THESIS
2018
xvi, 81 pages : illustrations ; 30 cm
Abstract
The isolation of circulating tumor cell (CTC) is one of the key liquid biopsy technologies for
diagnosis and prognosis of cancer. Among various systems developed for CTC isolation, size-based
microfiltration chips face the challenge of low purity due to the overlapping size distribution of
CTCs and white blood cells (WBCs), and no reliable design rules, resulting in lower detection
performances. To address these issues, we propose a nonlinear mass-damper-spring model to
predict the performance of Microfluidic-Elasto-Filtration (MEF) chips which based on the Elasto-Capillary number (Ca
e) to isolate CTCs from peripheral blood. Ca
e is the ratio of viscous forces to
cell elastic forces. Compact design guidelines for the MEF chips to achieve high capture efficiency and purity in CTC is...[
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The isolation of circulating tumor cell (CTC) is one of the key liquid biopsy technologies for
diagnosis and prognosis of cancer. Among various systems developed for CTC isolation, size-based
microfiltration chips face the challenge of low purity due to the overlapping size distribution of
CTCs and white blood cells (WBCs), and no reliable design rules, resulting in lower detection
performances. To address these issues, we propose a nonlinear mass-damper-spring model to
predict the performance of Microfluidic-Elasto-Filtration (MEF) chips which based on the Elasto-Capillary number (Ca
e) to isolate CTCs from peripheral blood. Ca
e is the ratio of viscous forces to
cell elastic forces. Compact design guidelines for the MEF chips to achieve high capture efficiency and purity in CTC isolation have been proposed based on Ca
e and the normalized cell diameter
(d*). An optimized Ca
e* = 0.043 (regarding CTCs) has been identified to achieve the maximum
capture efficiency of CTCs and optimized depletion efficiency of WBCs by both numerical
simulations and systematic experiments. Based on the guidelines, Microfluidic-Elasto-Filtration
(MEF) CTC chips in excellent uniformity of pore arrays were designed and fabricated with 4-inch
silicon-on-insulator (SOI) wafers using Deep Reactive-Ion Etching (DRIE) technology. And
experimental tests have been conducted using MEF CTC chips to verify that the new SOI-wafer
based CTC chips could achieve high efficiency in CTC isolation based on the cell size difference
and the variation in cell elasticity. In addition, the surface hydrophobicity effect of MEF chips was
also studied and a critical d*(~2.1) was identified by both experiments and simulations to determine
whether the hydrophobicity effect can enhance the cancer cell capturing in MEF under the
optimized Ca
e(c)*. With more advanced MEF systems developed, the MEF technique will be highly
promising for early detection of cancer metastasis and monitoring of cancer treatment.
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