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Tapered-slit membrane filters for high-throughput viable circulating tumor cell isolation

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Abstract

This paper presents tapered-slit membrane filters for high-throughput viable circulating tumor cell (CTC) isolation. The membrane filter with a 2D array of vertical tapered slits with a gap that is wide at the entrance and gradually decreases with depth, provide minimal cell stress and reduce 82.14 % of the stress generated in conventional straight-hole filters. We designed two types of tapered-slit filters, Filters 6 and 8, respectively, containing the tapered slits with outlet widths of 6 μm and 8 μm at a slit density of 34,445/cm2 on the membrane. We fabricated the vertical slits with a tapered angle of 2 ° on a SU8 membrane by adjusting the UV expose dose and the air gap between the membrane and the photomask during lithography. In the experimental study, the proposed tapered-slit filter captured 89.87 % and 82.44 % of the cancer cells spiked in phosphate buffered saline (PBS) and diluted blood (blood: PBS = 1:4), respectively, at a sample flow rate of 5 ml per hour, which is 33.3 times faster than previous lateral tapered-slit filters. We further verified the capability to culture on chip after capturing: 72.33 % of cells among the captured cells still remained viable after a 5-day culture. The proposed tapered-slit membrane filters verified high-throughput viable CTC isolation capability, thereby inaugurating further advanced CTC research for cancer diagnosis and prognosis.

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Acknowledgments

This research was supported by the Converging Research Center Program funded by the Ministry of Science, ICT and Future Planning (Project No. 2014048778)

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Authors and Affiliations

  1. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea

    Yoon-Tae Kang, Il Doh & Young-Ho Cho

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  1. Yoon-Tae Kang
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  2. Il Doh
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Correspondence to Young-Ho Cho.

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Kang, YT., Doh, I. & Cho, YH. Tapered-slit membrane filters for high-throughput viable circulating tumor cell isolation. Biomed Microdevices 17, 45 (2015). https://doi.org/10.1007/s10544-015-9949-6

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  • DOI: https://doi.org/10.1007/s10544-015-9949-6

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