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Li P , Mao Z , Peng Z , Zhou L , Chen Y , Huang PH , Truica CI , Drabick JJ , El-Deiry WS , Dao M , Suresh S , Huang TJ
Acoustic separation of circulating tumor cells
Proc Natl Acad Sci U S A. 2015 Apr 21;112(16) :4970-5
PMID: 25848039    PMCID: PMC4413297    URL: http://www.ncbi.nlm.nih.gov/pubmed/25848039
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Circulating tumor cells (CTCs) are important targets for cancer biology studies. To further elucidate the role of CTCs in cancer metastasis and prognosis, effective methods for isolating extremely rare tumor cells from peripheral blood must be developed. Acoustic-based methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contact-free sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients owing to technical constraints, insufficient throughput, and lack of long-term device stability. In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients. Our method uses tilted-angle standing surface acoustic waves. Parametric numerical simulations were performed to design optimum device geometry, tilt angle, and cell throughput that is more than 20 times higher than previously possible for such devices. We first validated the capability of this device by successfully separating low concentrations ( approximately 100 cells/mL) of a variety of cancer cells from cell culture lines from WBCs with a recovery rate better than 83%. We then demonstrated the isolation of CTCs in blood samples obtained from patients with breast cancer. Our acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.
Li, Peng Mao, Zhangming Peng, Zhangli Zhou, Lanlan Chen, Yuchao Huang, Po-Hsun Truica, Cristina I Drabick, Joseph J El-Deiry, Wafik S Dao, Ming Suresh, Subra Huang, Tony Jun ENG U01 HL114476/HL/NHLBI NIH HHS/ U01HL114476/HL/NHLBI NIH HHS/ R33 EB019785/EB/NIBIB NIH HHS/ R01 GM112048/GM/NIGMS NIH HHS/ DP2 OD007209/OD/NIH HHS/ 1R33EB019785-01/EB/NIBIB NIH HHS/ R21 CA181419/CA/NCI NIH HHS/ 1 R01 GM112048-01A1/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2015/04/08 06:00 Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):4970-5. doi: 10.1073/pnas.1504484112. Epub 2015 Apr 6.