Chemically-Sensitive FETs for Label-Free DNA Sequencing
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Solution Overview
Problem
Current nucleic acid sequencing technologies face challenges in generating full-length genomic sequences and determining genetic variants due to the limitations of Next Generation Sequencing (NGS) methods, which produce short DNA fragments that require extensive time and effort to assemble and align, and are hindered by the need for bulky, costly instrumentation for optical detection.
Innovation Solution
Development of chemically-sensitive field-effect transistors (FETs) with shorter gate lengths and 1D or 2D channels, integrated into CMOS structures, which enable direct, label-free DNA sequencing by detecting changes in conductance associated with chemical reactions, facilitating more sensitive and accurate nucleic acid analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If Next Generation Sequencing (NGS) methods are used to generate DNA sequences, then nucleic acid detection and sequencing can be performed, but the produced short DNA fragments require extensive time and effort to assemble and align
Solution Approach 1:
The patent replaces optical detection systems with field-effect transistor (FET) based electrical detection. The FET device directly detects nucleic acid molecules through changes in electrical conductance, eliminating the need for optical labels and complex imaging systems. This substitution enables real-time detection and sequencing without the time-consuming assembly and alignment processes required by traditional NGS methods.
Solution Approach 2:
The invention changes the detection parameter from optical signals to electrical conductance measurements. By using FET devices that respond to the presence and properties of nucleic acid molecules through electrical parameter changes, the system achieves direct detection that provides full-length sequence information, eliminating the need for fragment assembly and alignment.
2Measurement precision
If optical detection instrumentation is used for DNA sequencing, then nucleic acid sequences can be detected, but the instrumentation is bulky and costly
Solution Approach 1:
The patent replaces bulky optical detection instrumentation with miniaturized field-effect transistor devices. The FET-based detection system uses electrical fields to detect nucleic acid molecules, eliminating the need for large optical components such as lasers, lenses, and cameras. This results in a compact, cost-effective device that maintains high detection precision through direct electrical measurement of nucleic acid properties.
3Ease of operation
If conventional FET structures are used, then transistor functionality is achieved, but measurement sensitivity and accuracy for chemical reactions are insufficient
Solution Approach 1:
The patent applies local quality by creating a specialized gate structure with chemically-sensitive materials deposited only in the region directly above the channel. This localized sensitivity enhancement allows the FET to detect chemical reactions and nucleic acid molecules with high precision while maintaining standard transistor functionality elsewhere in the device structure.
Solution Approach 2:
The invention uses composite materials by combining conventional semiconductor materials with chemically-sensitive coating materials on the FET gate. This composite structure provides both the electrical functionality of the transistor and the chemical sensitivity required for detecting nucleic acid molecules, achieving dual functionality in a single integrated device.
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 chemically-sensitive FETs enhance measurement sensitivity and accuracy, allowing for rapid data acquisition and reducing the complexity and cost of nucleic acid sequencing, enabling more efficient assembly of genomic sequences and genetic variant determination.
Implementation Method 1
sensing the occurrence of a desired chemical reaction, e.g., detection of a target biological compound or reactant thereof, produces a shift in an I-V curve or an I-Vg curve corresponding to that change in conductance as determined by the chemically-sensitive field effect transistor
Data Source
AI summary
This invention concerns chemically-sensitive field effect transistors (FETs) are preferably fabricated using semiconductor fabrication methods on a semiconductor wafer, and in preferred embodiments, on top of an integrated circuit structure made using semiconductor fabrication methods. The instant chemically-sensitive FETs typically comprise a conductive source, a conductive drain, and a channel composed of a one-dimensional (1D) or two-dimensional (2D) transistor material, which channel extends from the source to the drain and is fabricated using semiconductor fabrication techniques on top of a wafer. Such chemically-sensitive FETs, preferably configured in independently addressable arrays, may be employed to detect a presence and/or concentration changes of various analyte types in chemical and/or biological samples, including nucleic acid hybridization and/or sequencing reactions.