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Plasma Isolation in a Syringe by Conformal Integration of Inertial Microfluidics

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Abstract

A thermoplastic microfluidic substrate is conformally integrated onto the cylindrical barrel of a conventional venipuncture syringe, forming a spiral inertial separation element supporting the isolation of plasma from diluted whole blood. The cylindrical shape of the syringe itself serves to define the flow path required for inertial separation by transforming a linear microchannel to a spiral topology. The hybrid system enables inertial plasma separation by Dean flow focusing within the same syringe used for a patient blood draw, with the seamlessly interconnected microfluidic element operated by automated or manual actuation of the syringe plunger. Plasma isolation is achieved without the need for external instrumentation. Device design and fabrication challenges are discussed, and effective plasma isolation within the system is demonstrated, with a peak separation efficiency above 97% using 25 × diluted blood.

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References

  1. Amini, H., W. Lee, and D. Di Carlo. Inertial microfluidic physics. Lab Chip 14:2739–2761, 2014.

    CAS  PubMed  Google Scholar 

  2. Bhamla, M. S., B. Benson, C. Chai, G. Katsikis, A. Johri, and M. Prakash. Hand-powered ultralow-cost paper centrifuge. Nat. Biomed. Eng. 1:9, 2017.

    CAS  Google Scholar 

  3. Brown, J., L. Theis, L. Kerr, N. Zakhidova, K. O’Connor, M. Uthman, Z. M. Oden, and R. Richards-Kortum. A hand-powered, portable, low-cost centrifuge for diagnosing anemia in low-resource settings. Am. J. Trop. Med. Hyg. 85:327–332, 2011.

    PubMed  PubMed Central  Google Scholar 

  4. Burke, J. M., R. E. Zubajlo, E. Smela, and I. M. White. High-throughput particle separation and concentration using spiral inertial filtration. Biomicrofluidics 8:024105, 2014.

    PubMed  PubMed Central  Google Scholar 

  5. Chin, C. D., T. Laksanasopin, Y. K. Cheung, D. Steinmiller, V. Linder, H. Parsa, J. Wang, H. Moore, R. Rouse, G. Umviligihozo, E. Karita, L. Mwambarangwe, S. L. Braunstein, J. van de Wijgert, R. Sahabo, J. E. Justman, W. El-Sadr, and S. K. Sia. Microfluidics-based diagnostics of infectious diseases in the developing world. Nat. Med. 17:1015–1019, 2011.

    CAS  PubMed  Google Scholar 

  6. Di Carlo, D. Inertial microfluidics. Lab Chip 9:3038, 2009.

    PubMed  Google Scholar 

  7. Fernández, L., and S. A. Schaefer. Relationships among the Neotropical Candirus (Trichomycteridae, Siluriformes) and the evolution of parasitism based on analysis of mitochondrial and nuclear gene sequences. Mol. Phylogenet. Evol. 52:416–423, 2009.

    PubMed  Google Scholar 

  8. Garg, N., T. M. Westerhof, V. Liu, R. Liu, E. L. Nelson, and A. P. Lee. Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming. Microsyst. Nanoeng. 4:17085, 2018.

    CAS  Google Scholar 

  9. Gossett, D. R., and D. Di Carlo. Particle focusing mechanisms in curving confined flows. Anal. Chem. 2009. https://doi.org/10.1021/ac901306y.

    Article  PubMed  Google Scholar 

  10. Guan, G., L. Wu, A. A. Bhagat, Z. Li, P. C. Y. Chen, S. Chao, C. J. Ong, and J. Han. Spiral microchannel with rectangular and trapezoidal cross-sections for size based particle separation. Sci. Rep. 3:1475, 2013.

    PubMed  PubMed Central  Google Scholar 

  11. Hou, H. W., R. P. Bhattacharyya, D. T. Hung, and J. Han. Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics. Lab Chip 15:2297–2307, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Huh, D., J. H. Bahng, Y. Ling, H.-H. H. Wei, O. D. Kripfgans, J. B. Fowlkes, J. B. Grotberg, and S. Takayama. Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification. Anal. Chem. 79:1369–1376, 2007.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Inglis, D. W., J. A. Davis, R. H. Austin, and J. C. Sturm. Critical particle size for fractionation by deterministic lateral displacement. Lab Chip 6:655, 2006.

    CAS  PubMed  Google Scholar 

  14. Jiang, H., X. Weng, C. H. Chon, X. Wu, and D. Li. A microfluidic chip for blood plasma separation using electro-osmotic flow control. J. Micromech. Microeng. 21:085019, 2011.

    Google Scholar 

  15. Jung, J., and K.-H. H. Han. Lateral-driven continuous magnetophoretic separation of blood cells. Appl. Phys. Lett. 93:223902, 2008.

    Google Scholar 

  16. Kendall, E. L., M. S. Wiederoder, J. Y. Han, A. Sposito, A. Wilson, and D. L. DeVoe. Soft lithography microfabrication of functionalized thermoplastics by solvent casting. J. Polym. Sci. B Polym. Phys. 53:1315–1323, 2015.

    CAS  Google Scholar 

  17. Kim, B., S. Oh, D. You, and S. Choi. Microfluidic pipette tip for high-purity and high-throughput blood plasma separation from whole blood. Anal. Chem. 89:1439–1444, 2017.

    CAS  PubMed  Google Scholar 

  18. Kuntaegowdanahalli, S. S., A. A. S. Bhagat, G. Kumar, and I. Papautsky. Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip 9:2973–2980, 2009.

    CAS  PubMed  Google Scholar 

  19. Laurell, T., F. Petersson, and A. Nilsson. Chip integrated strategies for acoustic separation and manipulation of cells and particles. Chem. Soc. Rev. 36:492–506, 2007.

    CAS  PubMed  Google Scholar 

  20. Lee, W., D. Kwon, W. Choi, G. Y. Jung, A. K. Au, A. Folch, and S. Jeon. 3D-printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid cross-section. Sci. Rep. 5:7717, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee, B. S., J.-N. Lee, J.-M. Park, J.-G. Lee, S. Kim, Y.-K. Cho, and C. Ko. A fully automated immunoassay from whole blood on a disc. Lab Chip 9:1548, 2009.

    CAS  PubMed  Google Scholar 

  22. Lee, M. G., J. H. Shin, S. Choi, and J.-K. Park. Enhanced blood plasma separation by modulation of inertial lift force. Sens. Actuators B Chem. 190:311–317, 2014.

    CAS  Google Scholar 

  23. MacDonald, M. P., G. C. Spalding, and K. Dholakia. Microfluidic sorting in an optical lattice. Nature 426:421–424, 2003.

    CAS  PubMed  Google Scholar 

  24. Martel, J. M., and M. Toner. Particle focusing in curved microfluidic channels. Sci. Rep. 3:3340, 2013.

    Google Scholar 

  25. Martel, J. M., and M. Toner. Inertial focusing in microfluidics. Annu. Rev. Biomed. Eng. 16:371–396, 2014.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Nakashima, Y., S. Hata, and T. Yasuda. Blood plasma separation and extraction from a minute amount of blood using dielectrophoretic and capillary forces. Sens. Actuators B Chem. 145:561–569, 2010.

    CAS  Google Scholar 

  27. Nayak, S., T. Guo, J. Lopez-Rios, C. Lentz, S. Arumugam, J. Hughes, C. Dolezal, V. Linder, A. Carballo-Diéguez, I. C. Balán, and S. K. Sia. Integrating user behavior with engineering design of point-of-care diagnostic devices: theoretical framework and empirical findings. Lab Chip 19:2241–2255, 2019.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Nivedita, N., and I. Papautsky. Continuous separation of blood cells in spiral microfluidic devices. Biomicrofluidics 7:54101, 2013.

    PubMed  Google Scholar 

  29. Oh, K. W., K. Lee, B. Ahn, and E. P. Furlani. Design of pressure-driven microfluidic networks using electric circuit analogy. Lab Chip 12:515, 2012.

    CAS  PubMed  Google Scholar 

  30. Peeling, R. W., K. K. Holmes, D. Mabey, and A. Ronald. Rapid tests for sexually transmitted infections (STIs): the way forward. Sex. Transm. Infect. 2006. https://doi.org/10.1136/sti.2006.024265.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Peeling, R. W., D. Mabey, A. Herring, and E. W. Hook. Why do we need quality-assured diagnostic tests for sexually transmitted infections? Nat. Rev. Microbiol. 4:909–921, 2006.

    CAS  PubMed  Google Scholar 

  32. Pretlow, T. G., and T. P. Pretlow. Cell separation: methods and selected applications. Cambridge Academic Press 1983. https://doi.org/10.1002/cyto.990060517.

    Article  Google Scholar 

  33. Rafeie, M., J. Zhang, M. Asadnia, W. Li, and M. E. Warkiani. Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation. Lab Chip 16:2791–2802, 2016.

    CAS  PubMed  Google Scholar 

  34. Robinson, M., H. Marks, T. Hinsdale, K. Maitland, and G. Coté. Rapid isolation of blood plasma using a cascaded inertial microfluidic device. Biomicrofluidics 11:024109, 2017.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Sajeesh, P., and A. K. Sen. Particle separation and sorting in microfluidic devices: a review. Microfluid Nanofluidics 17:1–52, 2014.

    Google Scholar 

  36. Siemann, U. Solvent cast technology—a versatile tool for thin film production. Prog. Colloid Polym. Sci. 130:1–14, 2005.

    CAS  Google Scholar 

  37. Sollier, E., H. Rostaing, P. Pouteau, Y. Fouillet, and J.-L. Achard. Passive microfluidic devices for plasma extraction from whole human blood. Sens. Actuators B Chem. 141:617–624, 2009.

    CAS  Google Scholar 

  38. Song, S., M. S. Kim, and S. Choi. Smart microfluidic pipette tip enabled by flow-rate insensitive particle ordering. Small 10:4123–4129, 2014.

    CAS  PubMed  Google Scholar 

  39. Tripathi, S., Y. V. B. Kumar, A. Agrawal, A. Prabhakar, and S. S. Joshi. Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects. Sci. Rep. 6:26749, 2016.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Tripathi, S., Y. V. B. Varun Kumar, A. Prabhakar, S. S. Joshi, and A. Agrawal. Passive blood plasma separation at the microscale: a review of design principles and microdevices. J. Micromech. Microeng. 25:083001, 2015.

    Google Scholar 

  41. Wang, X., H. Gao, N. Dindic, N. Kaval, and I. Papautsky. A low-cost, plug-and-play inertial microfluidic helical capillary device for high-throughput flow cytometry. Biomicrofluidics 11:14107, 2017.

    Google Scholar 

  42. Warkiani, M. E., G. Guan, K. B. Luan, W. C. Lee, A. A. S. Bhagat, P. KantChaudhuri, D. S. W. Tan, W. T. Lim, S. C. Lee, P. C. Y. Chen, C. T. Lim, and J. Han. Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip 14:128–137, 2014.

    CAS  PubMed  Google Scholar 

  43. Washington, J. A. Principles of Diagnosis. In: Medical Microbiology, edited by S. Baron. Galveston, TX: University of Texas Medical Branch at Galveston, 1996. https://www.ncbi.nlm.nih.gov/books/NBK8014/

  44. Wong, A. P., M. Gupta, S. S. Shevkoplyas, and G. M. Whitesides. Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. Lab Chip 8:2032–2037, 2008.

    CAS  PubMed  Google Scholar 

  45. Wu, L., G. Guan, H. W. Hou, A. A. S. Bhagat, and J. Han. Separation of leukocytes from blood using spiral channel with trapezoid cross-section. Anal. Chem. 84:9324–9331, 2012.

    CAS  PubMed  Google Scholar 

  46. Xi, W., F. Kong, J. C. Yeo, L. Yu, S. Sonam, M. Dao, X. Gong, and C. T. Lim. Soft tubular microfluidics for 2D and 3D applications. Proc. Natl. Acad. Sci. 114:10590–10595, 2017.

    CAS  PubMed  Google Scholar 

  47. Xiang, N., and Z. Ni. High-throughput blood cell focusing and plasma isolation using spiral inertial microfluidic devices. Biomed. Microdevices 17:110, 2015.

    PubMed  Google Scholar 

  48. Xiang, N., X. Shi, Y. Han, Z. Shi, F. Jiang, and Z. Ni. Inertial microfluidic syringe cell concentrator. Anal. Chem. 90:9515–9522, 2018.

    CAS  PubMed  Google Scholar 

  49. Yeh, E.-C. C., C.-C. C. Fu, L. Hu, R. Thakur, J. Feng, and L. P. Lee. Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip. Sci. Adv. 3:e1501645, 2017.

    PubMed  PubMed Central  Google Scholar 

  50. Yu, W. S., H. van Duinen, and S. C. Gandevia. Limits to the control of the human thumb and fingers in flexion and extension. J. Neurophysiol. 103:278–289, 2009.

    PubMed  Google Scholar 

  51. Zhang, L., F. Tian, C. Liu, Q. Feng, T. Ma, Z. Zhao, T. Li, X. Jiang, and J. Sun. Hand-powered centrifugal microfluidic platform inspired by the spinning top for sample-to-answer diagnostics of nucleic acids. Lab Chip 18:610–619, 2018.

    CAS  PubMed  Google Scholar 

  52. Zhang, X.-B., Z.-Q. Wu, K. Wang, J. Zhu, J.-J. Xu, X.-H. Xia, and H.-Y. Chen. Gravitational sedimentation induced blood delamination for continuous plasma separation on a microfluidics chip. Anal. Chem. 84:3780–3786, 2012.

    CAS  PubMed  Google Scholar 

  53. Zhou, J., and I. Papautsky. Fundamentals of inertial focusing in microchannels. Lab Chip 13:1121, 2013.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by NSF Grants ECCS1609074 and CMMI1562468. The authors acknowledge the support of the Maryland NanoCenter and its FabLab.

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Correspondence to Don L. DeVoe.

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Han, J.Y., DeVoe, D.L. Plasma Isolation in a Syringe by Conformal Integration of Inertial Microfluidics. Ann Biomed Eng 49, 139–148 (2021). https://doi.org/10.1007/s10439-020-02526-9

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