Life Technologies Corporation

Melville Davey

Simon Cawley

Todd Rearick

Alan J Williams

Mark Beauchemin

Marcin Sikora

Michael Meyer

Kirk Pastorian

Jonathan Marc Rothberg

Wolfgang Hinz

John R Nobile

Jonathan M Schultz

John Harris Leamon

David Marran

William Julian Mileski

John F Davidson

Christian Koller

Antoine Van Oijen

George Roth

Bradley Hann

David Kulp

Alan Williams

A method for nucleic acid sequencing includes receiving a plurality of signals indicative of a parameter measured for a plurality of defined spaces, at least some of the defined spaces including one or more sample nucleic acids, the signals being responsive to a plurality of nucleotide flows introducing nucleotides to the defined spaces; determining, for at least some of the defined spaces, whether the defined space includes a sample nucleic acid; processing, for at least some of the defined spaces determined to include a sample nucleic acid, the received signals to improve a quality of the received signals; and predicting a plurality of nucleotide sequences corresponding to respective sample nucleic acids for the defined spaces based on the processed signals and the nucleotide flows.

Methods, systems, and computer readable media for nucleic acid sequencing

A method, computer program product, and system are provided to calibrate a sensor array with a plurality of sensors. The method can include sweeping a voltage of a reference electrode from a first voltage to a second voltage, where the reference electrode is in fluid communication with the sensor array. The output voltage of each of the plurality of sensors can be monitored at one or more voltages within the first and second voltages. An overall average gain of the plurality of sensors can be calculated at each of the one or more voltages. Further, an acquisition window for the sensor array can be determined. The acquisition window can include a maximum distribution of sensors that provides a maximal overall average gain at a particular reference electrode voltage.

Methods and apparatus for measuring analytes

A method for nucleic acid sequencing includes receiving a plurality of observed or measured signals indicative of a parameter observed or measured for a plurality of defined spaces; determining, for at least some of the defined spaces, whether the defined space comprises one or more sample nucleic acids; processing, for at least some of the defined spaces, the observed or measured signal to improve a quality of the observed or measured signal; generating, for at least some of the defined spaces, a set of candidate sequences of bases for the defined space using one or more metrics adapted to associate a score or penalty to the candidate sequences of bases; and selecting the candidate sequence leading to a highest score or a lowest penalty as corresponding to the correct sequence for the one or more sample nucleic acids in the defined space.

Methods, systems, and computer readable media for making base calls in nucleic acid sequencing

A method of estimating a parameter related to sequencing of a sample nucleic acid template includes: receiving signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto an array of wells including (i) a first well containing the sample nucleic acid template and (ii) a plurality of other sample-containing wells; determining sequence information for the sample nucleic acid template using signal data from the first well; and constructing a phase-state model for a set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter that is determined using signal data from the plurality of other sample-containing wells.

Methods and apparatuses for estimating parameters in a predictive model for use in sequencing-by-synthesis

A method, computer program product, and system are provided to calibrate a sensor array with a plurality of sensors. The method can include sweeping a voltage of a reference electrode from a first voltage to a second voltage, where the reference electrode is in fluid communication with the sensor array. The output voltage of each of the plurality of sensors can be monitored at one or more voltages within the first and second voltages. An overall average gain of the plurality of sensors can be calculated at each of the one or more voltages. Further, an acquisition window for the sensor may can be determined. The acquisition window can include a maximum distribution of sensors that provides a maximal overall average gain at a particular reference electrode voltage.

The invention provides apparatuses and methods of use thereof for sequencing nucleic acids subjected to a force, and thus considered under tension. The methods may employ but are not dependent upon incorporation of extrinsically detectably labeled nucleotides.

Methods for sequencing individual nucleic acids under tension

A method of obtaining a more accurate estimate of a signal correction parameter(s) in sequencing-by-synthesis operations, such as incomplete extension rates, carry forward rates, and/or signal droop rates. The sequencing operation produces signal data. A model is constructed to simulate a population of template strands as it undergoes the sequencing process and becomes divided into different phase-states as the sequencing-by-synthesis progresses. For example, the model may be a phase-state model. The output from the model is used to adjust the signal correction parameter(s). For example, the model may be fitted to the signal data. This fitting results in a more accurate estimate of the signal correction parameter(s). In another embodiment, the signal droop rate is modeled as a decaying function and this decaying function is fitted to the signal data to obtain an improved estimate of the signal droop rate.

Predictive model for use in sequencing-by-synthesis

A system including a communication interface to communicatively couple to a sensor cartridge, a fluidic subsystem to exchange a reagent solution with the sensor cartridge, and a computational circuitry communicatively coupled to the communication interface and the fluidic subsystem. The computation circuitry is to monitor a sensor signal of a sensor of the sensor cartridge, detect a leak based on the sensor signal, and control fluid flow of the fluidic subsystem in response to detecting.

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Westbrook, CT, United States of America

Melville Davey