Signal detection techniques for the detection of analytes

• US 9,874,542 B2
• Filed: 10/14/2014
• Issued: 01/23/2018
• Est. Priority Date: 09/17/1998
• Status: Expired due to Fees

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Umek, Robert M., Blackburn, Gary, Irvine, Bruce D., Terbrueggen, Robert, Yu, Changjun, Vielmetter, Jost G.
• Primary Examiner(s): Lu, Frank
• Application Number:
  US14/513,616
• Publication Number:
  US 20150126391A1
• Time in Patent Office: 1,197 Days
• Field of Search: 435 61, 435 611, 435 911, 435183, 4352831, 4352871, 4352872, 436 94, 436501, 536 231, 536 243, 536 2433, 422 50, 422 681
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 27/416 Systems G01N27/27 takes precedence
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The invention relates to the use of signal processing methods in order to achieve higher signal to noise ratios, to increase the detection limits of target analytes. These techniques include the monitoring of the output signal at higher harmonic frequencies.

Claims

1. A method of detecting a target nucleic acid in a sample on a biochip, said method comprising:

a) providing a biochip comprising detection electrodes;

b) contacting the detection electrodes of said biochip with said sample in the presence of a label probe specifically hybridizable to said target nucleic acid under conditions permitting hybridization of said label probe to said target nucleic acid, said label probe comprising a covalently attached electrochemical detection label comprising a ferrocene derivative;

c) performing a wash step to remove non-specific binding of said label probe to said biochip;

d) applying an input electric signal to said biochip;

e) detecting an output electric signal from said biochip, compared with an output electric signal obtained from said method which is performed when the target is not present, the presence of higher amplitudes of harmonic peaks from said output signal at different higher harmonic frequencies indicates the presence of said target nucleic acid in the sample.

2. The method according to claim 1, wherein said detecting said output electric signal is done using voltammetry.

3. A method of detecting a plurality of target nucleic acids in a sample on a biochip, said method comprising:

a) providing a biochip comprising at least one detection electrode;

b) contacting the at least one detection electrode of said biochip with said sample in the presence of a plurality of label probes specifically hybridizable to said plurality of target nucleic acids under conditions permitting hybridization of said plurality of label probes to said plurality of target nucleic acids, each of said label probes comprising a covalently attached electrochemical detection label comprising one of a plurality of ferrocene derivatives, wherein each of said label probes is specifically hybridizable to a different target nucleic acid of said plurality of target nucleic acids and comprises one of the ferrocene derivatives with a distinguishable redox property which is different from another of the ferrocene derivatives of said plurality of ferrocene derivatives;

c) performing a wash step to remove non-specific bindings of said plurality of label probes to said biochip;

d) applying input electric signals to said biochip;

e) detecting output electric signals from said plurality of ferrocene derivatives biochip, compared with an output electric signal obtained from said method which is performed when the target is not present, the presence of higher amplitudes of harmonic peaks from two or more of said output signals at different higher harmonic frequencies indicates the presence of said plurality of target nucleic acids in the sample.

4. The method according to claim 3, wherein said detecting of the output electric signals is performed using voltammetry.