Body-less ISFET Arrays for DNA Sequencing
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Solution Overview
Problem
Conventional ISFET arrays for pH measurements face limitations in achieving high signal linearity over a wide pH range and are prone to nonlinear performance due to the body effect, and they lack sensitivity to detect nucleotide incorporation during DNA sequencing, which is essential for efficient nucleic acid analysis.
Innovation Solution
The development of large-scale chemically-sensitive FET arrays, specifically configured ISFET arrays with improved pixel density and signal-to-noise ratio, capable of detecting hydrogen ions and other analytes, and employing non-enzymatic methods to monitor nucleic acid sequencing reactions by detecting inorganic pyrophosphate (PPi) directly, allowing for pH-insensitive environments and increased sensitivity to nucleotide incorporation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional ISFET arrays are used for pH measurements, then they can measure hydrogen ion concentration, but they suffer from nonlinear performance due to the body effect and lack sensitivity to detect nucleotide incorporation
Solution Approach 1:
The patent extracts the body connection from the ISFET structure, creating a body-less ISFET where the body region is disconnected from electrical contact. This eliminates the body effect that causes nonlinear performance, allowing the sensor to maintain linear response across a wide pH range while improving detection sensitivity for nucleotide incorporation events.
Solution Approach 2:
The patent changes the electrical parameters of the ISFET by disconnecting the body connection, thereby altering the device's electrical characteristics. This parameter change eliminates the body effect and enables the sensor to operate with improved linearity and sensitivity for detecting pH changes during DNA sequencing reactions.
2Productivity
If ISFET arrays are designed with high pixel density, then measurement speed and throughput increase, but signal-to-noise ratio deteriorates
Solution Approach 1:
The patent combines multiple ISFET sensors into an integrated array on a single chip, with each sensor element sharing common circuitry and readout infrastructure. This merging approach increases pixel density and measurement throughput while the body-less design maintains signal quality by eliminating the body effect that degrades signal-to-noise ratio in conventional arrays.
3Ease of manufacture
If conventional ISFET pixel design is used, then fabrication is straightforward, but pixel complexity increases measurement range requirements
Solution Approach 1:
The patent removes the body connection structure from the conventional ISFET pixel design, simplifying the pixel architecture. This extraction reduces pixel complexity and allows for more straightforward fabrication processes while maintaining ease of manufacture through standard CMOS compatibility.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution enables high-speed, high-density determination of analyte concentrations, improving the accuracy and efficiency of nucleic acid sequencing and other chemical/biological processes by enhancing pixel density and signal processing, while reducing the complexity of pixel design and measurement range, thus overcoming the limitations of conventional ISFET arrays.
Implementation Method 1
an ion-sensitive field effect transistor, often denoted in the relevant literature as ISFET (or pHFET)... ISFETs conventionally have been explored, primarily in the academic and research community, to facilitate measurement of the hydrogen ion concentration of a solution
Implementation Method 2
employing non-enzymatic methods to monitor nucleic acid sequencing reactions by detecting inorganic pyrophosphate (PPi) directly
Data Source
AI summary
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.