Cell Detection Sensor Using Pulse Voltage and Membrane Potential

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Solution Overview

Problem

Current methods for detecting circulating tumor cells (CTCs) face challenges with low sensitivity, accuracy, and high detection limits due to issues with receptor specificity and the need for large sample volumes in immunomagnetic separation and flow cytometric techniques.

Innovation Solution

A method utilizing a sensor device with a response electrode and a base, applying pulse voltages to generate electric fields and measure detection currents to detect target cells by changing their membrane potential, allowing for high sensitivity and accuracy with a low detection limit, and using an acceptor such as an antibody or aptamer for specific bonding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If immunomagnetic separation or immunofluorescence is used for CTC detection, then the detection can be performed with available technology, but the receptor specificity is insufficient leading to low accuracy

Engineering Contradiction:
Improvedetection accuracyVSAvoidreceptor specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention changes the detection parameter from optical/chemical methods to electrical field-based detection. By applying electric fields to detect membrane potential changes and using electrical impedance to detect cell presence, the method achieves higher receptor specificity and detection accuracy without relying on traditional immunological receptors.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If flow cytometric technique is used for CTC detection, then the detection can be performed, but a large amount of sample is required leading to high detection limit

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention extracts and utilizes the electrical properties (membrane potential and impedance) of individual cells as the detection basis. By focusing on these intrinsic electrical characteristics rather than requiring bulk sample analysis, the method achieves high detection sensitivity with minimal sample volume.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the mechanical/optical flow cytometry system with an electrical field-based detection system. Instead of using fluid flow and optical scattering, the method uses electric fields to interact with cell membrane potentials and impedance, enabling detection with much smaller sample volumes.

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

3Quantity of substance

If traditional detection methods are used, then the detection process can be completed, but the detection limit is high and sensitivity is low

Engineering Contradiction:
Improvedetection limitVSAvoiddetection sensitivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The invention applies periodic pulse voltages to the detection electrode to stimulate and detect membrane potential changes in cells. This periodic electrical stimulation enables dynamic detection of cell electrical properties, significantly improving detection sensitivity and lowering the detection limit compared to static measurement methods.

Inventive Principle:
Principle #19Periodic action

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

The method effectively detects target cells with high sensitivity and accuracy, overcoming the limitations of existing techniques by measuring changes in current gain to determine cell presence without the need for large sample volumes or complex calibration procedures.

Implementation Method 1

a first pulse voltage is applied to the response electrode to generate a first electric field between the response electrode and the gate end of the base

Methodology Applied
Scientific EffectElectric field: Electric Field

Implementation Method 2

A membrane potential of the target cell is changed, a second pulse voltage is applied to the response electrode to generate a second electric field

Methodology Applied
Scientific EffectMembrane potential:

Implementation Method 3

a first detection current generated by the base is measured. A membrane potential of the target cell is changed, a second pulse voltage is applied to the response electrode

Methodology Applied
Scientific EffectElectrical signal generation:

Data Source

PatentUS11029279B2Method of detecting cells
Publication Date: 2021.06.08 NATIONAL TSING HUA UNIVERSITY
  • US11029279B2 patent drawing
  • US11029279B2 patent drawing
  • US11029279B2 patent drawing

AI summary

A method of detecting cells is provided. The method includes the following steps. A sensor device including a base and at least one response electrode is provided, wherein the response electrode is spaced apart from the base with respect to a gate end of the base. A test solution containing a target cell is placed on the response electrode, a first pulse voltage is applied to the response electrode, and a first detection current generated from the base is measured. A membrane potential of the target cell is changed, a second pulse voltage is applied to the response electrode, and a second detection current generated from the base is measured, wherein a sign of the first detection current and a sign of the second detection current are opposite.