Graphene FET devices, systems, and methods of using the same for sequencing nucleic acids
Inventors
Van Rooyen, Pieter • Lerner, Mitchell • Hoffman, Paul • Goldsmith, Brett R.
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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-10968481-B2
Publication Date
2021-04-06
Expiration Date
Abstract
Chemically-sensitive field effect transistors for biosensor chips and system are disclosed. The itransisitors have a multi-layered structure for performing a set of measurements of a biological reaction involving a binding event for one or more biological analytes that may be label-free. The multilayer structure includes a first insulating layer above a substrate layer and a source electrode and a drain electrode disposed positioned over the first insulating layer; a second insulating layer above the first insulating layer and proximate the source and drain electrodes forming side wall members of a well for a fluid comprising the analytes; a 2D graphene layer forming a channel between source and drain electrodes; a solution gate, formed by fluid flowed over the channel, configured to enable determining differences between one or more sample I-Vg curves having a shifted and changed shape relative to a reference curve; embodiments may include ion-selective membranes and/or ion getters.
Core Innovation
Chemically-sensitive field effect transistors, biosensor chips, systems, and methods are disclosed that employ a multi-layered structure including a substrate layer, a first insulating layer, a source electrode and a drain electrode disposed over the first insulating layer, a second insulating layer forming side wall members of a well, and a two-dimensional (2D) graphene layer forming a channel between the source and drain electrodes; a solution gate is formed by a fluid flowed over the graphene channel and the device is configured to enable determining differences between reference and reaction I-Vg curves; embodiments may include ion-selective membranes and/or ion getters.
The disclosure addresses limitations of existing sequencing and electronic detection approaches by providing FET sensors and arrays that increase measurement sensitivity and signal to noise characteristics while enabling smaller sensor dimensions and denser arrays. The background identifies the lack of sensor sensitivity and degraded performance of MOSFET/ISFET devices as gate length scales down and states that channels that are very thin in the vertical dimension are needed for increased sensor sensitivity and high-speed carrier transmission; the present devices are configured to provide such thin-channel sensing for biological applications.
The systems integrate arrays of the chemically-sensitive transistors with fluidics, circuitry, and computing components to run reactions and to generate and compare I-V and I-Vg curves (for example to detect shifts in Dirac voltage, changes in Ion, and changes in transconductance) so as to detect presence, concentration changes, and identities of analytes including DNA hybridization and sequencing; the chips are described as CMOS-compatible, may include wells that receive beads or templates, may use electric or magnetic fields to position beads, and may include membrane or getter layers over channels to enhance detection and reduce interfering ions.
Claims Coverage
The patent includes three independent claims and seven main inventive features extracted from those claims.
Multi-layered FET with well-forming second insulating layer
A chemically-sensitive field effect transistor having a multi-layered structure comprising a substrate layer, a first insulating layer positioned above the substrate layer, and a second insulating layer positioned above the first insulating layer that is configured to form one or more side wall members of a well for a fluid containing an analyte, with source and drain electrodes disposed within or over the first insulating layer.
Graphene monolayer channel between source and drain
A graphene layer comprising a two-dimensional (2D) monolayer of carbon atoms arranged as a lattice structure positioned above the first insulating layer and forming a channel between the source electrode and drain electrode.
Solution gate enabling I-Vg curve difference measurements
A solution gate region configured to form a solution gate above the channel in response to fluid being flowed over the channel at the bottom of the well opening, wherein the solution gate is configured to enable a set of measurements to determine differences between a reference I-Vg curve and a second I-Vg curve having a shifted and changed shape.
Biosensor chip comprising plurality of chemically-sensitive FETs for label-free analytes
A biosensor chip comprising a plurality of chemically-sensitive field effect transistors, individually having a multi-layered structure configured to perform a set of measurements of a biological reaction involving a binding event of one or more label-free biological analytes.
Graphene layer at bottom of well forming channel in biosensor array
Each field effect transistor of the biosensor chip includes a graphene layer positioned at a bottom of an opening of the well above the first insulating layer and extending between the source and drain electrodes thereby forming a channel and a solution gate region configured to enable the specified I-Vg measurements.
System comprising biosensor chip with graphene FET array enabling I-Vg measurements
A system comprising a biosensor chip having a plurality of chemically-sensitive field effect transistors with a multi-layered structure including a graphene layer positioned between insulating layers and extending between source and drain electrodes, and a solution gate region configured to form a solution gate when fluid is flowed over the channel to enable measurements determining differences between individual I-Vg curves.
Set of I-Vg measurements for analyzing analyte characteristics
The set of measurements for individual I-Vg curves includes an on-state drain current (Ion) measurement taken from a p-type portion, a first transconductance measurement taken at the steepest and/or flattest sections of the p-type portion, a Dirac voltage (VDirac) measurement taken at a lowest point of the I-Vg curve, a second transconductance measurement taken at the steepest and/or flattest sections of the n-type portion, and an Ion measurement taken from the n-type portion.
Independent claims cover a multilayer FET architecture with a graphene monolayer channel and a solution-gated well that enables a defined set of I-Vg measurements to detect analyte-related shifts and shape changes, embodiments scaled to arrays in a biosensor chip, and systems that include such biosensor chips to perform analyte characterization.
Stated Advantages
Increases measurement sensitivity and accuracy of the sensor and associated arrays.
Facilitates significantly smaller sensor sizes and denser gFET sensor-based arrays.
Provides rapid data acquisition from small sensors to large, including dense arrays of sensors.
Direct electronic detection can be incorporated in the substrate enabling automatic recognition in real time and operation at lower cost; such detectors are described as simple, inexpensive, and portable.
Graphene-based sensors perform better as biological sensors than typical CMOS-FET devices due to single-atom thickness, higher carrier mobility, and faster detection.
Inclusion of an ion-exclusive membrane can produce greater sensitivity (the disclosure states the gFET surpasses the theoretical 59 mV maximum for an ISFET when an ion exclusive membrane is included).
Documented Applications
Detection of the presence of an analyte, changes in analyte concentration, and identity of analyte types.
DNA hybridization detection.
Nucleic acid sequencing, including DNA and RNA sequencing (sequencing by synthesis and related sequencing reactions).
Whole genome analysis.
Genome typing analysis.
Micro-array analysis.
Panels analysis and exome analysis.
Micro-biome analysis.
Clinical analysis including cancer analysis, non-invasive prenatal testing (NIPT) analysis, and UCS analysis.
Use as pH and ion-concentration sensors (monitoring hydrogen ion concentration and other ion changes).
Bead-based assays including positioning microbeads with analyte templates in wells for sequencing and verifying well occupancy.
Protein sequencing and other chemical/biological analyte measurements described in the context of 1D/2D/3D FET sensor arrays.
Interested in licensing this patent?