Capturing and Clinical Applications of Circulating Tumor Cells with Wave Microfluidic Chip
- 35 Downloads
Abstract
As a “liquid biopsy,” circulating tumor cell (CTC) enumeration with microfluidic chips has great significance in cancer prognosis. CTCs carry significant information as the original tumor. Integrated microfluidic chips are combining with affinity- and physical-based such as wave chip offers a new way to segregate CTCs. In this work, we further study capturing clinical applications of CTCs with wave chip. When cell suspension moves across the microposts array, CTCs squeeze out from narrow gaps organized by microposts. This movement renders CTCs to obtain a tilted velocity to fluid direction. This tilted velocity would direct CTCs to be captured by the smaller neighboring gaps next array. Simultaneously, interaction or friction time is longer due to barrier of modified microposts. These microposts would be effective for realizing binding of antigen and antibody. Therefore, both antibody-coated and physical-based isolations could be combined in isolating CTCs. Capture percentage concentrated on the first several arrays is shown theoretically and experimentally. Efficient capture could be obtained for artificial patient blood. Clinically, CTCs were tested positive for three metastatic human breast cancer patient samples. This wave chip is prospectively to be a valid tool for clinical enumeration of CTCs, carrying out anti-cancer drug assay.
Keywords
Wave chip Circulating tumor cells (CTCs) Capturing Affinity-based Biorheological propertyNotes
Funding Information
This research work was supported by the Anhui Natural Science Foundation of China (1908085MF197) and Postdoctoral Research Funding (2014M550794).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Research Involving Human Participants and/or Animals
Patient blood samples were supplied by Longhua Hospital Affiliated to Shanghai Medical University under approval.
Informed Consent
The manuscript is approved by all authors for publication.
References
- 1.Pantel, K., Brakenhoff, R. H., & Brandt, B. (2008). Detection, clinical relevance and specific biological properties of disseminating tumor cells. Nature Reviews Cancer, 8(5), 329–340.CrossRefGoogle Scholar
- 2.Mehlen, P., & Puisieux, A. (2006). Metastasis: a question of life or death. Nature Reviews Cancer, 6(6), 449.CrossRefGoogle Scholar
- 3.Fehm, T., Morrison, L., Saboorian, H., Hynan, L., Tucker, T., & Uhr, J. (2002). Patterns of aneusomy for three chromosomes in individual cells from breast cancer tumors. Breast Cancer Research and Treatment, 75, 227.CrossRefGoogle Scholar
- 4.Cristofabilli, M., Budd, G. T., Stopeck, A., Matera, J., Miller, M. C., Reuben, J. M., Doyle, G. V., Allard, W. J., Terstappen, L. W., & Hayes, D. F. (2004). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. The New England Journal of Medicine, 351, 781.CrossRefGoogle Scholar
- 5.Fan, T., Zhao, Q., Chen, J. J., Chen, W.-T., & Pearl, M. L. (2009). Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer. Gynecologic Oncology, 112, 185.CrossRefGoogle Scholar
- 6.Hsiao, Y.-S., Ho, B.-C., Yan, H.-X., Kuo, C.-W., Chueh, D.-Y., Yu, H.-H., & Chen, P. (2015). Integrated 3D conducting polymer-based bioelectronics for capture and release of circulating tumor cells. Journal of Materials Chemistry B, 3(25), 5103–5110.CrossRefGoogle Scholar
- 7.Sollier, E., Go, D. E., Che, J., Gossett, D. R., O’Byrne, S., Weaver, W. M., Kummer, N., Rettig, M., Goldman, J., Nickols, N., McCloskey, S., Kulkarni, R. P., & Di Carlo, D. (2014). Size-selective collection of circulating tumor cells using Vortex technology. Lab on a Chip, 14(1), 63–77.CrossRefGoogle Scholar
- 8.Attard, G., Swennenhuis, J. F., Olmos, D., Reid, A. H., Vickers, E., A'Hern, R., Levink, R., Coumans, F., Moreira, J., Riisnaes, R., Oommen, N. B., Hawche, G., Jameson, C., Thompson, E., Sipkema, R., Carden, C. P., Parker, C., Dearnaley, D., Kaye, S. B., Cooper, C. S., Molina, A., Cox, M. E., Terstappen, L. W. M. M., & de Bono, J. S. (2009). Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Research, 69(7), 2912–2918.CrossRefGoogle Scholar
- 9.Hyun, K. A., & Jung, H. I. (2014). Advances and critical concerns with the microfluidic enrichments of circulating tumor cells. Lab on a Chip, 14(1), 45–56.CrossRefGoogle Scholar
- 10.Nagrath, S., Sequist, L. V., Maheswaran, S., Bell, D. W., Irimia, D., Ulkus, L., Smith, M. R., Kwak, E. L., Digumarthy, S., & Muzikansky, A. (2007). Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature, 450(7173), 1235–1239.CrossRefGoogle Scholar
- 11.Stott, S. L., Hsu, C.-H., Tsukrov, D. I., Yu, M., Miyamoto, D. T., Waltman, B. A., Rothenberg, S. M., Shah, A. M., Smas, M. E., Korir, G. K., Floyd, F. P., Gilman, A. J., Lord, J. B., Winokur, D., Springer, S., Irimia, D., Nagrath, S., Sequist, L. V., Lee, R. J., Isselbache, K. J., Maheswaran, S., Haber, D. A., & Toner, M. (2010). Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proceedings of the National Academy of Sciences of the United States of America, 107(43), 18392–18397.CrossRefGoogle Scholar
- 12.Yoon, H. J., Kim, T. H., Zhang, Z., Azizi, E., Pham, T. M., Paoletti, C., Lin, J., Ramnath, N., Wicha, M. S., Hayes, D. F., Simeone, D. M., & Nagrath, S. (2013). Sensitive capture of circulating tumour cells by functionalised graphene oxide nanosheets. Nature Nanotechnology, 8(10), 735–741.CrossRefGoogle Scholar
- 13.Li, N., Xiao, T., Zhang, Z., He, W., Cao, Y., Zhang, W., & Chen, Y. (2015). A 3D graphene oxide microchip and a Au-enwrapped silica nanocomposite-based supersandwich cytosensor toward capture and analysis of circulating tumor cells. Nanoscale, 7, 16354–16360.CrossRefGoogle Scholar
- 14.Murlidhar, V., Zeinali, M., Grabauskiene, S., Ghannad-Rezaie, M., Wicha, M. S., Simeone, M., Ramnath, N., Reddy, R. M., & Nagrath, S. (2014). A radial flow microfluidic device for ultra-high-throughput affinity-based isolation of circulating tumor cells. Small, 10, 4895–4904.CrossRefGoogle Scholar
- 15.Yoon, H. J., Shanker, A., Wang, Y., Kozminsky, M., Jin, Q., Palanisamy, N., Burness, M. L., Azizi, E., Simeone, D. M., Wicha, M. S., Kim, J., & Nagrath, S. (2016). Tunable thermal-sensitive polymer-graphene oxide composite for efficient capture and release of viable circulating tumor cells. Advanced Materials, 28(24), 4891–4897.CrossRefGoogle Scholar
- 16.Shah, P., Kaushik, A., Zhu, X., Zhang, C., & Li, C. (2014). Chip based single cell analysis for nanotoxicity assessment. Analyst, 139(9), 2088–2098.CrossRefGoogle Scholar
- 17.Shah, P., Zhu, X., Chen, C., Hu, Y., & Li, C. Z. (2014). Lab-on-chip device for single cell trapping and analysis. Biomedical Microdevices, 16(1), 35–41.CrossRefGoogle Scholar
- 18.Zhang, Z., Xu, J., & Drapaca, C. (2018). Particle squeezing in narrow confinements. Microfluidics and Nanofluidics, 22, 120.CrossRefGoogle Scholar
- 19.Zhang, Z., Drapaca, C., Chen, X., & Xu, J. (2017). Droplet squeezing through a narrow constriction minimum impulse and critical velocity. Physics of Fluids, 29, 072102.CrossRefGoogle Scholar
- 20.Di Carlo, D., Irimia, D., Tompkins, R. G., & Toner, M. (2007). Continuous inertial focusing, ordering, and separation of particles in microchannels. Proceedings of the National Academy of Sciences, 104(48), 18892–18897.CrossRefGoogle Scholar
- 21.Li, P., Mao, Z., Peng, Z., Zhou, L., Chen, Y., .Huang, P.-H., Truica, C. I., Drabick, J. J., El-Deiry, W. S., & Dao, M., (2015) Acoustic separation of circulating tumor cells. Proceedings of the National Academy of Sciences, 112(16), 4970–4975.CrossRefGoogle Scholar
- 22.Zhang, Z., Xu, J., Hong, B., & Chen, X. (2014). The effects of 3D channel geometry on CTC passing pressure-towards deformability-based cancer cell separation. Lab on a Chip, 14(14), 2576–2584.CrossRefGoogle Scholar
- 23.Ahmmed, S. M., Bithi, S. S., Pore, A. A., Mubtasim, N., Schuster, C., Gollahon, L. S., & Vanapalli, S. A. (2018). Multi-sample deformability cytometry of cancer cells. APL Bioeng., 2(3), 032002.CrossRefGoogle Scholar
- 24.Shi, W., Wang, S., Maarouf, A., Uhl, C. G., He, R., Yunus, D., & Liu, Y. (2017). Magnetic particles assisted capture and release of rare circulating tumor cells using wavy-herringbone structured microfluidic devices. Lab on a Chip, 17(19), 3291–3299.CrossRefGoogle Scholar
- 25.Liu, F., KC, P., Zhang, G., & Zhe, J. (2015). Microfluidic magnetic bead assay for cell detection. Analytical Chemistry, 88(1), 711–717.CrossRefGoogle Scholar
- 26.Chen, H., Zhang, Z., Liu, H., Zhang, Z., Lin, C., & Wang, B. (2019). Hybrid magnetic and deformability based isolation of circulating tumor cells using microfluidics. AIP Advances, 9, 025023.CrossRefGoogle Scholar
- 27.Chen, H., Zhang, Z., & Wang, B. (2018). Size and deformability-based isolation of circulating tumor cells with microfluidic chips and their clinical studies. AIP Advances, 8, 120701.CrossRefGoogle Scholar
- 28.Chen, H., & Zhang, Z. (2018). An inertia-deformability hybrid CTC chip: design, clinical test and numerical study. Journal of medical devices, ASME, 12, 041004–041001.CrossRefGoogle Scholar
- 29.Chen H., Cao B.,Sun B., Cao Y., Yang K.,& Lin Y(2017) Highly-sensitive capture of circulating tumor cells using micro-ellipse filters. Scientific Reports, 7:610.Google Scholar
- 30.Gogoi, P., Sepehri, S., Zhou, Y., Gorin, M. A., Paolillo, C., Capoluongo, E., Gleason, K., Payne, A., Boniface, B., Cristofanilli, M., Mogan, T. M., Fortina, P., Pienta, K. J., Handique, K., & Wang, Y. (2016). Development of an automated and sensitive microfluidic device for capturing and characterizing circulating tumor cells (CTCs) from clinical blood samples. PLoS One, 11(1), e0147400.CrossRefGoogle Scholar
- 31.Tan, J., Sohrabi, S., He, R., & Liu, Y. (2018). Numerical simulation of cell squeezing through a micropore by the immersed boundary method. Proc.Inst. Mech. Eng., Part C, 232(3), 502–514.CrossRefGoogle Scholar
- 32.Mohamed, H., Murray, M., Turner, J. N., & Caggana, M. (2009). Isolation of tumor cells using size and deformation. Journal of Chromatography. A, 1216(47), 8289–8295.CrossRefGoogle Scholar
- 33.Ahmmed, S. M., Suteria, N. S., Garbin, V., & Vanapalli, S. A. (2018). Hydrodynamic mobility of confined polymeric particles, vesicles, and cancer cells in a square microchannel. Biomicrofluidics, 12(1), 014114.CrossRefGoogle Scholar
- 34.Sarioglu, F., Aceto, A., Kojic, N., Donaldson, M. C., Zeinali, M., Hamza, B., Engstrom, A., Hamza, B., Zeigstrom, A., Zhu, H., Sundaresan, T. K., Miyamoto, D. T., Luo, X., Bardia, A., Wittner, B. S., Ramaswamy, S., Shiodae, T., Ting, D. T., Stott, S. L., Kapur, R., Maheswaran, S., Haber, D. A., & Toner, M. (2015). A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nature Methods, 12(7), 685–691.CrossRefGoogle Scholar
- 35.Kim, T. H., Yoon, H. J., Stella, P., & Nagrath, S. (2014). Cascaded spiral microfluidic device for deterministic and high purity continuous separation of circulating tumor cells. Biomicrofluidics, 8, 064117.CrossRefGoogle Scholar
- 36.Todenhofer, T., Park, E. S., Duffy, S., Deng, X., Jin, C., Abdi, H., Ma, H., & Black, P. C. (2016). Microfluidic enrichment of circulating tumor cells in patients with clinically localized prostate cancer. Urologic oncology, 34(11), 483.e9–483.e16.CrossRefGoogle Scholar
- 37.Kim, M. S. (2012). SSA-MOA: a novel CTC isolation platform using selective size amplification (SSA) and a multi-obstacle architecture (MOA) filter. Lab on a Chip, 12(16), 2874–2880.CrossRefGoogle Scholar
- 38.Hosseini, S. A., Abdolahad, M., Dahmardeh, M., Gharooni, M., Abiri, H., Alikhani, A. S., Mohajerzadeh, A. S., & Mashinchian, O. (2016). Nanoelectromechanical chip (NELMEC) combination of nanoelectronics and microfluidics to diagnose epithelial and mesenchymal circulating tumor cells from leukocytes. Small, 12(7), 883–891.CrossRefGoogle Scholar
- 39.Li, D., Zhang, Y., Li, R., Guo, J., Wang, J., & Tang, C. (2015). Selective capture and quick detection of targeting cells with SERS-coding microsphere suspension chip. Small, 11, 2200.CrossRefGoogle Scholar
- 40.Chung, J., Issadore, D., Ullal, A., Lee, K., Weissleder, R., & Lee, H. (2013). Rare cell isolation and profiling on a hybrid magnetic/size-sorting chip. Biomicrofluidics, 7, 9.CrossRefGoogle Scholar
- 41.Chen, H., Chen, H., Lin, Y., & Zhang, J. (2017). Combination of antibody-coated, physical-based microfluidic chip with wave-shaped arrays for isolating circulating tumor cells. Biomedical Microdevices, 19(3), 66.CrossRefGoogle Scholar