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-10494670-B2
Publication Date
2019-12-03
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 herein are devices, systems, and methods directed in part to graphene field effect transistor (gFET) sensors, arrays, and integrated circuits employing the same for analyte measurements, wherein 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 facilitate significantly small sensor sizes and dense GFET sensor based arrays. The disclosure emphasizes reaction zones configured to include a one- or two-dimensional surface element, such as a graphene layer, and describes solution-gated wells or chambers positioned proximate a graphene channel so that chemical and biological reactions take place proximate the graphene layer to produce detectable shifts in I-V or I-Vg characteristics.
The disclosure addresses limitations of prior art ISFET/MOSFET biosensors by employing very thin 1D or 2D transistor materials as reaction layers to achieve higher carrier mobility, improved electrostatics against short-channel effects, and increased sensitivity and accuracy, thereby enabling smaller gates and denser sensor arrays suitable for DNA hybridization and sequencing workflows. In addition to sensor and array architectures, the disclosure describes system-level components including fluidics, bias and sense circuitry, and computing components for base calling, mapping, alignment, sorting, and variant calling to support sequencing and bioinformatics analysis.
Claims Coverage
The independent claims define three main inventive features corresponding to three independent integrated-circuit-level inventions.
Graphene channel with overlying reaction well
An integrated circuit comprising an array of graphene field effect transistors in which each transistor comprises a first nonconductive material over the substrate, a source and a drain formed in the first nonconductive material separated by a channel, the channel being formed of a layer of graphene, and a gate layer formed over the channel whose surface structure 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.
Chemically-sensitive bead in reaction chamber for ion-detection
A graphene field effect transistor with a chemically-sensitive bead provided in the reaction chamber, the chemically-sensitive bead being configured with one or more reactants to interact with strands of nucleic acids such that the associated graphene layer 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.
Stacked-layer GFET array configured for sequencing reaction detection
An integrated circuit having primary, secondary (first nonconductive) and tertiary layers wherein source and drain are formed in the secondary layer separated by a graphene channel, and the tertiary layer comprises a gate and a surface structure defining wells over portions of the graphene layer to form reaction chambers in which the graphene layer is configured to detect changes in ion concentration by a change in current flow resulting from sequencing reactions.
The independent claims center on (1) using a graphene layer as the channel with a gate-layer surface structure that defines solution-gated wells, (2) placing chemically-sensitive beads/reactants within those wells so graphene detects ion-concentration changes via current modulation, and (3) implementing these features in a stacked-layer integrated circuit arranged as an array for sequencing reactions.
Stated Advantages
Increased measurement sensitivity and accuracy relative to conventional MOSFET/ISFET sensors.
Facilitation of significantly smaller sensor (pixel) sizes and denser GFET sensor arrays.
Rapid data acquisition from small sensors to large and dense arrays of sensors.
Compatibility with conventional CMOS processing techniques enabling mass-producible, lower-cost, and portable implementations (real-time electronic detection on-chip).
Documented Applications
DNA hybridization detection.
DNA and RNA sequencing (sequencing by synthesis and related sequencing reactions).
Monitoring changes in hydrogen ion concentration (pH) and other analyte concentrations as indicators of chemical or biochemical reactions.
Whole genome analysis, genome typing analysis, micro-array analysis, panels analysis, and exome analysis.
Micro-biome analysis and clinical analyses such as cancer analysis, NIPT analysis, and UCS analysis.
Positioning and verification of microbeads (e.g., beads bearing nucleic acid templates) in reaction wells using electric and/or magnetic fields for sequencing workflows.
Use of GFET sensor arrays as solution-gated biosensors and integrated sequencing platforms with on-chip fluidics, bias/sense circuitry, and computing modules for base calling, mapping, alignment, sorting, and variant calling.
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