Microfluidic rare cell analysis beyond counting: workflow design from enrichment to multi-omics

Area of Science:

• Biotechnology
• Analytical Chemistry
• Cell Biology

Background:

• Rare cells like circulating tumor cells (CTCs) and immune cells are crucial for diagnostics and therapeutics.
• Cell rarity poses challenges for accurate molecular and functional assays due to sampling statistics and workflow biases.
• Microfluidics offers deterministic cell handling and integrated workflows for rare cell analysis.

Purpose of the Study:

• To review microfluidic rare-cell platforms as information-preserving workflows.
• To define rare-cell contexts, workflow constraints, and design rules for optimal performance.
• To compare different enrichment strategies and analytical modules for rare cell analysis.

Main Methods:

• Discussion of microfluidic principles for rare cell handling and enrichment.
• Comparison of label-free, label-based, and hybrid enrichment strategies.
• Overview of analytical modules for captured rare cells, including omics-enabled workflows.

Main Results:

• Microfluidics enables deterministic handling, low-dead-volume processing, and integrated enrichment/readout.
• Scenario-dependent design rules link input burden, target/background contrast, and assay compatibility.
• Trade-offs in recovery, purity, throughput, viability, and phenotype preservation are highlighted for different methods.

Conclusions:

• Microfluidic platforms offer a route beyond capture-and-count for robust rare cell analysis.
• These workflows are essential for advancing diagnosis, drug screening, and cell-therapy development.
• Translation to clinical implementation and industrial adoption requires careful consideration of workflow stability and assay compatibility.