Method and apparatus for analysis and sorting of polynucleotides based on size
AssigneeCalifornia Institute of Technology
InventorsStephen Quake, Wayne D. Volkmuth
Life of this patent
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Abstract
The invention relates to a microfabricated device and methods of using the device for analyzing and sorting of single polynucleotides, e.g. by size, according to an optical signal measured within a detection region of the device. An optical signal such as fluorescence from a reporter molecule associated with the polynucleotide molecules can be used to determine polynucleotide size or to direct selected polynucleotides into one or more selected branch channels of the device.
Claims46
A device for processing a flow of polynucleotide molecules comprising a chip having a substrate and an analysis unit, wherein the analysis unit comprises:
- a) a main channel having a polynucleotide sample inlet, a detection region downstream of the sample inlet, and a branch point discrimination region adjacent to and downstream of the detection region, wherein on average one polynucleotide molecule at a time is placed within the detection region;
- (b) at least two branch channels originating at the branch point discrimination region and in communication with the main channel;
- (c) a detector sensitive to each polynucleotide molecule passing through the detection region;
- and
- (d) a flow control responsive to the detector and acting to direct each polynucleotide molecules at the discrimination region into a selected branch channel.
A device for processing a flow of polynucleotide molecules comprising a chip having a substrate and an analysis unit, wherein the analysis unit comprises:
- (a) a main channel having a polynucleotide sample inlet, a detection region downstream of the sample inlet, and a branch point discrimination region adjacent to and downstream of the detection region, wherein on average one polynucleotide molecule at a time is placed within the detection region;
- (b) at least two branch channels originating at the branch point discrimination region and in communication with the main channel;
- (c) a detector sensitive to each polynucleotide molecule passing through the detection region;
- and
- (d) a flow control responsive to the detector and comprising a pair of electrodes that apply an electric field across the discrimination region and into a branch channel.
A device for processing a flow of polynucleotide molecules comprising a chip having a substrate and an analysis unit, wherein the analysis unit comprises:
- (a) a main channel having a polynucleotide sample inlet, a detection region downstream of the sample inlet, and a branch point discrimination region adjacent to and downstream of the detection region, wherein on average one polynucleotide molecule at a time is placed within the detection region;
- (b) at least two branch channels originating at the branch point discrimination region and in communication with the main channel;
- (c) a detector sensitive to each polynucleotide molecule passing through the detection region;
- and
- (d) a flow control responsive to the detector and comprising a pressure differential, wherein the flow of polynucleotide molecules is directed by adjusting the pressure at the outlet of each branch channel to allow or curtail flow through the channel.
A device for processing a flow of polynucleotide molecules comprising a chip having a substrate and an analysis unit, wherein the analysis unit comprises:
- (a) a main channel having a polynucleotide sample inlet, a detection region downstream of the sample inlet, and an outlet region adjacent to and downstream of the detection region;
- (b) a detector sensitive to each polynucleotide passing through the detection region, wherein on average one polynucleotide molecule at a time is placed within the detection region.
Dependencies are inferred from the claim text.