Charge detector and process for sensing a charged analyte
Inventors
Balijepalli, Arvind Kumar • Richter, Curt Andrew • Le, Son Truong • Suehle, John S.
Assignees
United States Department of Commerce
Publication Number
US-11493476-B2
Publication Date
2022-11-08
Expiration Date
2037-03-08
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Abstract
A charge detector includes: a charge sensor that senses a charged analyte and produces a charge signal in response to contact with the charged analyte; a transducer in electrical communication with the charge sensor and that: receives the charge signal from the charge sensor, receives a feedback control signal; and produces a transduction signal in response to receipt of the charge signal and the feedback control signal; and a sensitivity controller in electrical communication with the transducer and that: receives the transduction signal from the transducer; produces the feedback control signal in response to receipt of the transduction signal from the transducer; and produces a charge readout in response to receipt of the transduction signal from the transducer.
Core Innovation
The invention disclosed is a charge detector that operates a dual-gated field effect transistor (FET) at a quantum capacitance limit to perform ultrasensitive biosensing. The charge detector includes a charge sensor that senses a charged analyte and produces a charge signal in response, a transducer that receives this charge signal and a feedback control signal to produce a transduction signal, and a sensitivity controller that receives the transduction signal, produces the feedback control signal, and outputs a charge readout. The dual gate FET comprises an analyte gate, a two-dimensional active layer disposed on the analyte gate, source and drain electrodes in communication with the active layer, and a control gate that modulates current between the source and drain based on charge changes at the analyte gate due to the charged analyte.
The system is designed to produce an integrated chip-scale device with enhanced sensitivity by operating the dual-gated FET at the quantum capacitance limit of the two-dimensional active layer. This operation amplifies voltage signals and achieves up to 200 times greater sensitivity than conventional devices, allowing measurements of pH and charged biological molecules at sensitivities exceeding the Nernst limit. The charge sensor also enables dynamic tuning of sensitivity by varying the gate voltage and provides improved signal-to-noise ratio unlike conventional ion-sensitive FETs and chemFETs.
The detector further employs components such as a high impedance amplifier to preserve signal fidelity, an adder to combine gate voltage with charge signals, control loop feedback devices, and phase-sensitive detectors to enhance measurement accuracy. The design of the dual gate FET includes materials such as transition metal dichalcogenides for the two-dimensional active layer and specific geometries to facilitate sensitive detection of charged analytes including biomolecules. The invention addresses the challenge of detecting charged analytes with high sensitivity and low noise by leveraging the quantum capacitance limit and integrated feedback control mechanisms, overcoming limitations of conventional FET and chemFET devices.
Claims Coverage
The patent includes four independent claims, covering a sensing process and apparatus for ultrasensitive detection of charged analytes using a dual gate field effect transistor configured with feedback control and signal transduction mechanisms.
Process for sensing a charged analyte with feedback controlled transduction
A process comprising contacting a charge sensor with a charged analyte to produce a charge signal, communicating the charge signal to a transducer which receives a feedback control signal from a sensitivity controller, producing a transduction signal, and generating a charge readout by the sensitivity controller. The process includes summing the charge signal with a gate voltage to form a sum voltage applied to a dual gate FET which also receives drain voltage and feedback control signal, producing the transduction signal based on these inputs. The feedback control signal is produced via a control loop feedback device that compares a process signal derived from the transduction signal and a hold signal to adjust the feedback for sensing.
Enhanced sensing process with phase-sensitive detection
A further process comprising phase-sensitive detection of the transduction signal to produce a phase signal and a process signal, which are used along with a hold signal by a control loop feedback device to produce a controller signal. An adder receives the phase signal and controller signal to produce a feedback control signal that is applied to the dual gate FET for improved sensing.
Use of ionic liquid on the control gate
A process including disposing an ionic liquid on the control gate of the dual gate field effect transistor to enhance device performance.
Charge detector apparatus with integrated feedback and dual-gate transistor
A charge detector comprising a charge sensor with separate sensing and reference electrodes producing a charge signal; a transducer receiving the charge signal and a feedback control signal, producing a transduction signal; a dual gate FET with an analyte gate, two-dimensional active layer, source and drain electrodes, and a control gate controlling current flow in response to the sum voltage and feedback control signal; and a sensitivity controller receiving the transduction signal and producing the feedback control and charge readout signals. The sensing electrodes are structurally distinct from the dual gate FET elements.
The claims collectively cover an integrated charge detection system using a dual gate FET operated at quantum capacitance limits with a feedback control loop, incorporating phase-sensitive detection and ionic liquid gating, to perform ultrasensitive detection and measurement of charged analytes.
Stated Advantages
Improves measurement sensitivity by up to 200× over conventional field effect transistors.
Allows dynamic tuning of sensitivity and dynamic range by varying gate voltages.
Achieves higher signal-to-noise ratio with low noise operation, unusual for dual gate and chemFET devices.
Provides ultrasensitive charge measurement suitable for biosensing applications including pH and charged biomolecules.
Enables rapid and quantitative measurement of enzyme activity and interaction kinetics.
Enables low limit of detection, e.g., on the order of 0.001 pH units.
Reduces noise and leakage current due to use of two-dimensional active layer and ionic liquid gating.
Documented Applications
Ultrasensitive biosensing of charged analytes such as proteins, DNA, and charged biological molecules.
Measurement of pH with sensitivity exceeding the Nernst limit.
Label-free enzyme activity and kinetics measurement, e.g., measuring kinase activity implicated in Alzheimer's disease.
Quantification of molecular interactions and binding kinetics via changes in charge or potential.
Time-resolved biochemical sensing in microfluidic channels or test tubes.
Remote sensing via chip-scale integrated systems with separated sensor and transducer modules.
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