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Integrated Sensor Arrays for Biological and Chemical Analysis

A sensor array and sensor technology, applied in biochemical cleaning devices, biochemical equipment and methods, biochemical instruments, etc., can solve problems affecting measurement, deterioration, etc.

Inactive Publication Date: 2011-12-28
LIFE TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such an effort faces several difficult technical challenges, especially when ISFET sensor arrays have scales exceeding thousands of sensor elements and hundreds of sensor elements / mm 2 when the density
Such challenges include fabricating large-scale arrays with sensor elements that have uniform performance characteristics across sensors within the array, and fabricating sensor elements with a micron-scale footprint that can generate signals that can be obtained from the sensor array itself. and fluidic systems that transport reactants or analyte-containing samples to the array are detected over the background of many noise sources
For ISFET arrays containing sensor elements with charge-sensitive components such as floating gates, the former challenge is exacerbated by the accumulation of charge trapped in or near these components, a common feature of semiconductor fabrication technology. by-product
The latter challenge is exacerbated by the requirement that the target analyte directly or indirectly generate charged species that accumulate at or on the charge-sensitive component of the ISFET sensor
In very dense arrays, diffusion, analyte or surrogate reactivity, cross-contamination from adjacent sensors, and electrical noise in the sample fluid can adversely affect measurements

Method used

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  • Integrated Sensor Arrays for Biological and Chemical Analysis
  • Integrated Sensor Arrays for Biological and Chemical Analysis
  • Integrated Sensor Arrays for Biological and Chemical Analysis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0172] Detection of polymerase extension on a chip by pH shift on an ISFET array

[0173] Streptavidin-coated 2.8 micron beads carrying biotinylated synthetic templates (to which the sequencing primer and T4 DNA polymerase bind) were subjected to 3 sequential flows of each of the 4 nucleotides. Each nucleotide cycle consists of a stream of dATP, dCTP, dGTP, and dTTP, each interspersed only with a buffer wash stream. The flow from the first loop is shown in blue, the flow from the second loop is shown in red, and the third loop is yellow. Such as Figure 10A As shown, the signals generated by both dATP streams are very similar. Figure 10B shows that the first (blue) trace of dCTP is higher than the dCTP flux from subsequent cycles, corresponding to the flux where the polymerase should incorporate a single nucleotide into each template molecule. Figure 10C demonstrates that the first (blue) trace of dGTP is about 6 higher (peak to peak) counts than the dGTP flux from subse...

Embodiment 2

[0175] Sequencing and data manipulation in a closed system

[0176] Sequences have been obtained from 23-mer synthetic oligonucleotides and 25-mer PCR product oligonucleotides. Oligonucleotides were attached to beads, which were then loaded into individual wells on a chip with 1.55 million sensors in a 1348 x 1152 array with a 5.1 micron pitch (38400 sensors / mm 2 ). Each bead was loaded with approximately 1 million copies of synthetic oligonucleotides, and each bead was loaded with approximately 300,000 to 600,000 copies of PCR products. The cycle of 4 nucleotides in and on the array was 2 minutes long. Nucleotides were used at a concentration of 50 micromol / liter each. Polymerase is the only enzyme used in this process. Data was collected at 32 frames / sec.

[0177] Figure 11A Raw data on synthetic oligonucleotides measured directly from ISFETs are depicted. 1 millivolt is equivalent to 68 counts. At each sensor on the chip (1550200 sensors on a 314 chip), data is s...

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Abstract

The present invention relates to devices and chips comprising large scale chemical field effect transistor arrays including an array of sample retention regions capable of retaining a chemical or biological sample from a sample fluid for analysis. In one aspect, such an array of transistors has a pitch of 10 μm or less, and each sample retention region is located on at least one chemical field effect transistor arranged to generate at least one output signal, which signal is consistent with such related to the characteristics of the chemical or biological sample in the sample retention area. In one embodiment, said chemical or biological sample is characterized by the concentration of charged species, and wherein each of said chemical field effect transistors is an ion-sensitive field effect transistor having a floating The dielectric layer is in contact with the sample fluid and is capable of accumulating charge in proportion to the concentration of charged species in the sample fluid. In one embodiment, such charged species are hydrogen ions, whereby the sensor measures the change in pH of the sample fluid in or near its sample retention zone. The devices and chips of the present invention may be suitable for large-scale pH-based DNA sequencing and other bioscience and biomedical applications.

Description

[0001] related application [0002] This application claims under 35 U.S.C. § 119(e) U.S. Provisional Applications 61 / 196953, 61 / 198222, 61 / 205626, and claims priority under 35 U.S.C. §120 to U.S. nonprovisional applications 12 / 474897 and 12 / 475311, filed May 29, 2009, the entire contents of which are incorporated herein by reference. technical field [0003] The present disclosure relates generally to semiconductor chips for performing chemical measurements, and more particularly to single-chip ISFET arrays (and arrays of single-chip ISFET arrays) for monitoring one or more analytes. Background technique [0004] Fast and accurate measurement of biological and chemical analytes is important in many fields ranging from diagnostics to industrial process control, environmental monitoring, scientific research. Chemically sensitive (especially ion-sensitive) field-effect transistors (respectively "chemically-sensitive field effect transistor, chemFET" and "ion-sensitive field ...

Claims

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Application Information

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IPC IPC(8): G01N27/416C12M1/34
CPCG01N27/414G01N27/4145
Inventor 乔纳森·M·罗思伯格乔纳森·C·舒尔茨金·L·约翰逊托德·M·雷亚里克马克·詹姆斯·米尔格鲁大卫·马兰詹姆斯·M·布斯蒂略
Owner LIFE TECH CORP
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