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size-based CTC separation and enrichment. This method demonstrated robust broad-

spectrum capture across diverse tumor lines, irrespective of variable antigen expression

profiles.

(2) From Lab to Clinic: Validating 3D-Printed Microfluidic Systems for Ultra-

Sensitive Diagnostic Applications

Advancing clinical translation, Leitao et al. 125 engineered the RUBYchip™, a 3D

printed microfluidic platform demonstrating superior capture efficiency for renal cell

carcinoma (RCC) cells compared to conventional methods. Critically, their work

established a robust association between CTC enumeration and patient prognosis,

highlighting its clinical utility for disease monitoring. Complementing this, Law et al.

126 developed a vertically structured 3D-printed biosensor (V-BioChip) for high-

efficiency enrichment and detection of CTCs in gynecological malignancies

(cervical/endometrial cancers). Their analysis revealed novel prognostic relationships:
expression levels of HER2/GATA3 transcription factors and CD13 surface markers in

captured CTCs showed significant correlation with early cancer recurrence.
Collectively, these 3D-printed innovations—through optimized capture performance

and biomarker discovery—substantially accelerate the integration of CTC diagnostics

into clinical practice (Figure 6E).

5.3 Detection of Circulating Nucleic Acids, Exosomes, and Protein Biomarkers

Over the past decade, microfluidic devices for molecular analysis have made

remarkable progress, evolving from proof-of-concept demonstrations to sophisticated

platforms capable of performing complex analytical workflows. These miniaturized

systems now offer distinct advantages over conventional techniques, including reduced

sample/reagent consumption, faster analysis times, improved sensitivity through

enhanced mass transport, and the ability to integrate multiple processing steps on a

single chip. With demonstrated success in applications ranging from point-of-care

diagnostics to high-throughput omics analysis, microfluidics has reached a
technological maturity where it can legitimately compete with - and in some cases

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