Microfluidic Single Cell Separation and Detection
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Solution Overview
Problem
Existing methods for analyzing single cells face challenges such as non-uniform cell reactions, interference between cells, and cell adhesion to electrodes during measurement, leading to inaccurate results and difficulties in separating and storing desired cells.
Innovation Solution
A single cell separating apparatus using a fine fluid chip with a fluid channel, electrodes, and a detection system to apply electrical signals, count cells, and discharge them into fluid droplets, while a buffer unit prevents reverse flow and a well plate system stores cells separately to maintain purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If dielectrophoresis is used to capture single cells at a particular position, then cell positioning is improved, but cell stability deteriorates when voltage supply is cut off
Solution Approach 1:
The patent replaces the electrical field-based dielectrophoresis method with a microfluidic flow-based system. Cells are captured and positioned using controlled fluid flow through channels and junctions, eliminating the need for continuous voltage application while maintaining stable cell positioning. The microfluidic structure provides mechanical confinement and directional control without relying on electrical fields.
2Measurement precision
If rotational alternating current signals are applied to measure cell dielectric properties, then measurement capability is improved, but cell adhesion to electrodes occurs at high frequencies
Solution Approach 1:
The patent introduces a buffer fluid as an intermediary between the cell and the measurement system. The cell remains suspended in the buffer within the microfluidic channel, allowing electrical measurements to be performed through the buffer medium without direct contact between the cell and electrodes. This eliminates cell adhesion while preserving measurement capability.
Solution Approach 2:
The patent replaces direct electrical contact measurement methods with a microfluidic suspension system. Cells are kept in suspension through controlled fluid flow, and measurements are performed indirectly through the buffer medium, avoiding the high-frequency adhesion problem that occurs when cells directly contact electrodes.
3Productivity
If multiple cells are introduced to the measurement region, then sample throughput is improved, but interference between cells increases
Solution Approach 1:
The patent segments the measurement process into individual cell events using a microfluidic flow system. Cells are introduced in suspension but are spatially separated through controlled flow through narrow channels and junctions, ensuring that only one cell is measured at a time. This maintains high throughput by continuous flow while eliminating cell-to-cell interference through temporal and spatial separation.
4Measurement precision
If friction between cell membrane and bottom substrate is reduced, then cell rotation accuracy is improved, but cell confinement and positioning control deteriorates
Solution Approach 1:
The patent replaces direct substrate contact with a microfluidic suspension system. Cells are kept in suspension within the buffer-filled channel rather than contacting the bottom substrate directly. This eliminates friction between the cell membrane and substrate, improving rotational measurement accuracy, while the microfluidic channel walls and flow control provide alternative confinement and positioning mechanisms.
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
Effectively separates and counts single cells, prevents reverse flow during measurement, and maintains cell purity by independently storing heterologous and single cells, reducing errors in gene analyses.
Implementation Method 1
a detection electrode provided between the first electrode and the second electrode to detect the single cell in the sample
Implementation Method 2
first and second electrodes provided on the fluid channel to apply electrical signals to the sample being conveyed through the flow path of the fluid channel
Data Source
AI summary
An apparatus and method for separating single cells. The apparatus includes: a fluid channel having an upper panel, a lower panel, and a flow path formed therebetween that is configured to convey a sample including a single cell; a single cell measuring unit including first and second electrodes provided on the fluid channel in a predetermined spaced relationship for applying electrical signals to the sample in the flow path, and a detection electrode provided between the first and second electrodes to detect the single cell in the sample in the flow path, such that the single cell measuring unit applies the electrical signals to the sample in the flow path, detects the electrical signals of the sample, and detects whether there is the single cell in the sample; and a single cell separation control device which outputs a single cell separation control signal when the single cell is detected by the detection electrode.