Closed-loop controlled chemical apparatus
Inventors
Balijepalli, Arvind Kumar • Richter, Curt Andrew • Le, Son Truong
Assignees
United States Department of Commerce
Publication Number
US-11733191-B2
Publication Date
2023-08-22
Expiration Date
2040-09-23
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Abstract
A closed-loop controlled chemical apparatus includes: a compound sensor including: an analyte sensor and that: produces, by the analyte sensor, a voltage signal; a reference sensor in electrical communication with the analyte sensor; a transistor including a gate terminal such that a drain current of the transistor is maintained at a constant value and operated at an optimal transduction condition of peak sensitivity and minimum noise of the transistor; a feedback controller in electrical communication with the transistor and that: receives a transduction signal; determining a deviation of the transduction signal from a setpoint, the setpoint determined by transfer characteristics of the transistor; produces the feedback control signal that minimizes the deviation of the transduction signal from the based on a control model; and communicates the feedback control signal to the reference sensor for suppression of electrical noise fluctuations in the closed-loop controlled chemical apparatus.
Core Innovation
The invention disclosed is a closed-loop controlled chemical apparatus comprising a compound sensor with an analyte sensor that produces a voltage signal varying in response to an analyte that electrically perturbs the analyte sensor, changing the voltage from a target voltage referenced to a voltage provided by a reference sensor through a composition that includes the analyte. The reference sensor is in electrical communication with the analyte sensor and receives a feedback control signal from a feedback controller to actively null the difference between the voltage signal and the target voltage when perturbed, maintaining the analyte sensor at the target voltage to suppress electrical noise fluctuations affecting the voltage signal.
The apparatus includes a transistor with a gate terminal electrically connected to the analyte sensor so that the gate terminal receives a gate potential that maintains a constant drain current, operating the transistor at an optimal transduction condition of peak sensitivity and minimum noise based on the feedback control signal. The feedback controller is in electrical communication with the transistor, receives a transduction signal, determines deviation from a setpoint based on the transistor's transfer characteristics, produces a feedback control signal minimizing this deviation based on a control model, and communicates this signal to the reference sensor to suppress noise.
The background problem addressed concerns the technical deficiencies of prior compositions, such as highly nonlinear sensor response, high flicker noise at measurement bandwidths of interest, and non-uniform measurement resolution across the sensor dynamic range. The invention overcomes these limitations by actively nulling input to the transistor's gate from charge fluctuations at the analyte sensor's surface, providing a linear sensor response, consistently low noise across the dynamic range, and drastically improved measurement resolution through active noise suppression.
Claims Coverage
The patent includes multiple inventive features disclosed across independent claims related to a closed-loop controlled chemical apparatus and a process of closed-loop control involving components such as a compound sensor, transistor, reference sensor, and feedback controller.
Closed-loop control of chemical sensing apparatus
A compound sensor comprising an analyte sensor producing a voltage signal responsive to analyte perturbation, referenced to a reference voltage by a reference sensor that receives feedback control signal and actively nulls differences to maintain target voltage, paired with a transistor whose gate terminal receives a gate potential maintaining a constant drain current operating at optimal sensitivity and minimum noise, and a feedback controller determining deviation from a setpoint and producing feedback control signals to suppress electrical noise fluctuations.
Use of transistor drain current as transduction signal
The transduction signal comprises the drain current from the transistor.
Integration of phase-sensitive detector with transistor
Inclusion of a phase-sensitive detector connected to the transistor's drain and source terminals that compares drain current to oscillating voltage, produces a direct current signal proportional to their phase difference, and supplies this as the transduction signal to the feedback controller.
Gate potential comprising voltage signal from analyte sensor
The gate potential applied to the transistor’s gate terminal includes the voltage signal received from the analyte sensor.
Summing feedback control signal and analyte voltage for gate potential
A summer device electrically connected to the analyte sensor, feedback controller, and gate terminal that sums the feedback control signal with the analyte sensor’s voltage signal to produce the gate potential for the transistor.
Use of field-effect transistor in apparatus
The transistor incorporated in the chemical apparatus is a field-effect transistor (FET).
Analyte comprising pathological protein form
The analyte comprises a pathological form of a protein, specifically an enzyme implicated in Alzheimer’s disease.
Analyte comprising therapeutic agent
The analyte comprises a therapeutic agent that restores a nonpathological function of a pathogenic form of a protein.
Improved pH resolution through feedback control
The apparatus achieves a pH resolution of 3.5×10−3 pH units, which is more than three times greater than that of an ion-sensitive field-effect transistor operated without the feedback control signal.
Process of closed-loop control for the chemical apparatus
A process producing target voltage by analyte sensor, contacting analyte and reference sensors with composition, perturbing analyte sensor electrically by analyte, changing voltage signal, reference sensor receiving and actively nulling difference with feedback control, maintaining transistor drain current at a constant value at optimal transduction conditions, feedback controller receiving transduction signal, determining deviation and producing feedback signal minimizing deviation, and communicating feedback control to reference sensor to suppress noise and perform closed-loop control.
These inventive features collectively provide a closed-loop chemical sensing system that actively suppresses electrical noise, maintains optimal transistor operating conditions, and improves measurement resolution and accuracy, including for analytes such as pathological proteins and therapeutic agents, with specific enhancements in pH sensing resolution.
Stated Advantages
Provides about a three-fold improvement in pH resolution over conventional ion-sensitive field-effect transistors.
Actively suppresses electrical noise fluctuations affecting the voltage signal to maintain stable sensor operation.
Maintains the transistor at an optimal operating point for peak sensitivity and minimum noise.
Transforms sensor response to ensure consistently low noise across the dynamic range with linear sensor response.
Enables high-resolution, laboratory-grade bioanalytical measurements using commercially available transistors.
Supports rapid testing of candidate therapeutic molecules by measuring enzymatic activity accurately and sensitively.
Documented Applications
Measurement and quantification of enzymatic activity, specifically activity of the pathological kinase Cdk5 implicated in Alzheimer’s disease.
Evaluation of therapeutic agents, such as custom polypeptides (e.g., p5), that modulate enzyme function for treating neurodegenerative diseases.
High-resolution pH sensing in biochemical and bioanalytical contexts, improving detection sensitivity and noise reduction.
Remote biosensing applications where sensing elements are physically separated from the transistor gate for improved stability and reduced parasitic noise.
Drug discovery and clinical diagnostics involving detection and analysis of analytes that electrically perturb sensors, including pathological proteins and therapeutic agents.
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