Microfluidic Device for Single-Cell Capture and Analysis
Solution Overview
Problem
Current microfluidic devices face challenges in selectively capturing and analyzing rare cells like circulating tumor cells (CTCs) due to low capture efficiency, fluidic resistance issues, and limitations in on-chip analysis capabilities, particularly in high-throughput applications.
Innovation Solution
A microfluidic device with arrays of cell assay units, each comprising a reaction chamber, micropocket, and bipolar electrodes, allows for selective cell capture, transfer, and analysis using dielectrophoresis, with independent control over reaction volume and fluidic isolation, enabling rapid electrical lysis and high-throughput analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If dielectrophoresis is used for selective cell capture at bipolar electrodes, then cell capture efficiency is improved, but fluidic resistance increases
Solution Approach 1:
The device divides the microfluidic channel into multiple segments with alternating bipolar electrode arrays and reaction chambers. This segmentation allows cells to be captured at electrode arrays while maintaining fluid flow through reaction chambers, reducing overall fluidic resistance while preserving capture efficiency.
Solution Approach 2:
The reaction chamber acts as an intermediary element between bipolar electrode arrays. It provides a fluid passage that connects electrode arrays, allowing continuous fluid flow while cells are captured at the electrodes, thus mediating between capture efficiency and fluidic resistance requirements.
2Productivity
If multiple bipolar electrode arrays are integrated into a single microfluidic device, then throughput is improved, but device complexity increases
Solution Approach 1:
Multiple bipolar electrode arrays are merged into a single integrated microfluidic device with shared fluidic pathways and common reagent delivery systems. This combining approach increases throughput by enabling parallel cell capture across multiple arrays while avoiding the complexity of multiple independent devices.
Solution Approach 2:
The microfluidic device is designed with universal components that serve multiple functions: bipolar electrode arrays perform both cell capture and electrical lysis, reaction chambers serve as both cell retention zones and analysis preparation areas, and the fluidic system handles both reagent delivery and waste removal across all arrays.
3Reliability
If cells are captured and retained in reaction chambers, then cell viability is maintained, but analysis speed is reduced
Solution Approach 1:
Cells are captured and retained in reaction chambers in advance, allowing them to be prepared and maintained in a controlled environment before analysis. This preliminary retention ensures cell viability is maintained while enabling rapid subsequent analysis through pre-positioned cells in ready-state.
Solution Approach 2:
The system maintains continuous cell retention in reaction chambers while simultaneously performing electrical lysis and analysis operations. This continuity allows cells to remain viable throughout the process while analysis proceeds without interruption, achieving both viability maintenance and rapid analysis.
4Difficulty of detecting and measuring
If electrical lysis is applied to captured cells, then intracellular analysis is enabled, but cell damage occurs
Solution Approach 1:
Electrical lysis is applied in controlled periodic cycles rather than continuously. The voltage is applied intermittently to achieve sufficient intracellular content release for analysis while allowing brief recovery periods that minimize cell damage and maintain membrane integrity during non-lysis phases.
Solution Approach 2:
The electrical lysis process uses controlled parameter changes including voltage magnitude, frequency, and duration. By adjusting these parameters, the system achieves effective intracellular analysis while minimizing harmful effects, as the electrical field strength and application time are optimized to lyse cells only when necessary and to the extent required.
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 device achieves efficient and scalable selective capture and analysis of single cells, maintaining cell viability and facilitating downstream assays, suitable for point-of-care applications and cancer diagnosis.
Implementation Method 1
The device utilizes dielectrophoresis at a wireless bipolar electrode (BPE) array for selective and high-throughput single-cell capture
Implementation Method 2
The use of dielectrophoresis (DEP) at a wireless bipolar electrode (BPE) array was demonstrated to be suitable for selective and high-throughput single-cell capture
Data Source
AI summary
A microfluidic device comprising one or more fluidic microchannels and one or more arrays of cell assay units is disclosed. Each cell assay unit in turn comprises at one bipolar electrode, micropocket, reaction chamber, and leak channel. In some embodiments, the cell assay unit further comprises two or more split BPEs inside the reaction chamber. The disclosed microfluidic device can be used to separate cells, especially rare cells, from its biological matrix and then analyze the isolated cell inside the reaction chamber. The disclosed device can isolate and analyze cells in a high-throughput fashion and without any modification or labelling to the cells. Cells isolated using the disclosed devices does not lose their vitality.