluorescent Protein spot covers the at least one working electrode that covers the first area of the support substrate; and

(ii) a second portion of the single Green Fluorescent Protein spot covers the second area of the support substrate without any working electrodes arranged between the second area of the support substrate and the second portion of the single Green Fluorescent Protein spot that covers the second area of the support substrate; and

(c) independently with respect to each test site of the multisite array of test sites;

(i) the device is configured to repeatedly perform the following;

(1) determine the pH level in the first area of the support substrate by detection of a fluorescence intensity of the first portion of the single Green Fluorescent Protein spot covering the at least one working electrode; and

(2) determine the pH level in the second area of the support substrate by detection of a fluorescence intensity of the second portion of the single Green Fluorescent Protein spot covering the second area of the support substrate; and

(ii) the pH level determined for the second area of the support substrate is a control by which the device is configured to determine when the pH level determined for the first area of the support substrate has reverted to a base level.

2. The device according to claim 1, wherein the at least one working electrode and the one or more counter-electrodes are selected from the group consisting of an indium tin oxide electrode, a gold electrode, a platinum electrode, a silver electrode, and a carbon electrode.

3. The device according to claim 2, wherein the at least one working electrode is an indium oxide electrode and the one or more counter-electrodes are selected from the group consisting of an indium tin oxide electrode, a gold electrode, a platinum electrode, a silver electrode, and a carbon electrode.

4. The device according to claim 1, further comprising an aqueous solution with which the support substrate is in contact.

5. The device according to claim 4, wherein the aqueous solution comprises a diluted phosphate buffer and wherein the pH of the aqueous solution is between pH=5 to pH=8.

6. The device according to claim 4, wherein the aqueous solution comprises electrolytes selected from the group consisting of sodium sulfate, sodium or potassium chloride, sodium or potassium bromide, sodium or potassium iodide, sodium or potassium perchlorate, sodium or potassium nitrate, tetraalkylammonium bromide, tetraalkylammonium iodide, and combinations thereof.

7. The device according to claim 4, wherein the aqueous solution comprises at least one soluble polymer selected from the group consisting of poly(allylamine hydrochloride), poly (diallyldimethyl ammonium chloride), poly(vinylpyrrolidone), poly(ethyleneimine), poly(vinylamine), poly(4-vinylpyridine), and tris(2-carboxyethyl)phosphine hydrochloride.

8. The device according to claim 4, wherein the aqueous solution comprises a water-miscible organic co-solvent selected from the group consisting of acetonitrile, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N,N-dimethyl acetamide (DMAc), and mixtures thereof.

9. The device according to claim 4, wherein the aqueous solution comprises an electrochemically active agent selected from the group consisting of dopamine hydrochloride, ascorbic acid, phenol, benzoquinones, naphthoquinones, and 9,10-anthraquinone.

10. The device according to claim 1, wherein the at least one working electrode and the one or more counter-electrodes are connected to an electronic board via pogo-pins.

11. The device according to claim 10, wherein the electronic board is powered by a power source selected from the group consisting of a printed battery, a small battery bound to the substrate, a magnetically coupled power transfer using coils on the substrate, and a radiofrequency (rf)-coupled power transfer using coils on the substrate.

12. The device according to claim 1, wherein the biosensor comprises a complementary metal-oxide-semiconductor (CMOS).

13. The device according to claim 1, wherein the at least one working electrode and the one or more counter-electrodes are connected to a chip on foil via z-axis adhesive or to a chip on the substrate.

14. The device according to claim 1, wherein the biosensor comprises a thin-film transistor (TFT) based system.

15. The device according to claim 13, wherein the chip is powered by a power source selected from the group consisting of a printed battery, a small battery bound to the substrate, a magnetically coupled power transfer using coils on the substrate, and a radiofrequency (rf)-coupled power transfer using coils on the substrate.