Two-dimensional channel FET devices, systems, and methods of using the same for sequencing nucleic acids
Inventors
Van Rooyen, Pieter • Lerner, Mitchell • Hoffman, Paul • Goldsmith, Brett R.
Assignees
Publication Number
US-11732296-B2
Publication Date
2023-08-22
Expiration Date
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
An apparatus includes a biosensor integrated circuit (IC) chip having multiple well structures configured to receive a liquid comprising one or more biological analytes. The well structures include a passivation layer with an opening over one or more field effect transistors (gFETs) which include a layer of 2D channel material selected from molybdenum disulfide (MoS2) and graphene; a drain electrode connected to a first end of the channel; a source electrode connected to a second end of the channel, wherein the individual gFETs are configured such that liquid received by the well structure is confined to form a liquid gate above a top surface of the channel. A system and method perform various functions of the apparatus.
Core Innovation
The disclosure provides an apparatus including a biosensor integrated circuit chip having multiple well structures configured to receive a liquid comprising one or more biological analytes. The well structures include a passivation layer with an opening over one or more field effect transistors (gFETs) which include a layer of two-dimensional channel material selected from molybdenum disulfide (MoS2) and graphene, a drain electrode connected to a first end of the channel, and a source electrode connected to a second end of the channel, wherein the individual gFETs are configured such that liquid received by the well structure is confined to form a liquid gate above a top surface of the channel. A system and method perform various functions of the apparatus.
The background states that conventional MOSFET/ISFET biosensors suffer from a lack of sensor sensitivity and signal to noise characteristics as the semiconductor node scales down and that short-channel effects degrade sensitivity; the patent identifies a need for FET devices with channels very thin in the vertical dimension and shorter gates for biological applications such as nucleic acid sequencing. The disclosure is directed to chemically-sensitive field effect transistors having a reaction layer that includes one-dimensional or two-dimensional materials associated therewith so as to increase measurement sensitivity and accuracy. The invention is presented as solving problems associated with sequencing and genetic diagnostics by using thin channel materials.
The brief summary and detailed description describe FET sensors, arrays, and integrated circuits that employ 1D or 2D reaction layers to increase measurement sensitivity and accuracy and to facilitate significantly small sensor sizes and dense gFET sensor-based arrays, including solution-gated wells where the solution serves as a gate and reaction zones include graphene or other 2D materials. The devices are described as stacked structures having a conductive source and drain, a 1D or 2D channel material, optional reaction and passivation layers, and wells or chambers aligned with the channel, and the system components include fluidics, circuitry, and computing components for running and processing reactions. The disclosure describes using differences between reference I-Vg curves and chemical reaction I-Vg curves, including shifts and shape changes, as detection metrics for analyte-related reactions.
Claims Coverage
Independent claims identified: three. Each independent claim claims (1) a multi-layered chemically-sensitive FET with a solution-gated 2D channel, (2) a biosensor chip comprising a plurality of such chemically-sensitive FETs in wells, and (3) a system comprising a biosensor chip having a MoS2 layer and a solution gate enabling a specified set of I-Vg measurements.
Multi-layered chemically-sensitive FET with solution gate and 2D channel
A chemically-sensitive field effect transistor having a multi-layered structure comprising: a substrate layer having an extended body; a first insulating layer positioned above the extended body of the substrate layer; a second insulating layer positioned above the first insulating layer, wherein the second insulating layer is configured to form one or more side wall members of a well for a fluid containing an analyte; a source electrode and a drain electrode each disposed within or over the first insulating layer and separated by a distance; a two-dimensional layer of channel material selected from molybdenum disulfide (MoS2) and graphene positioned above the first insulating layer and forming a channel between the source electrode and drain electrode; and a solution gate region configured to form a solution gate above the channel when fluid is flowed over the channel, wherein the solution gate enables a set of measurements to determine differences between individual I-Vg curves including Ion (p-type), a first transconductance at p-type steepest/flattest sections, a Dirac voltage (VDirac), a second transconductance at n-type steepest/flattest sections, and Ion (n-type).
Biosensor chip comprising plurality of chemically-sensitive field effect transistors with solution-gated 2D channels
A biosensor chip comprising a plurality of chemically-sensitive field effect transistors, individually having a multi-layered structure including: a substrate layer; a first insulating layer positioned above the substrate; source and drain electrodes disposed in or over the first insulating layer separated by a distance; a second insulating layer positioned above the first insulating layer and proximate the source and drain electrodes to form side wall members of a well for a fluid; and a two-dimensional layer of channel material selected from MoS2 and graphene positioned at the bottom of an opening of the well and extending between the source and drain electrodes to form a channel, together with a solution gate region configured to form a solution gate above the channel when fluid is flowed over the channel and to enable the set of I-Vg measurements (Ion p-type, p-type transconductance, VDirac, n-type transconductance, Ion n-type).
System comprising biosensor chip with MoS2 channel and solution gate enabling I-Vg measurement set
A system comprising a biosensor chip having chemically-sensitive field effect transistors, each transistor comprising: a substrate layer; a first insulating layer positioned above the substrate; source and drain electrodes positioned in or over the first insulating layer and separated by a distance; a second insulating layer positioned above the first insulating layer forming side wall members of a well for the fluid; a molybdenum disulfide (MoS2) layer positioned between the first and second insulating layers and substantially extending between outer side portions of the drain electrode and the source electrode to form a channel; and a solution gate region configured to form a solution gate above the channel when the fluid is flowed over the channel, wherein the solution gate enables a set of measurements to determine differences between individual I-Vg curves including Ion (p-type), a first transconductance at p-type steepest/flattest sections, VDirac, a second transconductance at n-type steepest/flattest sections, and Ion (n-type).
The independent claims cover (a) a multi-layered solution-gated chemically-sensitive FET having a 2D channel of MoS2 or graphene and defined well side walls and embedded source/drain, (b) a biosensor chip comprising an array of such solution-gated 2D-channel FETs, and (c) a system having a biosensor chip with a MoS2 channel and solution gate configured to enable a specified set of I-Vg measurements for detecting analyte-dependent shifts and shape changes in I-Vg curves.
Stated Advantages
Increased measurement sensitivity and accuracy through use of one-dimensional or two-dimensional reaction layers.
Facilitation of significantly small sensor sizes and dense gFET sensor-based arrays enabling higher sensor density.
Rapid data acquisition from small sensors to large and dense arrays of sensors.
Enables direct, label-free electronic detection of hybridization and sequencing reactions and integration with CMOS devices for on‑chip acquisition and processing.
Compatibility with conventional CMOS processing to support mass production and lower-cost, portable sequencing instrumentation.
Documented Applications
DNA and RNA sequencing, including sequencing by synthesis and related nucleic acid sequencing reactions.
DNA hybridization detection and hybridization-based assays.
Whole genome analysis and genome typing analysis.
Micro-array analysis and panels analysis.
Exome analysis and micro-biome analysis.
Clinical analyses including cancer analysis, non-invasive prenatal testing (NIPT) analysis, and UCS analysis.
Protein sequencing.
General analysis of biological and chemical materials using sensor arrays and I-Vg based detection metrics.
Interested in licensing this patent?