Biological analysis arrangement and approach therefor
First Claim
1. A method for determining a DNA sequence comprising:
- delivering a dNTP to a substrate comprising;
(i) an integrated circuit chip integrated withan array of optical sensors and circuitry for both analog and digital signal processing; and
an array of microwells, each microwell including a test site with a primed DNA template;
whereby the incorporation of a dNTP into the primed DNA template results in the release of pyrophosphate (PPi), and each microwell optically coupled to at least one optical sensor of the array of optical sensors and;
enzymatically generating light from the released PPi;
detecting the light at the array of optical sensors and producing analog signals representing the detected light; and
processing, for each optical sensor, the analog signals using the circuitry for analog and digital signal processing to determine the amount of dNTP incorporated at each test site.
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Abstract
Characteristics of a chemical or biological sample are detected using an approach involving light detection. According to an example embodiment of the present invention, an assaying arrangement including a light detector is adapted to detect light from a sample, such as a biological material. A signal corresponding to the detected light is used to characterize the sample, for example, by detecting a light-related property thereof. In one implementation, the assaying arrangement includes integrated circuitry having a light detector and a programmable processor, with the light detector generating a signal corresponding to the light and sending the signal to the processor. The processor provides an output corresponding to the signal and indicative of a characteristic of the sample.
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Citations
34 Claims
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1. A method for determining a DNA sequence comprising:
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delivering a dNTP to a substrate comprising; (i) an integrated circuit chip integrated with an array of optical sensors and circuitry for both analog and digital signal processing; and an array of microwells, each microwell including a test site with a primed DNA template;
whereby the incorporation of a dNTP into the primed DNA template results in the release of pyrophosphate (PPi), and each microwell optically coupled to at least one optical sensor of the array of optical sensors and;enzymatically generating light from the released PPi; detecting the light at the array of optical sensors and producing analog signals representing the detected light; and processing, for each optical sensor, the analog signals using the circuitry for analog and digital signal processing to determine the amount of dNTP incorporated at each test site. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method for determining a DNA sequence comprising:
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providing a substrate that includes a chip integrated with an array of sensors, a digital processing circuit, and an array of wells integral with the chip; associating multiple nucleic acids of different sequences with the substrate such that multiple wells of the array of wells are each associated with a respective nucleic acid, wherein a nucleic acid in at least one well is of a different type of nucleic acid with respect to a type of nucleic acid in at least one other well; delivering at least one nucleotide to the substrate such that incorporation of the at least one nucleotide into a strand complementary to a nucleic acid in a well of the array of wells, results in the release of pyrophosphate; generating signals based on the release of pyrophosphate; and detecting the signals to determine the incorporation of the at least one nucleotide at multiple individual wells of the array of wells. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A method for determining nucleic acid sequences comprising:
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receiving a substrate at a sequencing system, the substrate including a chip integrated with an array of sensors, a processing circuit configured to process signals from one or more sensor elements of the array of sensors, and an array of wells integral with the chip, the chip comprising a complementary metal-oxide-semiconductor (CMOS) circuit, and the chip comprising wells for sequencing that do not include a lens for light detection; receiving at the sequencing system a reagent container separate from the substrate, the reagent container configured to contain nucleotides for use in sequencing; associating multiple nucleic acids of different sequences with the substrate such that multiple wells of the array of wells are associated with a nucleic acid to be sequenced; delivering at least one nucleotide from the reagent container to the substrate such that incorporation of the at least one nucleotide into a strand complementary to the nucleic acid to be sequenced in a well of the array of wells results in an extended sequence complementary to the nucleic acid in that well; generating signals based on the incorporation of the at least one nucleotide into the strand complementary to the nucleic acid at multiple individual wells of the array of wells; and detecting the signals to determine the incorporation of the at least one nucleotide at multiple individual wells of the array of wells; wherein delivering the at least one nucleotide comprises delivering, for multiple rounds, nucleotides that can be used to provide information to identify at least one base in the nucleic acid to be sequenced different than a base identifiable from information based on nucleotides delivered in an immediately previous round of delivering nucleotides; wherein generating signals based on the incorporation comprises generating signals for each of the multiple rounds; and
wherein detecting the signals comprises detecting the signals for the multiple rounds. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34)
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Specification