INTEGRATED OPTOELECTRONIC READ HEAD AND FLUIDIC CARTRIDGE USEFUL FOR NUCLEIC ACID SEQUENCING
First Claim
1. A detection apparatus, comprising(a) a carriage comprising a plurality of microfluorometers,wherein each of the microfluorometers comprises an objective configured for wide-field image detection,wherein the plurality of microfluorometers is positioned to simultaneously acquire a plurality of the wide-field images in a common plane, andwherein each of the wide-field images is from a different area of the common plane;
- (b) a translation stage configured to move the carriage in at least one direction parallel to the common plane; and
(c) a sample stage configured to hold a substrate in the common plane.
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Abstract
A detection apparatus having a read head including a plurality of microfluorometers positioned to simultaneously acquire a plurality of the wide-field images in a common plane; and (b) a translation stage configured to move the read head along a substrate that is in the common plane. The substrate can be a flow cell that is included in a cartridge, the cartridge also including a housing for (i) a sample reservoir; (ii) a fluidic line between the sample reservoir and the flow cell; (iii) several reagent reservoirs in fluid communication with the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the flow cell; and (v) at least one pressure source configured to move liquids from the reservoirs to the flow cell. The detection apparatus and cartridge can be used together or independent of each other.
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Citations
27 Claims
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1. A detection apparatus, comprising
(a) a carriage comprising a plurality of microfluorometers, wherein each of the microfluorometers comprises an objective configured for wide-field image detection, wherein the plurality of microfluorometers is positioned to simultaneously acquire a plurality of the wide-field images in a common plane, and wherein each of the wide-field images is from a different area of the common plane; -
(b) a translation stage configured to move the carriage in at least one direction parallel to the common plane; and (c) a sample stage configured to hold a substrate in the common plane. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A method of imaging a substrate, comprising
(a) providing a substrate comprising fluorescent features on a surface; -
(b) acquiring a plurality of wide-field images of a first portion of the surface using a plurality of microfluorometers, wherein each of the microfluorometers acquires a wide-field image from a different location of the surface, wherein the plurality of microfluorometers are affixed to a carriage; and (c) translating the carriage in a direction parallel to the surface and repeating (b) for a second portion of the surface. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A fluidics cartridge, comprising
a flow cell comprising an optically transparent surface, an inlet and an outlet; - and
a housing comprising a material that is optically opaque and impermeable to aqueous liquids, wherein the housing holds; (i) a sample reservoir; (ii) a fluidic line between the sample reservoir and the inlet of the flow cell; (iii) a plurality of reagent reservoirs in fluid communication with the flow cell via the inlet of the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the inlet of the flow cell; and (v) at least one pressure source configured to move liquids from the sample reservoir or the reagent reservoirs to the flow cell via the inlet of the flow cell, wherein an optically transparent window interrupts the housing and an inlet port interrupts the housing, wherein the inlet port is in fluid communication with the sample reservoir, and wherein the optically transparent surface is positioned in the window.
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27. Method of sequencing nucleic acids, comprising
(a) providing a fluidic cartridge comprising (i) a flow cell comprising an optically transparent surface, (ii) a nucleic acid sample, (iii) a plurality of reagents for a sequencing reaction, and (iv) a fluidic system for delivering the reagents to the flow cell; -
(b) providing a detection apparatus comprising (i) a plurality of microfluorometers, wherein each of the microfluorometers comprises an objective configured for wide-field image detection in an image plane in x and y dimensions, and (ii) a sample stage; (c) delivering the fluidic cartridge to the sample stage, wherein the optically transparent surface is placed in the image plane, and (d) carrying out fluidic operations of a nucleic acid sequencing procedure in the cartridge and detection operations of the nucleic acid sequencing procedure in the detection apparatus, wherein (i) the reagents are delivered to the flow cell by the fluidic system, and (ii) wide-field images of the nucleic acid features are detected by the plurality of microfluorometers.
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Specification