Diaphragm-based microfluidic platforms for reconfigurable sample manipulation: from enrichment to activated sorting

Precise manipulation of small sample volumes through enrichment, metering, routing, and selective sorting defines the analytical performance of microfluidic systems. While passive approaches such as deterministic lateral displacement and inertial microfluidics offer robust geometry-encoded separations and field-based techniques like dielectrophoresis, magnetophoresis, and acoustofluidics provide dynamic control, they are limited by inability for tuning, susceptibility to sample media properties, and hardware complexity. Diaphragm-based actuation overcomes these constraints by introducing deformable membranes that dynamically reconfigure channel geometry to achieve sub-second fluidic control without direct exposure to external fields. This review consolidates diaphragm-actuated microfluidic strategies as a unified framework for active sample manipulation, spanning two key functions, enrichment (analyte/cell trapping, ion-transport focusing, and nanoconfinement) and activated sorting (label-based, label-free, and hybrid modalities). Diaphragm materials, geometries, and actuation schemes (pneumatic, piezoelectric, electrostatic, electromagnetic, thermo-pneumatic, and shape-memory) are benchmarked against quantitative performance metrics like pressure-deflection transfer, latency, enrichment efficiency, selectivity, and gating accuracy. Emerging directions include smart fatigue-resistant diaphragm materials, sensor-integrated feedback control, real-time programmable gating, scalable fabrication, and artificial intelligence (AI) to process multimodal data to trigger actuation. By bridging sample enrichment and activated sorting within a single mechanical paradigm, diaphragm-based actuation provides a versatile route towards autonomous, label-free, and high-content lab-on-a-chip systems for next-generation diagnostics, single-cell analytics, and biomanufacturing workflows.