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5.2 Integrated Microfluidic Systems for CTC Capture and Molecular Profiling

Leveraging the capabilities of microfluidic devices for microchannel fluid
pumping, analyte filtration, and selective capture, alongside the high design flexibility

and material versatility offered by 3D printing technology in the fabrication of such

devices, researchers have developed diverse and efficient strategies for capturing

circulating tumor cells (CTCs).

(1) Optimized Microfluidic Geometries Enhancing Separation Purity and

Throughput

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Leveraging additive manufacturing, Chen et al. employed 3D printing to
fabricate microfluidic devices featuring tailored microchannel geometries and

specialized surface modifications. This innovative approach significantly enhanced
CTC capture efficiency by optimizing cell-surface interactions. Stiefel et al. 120

integrated immunomagnetic bead enrichment, microfluidic fluorescence activation

sorting, and single-cell droplet distribution modules, and designed a multifunctional

microfluidic chip including sample storage area, hydrodynamic focusing channel,

optical detection area, and cell dispensing nozzle to achieve efficient separation of rare

cells, and successfully isolated CTC subsets of HNSCC patients, showing good clinical

translation potential and providing real-time monitoring tools for personalized

treatment (Figure 6B). Building on geometric innovation, Tan et al. 121 engineered

microchannels integrated with crescent-shaped isolation well arrays. These structures

incorporated precisely calibrated 5-micron gaps that selectively expelled smaller blood

components while retaining target cells, achieving both high-purity capture and

efficient background depletion. Further advancing structural design, Wang et al. 122,123

systematically compared 3D anti-EpCAM antibody-coated micropillar arrays against
conventional planar substrates. Their results confirmed that the 3D-printed

nanostructured substrates dramatically increased capture efficiency, attributed to their

expanded surface area for ligand binding and optimized local hydrodynamics (Figure

6C, D). For broader clinical applicability, Cohen et al. 124 utilized the commercial

Parsortix® PR1 system, which exploits serpentine microchannels to perform label-free,
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