THESIS
2017
xxii, 140 pages : illustrations (some color) ; 30 cm
Abstract
Circulating tumor cell (CTC) isolation has made positive impacts on metastatic detection
and therapy analyses for cancer patients. Among various systems developed for CTC isolation,
size-based microfiltration systems face the challenge of low purity due to the size overlap of
CTCs and white blood cells (WBCs), and no reliable design rules, resulting in the diminished
performances. To address these issues, we propose a Microfluidic-Elasto-Filtration (MEF)
method which based on the Elasto-Capillary number (Ca
e) to isolate CTCs from peripheral
blood, in which the Ca
e is the ratio of viscous forces to cell elastic forces. Compact design
guidelines for the MEF chips to achieve high capture efficiency, purity and viability in CTC
isolation have been proposed based on Ca
e and the norma...[
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Circulating tumor cell (CTC) isolation has made positive impacts on metastatic detection
and therapy analyses for cancer patients. Among various systems developed for CTC isolation,
size-based microfiltration systems face the challenge of low purity due to the size overlap of
CTCs and white blood cells (WBCs), and no reliable design rules, resulting in the diminished
performances. To address these issues, we propose a Microfluidic-Elasto-Filtration (MEF)
method which based on the Elasto-Capillary number (Ca
e) to isolate CTCs from peripheral
blood, in which the Ca
e is the ratio of viscous forces to cell elastic forces. Compact design
guidelines for the MEF chips to achieve high capture efficiency, purity and viability in CTC
isolation have been proposed based on Ca
e and the normalized cell diameter (d
*) with respect
to the pore diameter. An optimized Ca
e* = 0.043 (regarding to 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. At the optimized Ca
e*, MEF
achieved 92% capture efficiency for MCF-7 cells, 4-log depletion of WBCs and 85% cell
viability. In addition, given the enormous variations in blood properties of cancer patients, such
as its viscosity, a personalized isolation methodology of CTCs, personalized MEF (pMEF), has
been proposed and tested to be with consistent and reliable clinical performance. Utilizing the
pMEF approach, CTCs were successfully identified in 1 or 2 mL peripheral blood of 19 out of
28 cancer patients, resulting in sensitivity as high as 87.5% in metastatic and 41.7% in non-metastatic
cancers and a specificity as high as 100%, outperforming the FDA-approved
CellSearch
TM system. With the next-generation filters, MEF chips and personalization
methodology, the pMEF technique will be highly promising for early detection of cancer
metastasis, monitoring of cancer treatment and early cancer detection.
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