Methods for electronic fluorescent perturbation for analysis and electronic perturbation catalysis for synthesis

• US 20040086917A1
• Filed: 07/18/2003
• Published: 05/06/2004
• Est. Priority Date: 09/27/1995
• Status: Abandoned Application

• Current Assignee: Nanogen, Inc.
• Original Assignee: Nanogen, Inc.
• Inventors: OʼConnell, James P., Tu, Eugene, Heller, Michael J., Sosnowski, Ronald G.
• Application Number:
  US10/623,080
• Publication Number:
  US 20040086917A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2563/103 luminescence
• CPC Class Codes: C12Q 2565/101 Interaction between at least two labels
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 comprising bio-molecules
• CPC Class Codes: G11C 13/04 using optical elements ; using other beam accessed elements, e.g. electron or ion beam
• CPC Class Codes: H01L 25/50 Multistep manufacturing processes of assemblies consisting of devices, each device being of a type provided for in group H01L27/00 or H01L29/00 H01L21/50 takes precedence
• CPC Class Codes: H01L 2924/00 Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/0002 : Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
• CPC Class Codes: H01L 2924/01005 : Boron [B]

Abstract

Methods for electronic perturbation of fluorescence, chemilluminescence and other emissive materials provide for molecular biological analysis. In a preferred method for hybridization analysis of a sample, an electronic stringency control device is used to perform the steps of: forming a double-stranded hybridization product comprising a sample nucleic acid and a probe of known sequence, wherein the sequences of the sample nucleic acid and probe either are the same or differ by one nucleotide, an environmentally sensitive emissive fluorescent label being associated with the hybridization product in proximity to the nucleic acid to be identified, wherein either the sample nucleic acid or the probe is attached the electronic stringency device, subjecting the double-stranded hybridization product to a varying electrophoretic force, monitoring the fluorescence from the double-stranded hybridization product while varying the electrophoretic force over time, and analyzing the fluorescent signal to identify the nucleic acid of the sample.

Claims

1. A method for identifying a nucleic acid with an electronic stringency device, comprising the steps of:

forming a double-stranded hybridization product comprising a sample nucleic acid and a probe of known sequence, wherein the sequences of the sample nucleic acid and probe either are the same or differ by one nucleotide, an environmentally sensitive emissive fluorescent label being associated with the hybridization product in proximity to the nucleic acid to be identified, wherein either the sample nucleic acid or the probe is attached the electronic stringency device,

subjecting the double-stranded hybridization product to a varying electrophoretic force,

monitoring the fluorescence from the double-stranded hybridization product while varying the electrophoretic force over time, and

analyzing the fluorescent signal to identify the nucleic acid of the sample.

2. The method of claim 1, wherein the environmentally sensitive emissive label is selected from the group consisting of environmentally sensitive dyes, fluorophores and chromophores.

3. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to hydrophilicity.

4. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to hydrophobicity.

5. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to pH.

6. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to electrostatic charge.

7. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to Van der Waals interactions.

8. The method of claim 1, wherein the environmentally sensitive emissive dye is sensitive to DNA sequence variability.

10. The method of claim 1, wherein the varying electrophoretic force is a pulsed sequence.

9. A method for analyzing a nucleic acid sequence, utilizing an electronic stringency control device, comprising the steps of:

providing the nucleic acid sequence, a probe of known sequence, and a label in proximity to the nucleic acid to be identified on the electronic stringency control device to form a labeled double-stranded hybridization product, the nucleic acid sequence having a net charge of a first sign, the label having a net charge of a sign opposite to the first sign,

subjecting the double-stranded hybridization product to an electrophoretic force,

monitoring the emission from the double-stranded hybridization product while varying the electrophoretic force over time, and

analyzing the emission to determine the sequence of the sample nucleic acid.