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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-11215580-B2
Publication Date
2022-01-04
Expiration Date
Abstract
A DNA sequencing and blood chemistry analysis system and method are provided including one or more sensor chips and one or more sample wells, wherein each sample well is configured to form a seal with one of the sensors. The one or more sensor chips may comprise Graphene transistors, and each transistor having an associated sequencing probe. The sensor chips interact with a biological sample introduced into the sample well, wherein changes in the current, transconductance, and resistance of the Graphene transistors are indicative of a DNA binding process. Based on the associated sequencing probes, the DNA sequence present in a biological sample can be identified.
Core Innovation
A DNA sequencing and blood chemistry analysis system and method are provided including one or more sensor chips and one or more sample wells, wherein each sample well is configured to form a seal with one of the sensors. The one or more sensor chips may comprise Graphene transistors, and each transistor having an associated sequencing probe. The sensor chips interact with a biological sample introduced into the sample well, wherein changes in the current, transconductance, and resistance of the Graphene transistors are indicative of a DNA binding process. Based on the associated sequencing probes, the DNA sequence present in a biological sample can be identified.
The present disclosure addresses diagnostic limitations in which current diagnostic technologies generally do not have the sensitivity to directly detect the presence of infectious agents before an immune response occurs, rely on antibody detection, require reporter molecules or labels, require significant time, expertise, and expensive automation equipment, and are operator-dependent. The disclosure describes an electronic biological sample analysis system and method that measures changes in electrical properties of a nanoelectronic circuit in contact with a biological sample to determine binding events, and notes that this technique can be extraordinarily sensitive and can be engineered to tailor the sensitivity of the electronic circuit system to obtain desired measurements.
Example systems include an electronic biological sample sensor system with one or more sensor chips electronically coupled to an external connector and enclosed in a case with one or more sample wells configured to form a liquid-tight seal with sensor chips, and example methods include introducing a biological sample into the sample well, [procedural detail omitted for safety], and analyzing changes in electrical properties caused by DNA binding to identify DNA sequences. Example embodiments further describe a sensing section with sensor chips and sequencing probes, a plate section with biological sample wells, and a processing section including a processing module.
Claims Coverage
This patent includes 9 inventive features extracted from three independent claims (method, system, and apparatus) that relate to graphene-based sensors with distinct biomolecule attachment modalities and measurement of a vector of electrical characteristics to identify binding events.
Sample well comprising a sensor
introducing a liquid comprising a biological sample into a sample well, the sample well comprising a sensor;
Graphene transistors with distinct biomolecule attachment modalities
[procedural detail omitted for safety] wherein the sensor comprises a plurality of biomolecules selected from sequencing probes and antibodies and a plurality of graphene transistors comprising one or more first transistors and one or more second transistors, wherein a first biomolecule comprising a first sequencing probe is covalently bound directly or through a linker to a scattering site comprising sp3 hybridized carbon formed in a top surface of the graphene of the first transistors and a second biomolecule different from the first biomolecule is immobilized adjacent to the top surface of the graphene of one or more second transistors by an immobilization layer disposed directly on the top surface of the second transistors instead of being covalently bound thereto directly or through a linker;
Identification by measuring a measurement vector
identifying DNA or RNA in the liquid by measuring changes in a vector comprising a liquid gate voltage, an output current, and a slope of the transconductance of the respective first and second transistors, the changes indicating a binding event between one or more components of the biological sample selected from DNA, RNA, and antibodies, in the liquid to the first biomolecules that are covalently bound directly or through a linker to the graphene of the first transistors, or indicating a binding event between the one or more components and the second biomolecules that instead of being covalently bound directly or through a linker are immobilized adjacent to the graphene of the second transistors by an immobilization layer on top of the graphene of the second transistors.
Sensing section with graphene sensor chip and sequencing probes
a sensing section including a sensor chip comprising a plurality of graphene transistors comprising first transistors and second transistors and a plurality of sequencing probes, the sensor chip including a top surface and a bottom surface;
Plate section with biological sample wells aligned to sensors
a plate section including one or more biological sample wells configured to receive a sample liquid, each well having one or more of the plurality of graphene transistors configured to measure a vector of electrical characteristics for identifying DNA or RNA sequences in the liquid;
Processing section measuring changes in an electrical vector
a processing section including a processing module configured to measure changes in the vector comprising a liquid gate voltage, an output current, and a slope of the transconductance of the graphene transistors, the changes indicating a binding event between sequencing probes associated with the graphene transistors and the DNA or RNA sequences in the sample liquid that are complementary to the respective sequencing probes;
Scattering site with sp3 hybridized carbon
wherein at least one of the first transistors comprises a scattering site comprising Carbon that is sp3 hybridized formed in the top surface of the sensor chip;
First sequencing probe covalently bonded to scattering site
wherein a first sequencing probe of the plurality of sequencing probes is covalently bonded directly or through a linker to the scattering site of the first transistors;
Second sequencing probe immobilized by an immobilization layer
wherein a second sequencing probe of the plurality of sequencing probes for detecting a different nucleotide sequence from that of the first sequencing probe is immobilized adjacent to the top surface of the graphene of the second transistors by an immobilization layer disposed on a top surface of the graphene of the second transistors instead of being covalently bonded, directly or through a linker, to a scattering site on a top surface of the graphene of the second transistors.
The independent claims disclose graphene transistor sensor chips with first transistors having sequencing probes covalently bound to sp3 scattering sites and second transistors having sequencing probes immobilized by an immobilization layer, integrated into sample-well-based systems with a processing module that measures changes in a vector of electrical characteristics (liquid gate voltage, output current, slope of transconductance) to detect binding events and identify DNA or RNA.
Stated Advantages
Technique can be extraordinarily sensitive.
Sensitivity of the electronic circuit system can be engineered or tailored to obtain desired measurements.
Potential to increase sensitivity while reducing high cost and high operator-dependence of current tests.
Documented Applications
Electronic biological sample analysis including DNA sequencing and blood chemistry analysis.
Detection of viral or bacterial infections and other ailments by detecting antibodies and directly detecting binding events in biological samples.
Clinical biological sample analysis on blood or urine samples for diagnostic purposes, with examples including detection of Lyme disease.
Identification of DNA chains associated with hereditary diseases and predispositions to cancer by determining the precise order of nucleotides.
Use in plate-based DNA sequencing configurations, including embodiments with multiple open-air wells (for example, embodiments describing ninety-six open-air wells).
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