Microfluidic Tumor Cell Isolation for High-Purity Liquid Biopsy

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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.

Innovation Solution

A method using a silicon microchip with hundreds of thousands of micrometric electrodes to isolate tumor cells with a purity of at least 90%, employing pre-enrichment techniques and microfluidic systems for automated or semi-automated selection based on cell images, enabling high-purity specimens for molecular analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional isolation methods are used, then the process is simpler, but the purity of tumor cells is low

Engineering Contradiction:

Improvepurity of tumor cell specimenVSAvoidcomplexity of isolation method

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the tumor cell population into individual single cells using microfluidic devices with micrometric electrodes. This segmentation allows for precise isolation and purification of tumor cells from complex biological samples, achieving high purity specimens through automated single-cell manipulation and sorting.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses microfluidic devices with micrometric electrodes as an intermediary system between the complex biological sample and the final purified tumor cell specimen. This intermediary technology enables automated selection, manipulation, and purification of tumor cells, resolving the contradiction between simplicity and purity by providing a sophisticated yet integrated isolation platform.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If conventional isolation methods are used, then the procedure is less laborious, but the signal-to-noise ratio is inadequate

Engineering Contradiction:

Improvesignal-to-noise ratioVSAvoidtime required for isolation and analysis

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent implements self-service through automated microfluidic systems that perform selection, manipulation, and purification of tumor cells without extensive manual intervention. The system autonomously processes samples, isolates single cells, and generates high-purity specimens, thereby improving measurement precision while reducing the time loss associated with labor-intensive conventional methods.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent replaces manual mechanical isolation procedures with automated microfluidic systems controlled by micrometric electrodes. This substitution eliminates the need for time-consuming manual operations while achieving superior signal-to-noise ratios through precise automated single-cell manipulation and purification.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If invasive biopsy methods are used, then diagnostic reliability is high, but patient discomfort and cost increase

Engineering Contradiction:

Improvediagnostic reliabilityVSAvoidpatient comfort and procedural simplicity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts tumor cell information from liquid biopsies (blood or other body fluids) without requiring invasive tissue biopsy procedures. By isolating and analyzing circulating tumor cells or disseminated tumor cells from easily obtainable liquid samples, the method achieves diagnostic reliability comparable to invasive biopsies while significantly improving patient comfort and procedural simplicity.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the sampling parameter from invasive tissue biopsy to non-invasive liquid biopsy. By detecting and analyzing tumor cells in bodily fluids rather than requiring tissue extraction, the method maintains diagnostic reliability while improving ease of operation and patient comfort through a less invasive sampling approach.

Inventive Principle:

Principle #35Parameter changes

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 achieves high-purity tumor cell isolation, allowing for reliable diagnostic and predictive analyses, comparable to biopsy-level reliability, and enabling non-invasive early diagnosis and sensitive treatment follow-up, even in metastatic stages.

Implementation Method 1

manipulating individually single tumour cells in an automated way

Methodology Applied

Scientific EffectDielectrophoresis: Dielectric

Data Source

PatentUS10895575B2Method for identification, selection and analysis of tumour cells

Publication Date: 2021.01.19 MENARINI SILICON BIOSYSTEMS SPA

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.