Electronic detection of a target based on enzymatic cleavage of a reporter moiety
Inventors
Aran, Kiana • Kane, Alexander • GOLDSMITH, BRETT • Paytavi, Regis
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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-11561197-B2
Publication Date
2023-01-24
Expiration Date
Abstract
Apparatuses, systems, and methods are disclosed for target detection based on collateral cleavage of a reporter by an enzyme. A biologically gated transistor may include a channel and a reporter moiety immobilized to the channel. The state of the reporter moiety may affect one or more output signals from the biologically gated transistor when excitation conditions are applied to the biologically gated transistor and a sample fluid is applied in contact with the channel. A sample fluid may include an enzyme configured to activate in response to a target nucleic acid to cleave the reporter moiety. Excitation circuitry may apply the excitation conditions, and measurement circuitry may measure output signals from the biologically gated transistor. An analysis module may determine a parameter relating to presence of the target nucleic acid, based on the one or more measurements.
Core Innovation
A system is disclosed in which a biologically gated transistor includes a channel and a reporter moiety immobilized to the channel, and the biologically gated transistor is configured such that one or more output signals from the biologically gated transistor are affected by a state of the reporter moiety in response to application of one or more excitation conditions to the biologically gated transistor and application of a sample fluid in contact with the channel. The sample fluid may include an enzyme configured to activate in response to a target nucleic acid to cleave the reporter moiety. Excitation circuitry is configured to apply the one or more excitation conditions to the biologically gated transistor, measurement circuitry is configured to perform one or more measurements of at least one of the one or more output signals from the biologically gated transistor that are affected by the state of the reporter moiety, and an analysis module is configured to determine a parameter relating to presence of the target nucleic acid based on the one or more measurements.
The background describes that various biochemical assays for detecting a target molecule can be expensive or complex, and that amplification of a target nucleic acid using recombinase polymerase amplification (RPA) or another amplification technique may be time-consuming, adding to the expense or complexity of a test. The background further explains that optical techniques for target detection may involve expensive optical components and that test equipment configured for one target may be unsuitable for other targets. By contrast, the summary states that assays using biologically gated transistors may provide low cost and low complexity for electronic target detection or characterization, with or without amplification of the target, and that sensors including biologically gated transistors may be built using traditional electronics manufacturing techniques leading to lower costs and applicability to a wide variety of targets.
Claims Coverage
One independent system claim is identified. The main inventive features extracted from the independent claim are listed below.
Channel formed from a two-dimensional material
A channel formed from a two-dimensional material disposed on a dielectric layer of a chip, the two-dimensional material selected from graphene or molybdenum disulfide, wherein an upper surface of the channel is configured to contact a sample fluid.
Dielectrically insulated source and drain
A conductive source and a conductive drain that are covered with a dielectric that electrically insulates the conductive source and the conductive drain from the sample fluid so that current between the conductive source and the conductive drain is through the channel.
Reporter moiety immobilized to the channel
A reporter moiety immobilized to the channel, the biologically gated transistor being configured such that one or more output signals are affected by a state of the reporter moiety at or near the channel surface in response to application of a sample fluid in contact with the channel, the sample fluid comprising an enzyme configured to activate, in response to a target nucleic acid, to cleave the reporter moiety.
Liquid gate with counter and reference electrodes
A biologically gated transistor having a liquid gate voltage adjusted via a counter electrode and measured by a reference electrode.
Excitation circuitry for liquid gate adjustments
Excitation circuitry configured to apply adjustments to the liquid gate voltage to the sample liquid via the counter electrode.
Measurement circuitry for output signals
Measurement circuitry configured to perform measurements of the one or more output signals from the biologically gated transistor that are modulated by the state of the reporter moiety.
Analysis module to determine target-related parameter
An analysis module configured to determine a parameter relating to presence of the target nucleic acid based on the measurements.
Sample fluid comprising an enzyme activated by target nucleic acid
A sample fluid comprising an enzyme configured to activate, in response to a target nucleic acid, to cleave the reporter moiety, whereby collateral cleavage of the reporter moiety affects the one or more output signals.
The independent system claim recites a biologically gated transistor with a two-dimensional channel and dielectrically insulated source and drain, a reporter moiety immobilized to the channel, a liquid gate controlled and measured via counter and reference electrodes, excitation and measurement circuitry to apply excitation and measure output signals affected by reporter state, an analysis module to determine parameters relating to presence of a target nucleic acid, and a sample fluid comprising an enzyme that activates in response to the target to cleave the reporter moiety.
Stated Advantages
Provides low cost and low complexity for electronic target detection or characterization.
Operates with or without amplification of the target, avoiding time-consuming amplification steps such as RPA.
Sensors may be built using traditional electronics manufacturing techniques, leading to lower costs.
May perform electronic target detection for a wide variety of targets, reducing the need for equipment specific to a single target.
Documented Applications
Detecting a nucleic acid target such as viral RNA sequence in a test to detect viral infection.
Detecting a cancer microRNA sequence in a test to detect cancer.
Quantification of enzyme activity such as trypsin activity in tissue culture, cell culture, and proteomics research based on cleavage of a peptide reporter.
Electronic detection of presence, absence, or concentration of a target nucleic acid in sample fluids including blood, saliva, mucus, cerebrospinal fluid, or stool.
Aggregating measurement information to a remote data repository for epidemiology purposes and analysis across multiple measurement apparatuses.
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