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...[ Read more ]

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.