Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
1999-09-17
2004-05-25
Whisenant, Ethan (Department: 1634)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S006120, C435S007100, C435S091100, C435S287100
Reexamination Certificate
active
06740518
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the use of signal processing methods in order to acheive 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.
BACKGROUND OF THE INVENTION
There are a number of assays and sensors for the detection of the presence and/or concentration of specific substances in fluids and gases. Many of these rely on specific ligand/antiligand reactions as the mechanism of detection. That is, pairs of substances (i.e. the binding pairs or ligand/antiligands) are known to bind to each other, while binding little or not at all to other substances. This has been the focus of a number of techniques that utilize these binding pairs for the detection of the complexes. These generally are done by labelling one component of the complex in some way, so as to make the entire complex detectable, using, for example, radioisotopes, fluorescent and other optically active molecules, enzymes, etc.
Other assays rely on electronic signals for detection. Of particular interest are biosensors. At least two types of biosensors are known; enzyme-based or metabolic biosensors and binding or bioaffinity sensors. See for example U.S. Pat. Nos. 4,713,347; 5,192,507; 4,920,047; 3,873,267; and references disclosed therein. While some of these known sensors use alternating current (AC) techniques, these techniques are generally limited to the detection of differences in bulk (or dielectric) impedance.
Similarly, electronic detection of nucleic acids using electrodes is also known; see for example U.S. Pat. Nos. 5,591,578; 5,824,473; 5,705,348; 5,780,234 and 5,770,369; U.S. Ser. Nos. 08/873,598 08/911,589; and WO 98/20162; PCT/US98/12430; PCT/US98/12082; PCT/US99/10104; PCT/US99/01705, and PCT/US99/01703.
In the area of electrochemical sensing, there are a number of electrochemical techniques that have been employed. Traditionally, electrochemical methods generally improve their signal to noise ratios by discriminating the faradaic signal form the background components in the time domain through the application of pulsed waveforms, i.e. differnetail pulse polarography and square wave voltammetry. Pulse methods are able to discriminate the faradaic current from the changing current in the time domain. Changing currents decay much more rapidly than faradaic current, i.e. exponentially as compared the inverse square root. Similarly, modulation techniques have also be used to improve signal to noise ratios; these methods utilize the imposition of a modulated carrier wave (sine wave) on the signal.
The frequency domain has only bene used in a few electrochemical techniques to enhance the signal to noise ratio. In AC voltammetry, a potential ramp is applied to the electrode, and a small amplitude sine wave is superimposed on the linear ramp. However, the use of large amplitude sinosoidal voltammetry in conjunction with the detection at higher harmonic frequencies using Fourier transforms has proven to be a useful method. See U.S. Pat. No. 5,650,061; Singhai et al., Anal. Chem. 69:1552 (1997); Singhal and Kuhr, Anal. Chem. 69:4828 (1997); Singhal et al., Anal. Chem. 69:3553 (1997); and Dontha et al., Anal. Chem. 69:2619 (1997), all of which are expressly incorporated by reference herein.
However, further methods are still needed to exploit signal processing advantages in detecting biomolecules such as target analytes.
Accordingly, it is an object of the invention to provide novel methods and compositions for the detection analytes using AC techniques. These techniques find particular use in array formats, and for the detection of biomolecules such as nucleic acids and proteins.
SUMMARY OF THE INVENTION
In accordance with the objects outlined above, the present invention provides compositions and methods useful in detecting target analytes in a sample. The methods comprise providing an array comprising a plurality of electrodes, at least one of which comprises an assay complex. The assay complex comprises a capture binding ligand covalently attached to the electrode, a target analyte, and an electron transfer moiety. At least a first input signal is applied to the assay complex and an output signal is received. The output signal is then processed to detect the presence of said target analytes. Preferred embodiments utilize a plurality of assay complexes each attached to a different cell or pad of the array.
REFERENCES:
patent: 4704193 (1987-11-01), Bowers et al.
patent: 4707352 (1987-11-01), Stavrianopoulos
patent: 4707440 (1987-11-01), Stavrianopoulos
patent: 4711955 (1987-12-01), Ward et al.
patent: 4755458 (1988-07-01), Rabbani et al.
patent: 4787963 (1988-11-01), MacConnell
patent: 4840893 (1989-06-01), Hill et al.
patent: 4849513 (1989-07-01), Smith et al.
patent: 4868103 (1989-09-01), Stavrianopoulos et al.
patent: 4882013 (1989-11-01), Turner et al.
patent: 4894325 (1990-01-01), Englehardt et al.
patent: 4943523 (1990-07-01), Stavrianopoulos
patent: 4945045 (1990-07-01), Forrest et al.
patent: 4952685 (1990-08-01), Stavrianopoulos
patent: 4964972 (1990-10-01), Sagiv et al.
patent: 4994373 (1991-02-01), Stavrianopoulos
patent: 5002885 (1991-03-01), Stavrianopoulos
patent: 5013831 (1991-05-01), Stavrianopoulos
patent: 5066372 (1991-11-01), Weetall
patent: 5082830 (1992-01-01), Brakel et al.
patent: 5089112 (1992-02-01), Skotheim et al.
patent: 5175269 (1992-12-01), Stavrianopoulos
patent: 5180968 (1993-01-01), Bruckenstein et al.
patent: 5241060 (1993-08-01), Englehardt et al.
patent: 5242828 (1993-09-01), Bergstrom et al.
patent: 5278043 (1994-01-01), Bannwarth et al.
patent: 5312527 (1994-05-01), Mikkelsen et al.
patent: 5328824 (1994-07-01), Ward et al.
patent: 5356786 (1994-10-01), Heller et al.
patent: 5391272 (1995-02-01), O'Daly et al.
patent: 5403451 (1995-04-01), Riviello et al.
patent: 5436161 (1995-07-01), Bergstrom et al.
patent: 5443701 (1995-08-01), Willner et al.
patent: 5449767 (1995-09-01), Ward et al.
patent: 5472881 (1995-12-01), Beebe et al.
patent: 5476928 (1995-12-01), Ward et al.
patent: 5552270 (1996-09-01), Khrapko et al.
patent: 5565552 (1996-10-01), Magda et al.
patent: 5571568 (1996-11-01), Ribi et al.
patent: 5573906 (1996-11-01), Bannwarth et al.
patent: 5591578 (1997-01-01), Meade et al.
patent: 5595908 (1997-01-01), Fawcett et al.
patent: 5601982 (1997-02-01), Sargent et al.
patent: 5620850 (1997-04-01), Bamdad et al.
patent: 5622821 (1997-04-01), Selvin et al.
patent: 5632957 (1997-05-01), Heller et al.
patent: 5650061 (1997-07-01), Kuhr et al.
patent: 5700667 (1997-12-01), Marble et al.
patent: 5705346 (1998-01-01), Okamoto et al.
patent: 5705348 (1998-01-01), Meade et al.
patent: 5741700 (1998-04-01), Ershov et al.
patent: 5756050 (1998-05-01), Ershov et al.
patent: 5770369 (1998-06-01), Meade et al.
patent: 5770721 (1998-06-01), Ershov et al.
patent: 5776672 (1998-07-01), Hashimoto et al.
patent: 5780234 (1998-07-01), Meade et al.
patent: 5795453 (1998-08-01), Gilmartin
patent: 5824473 (1998-10-01), Meade et al.
patent: 5837859 (1998-11-01), Teoule et al.
patent: 5849486 (1998-12-01), Heller et al.
patent: 5851772 (1998-12-01), Mirzabekov et al.
patent: 5874046 (1999-02-01), Megerle
patent: 5952172 (1999-09-01), Meade et al.
patent: 5976802 (1999-11-01), Ansorge et al.
patent: 6013459 (2000-01-01), Meade
patent: 6060023 (2000-05-01), Maracas
patent: 6060327 (2000-05-01), Keen
patent: 6071699 (2000-06-01), Meade et al.
patent: 6087100 (2000-07-01), Meade et al.
patent: 6090933 (2000-07-01), Kayyem et al.
patent: 6096273 (2000-08-01), Kayyem et al.
patent: 6096825 (2000-08-01), Garnier et al.
patent: 6107080 (2000-08-01), Lennox
patent: 6153737 (2000-11-01), Manoharan et al.
patent: 6177250 (2001-01-01), Meade et al.
patent: 6180352 (2001-01-01), Meade et al.
patent: 6197515 (2001-03-01), Bamdad et al.
patent: 6200761 (2001-03-01), Meade et al.
patent: 6203758 (2001-03-01), Marks et al.
patent: 6207369 (2001-03-01), Wohlstadter et al.
patent: 6221583 (2001-04-01), Kayyem et al.
patent: 6232062 (2001-05-01), Kayyem et
Duong Hau H.
Gonzalez Javier
Kayyem Jon Faiz
Litvack Daniel A.
O'Connor Stephen D.
Clinical Micro Sensors, Inc.
Dorsey & Whitney LLP
Kosslak Renee M.
Lu Frank
Silva Robin M.
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