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...[ Read more ]

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.