Multiplexed electrochemical detection system and method

• US 7,341,834 B2
• Filed: 12/13/2004
• Issued: 03/11/2008
• Est. Priority Date: 12/15/2003
• Status: Active Grant

• Current Assignee: Geneohm Sciences Incorporated (Becton, Dickinson & Co)
• Original Assignee: Geneohm Sciences Incorporated (Becton, Dickinson & Co)
• Inventors: Yang, Xing
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US11/011,490
• Publication Number:
  US 20050196776A1
• Time in Patent Office: 1,184 Days
• Field of Search: None
• US Class Current: 435/6.12
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48

Abstract

Multiplexed analysis of molecular structures of samples. A plurality of sample wells is arranged on a substrate. A plurality of electrodes is fabricated on a first side of the substrate. The electrodes are disposed on the side of the substrate exposed to the sample wells. The electrodes include working electrodes, counter electrodes, and optionally include reference electrodes. At least two of the sample wells includes a plurality of working electrodes. The plurality of electrodes is configured to allow electrochemical analysis of the associated sample wells in a multiplexed fashion. The plurality of electrodes is electrically coupled to an interface to a sample analysis system. The interface to the sample analysis system can include contacts or connections. The sample analysis system controls a signal to the electrodes in a multiplexed fashion and performs the electrochemical analysis.

Claims

1. An electrochemical detection system comprising:

a connection interface configured to electrically connect with contact pads of a sample array, the sample array comprising a plurality of zones each comprising a plurality of working electrodes, wherein at least one polymer probe is attached to each of the working electrodes and each zone is associated with a single counter electrode;

a multiplexer coupled to the connection interface and configured to selectively apply an electric potential to one of the plurality of electrodes in each of the zones by applying the electric potential to a single electrical connection in the connection interface, wherein the single electrical connection in the connection interface couples an electrode in each of the zones to the electric potential, the multiplexer being further configured to selectively apply an opposing electric potential to a selected counter electrode positioned proximate a selected zone in the sample array via the connection interface so that a current flows between only the one of the plurality of electrodes in the selected zone and the counter electrode; and

an analyzer configured to electrochemically detect at least one property of a sample in the selected zone based in part on the current.

2. The system of claim 1, wherein a second connection on the connection interface is electrically coupled to the counter electrode in the sample array.

3. The system of claim 1, wherein the analyzer is configured to detect hybridization of the sample.

4. The system of claim 1, wherein the analyzer is configured to detect the property based on coulometry.

5. The system of claim 1, wherein the analyzer is configured to detect the property based on amperometry.

6. The system of claim 1, further comprising a fluid dispenser configured to deliver a reagent to at least one well in the sample array.

7. A sample array for an electrochemical detection system, the sample array comprising:

a first sample well;

a second sample well;

a substrate bonded to the first and second sample wells;

a first electrode set comprising a plurality of working electrodes each coupled to at least one polymer probe, the first electrode set being positioned on the substrate in the first sample well; and

a second electrode set comprising a plurality of working electrodes each coupled to at least one polymer probe, the second electrode set being positioned in the second sample well, wherein at least one of the plurality of working electrodes positioned in the second sample well is electrically coupled to a corresponding working electrode in the first sample well via only an electrical connection of the sample array.

8. The sample array of claim 7, further comprising a plurality of polymer probes coupled to the working electrodes in the first electrode set.

9. A sample array for an electrochemical detection system, the sample array comprising:

a plurality of sample wells;

a substrate bonded to the plurality of sample wells;

a plurality of working electrodes positioned on a first side of the substrate, with at least two working electrodes positioned in each of the plurality of sample wells; and

at least one multiplexer selectively coupling contact pads positioned on the substrate to the plurality of working electrodes, wherein a single contact pad of the substrate is coupled to a single working electrode of each sample well such that an electric potential applied to a particular contact pad will be applied to a single working electrode in each sample well, and wherein the sample array comprises a single structure configured for coupling with a sample analyzer.

10. The sample array of claim 9, further comprising a plurality of counter electrodes positioned on the first side of the substrate, with at least one counter electrode positioned in each of the plurality of sample wells.

11. A method of detecting hybridization, the method comprising:

introducing a sample to a plurality of sample wells, each sample well comprising (1) a plurality of probes each coupled to one of a plurality of working electrodes and (2) a counter electrode;

applying a first potential to a first contact pad that is electrically coupled to a single working electrode in each of at least two different sample wells;

applying a second potential to a second contact pad that is electrically coupled to only one counter electrode; and

electrochemically detecting hybridization of the sample to at least one of the plurality of probes.

12. A sample array comprising:

at least a first well and a second well;

a substrate bonded to each of the first and second wells;

a plurality of working electrodes positioned on the substrate such that at least two working electrodes are positioned in each of the wells, wherein each working electrode in the first well is electrically coupled with a corresponding working electrode in the second well; and

at least one multiplexer selectively coupling a first electrical potential to at least one corresponding working electrode in each of the first and second wells via a single electrical lead from the multiplexer, the at least one multiplexer further coupling a second electrical potential to a counter electrode associated with each of the working electrodes of the first well.

13. The sample array of claim 12, further comprising a third well comprising at least two working electrodes positioned in the third well, wherein each of the working electrodes in the first well is electrically c6upled with a corresponding working electrode in the second well and a corresponding working electrode in the third well.

14. The sample array of claim 12, wherein the first electrical potential is coupled to each of the plurality of working electrodes.

15. The sample array of claim 12, wherein the first electrical potential is coupled to only one corresponding working electrode in each of the first and second wells.

16. A method of electrochemical analysis comprising:

depositing at least one sample into a plurality of sample wells, each sample well comprising (1) a counter electrode, and (2) a plurality of probes each coupled to at least one of a plurality of working electrodes;

applying a first potential to each of the plurality of working electrodes in each of the plurality of sample wells;

applying a second potential to a first counter electrode associated with a first of the plurality of sample wells; and

electrochemically detecting hybridization of the sample in the first well to at least one of the plurality of probes.

17. The method of claim 16, wherein each working electrode in a first of the plurality of wells is electrically coupled to a corresponding working electrode in each of the remaining plurality of wells.

18. The method of claim 16, further comprising:

electrically isolating the second potential from the first counter electrode;

applying the second potential to a second counter electrode associated with a second of the plurality of sample wells; and

electrochemically detecting hybridization of the sample in the second well to at least one of the plurality of probes.

19. The method of claim 18, further comprising:

electrically isolating the second potential from the second counter electrode;

applying the second potential to a third counter electrode associated with a third of the plurality of sample wells; and

electrochemically detecting hybridization of the sample in the third well to at least one of the plurality of probes.