Graphene FET devices, systems, and methods of using the same for sequencing nucleic acids
Inventors
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Assignees
MemberParagrafParagrafParagraf specializes in the development and manufacture of wafer-scale, silicon-compatible graphene electronic devices and sensors. Utilizing a proprietary process for direct, contamination-free graphene synthesis, the company delivers scalable solutions for magnetic field sensing, molecular and biosensing, and advanced electronics integration. These technologies address challenges in cryogenics, quantum computing, automotive, aerospace, environmental monitoring, and healthcare. With a focus on large-scale integration of 2D materials, Paragraf advances next-generation sensors and components for demanding and extreme environments.
Paragraf specializes in the development and manufacture of wafer-scale, silicon-compatible graphene electronic devices and sensors. Utilizing a proprietary process for direct, contamination-free graphene synthesis, the company delivers scalable solutions for magnetic field sensing, molecular and biosensing, and advanced electronics integration. These technologies address challenges in cryogenics, quantum computing, automotive, aerospace, environmental monitoring, and healthcare. With a focus on large-scale integration of 2D materials, Paragraf advances next-generation sensors and components for demanding and extreme environments.
Publication Number
US-10020300-B2
Publication Date
2018-07-10
Expiration Date
Abstract
Provided herein are integrated circuits for use in performing analyte measurements and methods of fabricating the same. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in chemical and/or biological processes, including DNA hybridization and/or sequencing reactions. The methods for fabricating the integrated circuits include steps of depositing an insulating layer on a semiconducting substrate, and forming trenches in the insulating dielectric layer. Conductive material may be deposited in the trenches to form electrodes, and the insulating layer may be conditioned so that the electrodes protrude above the insulating layer. A 2D material, such as graphene, may be deposited on the electrodes to form a channel between the electrodes.
Core Innovation
The invention provides integrated circuits, field effect transistor (FET) sensors, arrays, systems, and methods directed in part to devices that employ one-dimensional (1D), two-dimensional (2D), or three-dimensional (3D) reaction layers and/or structured layers, including graphene-containing FETs (gFETs), for analyte measurements and for molecular analysis such as nucleic acid analysis and sequencing. The devices and arrays are described as being fabricated in a complementary metal-oxide semiconductor (CMOS) format and configured so that a reaction zone or channel includes a 1D, 2D, or 3D material layer and may be formed as a solution-gated well or chamber proximate a source and drain to form a chemically-sensitive transistor.
The disclosure further describes that the improved devices and fabrication techniques increase measurement sensitivity and accuracy, facilitate significantly smaller sensor sizes and denser gFET sensor-based arrays, and provide for rapid data acquisition from small sensors to large, dense arrays. The methods for fabricating the integrated circuits are described conceptually and include conditioning an insulating dielectric, forming trenches to receive conductive electrodes that project above the insulating layer, and providing a 1D or 2D material layer, e.g., graphene, as a channel between the electrodes ([procedural detail omitted for safety]).
The background problem identified is the need for FET devices with very thin channel regions and improved sensitivity and signal-to-noise characteristics suitable for biological applications such as nucleic acid sequencing, noting limitations of conventional MOSFET/ISFET devices in sensitivity, scaling, and instrumentation bulk that hinder deployment in sequencing reactions.
Claims Coverage
Independent claims identified: 2. The main inventive features (6 total) are extracted below from the independent claims.
Semiconducting substrate with arrayed field effect transistors
A semi-conducting substrate having a plurality of extended planar surfaces offset from one another, being surrounded by side members, and having one or more transistor elements positioned between the plurality of surfaces, the substrate supporting an array of field effect transistors.
Secondary insulating layer with trench-formed electrodes projecting above surface
A secondary layer of a first non-conductive material comprising a plurality of trenches, each trench offset by a distance forming a channel region, with each trench including electrically conductive material to form an electrode whose side and top surface extends above a surface of the secondary layer, wherein electrodes on either side of each channel region serve as source and drain electrodes.
Tertiary 2D material forming channel over electrodes
A tertiary layer comprising a 2D material formed over side and top of the source and drain electrodes and formed over the channel region so as to electrically connect the source and the drain electrodes (2D material examples include graphene and listed alternative 2D materials).
2D material with electrode-proximate openings
A 2D material formed over electrodes and over the channel region that includes one or more openings proximate the electrodes, enabling contact between the 2D material, the electrodes, and additional conductive material.
Second conductive material contacting electrodes through 2D openings
A second layer of electrically conductive material formed over the openings of the 2D material and in electrical communication with the electrodes and the 2D material, providing electrical contact between the electrodes and the 2D material.
Surface structure defining a reaction well over 2D material
A surface structure (tertiary or additional layer) that overlaps the source and drain and defines a well having side walls and a bottom that extends over at least a portion of the 2D material so as to form a reaction chamber for the performance of a sequencing reaction.
The independent claims cover integrated circuit FET arrays on a semiconductor substrate featuring trench-formed electrodes that project above an insulating layer, a 2D-material-based channel formed over those electrodes and channel regions, embodiments with openings in the 2D material filled or contacted by a second conductive layer, and a surface structure forming wells or reaction chambers over the 2D channel.
Stated Advantages
Increased measurement sensitivity and accuracy of FET sensors and arrays.
Facilitation of significantly smaller sensor sizes and denser gFET sensor-based arrays.
Rapid data acquisition from small sensors to large, dense arrays.
Improved sensor sensitivity and transconductance associated with the use of 1D or 2D materials (e.g., graphene) and short channel geometries.
Ability to detect presence, concentration changes, and identity of analytes in chemical and biological processes, including label-free electronic detection suitable for DNA hybridization and sequencing.
Compatibility with CMOS processing enabling potential mass production with cost, portability, and real-time recognition advantages over optical NGS platforms.
Documented Applications
Detection of presence, concentration changes, and identity of analytes in chemical and biological processes, including DNA hybridization and DNA or RNA sequencing reactions.
Use in whole genome analysis, genome typing analysis, micro-array analysis, panels analysis, exome analysis, micro-biome analysis, and clinical analysis (including cancer analysis, NIPT analysis, and UCS analysis).
Formation of gFET sensor arrays configured as solution-gated wells or chambers for nucleic acid sequencing by sensing ion changes (e.g., pH) and binding events proximate a reaction zone.
Integration into a system with fluidics, circuitry, and computing components for sequencing workflows including base calling, mapping, alignment, sorting, and variant calling of sequencing reads.
Use of charged or paramagnetic microbeads carrying nucleic acid templates positioned in wells via electric or magnetic fields (electrophoresis or magnetism) for sequencing reactions and well occupancy verification.
Application as chemically-sensitive solution-gated FETs (ISFET-like devices) for monitoring ion concentrations, generating I-V/I-Vg curves, and detecting shifts associated with chemical reactions.
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