Abstract:
Various cell analysis systems of the present teachings can measure the electrical and metabolic activity of single, living cells with subcellular addressability and simultaneous data acquisition for between about 10 cells to about 500,000 cells in a single analysis. Various sensor array devices of the present teachings can have sensor arrays with between 20 million to 660 million ChemFET sensors built into a massively paralleled array and can provide for simultaneous measurement of cells with data acquisition rates in the kilohertz (kHz) range. As various ChemFET sensor arrays of the present teachings can detect chemical analytes as well detect changes in cell membrane potential, various cell analysis systems of the present teachings also provide for the controlled chemical and electrical interrogation of cells.
Abstract:
A manifestation of fluid potential noise is a periodic profile characterized by a periodic saw-tooth spike in a graph of average voltage across all columns of a sensor array as a function of time. This periodic profile is indicative of an adverse impact on the function of active sensor pixels that are proximal to reference pixels in sensor devices that include a large array of chemically-sensitive field effect transistor (ChemFET) sensors. Systems, devices, and methods are described that can mitigate the impact of reference pixels on fluid potential noise.
Abstract:
A method for correcting nucleotide incorporation signals for fluid potential effects or disturbances arising in nucleic acid sequencing-by-synthesis includes: disposing a plurality of template polynucleotide strands in a plurality of defined spaces disposed on a sensor array, the template polynucleotide strands having a sequencing primer and a polymerase bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed through a fluid manifold, the fluid manifold comprising passages for flowing nucleotide species and a branch passage for flowing a solution, the branch passage comprising a reference electrode and a sensing electrode; obtaining a plurality of nucleotide incorporation signals corresponding to the plurality of defined spaces, the nucleotide incorporation signals having a signal intensity related to a number of nucleotide incorporations; and correcting at least some of the plurality of nucleotide incorporation signals for fluid potential effects or disturbances.
Abstract:
Provided herein is a sensor comprising a substrate having a first reaction region and a second reaction region, a first electrode associated with the first reaction region, a second electrode associated with the second reaction region and a third electrode wherein the third electrode is common to both the first reaction region and the second reaction region.
Abstract:
Systems, devices and methods for cell analysis provide an end user with real-time cell analysis and imaging of single cells in a population. Various cell analysis systems can provide both optical imaging, as well as electroscopic imaging, which is an image of cellular response as detected by sensors covering a cell footprint or cellular efflux. An automated fluidic system can provide an end-user selected sequence of reagents to cells, while precision controlled sensor array device thermostatting, and analysis compartment environmental control provide consistency in the cell analysis system environment.
Abstract:
Analyzing cells disposed on a sensor array surface of a ChemFET sensor array, may include flowing a solution having a step change in pH across the sensor array surface, wherein ChemFET sensors of the sensor array generate signals in response to the step change in pH to produce electroscopic image data. Multiple frames of the electroscopic image data are acquired during an acquisition time interval. Each frame corresponds to signal samples generated by the sensor array measured at a sampling time during the acquisition time interval. Each frame comprises pixels, wherein a given pixel in the frame corresponds to a signal sample from a given sensor in the sensor array. The electroscopic image data is segmented, based on characteristics of the signal samples, into cell regions corresponding to locations of the cells on the sensor array surface and background regions corresponding to areas on the sensor array having no cells.
Abstract:
A method for correcting nucleotide incorporation signals for fluid potential effects or disturbances arising in nucleic acid sequencing-by-synthesis includes: disposing a plurality of template polynucleotide strands in a plurality of defined spaces disposed on a sensor array, the template polynucleotide strands having a sequencing primer and a polymerase bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed through a fluid manifold, the fluid manifold comprising passages for flowing nucleotide species and a branch passage for flowing a solution, the branch passage comprising a reference electrode and a sensing electrode; obtaining a plurality of nucleotide incorporation signals corresponding to the plurality of defined spaces, the nucleotide incorporation signals having a signal intensity related to a number of nucleotide incorporations; and correcting at least some of the plurality of nucleotide incorporation signals for fluid potential effects or disturbances.
Abstract:
A chemical sensor for analyte solutions utilizes AC excitation of a sample distributed in one or more micro-wells of a measurement device. The sensors utilize narrowband filtering of the measured signal(s), resulting in a large reduction in noise. Synchronous detection is utilized to provide high discrimination of the desired signal from noise or interfering sources. Conductance and by extension impedance is measured by applying a constant alternating current (AC) voltage across the electrodes of each micro-well and measuring the resulting current.
Abstract:
A method for correcting nucleotide incorporation signals for fluid potential effects or disturbances arising in nucleic acid sequencing-by-synthesis includes: disposing a plurality of template polynucleotide strands in a plurality of defined spaces disposed on a sensor array, the template polynucleotide strands having a sequencing primer and a polymerase bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed through a fluid manifold, the fluid manifold comprising passages for flowing nucleotide species and a branch passage for flowing a solution, the branch passage comprising a reference electrode and a sensing electrode; obtaining a plurality of nucleotide incorporation signals corresponding to the plurality of defined spaces, the nucleotide incorporation signals having a signal intensity related to a number of nucleotide incorporations; and correcting at least some of the plurality of nucleotide incorporation signals for fluid potential effects or disturbances.