Theoretical Modeling, Dimensional Analysis for Design and Fabrication of Hexagonal Microfiltration Array Chips for Isolation and Detection of CTCs & CTC Clusters

Abstract

Efficient isolation of both Circulating tumor cell (CTC) and CTC cluster is critical for cancer diagnostics, disease monitoring and personalized treatment. While CTC cluster shows higher specificity for malignancy than normal single CTC. Efficient isolation of both single CTC and CTC clusters from peripheral blood, while simultaneously depleting background white blood cells (WBCs), is essential for downstream culture, molecular profiling, and clinical decision-making. This thesis presents the conception, fabrication, characterization, and modelling of a new type of microfluidic elasto-filtration (MEF) device, i.e., hexagonal-shaft-and-membrane array (HSMA) microfiltration device that addresses these needs. A set of HSMA design was first derived from hydrodynamic considerations and realized through Deep Reactive Ion Etcher (DRIE) fabricated silicon device. A syringe-driven flow platform was developed to enable repeatable experiments with samples. Capture efficiency for single CTCs and CTC clusters was quantified for every design. The data were collapsed by means of generalized dimensional analysis, yielding six independent normalized parameters that govern capture performance. From these, two dimensionless numbers, i.e., Cortical-Capillary Number and Adhesion-Capillary Number, were extracted and extended to a semi-empirical model and a nonlinear Maxwell spring–damper model that links stresses to cell deformation, dissociation and retention.

This semi-empirical model was validated with two additional cell lines, predicting capture efficiency within less than ±2 % of experimental values across variation in flow rate and chip geometry. The clinical application of this chip was assessed by estimating the white blood cell depletion based on the model. The optimized HSMA chip achieved >90 % CTC and CTC cluster capture efficiency and a three-order-of-magnitude reduction in WBCs which satisfied for downstream genomic analysis. Collectively, this work delivers a physically interpretable design framework and an experimentally verified microfluidic platform that advances liquid biopsy technology toward routine clinical implementation.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Yi-Kuen LEE (Supervisor)