Optimization of Breast Tumor Cells Isolation Efficiency and Purity by Membrane Filtration

Authors: Bhuvanendran Nair Gourikutty Sajay, Liu Yuxin, Chang Chia-Pin, Poenar Daniel Puiu, Abdur Rub Abdur Rahman

Abstract:

Size based filtration is one of the common methods employed to isolate circulating tumor cells (CTCs) from whole blood. It is well known that this method suffers from isolation efficiency to purity tradeoff. However, this tradeoff is poorly understood. In this paper, we present the design and manufacturing of a special rectangular slit filter. The filter was designed to retain maximal amounts of nucleated cells, while minimizing the pressure on cells, thereby preserving their morphology. The key parameter, namely, input pressure, was optimized to retain the maximal number of tumor cells, whilst maximizing the depletion of normal blood cells (red and white blood cells and platelets). Our results indicate that for a slit geometry of 5 × 40 μm on a 13 mm circular membrane with a fill factor of 21%, a pressure of 6.9 mBar yields the optimum for maximizing isolation of MCF-7 and depletion of normal blood cells.

Keywords: Circulating tumor cells, Parylene slit membrane, Retention, White Blood Cell depletion.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1073539

References:

[1] Siyang Zheng, Henry K. Lin, Bo Lu, Anthony Williams, Ram Datar, Richard J. Cote and Yu-Chong Tai, "3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood", Biomedical Microdevices, vol. 13, no. 1, 2011, pp. 203-213.
[2] Rolle, " Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC(R) is a predictor for relaps: A preliminary report", World Journal of Surgical Oncology, pp. 3-18, 2005.
[3] Zieglschmid, V, Hollmann, C. & Bocher, "Detection of disseminated tumor cells in peripheral blood", Critical Reviews in Clinical Laboratory Sciences, vol. 2, no. 2, 2005, pp. 155-196.
[4] Kahn, H. J, "Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage", Breast cancer research and treatment, vol. 86, no. 3, 2004, pp. 237-247.
[5] Racila, E, "Detection and characterization of carcinoma cells in the blood", Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, Apr 1998, pp. 4589-4594.
[6] S. Zheng, H. Lin, J. Q. Liu, M. Balic, R. Datar, R. J. Cote and Y. -C. Tai, "Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells", Journal of Chromatography, vol. 1162, pp. 154-161, Aug 2007.
[7] Siyang Zheng, Henry K Lin, Bo Lu, Anthony Williams, Ram Datar, Richard J Cote, Yu-Chong Tai, "3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood", Biomedical Microdevices, vol. 13, 2010, pp. 203-213.
[8] B. Lu, S. Zheng, S. Xie and Y. -C. Tai, "Live capture of circulating tumor cells from human blood by a splittable 3D parylene membrane filtration device", Proc. of ╬╝TAS 2009, 2009, pp. 588-590.
[9] S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong and C. T. Lim, "Microdevice for the isolation and enumeration of cancer cells from blood", Biomedical Microdevices, vol. 11, no.4, pp. 883-892, 2009.
[10] P. Paterlini-Brechot and N. L. Benali, "Circulating tumor cells (CTC) detection: Clinical impact and future directions", Cancer Letters, vol. 253, pp. 180-204, 2007.
[11] Bo Lu, Tong Xu, Siyang Zheng, Amir Goldkorn, and Yu-Chong Tai, "Parylene membrane slot filter for the capture analysis and culture of viable circulating tumor cells", Micro Electro Mechanical Systems (MEMS), pp. 935-938, Jan 2010
[12] Tong Xu, Bo Lu, Yu-Chong Tai, and Amir Goldkorn,"A Cancer Detection Platform Which Measures Telomerase Activity from Live Circulating Tumor Cells Captured on a Microfilter", Cancer research, Aug 2010.
[13] Zhian Liu, Alberto Fusi1, Eva Klopocki, Alexander Schmittel, Ingeborg Tinhofer, Anika Nonnenmacher and Ulrich Keilholz, "Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients", Journal of Translational Medicine, vol. 9, 2011.
[14] Hong Miao Ji, Victor Samper, Yu Chen, Chew Kiat Heng, Tit Meng Lim and Levent Yobas, "Silicon based microfilters for whole blood cell separation", Biomed Microdevices, vol. 10, no. 2, 2008, pp. 251-257.
[15] Liang Zhu, Xue Li Peh, Hong Miao Ji, Cheng Yong Teo, Han Hua Feng, Wen-Tso Liu, "Cell loss in integrated microfluidic device", Biomed Microdevices, vol. 9, no. 5, 2007, pp. 745-750.