Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2001-08-24
2003-09-30
Wang, Andrew (Department: 1639)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S287100, C435S288200, C435S288400, C436S165000, C204S450000
Reexamination Certificate
active
06627433
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to electrophoretic separation systems for the analysis of bio-molecules, such as nucleic acids. More particularly, this invention relates to a multi-channel analyte-separation device employing side-entry illumination.
REFERENCES
Backhouse et al., DNA sequencing in a monolithic microchannel device, Electrophoresis 2000, 21, 150-156.
Dolnik et al., Capillary electrophoresis on microchip, Electrophoresis 2000, 21, 41-54.
Grossman and Colburn, Capillary Electrophoresis Theory and Practice, Chapter 1, Academic Press (1992).
Kambara et al., U.S. Pat. No. 5,192,142 (1993).
Madabhushi et al., U.S. Pat. No. 5,552,028 (1996).
Sambrook et al., eds., Molecular Cloning: A Laboratory Manual, Second Edition, Chapter 5, Cold Spring Harbor Laboratory Press (1989).
Woolley et al., Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips, Proc. Natl. Acad. Sci., vol. 91, pp. 11348-11352, November 1994, Biophysics.
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BACKGROUND OF THE INVENTION
Devices for carrying out separations of analytes, such as biomolecules (e.g., proteins, DNA, RNA, etc.), have gained widespread use in recent years.
In electrophoretic separations, it is often desirable to illuminate a plurality of migrating analytes, tagged with excitable reporters (e.g., fluorescent dyes), to stimulate detectable emission indicative of the nature (e.g., identity or composition) of the tagged analytes.
SUMMARY OF THE INVENTION
Various aspects of the present invention provide a multi-channel analyte-separation device (channel device) comprising a substrate defining an array of channels. According to various embodiments, adjacent channels of the device are separated by wall structure, which includes at least a portion that is substantially transparent. The transparent portions are disposed along a path or line crossing (e.g., co-planar and normal to) the longitudinal axes of the channels. An excitation-beam source (e.g., a laser) is adapted to direct an excitation beam of light along the path, such that the beam can simultaneously pass through each of the transparent portions and each of the channels. Plural samples migrating along the various channels, e.g., by electrophoresis, can thus be simultaneously irradiated and detected.
Various embodiments are particularly adapted to bio-molecule (e.g., DNA, RNA, PNA, etc.) sequence or other analysis methods, in which each of a plurality of different fragment types is labeled with a spectrally distinctive fluorescent dye. According to certain embodiments, a side-entry laser arrangement at a detection zone of a multi-channel electrophoresis device excites the dyes, while in the channels, to emit light. In various embodiments, emitted light from samples in the channels passes through a laser light filter, through a collection lens, through a transmission dispersion element, which spectrally separates the light, and through a focusing lens. The focused light can be incident on a detector array (e.g., CCD) capable of detecting the simultaneously spatially focused and spectrally diverged light from the detection regions of all the channels. Electronic signals from the detector array can provide information about the character or sequence of the DNA sample.
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Frazier Jeffery D.
Grossman Paul D.
Applera Corporation
Frazier Jeffery D.
Kilyk & Bowersox P.L.L.C.
Tran My Chau T
Wang Andrew
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