Single Cell Array Microchip for Precise Dielectrophoretic Positioning

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Solution Overview

Problem

Existing cell electrical measurement and electroporation technologies face inefficiencies and low precision due to random cell distribution on microchips, leading to high cell mortality rates and lack of control.

Innovation Solution

A single cell array microchip with a substrate, positioning electrodes forming a rhombus shape, and measuring electrode-pairs connected by lateral and longitudinal bars, allowing for precise cell positioning and electroporation using alternating current signals and bias voltages for improved measurement and reduced mortality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If cells are allowed to distribute randomly on the microchip, then the operation process is simplified, but the measurement precision and electroporation controllability deteriorate

Engineering Contradiction:
Improveoperation process simplicityVSAvoidsingle cell measurement precision
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The microchip is segmented into multiple independent positioning units, each comprising positioning electrodes arranged in specific patterns (e.g., interdigitated electrodes). Each unit can independently trap and position single cells, enabling precise control while maintaining overall system simplicity. The chip surface is divided into arrays of such units, allowing parallel processing of multiple cells.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Positioning electrodes serve as intermediaries between the external control system and the cells. By applying AC signals to these electrodes, dielectrophoretic forces are generated that manipulate cell positions without direct mechanical contact. This intermediary mechanism enables precise cell positioning while keeping the operation process automated and simple.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If cells are positioned precisely using positioning electrodes, then the measurement precision and electroporation controllability are improved, but the device complexity increases

Engineering Contradiction:
Improvesingle cell measurement precisionVSAvoidmicrochip structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The positioning electrodes serve multiple functions: they generate dielectrophoretic forces for cell positioning, enable electrical measurements through the positioned cells, and facilitate electroporation by controlling the electric field distribution. This multi-functionality reduces the need for separate components, thereby limiting device complexity while achieving precise cell control.

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

Solution Approach 2:

The patent combines positioning, measurement, and electroporation functions into a single integrated microchip structure. The positioning electrodes and measuring electrodes are co-integrated on the same substrate, and the entire system is controlled through a unified AC signal generation and detection platform. This merging approach simplifies the overall device architecture compared to using separate systems for each function.

Inventive Principle:
Principle #5Merging (Combining)

3Ease of operation

If conventional electrochemical measurement is used without cell positioning, then the operation process remains simple, but the efficiency and precision of measurement deteriorate

Engineering Contradiction:
Improvemeasurement operation simplicityVSAvoidmeasurement efficiency
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The positioned cells on the microchip enable automated measurement sequences. Once cells are trapped in position by the positioning electrodes, the system can automatically perform electrical measurements, analyze results, and proceed to electroporation if needed. This self-service capability increases measurement efficiency without requiring complex manual intervention, maintaining operational simplicity.

Inventive Principle:
Principle #25Self-service

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

Enhances the precision and efficiency of electrical measurements and electroporation while reducing cell mortality through controlled, label-free, and noninvasive manipulation of cells, enabling real-time, multi-mode analysis with automated control.

Implementation Method 1

Dielectrophoresis (DEP) is given prominence as a significant manipulation tool for the studies of cells, viruses, DNA in the field of life science.

Methodology Applied
Scientific EffectDielectrophoresis:

Implementation Method 2

electrical measurements, motility and physicochemical property measurement. The common methods adapted are acknowledged as observation via microscope, electrochemical measurement and optical measurement.

Methodology Applied
Scientific EffectElectrical measurement:

Implementation Method 3

electrical measurement and electroporation method thereof

Methodology Applied
Scientific EffectElectroporation:

Data Source

PatentUS9695412B2Single cell array microchip and fabrication, electrical measurement and electroporation method thereof
Publication Date: 2017.07.04 TSINGHUA UNIVERSITY
  • US9695412B2 patent drawing
  • US9695412B2 patent drawing
  • US9695412B2 patent drawing

AI summary

The present invention relates to single cell array micro-chips and fabrication, electrical measurement and electroporation method thereof. The single cell array microchip comprises a substrate (1), a plurality of positioning electrodes (2) formed in an array, a plurality of measuring electrode-pairs (3) formed in an array, and a micro sample pool (4). The invention integrates cell array positioning with electrical measurement and electroporation for living cells, which is characteristic of label-free and noninvasive methods to manipulate, position particles/cells as well as further measure their electrical parameters. Therefore, single-cell-array positioning and multi-mode in-situ real-time measurement can be realized for intensive analysis. Since the positioned cells are immobile, the precision of the electrical measurement of cells is effectively improved, so is the efficiency of electroporation with lower cell mortality rate.