Abstract:
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 μm 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.
Abstract:
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.
Abstract:
A sequencing system includes an automated sequencing instrument adapted to determine variant calls for one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls for 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases.
Abstract:
The invention is directed to apparatus and chips comprising a large scale chemical field effect transistor arrays that include an array of sample-retaining regions capable of retaining a chemical or biological sample from a sample fluid for analysis. In one aspect such transistor arrays have a pitch of 10 μm or less and each 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. In one embodiment, the characteristic of said chemical or biological sample is a concentration of a charged species and wherein each of said chemical field effect transistors is an ion-sensitive field effect transistor having a floating gate with a dielectric layer on a surface thereof, the dielectric layer contacting said sample fluid and being capable of accumulating charge in proportion to a concentration of the charged species in said sample fluid. In one embodiment such charged species is a hydrogen ion such that the sensors measure changes in pH of the sample fluid in or adjacent to the sample-retaining region thereof. Apparatus and chips of the invention may be adapted for large scale pH-based DNA sequencing and other bioscience and biomedical applications.
Abstract:
A method of sensing nucleotide reactions includes flowing at least one nucleotide solution from a container of at least two containers of a sensor system. The sensor system includes a sensor sensitive to a byproduct of nucleotide incorporation. Each container of the at least two containers includes a different nucleotide solution. The sensor system enters an idle mode after flowing. The method further includes cycling the at least two containers through at least two cycles. Each cycle includes depressurizing the at least two containers for a first period and pressurizing the at least two containers for a second period. The method also includes pressurizing the at least two containers when the sensor system enters an active mode.
Abstract:
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 μm 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.
Abstract:
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. The invention is particularly advantageous in apparatus for performing sensitive multistep reactions, such as pH-based DNA sequencing reactions.