FET Sensor Charge Detection for Nucleic Acid Analysis

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Solution Overview

Problem

Current nucleic acid sensors, particularly optics-based biosensors, are costly, time-consuming, and not suitable for routine clinical use due to high manufacturing costs and complexity, while integrated electrical sensors face limitations in manufacturability and robustness.

Innovation Solution

A sensor system with a fluidic chamber and a membrane having pores for electrolyte passage, utilizing an electric field to pull charged analytes into the pore and measure their charge, allowing for sensitive and robust detection of nucleic acids with improved manufacturability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optics-based sensing is used for nucleic acid detection, then detection sensitivity is improved, but device complexity and manufacturing cost increase significantly

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the optical sensing system with an electrical sensing system. Specifically, it uses a field-effect transistor (FET) sensor where the nucleic acid analyte modulates the electrical field between the gate electrode and source/drain electrodes, converting the detection mechanism from optical to electrical. This substitution reduces device complexity while maintaining detection capability through direct electrical signal measurement of the analyte's charge properties

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent extracts and utilizes the inherent charge property of the nucleic acid analyte for direct electrical detection. By designing the FET sensor to detect the charge of the analyte as it passes through or near the sensing region, the system eliminates the need for optical labels or complex optical pathways, achieving simplified detection based on the analyte's intrinsic electrical characteristics

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If optics-based sensing is used for nucleic acid detection, then detection sensitivity is improved, but manufacturing cost increases significantly

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmanufacturing cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces expensive optical components (light sources, detectors, optical pathways) with a relatively simple electrical sensing system based on FET technology. The electrical sensing approach uses standard semiconductor fabrication processes to create the sensor array, dramatically reducing manufacturing cost while maintaining detection sensitivity through direct electrical measurement of the analyte's charge

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs a disposable sensor array where each sensing element is a simple FET structure that can be mass-produced using standard semiconductor fabrication. The sensors are designed for single-use or limited-use applications, eliminating the need for expensive, complex optical systems that require maintenance and calibration, thereby reducing overall manufacturing and operational costs

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If integrated electrical sensors are used for nucleic acid detection, then manufacturing cost is reduced, but robustness deteriorates

Engineering Contradiction:
Improvemanufacturing costVSAvoidrobustness
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent designs a universal FET sensor platform that can detect various nucleic acid analytes through their common charge property. The sensor structure and detection principle remain the same across different applications, providing robust and reliable detection regardless of the specific analyte type. This universality enhances reliability by using a proven electrical sensing mechanism rather than application-specific optical configurations

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Measurement precision

If optics-based sensing is used for nucleic acid detection, then detection capability is improved, but time consumption increases

Engineering Contradiction:
Improvedetection capabilityVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces time-consuming optical detection processes with rapid electrical signal measurement. The FET sensor provides real-time electrical signal output as the analyte interacts with the sensing region, eliminating the need for complex optical setup, alignment, and data processing steps. This electrical measurement approach significantly reduces detection time while maintaining detection capability through direct charge sensing

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables fast, label-free, and cost-effective detection of nucleic acids, overcoming the limitations of existing sensors by providing a more sensitive, robust, and easily manufacturable solution for nucleic acid analysis.

Implementation Method 1

a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte upon the at least one charged analyte being pulled into the pore

Methodology Applied
Scientific EffectElectrical signal detection: Conduction (electrical)

Data Source

PatentUS20210048426A1Apparatuses and methods for determining analyte charge
Publication Date: 2021.02.18 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US20210048426A1 patent drawing
  • US20210048426A1 patent drawing
  • US20210048426A1 patent drawing

AI summary

The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.