Chemically differentiated sensor array
Inventors
Assignees
Publication Number
US-12372521-B2
Publication Date
2025-07-29
Expiration Date
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Abstract
Apparatuses, systems, and methods are disclosed for chemically differentiated sensor arrays and methods of manufacturing and using the same. In one or more examples. An integrated circuit chip includes a chemically differentiated array of graphene field effect transistors with one or more wells configured to receive a volume of biological sample liquid comprising a plurality of different types of biological substances to be distinguished using electrical measurements of output signals of the graphene field effect transistors. At least one electrode is configured to apply a changing gate bias voltage (VGs) that increases and decreases within a predetermined range to the sample liquid and at least one electrode is configured to monitor measurement vectors including slopes of drain current measurements relative to the voltage measurements and differences in slope of the measurement vectors distinguish different biological substances in the sample liquid. Systems and methods utilize the integrated circuit chip.
Core Innovation
An integrated circuit chip includes a chemically differentiated array of graphene field effect transistors with one or more wells configured to receive a volume of biological sample liquid comprising a plurality of different types of biological substances to be distinguished using electrical measurements of output signals of the graphene field effect transistors. At least one electrode is configured to apply a changing gate bias voltage (VGs) that increases and decreases within a predetermined range to the sample liquid and at least one electrode is configured to monitor measurement vectors including slopes of drain current measurements relative to the voltage measurements, and differences in slope of the measurement vectors distinguish different biological substances in the sample liquid. Systems and methods utilize the integrated circuit chip.
The array comprises environmentally-gated transistors formed on a chemically inert carbon-based semiconductor substrate such as graphene, with source and drain leads electrically insulated from an environmental gate that is a liquid. One or more transistors include a sensitization layer and the graphene channels can be functionalized with biomolecules to target different sample components so that changing the composition or dimensions of sensitization or functionalization changes the electrical properties of individual transistors. An electrical measurement device electrically coupled to leads and a computing module receive output signals and identify compositions or binding events based on the measured electrical properties and measurement vectors.
Claims Coverage
The claims include three independent claims and define the main inventive features of a chemically differentiated graphene field effect transistor array, a graphene transistor based system for multiplexed analysis including a computing device, and a method for electronic biological sample analysis.
Chemically differentiated array of graphene field effect transistors
A chemically differentiated array of graphene field effect transistors, the graphene field effect transistors individually including a source, a drain, and a graphene channel.
Wells formed above groups to receive biological sample liquid
One or more wells that are formed above one or more groups of the graphene field effect transistors of the array and are configured to receive a volume of biological sample liquid comprising a plurality of different types of biological substances to be distinguished using electrical measurements of output signals of the graphene field effect transistors.
Biomolecule functionalization for differential binding
A first type of biomolecule that functionalizes graphene channels of a first group and a second type of biomolecule that functionalizes graphene channels of a second group, the first and second types selected to bind to different types of biological substances in the sample liquid.
Top-surface electrodes applying gate bias and monitoring reference
One or more electrodes disposed on a top surface of the chip and offset horizontally from channels of the graphene field effect transistors, wherein at least one electrode is configured to apply a changing gate bias voltage (VGs) to the sample liquid and at least one electrode is configured to monitor a reference voltage (VREF) of the sample liquid.
Measurement vectors comprising VREF, current, and slope
Measurement vectors that individually comprise voltage measurements of the VREF of the sample liquid, current measurements of the graphene field effect transistor output signal, and slopes of drain current measurements relative to the voltage measurements, with differences in slope operable to distinguish different binding events.
Graphene transistor based system with computing device
A system comprising the integrated circuit chip and a computing device configured to perform measurements of current output of the graphene transistors and obtain measurement vectors indicative of binding, and to distinguish bindings based at least in part on differences in slope of the measurement vectors.
Method for electronic biological sample analysis using changing gate bias
A method comprising delivering a biological sample liquid to wells above groups of a chemically differentiated array, applying a supply voltage to transistor drains, applying a changing gate bias voltage (VGs) to the sample liquid using a top-surface electrode offset from transistor channels, monitoring VREF with a second top-surface electrode, determining measurement vectors including ID, VREF and slopes, and distinguishing bindings based on differences in slope.
The independent claims cover a graphene FET array with wells and biomolecule functionalization, top-surface offset electrodes that apply a changing gate bias and monitor a reference voltage, measurement vectors (VREF, current, slopes) whose slope differences distinguish bindings, a system combining the chip with a computing device for multiplexed analysis, and a method implementing these measurement and analysis steps.
Stated Advantages
Capability to distinguish different biological substances in a sample liquid by measuring differences in slope of measurement vectors comprising VREF, current, and slopes.
Sensitivity and specificity tunable by sensitization layers and biomolecule functionalization so the array can be sensitive to, and distinguish between, many different substances.
Multiplexed analysis enabling multiple groups of transistors with differing functionalization to detect multiple biological substances in a single sample.
Ability to quickly detect and identify different biomarkers, as illustrated by measured transconductance changes across sensor groups.
Suitability for DNA sequencing by detecting pH changes from binding events using graphene transistor electrical measurements.
Documented Applications
Biological sample analysis using a chemically differentiated graphene field effect transistor array to detect and distinguish multiple biological substances in liquid samples (e.g., blood, DNA, urine, saliva, cellular samples).
Antibody and protein detection for infections, diseases, and cancer markers by functionalizing graphene channels with biomolecules that bind respective antibodies or proteins.
Multiplexed analysis of biological samples where groups of graphene transistors are functionalized differently to detect different biological substances in the same sample.
DNA sequencing by measuring pH changes from nucleotide binding events via changes in electrical properties of graphene transistors to identify nucleotide sequences.
Integrated sensor systems and methods including cartridges, wells, and electronics for delivering samples to sensor chips and measuring electrical output for identification.
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