Life Technologies Corporation

Jonathan M Schultz

Todd Roswech

Jonathan Marc Rothberg

Todd Rearick

Kim L Johnson

David Marran

James M Bustillo

John Harris Leamon

John R Nobile

Mark James Milgrew

Wolfgang Hinz

Brian Reed

James A Ball

Prasanna Krishnan Thwar

Earl A Hubbell

John F Davidson

Jon A Hoshizaki

Albert L Carrillo

Chris Papalias

Kristopher Barbee

Chun Kiat Ho

Sean McCusker

Ryan Jones

Maximilian Carpino

John Andrew Sheridan

Chun Heen Ho

Melville Davey

Antoine Van Oijen

George Roth

Andrew Sheridan

Bradley Hann

Thomas Roth

A fluidic interconnect includes a first interface including a liquid port, a gas port, and a cradle; a second interface including a liquid port, a gas port, and a swing bar to engage the cradle, a weight of a container attached to one of the first or second interfaces to drive the liquid port of the first interface into connection with the liquid port of the second interface and the gas port of the first interface into connection with the gas port of the second interface.

Fluid interface to receive removable container

The invention is directed to apparatus and methods for delivering multiple reagents to, and monitoring, a plurality of analytical reactions carried out on a large-scale array of electronic sensors under minimal noise conditions. In one aspect, the invention provides method of improving signal-to-noise ratios of output signals from the electronic sensors sensing analytes or reaction byproducts by subtracting an average of output signals measured from neighboring sensors where analyte or reaction byproducts are absent. In other aspects, the invention provides an array of electronic sensors integrated with a microwell array for confining analytes and/or particles for analytical reactions and a method for identifying microwells containing analytes and/or particles by passing a sensor-active reagent over the array and correlating sensor response times to the presence or absence of analytes or particles. Such detection of analyte- or particle-containing microwells may be used as a step in additional noise reduction methods.

Apparatus and methods for performing electrochemical reactions

Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.

Methods and apparatus for measuring analytes using large scale FET arrays

An apparatus for preparing a reagent solution includes an enclosure and a container disposed within the enclosure. The container defines an internal cavity having a compressible volume and defines a passage providing fluidic communication between the internal cavity and the exterior of the container. Optionally, a compressible member is disposed within the internal cavity. A reagent is disposed within the internal cavity.

Reagent mixer and fluid control devices

A system for nucleic acid sequencing includes a machine-readable memory and a processor configured to execute machine-readable instructions. The instructions, when executed by the processor, cause the system to expose template polynucleotide strands in a plurality of defined spaces of a sensor array to a series of flows of nucleotide species, the series comprising a sequence of random flows; and obtain, for each of the series of flows of nucleotide species, a signal indicative of how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands.

Phase-protecting reagent flow orderings for use in sequencing-by-synthesis

Mathematical models for the analysis of signal data generated by sequencing of a polynucleotide strand using a pH-based method of detecting nucleotide incorporation(s). In an embodiment, the measured output signal from the reaction confinement region of a reactor array is mathematically modeled. The output signal may be modeled as a linear combination of one or more signal components, including a background signal component. This model is solved to determine the nucleotide incorporation signal. In another embodiment, the incorporation signal from the reaction confinement region of a reactor array is mathematically modeled.

Fluidic chemFET polynucleotide sequencing systems with confinement regions and hydrogen ion rate and ratio parameters

An apparatus comprising a chemical field effect transistor array in a circuit-supporting substrate is disclosed. The transistor array has disposed on its surface an array of sample-retaining regions capable of retaining a chemical or biological sample from a sample fluid. The transistor array has a pitch of 10 &#x3bc;m or less and a sample-retaining region is positioned on at least one chemical field effect transistor which is configured to generate at least one output signal related to a characteristic of a chemical or biological sample in such sample-retaining region.

Integrated sensor arrays for biological and chemical analysis

A buffered suspension includes a surfactant and a solid buffer particulate having a point of zero charge at least 1.2 pH units different that the pH of the buffered suspension. The buffered suspension can be prepared by mixing a stock solution with the solid buffer particulate and titrating. A method of preforming a pH sensitive process includes drawing the buffered suspension from a reservoir, filtering the solid buffer particulate from the buffered suspension, and applying the filtered solution to a sensor.

System and method incorporating solid buffer

The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion.

Fluidics system for sequential delivery of reagents

In one implementation, a method is described. The method includes determining an operational characteristic of sensors of a sensor array. The method further includes selecting a group of sensors in the array based on the operational characteristic of sensors in the group. The method further includes enabling readout of the sensors in the selected group. The method further includes receiving output signals from the enabled sensors.

Windowed sequencing

A method of preparing reagents includes inserting a cartridge into an instrument. The cartridge includes a plurality of reagent enclosures disposed in a cavity of the cartridge and exposing a port to an exterior of the cartridge. Each reagent enclosure includes a reagent container including a reagent and an internal cavity defining a compressible volume, an opening defined through the reagent container to the internal cavity. The method further includes connecting a plurality of fluid ports to the openings of the plurality of reagent enclosures; applying a solution through the fluid ports to at least partially fill the plurality of reagent enclosures; and cycling a pressure of the cavity, whereby for each of the reagent enclosures, during increasing pressure, the solution enters the internal cavity of the reagent container, combines with the reagent, and compresses the compressible volume, and during decreasing pressure, the compressible volume decreases and the reagent is ejected through the opening.

Sequencing device

A sample preparation apparatus includes a robotic system providing movement in three orthogonal directions to an arm operable to receive a pipette tip and to facilitate movement of fluid into and out of the pipette tip. Optionally, the robot can include a gripper arm in addition to the pipette receiving arm. In addition, the sample preparation apparatus can include a tray for receiving pipette tips, receptacles for receiving tubes, an apparatus for forming an emulsion, a device for forming particles that include copies of the polynucleotide, a device for enriching the particles, as well as a centrifuge for loading such particles onto a sensor array. The sample preparation apparatus can further include receptacles for holding containers of reagent solutions.

Growing community of inventors

Oxford, MA, United States of America

Jonathan M Schultz