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US 10,724,090 B2Granted
Integrated analytical system and method
AssigneePacific Biosciences of California, Inc.
InventorsNathaniel Joseph McCaffrey, Stephen Turner, Ravi Saxena, Scott Edward Helgesen
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Abstract
An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.
Claims18
A method for distinguishing fluorescently labeled species at a single molecule level comprising:
- providing pulsed illumination to an integrated chip, wherein the pulsed illumination comprises two or more pulses at different wavelengths and different times;
- the integrated chip comprising:
- a plurality of analytical devices, each analytical device having a reaction cell, an optical element, and a detection element;
- wherein the optical element is in optical communication with the reaction cell and the detection element;
- one or more integrated waveguides in optical communication with the reaction cells to deliver the pulsed illumination to the reaction cells;
- a fluidic region in fluidic contact with the reaction cells, the fluidic region comprising a sample comprising multiple types of fluorescently labeled species;
- whereby for each analytical device in the plurality of analytical devices, the pulsed illumination produces excitation events from the multiple types of fluorescently labeled species within the reaction cell, wherein an excitation event produces an emitted signal detected at the detection element;
- distinguishing between the multiple types of fluorescently labeled species within the sample by correlating the timing of the emitted signal detected at the detection element with the timing of the excitation event.
5 more elements
A method for distinguishing fluorescently labeled species at a single molecule level comprising:
- providing pulsed illumination to an integrated chip;
- the integrated chip comprising:
- a plurality of analytical devices, each analytical device having a reaction cell, an optical element, and a detection element;
- wherein the optical element is in optical communication with the reaction cell and the detection element;
- one or more integrated waveguides in optical communication with the reaction cells to deliver the pulsed illumination to the reaction cells;
- a fluidic region in fluidic contact with the reaction cells, the fluidic region comprising a sample comprising multiple types of fluorescently labeled species;
- whereby for each analytical device in the plurality of analytical devices, the pulsed illumination produces excitation events from the multiple types of fluorescently labeled species within the reaction cell, wherein an excitation event produces a signal at the detection element;
- and
- distinguishing between the multiple types of fluorescently labeled species within the sample by correlating the timing of the signal at the detection element with the timing of the excitation event;
- wherein each detection element comprises a plurality of storage elements;
- wherein the excitation events produce emitted photons, wherein the detection element:
- converts the photons into charges;
- relegates each respective charge into a storage element in the plurality of storage elements;
- and integrates the charges over time in each storage element in the plurality of storage elements to generate a plurality of electrical data signals.
11 more elements
A method for distinguishing fluorescently labeled species at a single molecule level comprising:
- providing pulsed illumination to an integrated chip;
- the integrated chip comprising:
- a plurality of analytical devices, each analytical device having a reaction cell, an optical element, and a detection element;
- wherein the optical element is in optical communication with the reaction cell and the detection element;
- one or more integrated waveguides in optical communication with the reaction cells to deliver the pulsed illumination to the reaction cells;
- a fluidic region in fluidic contact with the reaction cells, the fluidic region comprising a sample comprising multiple types of fluorescently labeled species;
- whereby for each analytical device in the plurality of analytical devices, the pulsed illumination produces excitation events from the multiple types of fluorescently labeled species within the reaction cell, wherein an excitation event produces a signal at the detection element;
- and
- distinguishing between the multiple types of fluorescently labeled species within the sample by correlating the timing of the signal at the detection element with the timing of the excitation event;
- wherein each detection element comprises a plurality of storage elements;
- wherein each respective storage element of the plurality of storage elements is turned off during intermediate stages of the illumination process to reduce noise contribution.
8 more elements
Dependencies are inferred from the claim text.