Microchip Tumor Cell Isolation via Dielectrophoresis

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Solution Overview

Problem

Current methods for isolating and analyzing circulating and disseminated tumor cells are complex, laborious, and result in low-purity specimens, which are not compatible with refined diagnostic procedures, leading to high risks of false positives and negatives due to inadequate signal-to-noise ratios, especially in cases of small samples or formalin-fixed paraffin-embedded tissues.

Innovation Solution

A method utilizing a silicon microchip with hundreds of thousands of micrometric electrodes to isolate tumor cells with high purity, combined with microfluidic systems for automatic or semi-automatic selection based on cell images, enabling the recovery of specimens with at least 90% purity for molecular analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to isolate tumor cells, then the isolation process can be performed with simple equipment, but the specimen purity is low and the process is complex and laborious

Engineering Contradiction:
Improvespecimen purityVSAvoidisolation process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent replaces conventional mechanical isolation methods with dielectrophoresis, an electrical field-based technique. The microchip device uses non-uniform electric fields to manipulate and isolate tumor cells based on their dielectric properties, achieving high purity (≥90%) without complex mechanical operations. This substitution of electrical fields for mechanical manipulation resolves the contradiction between simplicity and precision.

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

Solution Approach 2:

The patent changes the physical parameter used for cell isolation from mechanical properties to dielectric properties. By applying alternating electric fields with specific frequencies and amplitudes, the system exploits differences in dielectric characteristics between tumor cells and normal cells to achieve selective isolation. This parameter change enables high-purity isolation while maintaining operational simplicity.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional isolation methods are used, then the equipment required is simple, but the signal-to-noise ratio is inadequate leading to false positives and negatives

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidisolation system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces conventional mechanical separation methods with dielectrophoresis-based electrical field manipulation. This substitution enables precise discrimination between tumor and normal cells based on dielectric properties, significantly improving the signal-to-noise ratio and diagnostic accuracy while eliminating false positives and negatives associated with mechanical methods.

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

Solution Approach 2:

The patent introduces an electrical field as an intermediary between the isolation system and the cells. The dielectric properties of cells act as mediators that respond differently to the electrical field, enabling selective manipulation and isolation of tumor cells. This intermediary approach enhances diagnostic reliability by providing a clear physical basis for differentiation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If invasive procedures like biopsy are performed to improve diagnosis accuracy, then the diagnostic reliability improves, but the patient discomfort and cost increase

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidpatient comfort
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts and analyzes tumor cells from peripheral blood, eliminating the need for invasive tissue biopsies. By isolating circulating tumor cells (CTCs) or disseminated tumor cells (DTCs) from easily obtainable blood samples using dielectrophoresis, the system achieves biopsy-level diagnostic reliability without the discomfort, risks, and costs associated with invasive procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses peripheral blood as an intermediary medium to access tumor cell information without directly invading the tumor site. The dielectrophoresis-based isolation system processes this intermediary blood sample to extract diagnostic information, providing a non-invasive pathway to achieve high diagnostic reliability.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of operation

If small samples or formalin-fixed paraffin-embedded tissues are used, then the sampling invasiveness is reduced, but the specimen purity is insufficient for refined molecular analysis

Engineering Contradiction:
Improvesampling easeVSAvoidspecimen purity
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent replaces conventional mechanical processing of small or fixed tissue samples with dielectrophoresis-based electrical field manipulation. This substitution enables effective isolation and purification of tumor cells from small peripheral blood samples or formalin-fixed paraffin-embedded tissues, achieving ≥90% purity suitable for refined molecular analysis while maintaining sampling ease.

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

This approach allows for reliable and accurate identification, isolation, and analysis of tumor cells, improving diagnostic and therapeutic outcomes by providing high-purity specimens suitable for advanced molecular analyses, comparable to biopsy reliability, and enabling non-invasive early diagnosis and sensitive follow-up in cancer treatment.

Implementation Method 1

manipulating individually single tumour cells and isolating them in an automatic or semi-automatic non-manual way

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric

Data Source

PatentUS12153040B2Method for identification, selection and analysis of tumour cells
Publication Date: 2024.11.26 MENARINI SILICON BIOSYSTEMS SPA
  • US12153040B2 patent drawing
  • US12153040B2 patent drawing
  • US12153040B2 patent drawing

AI summary

The present invention relates to a method for the diagnosis of tumoural conditions and/or of the corresponding state of advance, wherein a sample from a patient comprising at least one tumour cell is obtained. According to the invention, a purified specimen of the at least one tumour cell is obtained by individually selecting and isolating single cells in a microfluidic device the purified specimen having a purity of at least 90%. On the purified specimen thus obtained there is subsequently performed a molecular analysis such as to highlight a characteristic thereof suited to enabling diagnosis.