Graphene FET devices, systems, and methods of using the same for sequencing nucleic acids
Inventors
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Assignees
Edico Genome Corp • Paragraf USA
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-9618474-B2
Publication Date
2017-04-11
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 directed to field effect transistor (FET) sensors, arrays, and integrated circuits that employ one- or two-dimensional reaction layers, including graphene, as reaction zones to perform biological and chemical analyses. The apparatuses include graphene FET (gFET) sensors and dense gFET sensor arrays that can be fabricated using conventional CMOS processing techniques and that increase measurement sensitivity and accuracy while facilitating smaller sensor sizes and higher sensor density. Such arrays are described for detecting presence, concentration changes, and identities of analytes, including DNA hybridization and sequencing reactions, by monitoring ion concentration changes, other analyte concentration changes, and binding events within a gated reaction chamber of the gFET sensor.
The disclosure addresses limitations of existing sequencing platforms that rely on optical labels and conventional MOSFET/ISFET biosensors, namely bulk, cost, portability, and fundamental sensitivity limits as transistor geometries scale. The invention provides chemically-sensitive FET devices having one-, two-, or three-dimensional channel materials and reaction layers that decrease effective sensor length and permit thin gate-controlled regions, thereby improving sensitivity, signal characteristics, and the ability to deploy FET-based detection for nucleic acid hybridization and sequencing.
Claims Coverage
This patent includes three independent claims. Seven main inventive features are extracted from those independent claims.
Integrated circuit for performing a sequencing reaction
An integrated circuit comprising a substrate and an array of graphene field effect transistors arranged on the substrate, the integrated circuit being for performing a sequencing reaction involving the sequencing of strands of nucleic acids.
Graphene channel gate with well forming reaction chamber
A tertiary layer comprising a gate formed over the channel where the channel is formed of a graphene layer, and the tertiary layer further comprises a surface structure that overlaps the source and the drain and defines a well having side walls and a bottom that extends over at least a portion of the graphene layer so as to form a reaction chamber for the performance of the sequencing reaction.
Multi-layer transistor structure with source, drain, and graphene channel
Each graphene field effect transistor comprises a primary base layer, and a secondary layer of a first nonconductive material comprising a source and a drain formed in the first nonconductive material separated by a channel, the source and the drain being formed of an electrically conductive material.
Chemically-sensitive bead reagents provided in wells
A chemically-sensitive bead provided in one or more wells of the array, each bead being configured with one or more reactants to interact with portions of the strands of nucleic acids so that the associated graphene field effect transistor detects a change in ion concentration of the reactants by a change in current flow from the source to the drain via activation of the graphene layer.
GFET array configured to detect ion-concentration changes via graphene activation
One or more graphene field effect transistors of the integrated circuit are configured for detecting a change in ion concentration by a change in current flow from the source to the drain via activation of the graphene layer resulting from the performance of the sequencing reaction.
Optional ion sensitive layer over graphene in well
An ion sensitive layer is disclosed as disposed over the portion of the graphene layer at the bottom of the well, the ion sensitive layer being formed of an ion sensitive material (as set forth in dependent claims).
Ion selective permeable membrane and solution-gate configuration
The integrated circuit may include an ion selective permeable membrane positioned over the graphene layer and the gate can be configured as a solution gate (as set forth in dependent claims).
Independent claims describe an integrated circuit comprising an array of graphene FETs built from layered substrate structures with graphene channels and wells forming reaction chambers, and include embodiments using chemically-sensitive beads, ion sensitive layers, ion-selective membranes, and solution-gate configurations to detect ion-concentration changes via changes in GFET current.
Stated Advantages
Increased measurement sensitivity and accuracy relative to conventional MOSFET/ISFET biosensors.
Facilitation of significantly smaller sensor sizes and denser GFET sensor arrays.
Rapid data acquisition from small sensors to large and dense arrays of sensors.
Ability to detect presence, concentration changes, and identity of analytes, including monitoring hydrogen ion concentration (pH), other analyte concentrations, and binding events associated with DNA synthesis.
Compatibility with conventional CMOS processing techniques enabling mass production with high quality and economy, and potential for lower cost and portability compared to optical label-based sequencers.
Enables direct, label-free electronic detection and on-chip acquisition and processing with potential for real-time automatic recognition.
Documented Applications
DNA hybridization detection.
DNA and RNA sequencing, including sequencing by monitoring pH and binding events during nucleotide incorporation.
Whole genome analysis.
Genome typing analysis.
Micro-array analysis.
Panels analysis.
Exome analysis.
Micro-biome analysis.
Clinical analysis including cancer analysis, NIPT analysis, and UCS analysis.
Protein sequencing (as an indicated application for 1D/2D/3D FET sensor arrays).
Bead-based sequencing workflows that use microbeads carrying nucleic acid templates and electrophoresis or magnetism to position beads within reaction wells.
Interested in licensing this patent?