Integrated Microfluidic Sensor for Single-Cell Biophysical Analysis

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Solution Overview

Problem

Current systems for biophysical characterization of cells face challenges in efficiently characterizing individual cells and increasing throughput due to difficulties in accurate sensor positioning within microfluidic channels, leading to averaged results that obscure disease-specific changes in specific subanatomical regions or cell types.

Innovation Solution

A programmable sensor system integrated with a microfluidic chip, featuring multiple sensors and branch channels, allows for mechanical, electrical, and chemical stimulation of cells to measure biophysical characteristics such as size, rigidity, shape recovery time, viscosity, and electrical impedance, with a sorting mechanism to separate cells based on these characteristics, enhancing efficiency and throughput.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If existing tweezers are introduced into the microfluidic channel through an opening in the side wall to capture and manipulate cells, then single cell manipulation capability is achieved, but accurate positioning becomes very difficult and system throughput decreases

Engineering Contradiction:
Improveease of sensor positioningVSAvoidsystem throughput
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The sensor is merged with the microfluidic channel structure itself, forming an integrated unit where the sensor forms part of the channel wall. This integration eliminates the need for separate positioning of tweezers relative to the channel, as the sensing capability is built into the channel structure at the desired location.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The sensor is pre-positioned and integrated into the microfluidic channel during fabrication, before the actual cell manipulation process. This preliminary integration ensures accurate positioning is achieved once during manufacturing, eliminating the need for difficult and time-consuming positioning operations during system operation.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If a mixture of cells with different biophysical characteristics is analyzed, then processing speed is maintained, but disease-specific changes in specific subanatomical regions or cell types are obscured by averaged results

Engineering Contradiction:
Improvecell analysis throughputVSAvoiddisease-specific change detection accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system segments the cell population by individually capturing and analyzing cells one at a time using the integrated sensor, rather than analyzing mixtures simultaneously. This segmentation allows disease-specific changes in individual cells or specific cell types to be detected without being obscured by averaging effects, while the automated sequential processing maintains high throughput.

Inventive Principle:
Principle #1Segmentation

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 system enables precise and efficient characterization of individual cells, allowing for the identification of disease-specific changes and increasing the number of cells that can be analyzed over time, while eliminating the need for precise sensor positioning, thus improving the accuracy and speed of biophysical analysis.

Implementation Method 1

the sensor has a pair of tips which are adapted to capture the single cell therebetween when the single cell flows between the tips of the sensor

Methodology Applied
Scientific EffectMechanical manipulation: Mechanical Force

Implementation Method 2

the sensor may be adapted to obtain biophysical characteristics of the single cell by stimulating the single cell in the microfluidic channel mechanically and/or electrically

Methodology Applied
Scientific EffectMechanical stimulation: Mechanical Force

Implementation Method 3

the sensor may be adapted to obtain biophysical characteristics of the single cell by stimulating the single cell in the microfluidic channel chemically and/or biologically

Methodology Applied
Scientific EffectChemical stimulation: Chemical Bonding

Data Source

PatentEP3551994B1Measuring system and process of measuring multiple biophysical characteristics of cells
Publication Date: 2023.08.09 NEUROINDX
  • EP3551994B1 patent drawingFigure 1
  • EP3551994B1 patent drawingFigure 2
  • EP3551994B1 patent drawingFigure 3~4

AI summary

The invention relates to a system (10) adapted to measure multiple biophysical characteristics of cells, the system (10) comprising: a microfluidic chip (12) provided with a microfluidic channel (14) which allows cells to flow through, the microfluidic channel (14) having an inlet (14a), an outlet (14b), and a lateral opening (14c) situated between the inlet (14a) and the outlet (14b); and a capacitive sensor (30) integrated in the microfluidic chip, adapted to obtain biophysical characteristics of a single cell in the microfluidic channel (14) by directly manipulating the single cell by sensor elements (31, 32) through the lateral opening (14c) of the microfluidic channel (14), the sensor (30) comprising a stationary part and an electrostatically driven movable part which is movable relative to the stationary part, the stationary part being fixed to the microfluidic chip (12), the movable part being arranged in the lateral opening (14c) of the microfluidic channel (14), wherein a portion of the sensor elements (31, 32) provides an interface between fluid and air in the system.