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Novel Approaches to Cell Isolation in Simple Inertial Microfluidic Devices

Zhou, Jian
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337716948

Abstract Details

2012, PhD, University of Cincinnati, Engineering and Applied Science: Electrical Engineering.
Cell sorting is essential in many biological and biomedical applications. One example is isolation of rare cells such as circulating tumor cells (CTCs) from blood, which are of great clinical significance as early indicator of cancer. Yet, isolation of CTCs is remarkably challenging, primarily due to their incredible rarity, and thus need for high separation selectivity, efficiency, and purity. Currently, the prevalent approach is based on immunodetection, which is effective but relies on availability and homogeneous expression of biomarkers. This work describes alternative approaches based on inertial microfluidics, which permits size-based, highly-selective separation of cells with high efficiency and purity. In these devices, cells experience inertial forces which are strongly size-dependent and cause them to migrate laterally to equilibrium positions within microchannel cross-section. The result is cell separation based on size only, leading to an effective high-throughput (104 cells per min) alternative to immunodetection. A new model of particle/cell migration was developed to explain lateral migration behavior and address limitations of the current understanding. Lift coefficients acting on neutrally-buoyant particles and cells were experimentally measured to confirm the new model, and to allow accurate prediction of particle/cell behavior. With guideline from the new model, three designs were developed to realize superior performance in cell separation and isolation. In the first design, highly-sensitive isolation (as low as 1 particle per mL) was demonstrated by suppression of wall induced lift force. This approach also showed very high selectivity (1:105) of separating different sized species. The second design modulated the shear force to achieve continuous filtration with extremely high efficiency (~100%) and capability of precise re-concentration. The third more advanced design, based on modulation of rotation induced forces, manipulated equilibrium positions of particles/cells for complete separation with ~100% efficiency and > purity. Blood spiked with human prostate cancer cells was used to characterize cell separation performance. A ~83% viability was achieved, with proliferation results showing preservation of functionality. All the three designs outperform the existing immunodetection-based and other separation platforms. The approaches demonstrated in this work offer promising alternatives to cell sorting, potentially including isolation of CTCs. Due to the planar structures and simple geometries, the devices should be easy to integrate with existing lab-on-a-chip systems.
Ian Papautsky, PhD (Committee Chair)
Phillip M. Ligrani, PhD (Committee Member)
Chong Ahn, PhD (Committee Member)
Jason Heikenfeld, PhD (Committee Member)
Susan Kasper, PhD (Committee Member)
150 p.
Electrical Engineering
inertial microfluidics; cell separation; cell isolation; lift forces; lift coefficient; inertial focusing;

Recommended Citations

Citations

  • Zhou, J. (2012). Novel Approaches to Cell Isolation in Simple Inertial Microfluidic Devices [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337716948

    APA Style (7th edition)

  • Zhou, Jian. Novel Approaches to Cell Isolation in Simple Inertial Microfluidic Devices. 2012. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337716948.

    MLA Style (8th edition)

  • Zhou, Jian. "Novel Approaches to Cell Isolation in Simple Inertial Microfluidic Devices." Doctoral dissertation, University of Cincinnati, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337716948

    Chicago Manual of Style (17th edition)

ucin1337716948
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© 2012, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.