Skip to main content
Log in

Self-aligned microfluidic contactless dielectrophoresis device fabricated by single-layer imprinting on cyclic olefin copolymer

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The trapping and deflection of biological cells by dielectrophoresis (DEP) at field non-uniformities in a microfluidic device is often conducted in a contactless dielectrophoresis (cDEP) mode, wherein the electrode channel is in a different layer than the sample channel, so that field penetration through the interceding barrier causes DEP above critical cut-off frequencies. In this manner, through physical separation of the electrode and sample channels, it is possible to spatially modulate electric fields with no electrode-induced damage to biological cells in the sample channel. However, since this device requires interlayer alignment of the electrode to sample channel and needs to maintain a thin interceding barrier (~ 15 μm) over the entire length over which DEP is needed (~ 1 cm), variations in alignment and microstructure fidelity cause wide variations in cDEP trapping level and frequency response across devices. We present a strategy to eliminate interlayer alignment by fabricating self-aligned electrode and sample channels, simultaneously with the interceding barrier layer (14-μm width and 50-μm depth), using a single-layer imprint and bond process on cyclic olefin copolymer. Specifically, by designing support structures, we preserve fidelity of the high aspect ratio insulating posts in the sample channel and the interceding barrier between the sample and electrode channels over the entire device footprint (~ 1 cm). The device operation is validated based on impedance measurements to quantify field penetration through the interceding barrier and by DEP trapping measurements. The presented fabrication strategy can eventually improve cDEP device manufacturing protocols to enable more reproducible DEP performance.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Murphy TW, Zhang Q, Naler LB, Ma S, Lu C. Recent advances in the use of microfluidic technologies for single cell analysis. Analyst. 2018;143(1):60–80.

    Article  CAS  Google Scholar 

  2. Luo T, Fan L, Zhu R, Sun D. Microfluidic single-cell manipulation and analysis: methods and applications. Micromachines. 2019;10(2):104.

    Article  PubMed Central  Google Scholar 

  3. Varhue WB, Langman L, Kelly-Goss M, Lataillade M, Brayman KL, Peirce-Cottler S, et al. Deformability-based microfluidic separation of pancreatic islets from exocrine acinar tissue for transplant applications. Lab Chip. 2017;17(21):3682–91.

    Article  PubMed  CAS  Google Scholar 

  4. McGrath J, Honrado C, Moore J, Adair S, Varhue W, Salahi A, et al. Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry. Anal Chim Acta. 2020;1101:90–8.

    Article  PubMed  CAS  Google Scholar 

  5. Jones TB. Electromechanics of particles. Cambridge University Press; 2005.

  6. Morgan H, Green NG. AC electrokinetics: colloids and nanoparticles. Research Studies Press; 2003.

  7. Rohani A, Sanghavi BJ, Salahi A, Liao K-T, Chou C-F, Swami NS. Frequency-selective electrokinetic enrichment of biomolecules in physiological media based on electrical double-layer polarization. Nanoscale. 2017;9(33):12124–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kim D, Luo J, Arriaga EA, Ros A. Deterministic ratchet for sub-micrometer (bio) particle separation. Anal Chem. 2018;90(7):4370–9.

    Article  PubMed  CAS  Google Scholar 

  9. Moore JH, Varhue WB, Su Y-H, Linton SS, Farmehini V, Fox TE, et al. Conductance-based biophysical distinction and microfluidic enrichment of nanovesicles derived from pancreatic tumor cells of varying invasiveness. Anal Chem. 2019;91(16):10424–31.

    Article  PubMed  CAS  Google Scholar 

  10. Fernandez RE, Rohani A, Farmehini V, Swami NS. Microbial analysis in dielectrophoretic microfluidic systems. Anal Chim Acta. 2017;966:11–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Rohani A, Moore JH, Kashatus JA, Sesaki H, Kashatus DF, Swami NS. Label-free quantification of intracellular mitochondrial dynamics using dielectrophoresis. Anal Chem. 2017;89(11):5757–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Burgarella S, Merlo S, Figliuzzi M, Remuzzi A. Isolation of Langerhans islets by dielectrophoresis. Electrophoresis. 2013;34(7):1068–75.

    Article  PubMed  CAS  Google Scholar 

  13. Hunt TP, Issadore D, Westervelt RM. Integrated circuit/microfluidic chip to programmably trap and move cells and droplets with dielectrophoresis. Lab Chip. 2008;8(1):81–7.

    Article  PubMed  CAS  Google Scholar 

  14. Barbulovic-Nad I, Xuan X, Lee JS, Li D. DC-dielectrophoretic separation of microparticles using an oil droplet obstacle. Lab Chip. 2006;6(2):274–9.

    Article  PubMed  CAS  Google Scholar 

  15. Lapizco-Encinas BH. On the recent developments of insulator-based dielectrophoresis: a review. Electrophoresis. 2019;40(3):358–75.

  16. Li M, Anand RK. Integration of marker-free selection of single cells at a wireless electrode array with parallel fluidic isolation and electrical lysis. Chem Sci. 2019;10(5):1506–13.

    Article  PubMed  CAS  Google Scholar 

  17. Reale R, De Ninno A, Businaro L, Bisegna P, Caselli F. A simple electrical approach to monitor dielectrophoretic focusing of particles flowing in a microchannel. Electrophoresis. 2019;40(10):1400–7.

    Article  PubMed  CAS  Google Scholar 

  18. Sanghavi BJ, Varhue W, Chávez JL, Chou C-F, Swami NS. Electrokinetic preconcentration and detection of neuropeptides at patterned graphene-modified electrodes in a nanochannel. Anal Chem. 2014;86(9):4120–5.

    Article  PubMed  CAS  Google Scholar 

  19. Hanson C, Barney JT, Bishop MM, Vargis E. Simultaneous isolation and label-free identification of bacteria using contactless dielectrophoresis and Raman spectroscopy. Electrophoresis. 2019;40(10):1446–56.

    Article  PubMed  CAS  Google Scholar 

  20. Shafiee H, Caldwell JL, Sano MB, Davalos RV. Contactless dielectrophoresis: a new technique for cell manipulation. Biomed Microdevices. 2009;11(5):997.

    Article  PubMed  CAS  Google Scholar 

  21. Salmanzadeh A, Romero L, Shafiee H, Gallo-Villanueva RC, Stremler MA, Cramer SD, et al. Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature. Lab Chip. 2012;12(1):182–9.

    Article  PubMed  CAS  Google Scholar 

  22. Gwon HR, Chang ST, Choi CK, Jung JY, Kim JM, Lee SH. Development of a new contactless dielectrophoresis system for active particle manipulation using movable liquid electrodes. Electrophoresis. 2014;35(14):2014–21.

    Article  PubMed  CAS  Google Scholar 

  23. Jen C-P, Maslov NA, Shih H-Y, Lee Y-C, Hsiao F-B. Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures. Microsyst Technol. 2012;18(11):1879–86.

    Article  CAS  Google Scholar 

  24. Chen C-C, Lin P-H, Chung C-K. Microfluidic chip for plasma separation from undiluted human whole blood samples using low voltage contactless dielectrophoresis and capillary force. Lab Chip. 2014;14(12):1996–2001.

    Article  PubMed  CAS  Google Scholar 

  25. Rahmani A, Mohammadi A, Kalhor HR. A continuous flow microfluidic device based on contactless dielectrophoresis for bioparticles enrichment. Electrophoresis. 2018;39(3):445–55.

    Article  PubMed  CAS  Google Scholar 

  26. Podoynitsyn SN, Sorokina ON, Klimov MA, Levin II, Simakin SB. Barrier contactless dielectrophoresis: a new approach to particle separation. Sep Sci Plus. 2019;2(2):59–68.

  27. Hanson C, Vargis E. Alternative cDEP design to facilitate cell isolation for identification by Raman spectroscopy. Sensors (Basel). 2017;17(2):327.

    Article  Google Scholar 

  28. Čemažar J, Douglas TA, Schmelz EM, Davalos RV. Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures. Biomicrofluidics. 2016;10(1):014109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Sano MB, Salmanzadeh A, Davalos RV. Multilayer contactless dielectrophoresis: theoretical considerations. Electrophoresis. 2012;33(13):1938–46.

    Article  PubMed  CAS  Google Scholar 

  30. Cottet J, Vaillier C, Buret F, Frénéa-Robin M, Renaud P. A reproducible method for μ m precision alignment of PDMS microchannels with on-chip electrodes using a mask aligner. Biomicrofluidics. 2017;11(6):064111.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Nunes PS, Ohlsson PD, Ordeig O, Kutter JP. Cyclic olefin polymers: emerging materials for lab-on-a-chip applications. Microfluid Nanofluid. 2010;9(2–3):145–61.

    Article  CAS  Google Scholar 

  32. Aghvami SA, Opathalage A, Zhang Z, Ludwig M, Heymann M, Norton M, et al. Rapid prototyping of cyclic olefin copolymer (COC) microfluidic devices. Sensors Actuators B Chem. 2017;247:940–9.

    Article  CAS  Google Scholar 

  33. Lamonte RR, McNally D. Cyclic olefin copolymers. Adv Mater Process. 2001;159(3):33–6.

    CAS  Google Scholar 

  34. Farmehini V, Varhue W, Salahi A, Hyler AR, Čemažar J, Davalos R, et al. On-chip impedance for quantifying parasitic voltages during AC electrokinetic trapping. IEEE Trans Biomed Eng. 2019. https://doi.org/10.1109/TBME.2019.2942572.

  35. Cohen CA, Shea AA, Heffron CL, Schmelz EM, Roberts PC. The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis. Cancer Prev Res. 2013;6(11):1182–93.

    Article  CAS  Google Scholar 

  36. Creekmore AL, Silkworth WT, Cimini D, Jensen RV, Roberts PC, Schmelz EM. Changes in gene expression and cellular architecture in an ovarian cancer progression model. PLoS One. 2011;6(3):e17676.

  37. Roberts PC, Mottillo EP, Baxa AC, Heng HH, Doyon-Reale N, Gregoire L, et al. Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model. Neoplasia. 2005;7(10):944.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Simon MG, Li Y, Arulmoli J, McDonnell LP, Akil A, Nourse JL, et al. Increasing label-free stem cell sorting capacity to reach transplantation-scale throughput. Biomicrofluidics. 2014;8(6):064106.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Adams TN, Jiang AY, Vyas PD, Flanagan LA. Separation of neural stem cells by whole cell membrane capacitance using dielectrophoresis. Methods. 2018;133:91–103.

    Article  PubMed  CAS  Google Scholar 

  40. Taylor LC, Lavrik NV, Sepaniak MJ. High-aspect-ratio, silicon oxide-enclosed pillar structures in microfluidic liquid chromatography. Anal Chem. 2010;82(22):9549–56.

    Article  PubMed  CAS  Google Scholar 

  41. Farmehini V, Rohani A, Su Y-H, Swami NS. A wide-bandwidth power amplifier for frequency-selective insulator-based dielectrophoresis. Lab Chip. 2014;14(21):4183–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This study was funded by the US AFOSR contract FA2386-18-1-4100, the CytoRecovery, Inc., the Virginia Catalyst (VBHRC), and the National Center for Advancing Translational Sciences of the National Institutes of Health, under Award Number UL1TR003015.

Author information

Authors and Affiliations

Authors

Contributions

The manuscript was written through contributions of all authors and all authors approved the final version.

Corresponding author

Correspondence to Nathan S. Swami.

Ethics declarations

Conflicts of interest

Co-author ARH is an employee of CytoRecovery, Inc. and co-author RVD is on the company’s Scientific Advisory Board. All other authors have no conflicts to declare.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Additional information

Published in the topical collection Bioanalytics and Higher Order Electrokinetics with guest editors Mark A. Hayes and Federica Caselli.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 2241 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salahi, A., Varhue, W.B., Farmehini, V. et al. Self-aligned microfluidic contactless dielectrophoresis device fabricated by single-layer imprinting on cyclic olefin copolymer. Anal Bioanal Chem 412, 3881–3889 (2020). https://doi.org/10.1007/s00216-020-02667-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02667-9

Keywords

Navigation