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-10811539-B2
Publication Date
2020-10-20
Expiration Date
Abstract
Provided herein are devices, systems, and methods of employing the same for the performance of bioinformatics analysis. The apparatuses and methods of the disclosure are directed in part to large scale graphene FET sensors, arrays, and integrated circuits employing the same for analyte measurements. The present GFET sensors, arrays, and integrated circuits may be fabricated using conventional CMOS processing techniques based on improved GFET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense GFET sensor based arrays. Improved fabrication techniques employing graphene as a reaction layer provide for rapid data acquisition from small sensors to large and dense arrays of sensors. 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, including DNA hybridization and/or sequencing reactions. Accordingly, GFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis within a gated reaction chamber of the GFET based sensor.
Core Innovation
Provided are devices, systems, and methods employing large scale graphene FET (gFET) sensors, arrays, and integrated circuits fabricated using conventional CMOS processing techniques based on improved gFET pixel and array designs that increase measurement sensitivity and accuracy while facilitating significantly small pixel sizes and dense gFET sensor based arrays. Improved fabrication techniques employing 1D or 2D reaction layers, including graphene, provide for rapid data acquisition from small sensors to large and dense arrays of sensors that may be employed to detect presence and/or concentration changes and/or identity of analytes in a wide variety of chemical and biological processes, including DNA hybridization and sequencing reactions. The gFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis within a gated reaction chamber of the gFET sensor.
The background identifies a need for low-cost, high-throughput sequencing that can be mass produced by leveraging CMOS chip fabrication, and notes limitations of existing approaches that rely on optically detectable labels which require bulky, costly, non-portable instrumentation. The disclosure states that fundamental limits arise when applying MOSFET/ISFET technologies as biosensors, including lack of sensor sensitivity and signal-to-noise degradation as transistor nodes scale and short-channel effects such as threshold-voltage roll-off and drain-induced barrier lowering. What is needed, therefore, is a FET device configured to include much thinner channels and a shorter gate than currently achievable so as to increase sensor sensitivity and enable deployment in sequencing reactions.
Claims Coverage
Overview: Six main inventive features were extracted from the independent claims, each reflecting structures and configurations directed to multi-layered chemically-sensitive FETs, electrode geometries, graphene channel placement, well structures, and integrated circuits for sequencing.
Multi-layered structure with curvilinear electrode pairs and graphene channel in well
A chemically-sensitive FET comprising a substrate layer, first and second non-conductive material layers, one or more electrode pairs comprising a source and a drain with impingement and receiving members formed of concentrically curved arcs, a graphene layer positioned within the distance between the first and second non-conductive material layers extending between source and drain thereby forming a channel, and a well structure provided at least within the second non-conductive material layer having a chamber bounded by one or more bounding members that include the source and drain electrodes and the graphene layer.
Interdigitated source and drain with graphene channel adjacent bounding member
A chemically-sensitive FET in which a well structure is provided in at least the second insulating layer defining a chamber bounded by a bounding member, and one or more electrode pairs comprising a source and a drain having an interdigitated configuration positioned proximate the second insulating layer adjoining the bounding member, the source separated from the drain by a space, with a graphene layer positioned in the space between the source and drain electrodes to form a channel therebetween.
Well structure in second insulating layer with curvilinear source and drain and graphene channel
A multi-layered chemically-sensitive FET having a first and second insulating layer, a well structure provided at least in the second insulating layer with an opening defined by a bounding member, one or more electrode pairs comprising a source and a drain positioned within the second insulating layer proximate the bounding member with the source and drain formed on concentrically curved arcs, and a graphene layer positioned between the source and drain electrodes to form a channel thereunder.
Opening with side and bottom surfaces having electrodes and graphene positioned therein
A chemically-sensitive FET having an opening provided in the second insulating layer defined by a side surface and a bottom surface, one or more electrode pairs comprising a source and a drain separated by a distance and formed on concentrically curved arcs, and a graphene layer positioned within the distance between the source and drain electrodes with the source electrode, the graphene layer, and the drain electrode being positioned within one or both of the side surface and the bottom surface defining the opening.
Integrated circuit with array of graphene FETs having graphene gate and reaction well for sequencing
An integrated circuit comprising a substrate and an array of graphene field effect transistors where each transistor includes a primary base layer, a secondary layer formed of a first nonconductive material with source and drain formed therein separated by a channel, and a tertiary layer over the secondary layer comprising a gate formed of a graphene layer that overlaps the source and drain and defines a well with side walls and a bottom extending over at least a portion of the graphene gate so as to form a reaction chamber for performance of a sequencing reaction, wherein one or more transistors detect a change in ion concentration by a change in current flow from source to drain via activation of the graphene layer.
Integrated circuit with graphene gate and well forming reaction chamber
An integrated circuit having an array of graphene FETs in which a primary layer forms a base, an intermediary layer of nonconductive material comprises electrode pairs of source and drain formed on concentrically curved arcs and separated by a channel, and a tertiary layer over the intermediary layer comprises a graphene gate and a surface structure that overlaps the source and drain to define a well with side walls and a bottom that extends over a portion of the graphene gate so as to form a reaction chamber for sequencing.
The independent claims disclose multi-layered chemically-sensitive FET structures that place a graphene layer between non-conductive layers to form a channel, use interdigitated/curvilinear source and drain electrode geometries disposed in well sidewalls and/or bottoms to maximize channel width-to-length, and integrate graphene-gated wells into arrays and integrated circuits configured to detect ion concentration changes and to serve as reaction chambers for sequencing reactions.
Stated Advantages
Increased measurement sensitivity and accuracy of FET sensors and arrays.
Facilitation of significantly smaller sensor/pixel sizes and denser sensor arrays.
Rapid data acquisition from small sensors to large and dense arrays of sensors.
Capability to detect presence and/or concentration changes and identities of analytes, including monitoring pH and binding events associated with DNA hybridization and sequencing.
Compatibility with conventional CMOS processing enabling potential mass production.
Documented Applications
DNA hybridization and sequencing reactions including sequencing by synthesis based on monitoring hydrogen ion concentration (pH), other analyte concentrations, and binding events.
Whole genome analysis, genome typing analysis, micro-array analysis, panels analysis, and exome analysis.
Micro-biome analysis and clinical analysis, including cancer analysis, NIPT analysis, and UCS analysis.
Nucleotide and protein sequencing reactions and other analyses of biological or chemical materials where ion concentration or binding events are monitored in solution-gated wells.
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