Optimization of Breast Tumor Cells Isolation Efficiency and Purity by Membrane Filtration
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.
[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.
[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.
@article{"International Journal of Medical, Medicine and Health Sciences:58907", author = "Bhuvanendran Nair Gourikutty Sajay and Liu Yuxin and Chang Chia-Pin and Poenar Daniel Puiu and Abdur Rub
Abdur Rahman", title = "Optimization of Breast Tumor Cells Isolation Efficiency and Purity by Membrane Filtration", 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.", volume = "6", number = "9", pages = "441-4", }
