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Apparatus and method for the analysis of nucleic acids hydbridization on high density NA chips

a nucleic acid hybridization and nucleic acid technology, applied in biochemistry apparatus and processes, specific use bioreactors/fermenters, after-treatment of biomass, etc., can solve the problems of short shelf life of common labels and the safety hazards of radioactive compounds, and achieve the effect of improving spectral sensitivity

Inactive Publication Date: 2005-03-10
POPONIN VLADIMIR
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

"The present invention provides a novel method and apparatus for detecting molecular hybridization using near-field optics and SERS techniques. This approach offers improved spectral sensitivity and allows for faster and more accurate detection of nucleic acid hybridization without the need for labeling. The invention also provides a method for detecting hybridized DNA by analyzing the unique spectrum of low-frequency vibrations in each hybridization member. The apparatus includes a near-field SERS substrate, a coherent radiation source, a photonic collector, a Raman spectrograph, and a spectral to electronic converter. The invention has various applications, including high throughput screening of DNA without PCR amplification and detecting hybridized DNA on high-density nucleic acid chips."

Problems solved by technology

A variety of disadvantages are associated with the use of radioactive labels, including the short shelf life of common labels and the safety hazards associated with the use of radioactive compounds.

Method used

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  • Apparatus and method for the analysis of nucleic acids hydbridization on high density NA chips
  • Apparatus and method for the analysis of nucleic acids hydbridization on high density NA chips
  • Apparatus and method for the analysis of nucleic acids hydbridization on high density NA chips

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third embodiment

[0039] In a third embodiment, random array technology may be used in combination with a fiber optic sensor (e.g., a sensor arrangement of the type disclosed in U.S. Pat. Nos. 5,244,636 and 5,244,813). In this embodiment, ultimate spatial resolution is 5 microns per pixel, enabling the speed at which the chip can be read to be reduced to microseconds.

[0040] Optical IR fiber employed in the practice of the present invention may be single-mode fiber or a multi-mode fiber bundle. Multi-mode fiber bundles, which commonly have up to 2000 fibers in one bundle, may be used in multichannel recording.

[0041] A fiber coupler may be used to transfer illuminating and scattered optical signals into large aperture beams and vice versa. A splitter can be used to send reflected light through wide-field or confocal optics into the Raman spectrograph.

[0042] The preferred source of illuminating radiation is an argon ion laser, although other suitable radiation sources may be usefully employed in the g...

first embodiment

[0044] Where the SNOM is employed (first embodiment above), a signal from the piezo scanning device 30 is transferred to the control electronics system.

[0045] The spectral range of Raman spectra used in the near field SERS molecular hybridization detection system of the present invention is preferably in the range of about 0 to about 1700 sm−1 with the preferred spectral interval ranging from about 0 to about 300 sm−1. It is anticipated that the best results will be in a spectral interval which ranges from 10 to about 150 sm−1.

[0046] The present invention also provides a method for detecting hybridization of molecules using the near field SERS technology of the present invention. The method is enabled by the fundamental property that single stranded and double stranded fragments of nucleic acids have different characteristic frequencies in Raman spectra. In fact, each complimentary fragment of DNA from a set of double stranded DNA fragments has an intrinsic low frequency vibrationa...

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Abstract

The invention generally relates to a new gene probe biosensor employing near field surface enhanced Raman scattering (NFSERS) for direct spectroscopic detection of hybridized molecules (such as hybridized DNA) without the need for labels, and the invention also relates to methods for using the biosensor.

Description

1. FIELD OF THE INVENTION 1.1 BRIEF DESCRIPTION OF THE INVENTION [0001] The invention disclosed herein relates to a new gene probe biosensor employing near field surface enhanced Raman scattering (NFSERS) for direct spectroscopic detection of DNA hybridization without the need for labels, and the invention also relates to methods for using the biosensor. 1.2 BACKGROUND OF THE INVENTION [0002] In 1928, C. V. Raman and his collaborator, K. S. Krishnan, established that the spectrum of inelastically scattered light can provide a unique fingerprint of molecular structure. Since this initial discovery, Raman spectroscopy has advanced dramatically. Many Raman-related analytical instruments have been developed, some of which have applicability to proteins and nucleic acids. Recent developments have enabled the use of Raman spectroscopy to obtain information such as conformation and / or orientation of molecules and some molecular groups, local hydrogen bonding interactions, and time dependen...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68
CPCC12Q1/6825C12Q2565/632
Inventor POPONIN, VLADIMIR
Owner POPONIN VLADIMIR
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