Skip to main content
SpringerLink
Log in

High-performance bioanalysis based on ion concentration polarization of micro-/nanofluidic devices

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Micro-/nanofluidics has received considerable attention over the past two decades, which allows efficient biomolecule trapping and preconcentration due to ion concentration polarization (ICP) within nanostructures. The rich scientific content related to ICP has been widely exploited in different applications including protein concentration, biomolecules sensing and detection, cell analysis, and water purification. Compared to pure microfluidic devices, micro-/nanofluidic devices show a highly efficient sample enrichment capacity and nonlinear electrokinetic flow feature. These two unique characterizations make the micro-/nanofluidic systems promising in high-performance bioanalysis. This review provides a comprehensive description of the ICP phenomenon and its applications in bioanalysis. Perspectives are also provided for future developments and directions of this research field.

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

Access this article

Log in via an institution

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. Ansari MIH, Hassan S, Qurashi A, Khanday FA. Microfluidic-integrated DNA nanobiosensors. Biosens Bioelectron. 2016;85:247–60.

    Article  CAS  PubMed  Google Scholar 

  2. Kim SJ, Song YA, Han J. Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications. Chem Soc Rev. 2010;39(3):912–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lee JH, Song YA, Han J. Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. Lab Chip. 2008;8(4):596–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Valenca J, Jogi M, Wagterveld RM, Karatay E, Wood JA, Lammertink RGH. Confined electroconvective vortices at structured ion exchange membranes. Langmuir. 2018;34(7):2455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang C, Ouyang J, Wang YY, Ye DK, Xia XH. Sensitive assay of protease activity on a micro/nanofluidics preconcentrator fused with the fluorescence resonance energy transfer detection technique. Anal Chem. 2014;86(28):3216–21.

    Article  CAS  PubMed  Google Scholar 

  6. Wang YC, Stevens AL, Han J. Million-fold preconcentration of proteins and peptides by nanofluidic filter. Anal Chem. 2005;77(14):4293–9.

    Article  CAS  PubMed  Google Scholar 

  7. Plecis A, Pallandre A, Haghiri-Gosnet A. Ionic and mass transport in micro-nanofluidic devices: a matter of volumic surface charge. Lab Chip. 2011;11:795–804.

    Article  CAS  PubMed  Google Scholar 

  8. Hua N, Aic Y, Qian SZ. Field effect control of electrokinetic transport in micro/nanofluidics. Sensors Actuators B Chem. 2012;161:1150–67.

    Article  CAS  Google Scholar 

  9. Santra TS, Tseng FG. Recent trends on micro/nanofluidic single cell electroporation. Micromachines. 2013;4:333–56.

    Article  Google Scholar 

  10. Hibara A, Fukuyama M, Chung M, Priest C, Proskurnin MA. Interfacial phenomena and fluid control in micro/nanofluidics. Anal Sci. 2016;32:11–21.

    Article  CAS  PubMed  Google Scholar 

  11. Rems L, Kawale D, Lee LJ, Boukany PE. Flow of DNA in micro/nanofluidics: from fundamentals to applications. Biomicrofluidics. 2016;10:043403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen XY, Zhang SZ, Zhang L, Yao Z, Chen XD, Zheng Y, et al. Applications and theory of electrokinetic enrichment in micro-nanofluidic chips. Biomed Microdevices. 2017;19:19.

    Article  CAS  PubMed  Google Scholar 

  13. Fu LM, Hou HH, Chiu PH, Yang RJ. Sample preconcentration from dilute solutions on micro/nanofluidic platforms: a review. Electrophoresis. 2018;39:289–310.

    Article  CAS  PubMed  Google Scholar 

  14. Chun HG, Chung TD, Ramsey JM. High yield sample preconcentration using a highly ion-conductive charge-selective polymer. Anal Chem. 2010;82(14):6287–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chun H. Electroosmotic effects on sample concentration at the interface of a micro/nanochannel. Anal Chem. 2017;89(17):8924–30.

    Article  CAS  PubMed  Google Scholar 

  16. Chun H. Electropreconcentration-induced local pH change. Electrophoresis. 2018;39(3):521–5.

    Article  CAS  PubMed  Google Scholar 

  17. Kim M, Kim T. Integration of nanoporous membranes into microfluidic devices: electrokinetic bio-sample pre-concentration. Analyst. 2013;138(20):6007–15.

    Article  CAS  PubMed  Google Scholar 

  18. Dziomba S, Araya-Farias M, Smadj C, Taverna M, Carbonnier B, Tran NT. Solid supports for extraction and preconcentration of proteins and peptides in microfluidic devices: a review. Anal Chim Acta. 2017;955:1–26.

    Article  CAS  PubMed  Google Scholar 

  19. Yamamoto S, Okada F, Kinoshita M, Suzuki S. On-line microchip electrophoresis-mediated preconcentration of cationic compounds utilizing cationic polyacrylamide gels fabricated by in situ photopolymerization. Analyst. 2018;143(18):4429–35.

    Article  CAS  PubMed  Google Scholar 

  20. Chun H. Development of a low flow-resistive charged nanoporous membrane in a microchip for fast electropreconcentration. Electrophoresis. 2018;39(17):2181–7.

    Article  CAS  PubMed  Google Scholar 

  21. Kim KB, Han JH, Choi H, Kim HC, Chung TD. Dynamic preconcentration of gold nanoparticles for surface-enhanced Raman scattering in a microfluidic system. Small. 2012;8(3):378–83.

    Article  CAS  PubMed  Google Scholar 

  22. Wu ZY, Fang F, He YQ, Li TT, Li JJ, Tian L. Flexible and efficient eletrokinetic stacking of DNA and proteins at an HF etched porous junction on a fused silica capillary. Anal Chem. 2012;84(16):7085–91.

    Article  CAS  PubMed  Google Scholar 

  23. Chen YY, Chiu PH, Weng CH, Yang RJ. Preconcentration of diluted mixed-species samples following separation and collection in a micro-nanofluidic device. Biomicrofluidics. 2016;10(1):014119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pu Q, Yun J, Temkin H, Liu S. Ion-enrichment and ion-depletion effect of nanochannel structures. Nano Lett. 2014;4(6):1099–103.

    Article  CAS  Google Scholar 

  25. Yu Q, Silber-Li Z. Measurements of the ion-depletion zone evolution in a micro/nano-channel. Microfluid Nanofluid. 2011;11(5):623–31.

    Article  CAS  Google Scholar 

  26. Kim SM, Burns MA, Hasselbrink EF. Electrokinetic protein preconcentration using a simple glass/poly (dimethylsiloxane) microfluidic chip. Anal Chem. 2006;78(14):4779–85.

    Article  CAS  PubMed  Google Scholar 

  27. Plecis A, Schoch RB, Renaud P. Ionic transport phenomena in nanofluidics: experimental and theoretical study of the exclusion-enrichment effect on a chip. Nano Lett. 2005;5(6):1147–55.

    Article  CAS  PubMed  Google Scholar 

  28. Yu H, Lu Y, Zhou YG, Wang FB, He FY, Xia XH. A simple, disposable microfluidic device for rapid protein concentration and purification via direct-printing. Lab Chip. 2008;8(9):1496–501.

    Article  CAS  PubMed  Google Scholar 

  29. Wang C, Ouyang J, Gao HL, Chen HW, Xu JJ, Xia XH. UV-ablation nanochannels in micro/nanofluidics devices for biochemical analysis. Talanta. 2011;85(1):298–303.

    Article  CAS  PubMed  Google Scholar 

  30. Mai J, Miller H, Hatch AV. Spatiotemporal mapping of concentration polarization induced pH changes at nanoconstrictions. ACS Nano. 2012;6(11):10206–15.

    Article  CAS  PubMed  Google Scholar 

  31. Wang YC, Han J. Pre-binding dynamic range and sensitivity enhancement for immuno-sensors using nanofluidic preconcentrator. Lab Chip. 2008;8(3):392–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Choi E, Kwon K, Lee SJ, Kim D, Park J. In-situ self-assembled colloidal crystals within microchannels using one step stamping for direct seawater desalination by ion concentration polarization. IEEE MEMS. 2012;59:1213–5.

    Google Scholar 

  33. Choi E, Kwon K, Lee SJ, Kim D, Park J. Non-equilibrium electrokinetic micromixer with 3D nanochannel networks. Lab Chip. 2015;15(8):1794–8.

    Article  CAS  PubMed  Google Scholar 

  34. Syed A, Mangano L, Mao P, Han J, Song YA. Creating sub-50 nm nanofluidic junctions in a PDMS microchip via self-assembly process of colloidal silica beads for electrokinetic concentration of biomolecules. Lab Chip. 2014;14(23):4455–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hu YL, Lu Y, Wu ZQ, Wang C, Li Y, Xu JJ, et al. Interconnected ordered nanoporous networks of colloidal crystals integrated on a microfluidic chip for highly efficient protein concentration. Electrophoresis. 2011;32(23):3424–30.

    Article  CAS  PubMed  Google Scholar 

  36. Choi E, Kwon K, Kim D, Park J. An electrokinetic study on tunable 3D nanochannel networks constructed by spatially controlled nanoparticle assembly. Lab Chip. 2015;15(2):512–23.

    Article  CAS  PubMed  Google Scholar 

  37. Kim SJ, Wang YC, Lee JH, Jang HC, Han JY. Concentration polarization and nonlinear electrokinetic flow near a nanofluidic channel. Phys Rev Lett. 2007;99(4):044501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim SJ, Li LD, Han JY. Amplified electrokinetic response by concentration polarization near nanofluidic channel. Langmuir. 2009;25(13):7759–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yossifon G, Chang HC. Selection of nonequilibrium overlimiting currents: universal depletion layer formation dynamics and vortex instability. Phys Rev Lett. 2008;101(25):254501.

    Article  CAS  PubMed  Google Scholar 

  40. Yossifon G, Chang YC, Chang HC. Rectification, gating voltage, and interchannel communication of nanoslot arrays due to asymmetric entrance space charge polarization. Phys Rev Lett. 2009;103(15):154502.

    Article  CAS  PubMed  Google Scholar 

  41. Jin XZ, Joseph S, Gatimu EN, Bohn PW, Aluru NR. Induced electrokinetic transport in micro-nanofluidic interconnect devices. Langmuir. 2007;23(26):13209–22.

    Article  CAS  PubMed  Google Scholar 

  42. Dukhin SS. Electrokinetic phenomena of the second kind and their applications. Adv Colloid Interf Sci. 1991;35:173–96.

    Article  CAS  Google Scholar 

  43. Mishchuk NA, Takhistov PV. Electroosmosis of the second kind. Colloid Surf A. 1995;95(2–3):119–31.

    Article  CAS  Google Scholar 

  44. Mishchuk NA. Concentration polarization of interface and non-linear electrokinetic phenomena. Adv Colloid Interf Sci. 2010;160(1–2):16–39.

    Article  CAS  Google Scholar 

  45. Ben YX, Demekhin EA, Chang HC. Nonlinear electrokinetics and “superfast” electrophoresis. J Colloid Interface Sci. 2004;276(2):483–97.

    Article  CAS  PubMed  Google Scholar 

  46. Zaltzman B, Rubinstein I. Electro-osmotic slip and electroconvective instability. J Fluid Mech. 2007;579:173–226.

    Article  Google Scholar 

  47. Yaroshchuk A, Zholkovskiy E, Pogodin S, Baulin V. Coupled concentration polarization and electroosmotic circulation near micro/nanointerfaces: Taylor-Aris model of hydrodynamic dispersion and limits of its applicability. Langmuir. 2011;27(18):11710–21.

    Article  CAS  PubMed  Google Scholar 

  48. Wang C, Shi Y, Wang J, Pang J, Xia XH. Ultrasensitive protein concentration detection on a micro/nanofluidic enrichment chip using fluorescence quenching. ACS Appl Mater Interface. 2015;7(12):6835–41.

    Article  CAS  Google Scholar 

  49. Lee JH, Song YA, Tannenbaum SR, Han J. Increase of reaction rate and sensitivity of low-abundance enzyme assay using micro/nanofluidic preconcentration chip. Anal Chem. 2008;80(9):3198–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sarkar A, Han J. Non-linear and linear enhancement of enzymatic reaction kinetics using a biomolecule concentrator. Lab Chip. 2011;11(15):2569–76.

    Article  CAS  PubMed  Google Scholar 

  51. Lee JH, Han J. Concentration-enhanced rapid detection of human chorionic gonadotropin as a tumor marker using a nanofluidic preconcentrator. Microfluid Nanofluid. 2010;9(4–5):973–9.

    Article  CAS  PubMed  Google Scholar 

  52. Kwak R, Kim SJ, Han J. Continuous-flow biomolecule and cell concentrator by ion concentration polarization. Anal Chem. 2011;83(19):7348–55.

    Article  CAS  PubMed  Google Scholar 

  53. Lee JH, Cosgrove BD, Lauffenburger DA, Han J. Microfluidic concentration-enhanced cellular kinase activity assay. J Am Chem Soc. 2009;131(30):10340–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zeng Y, Harrison DJ. Self-assembled colloidal arrays as three-dimensional nanofluidic sieves for separation of biomolecules on microchips. Anal Chem. 2007;79(6):2289–95.

    Article  CAS  PubMed  Google Scholar 

  55. Lee SJ, Kim D. Millisecond-order rapid micromixing with non-equilibrium electrokinetic phenomena. Microfluid Nanofluid. 2012;12(6):897–906.

    Article  CAS  Google Scholar 

  56. Kim SJ, Ko SH, Kang KH, Han J. Direct seawater desalination by ion concentration polarization. Nat Nanotechnol. 2010;5(4):297–301.

    Article  CAS  PubMed  Google Scholar 

  57. Kim P, Kim SJ, Han J, Suh KY. Stabilization of ion concentration polarization using a heterogeneous nanoporous junction. Nano Lett. 2010;10(1):16–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ko SH, Song YA, Kim SJ, Kim M, Han J, Kang KH. Nanofluidic preconcentration device in a straight microchannel using ion concentration polarization. Lab Chip. 2012;12(21):4472–82.

    Article  CAS  PubMed  Google Scholar 

  59. Ko SH, Chandra D, Ouyang W, Kwon T, Karande P, Han J. Nanofluidic device for continuous multiparameter quality assurance of biologics. Nat Nanotechnol. 2017;12(8):804–12.

    Article  CAS  PubMed  Google Scholar 

  60. Chen Z, Wang YS, Wang W, Li ZH. Nanofluidic electrokinetics in nanoparticle crystal. Appl Phys Lett. 2009;95(10):102105.

    Article  CAS  Google Scholar 

  61. Ouyang W, Han J, Wang W. Enabling electrical biomolecular detection in high ionic concentrations and enhancement of the detection limit thereof by coupling a nanofluidic crystal with reconfigurable ion concentration polarization. Lab Chip. 2017;17(22):3772–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhao WD, Wang BJ, Wang W. Biochemical sensing by nanofluidic crystal in a confined space. Lab Chip. 2016;16(11):2050–8.

    Article  CAS  PubMed  Google Scholar 

  63. Gong MM, Sinton D. Turning the page: advancing paper-based microfluidics for broad diagnostic application. Chem Rev. 2017;117(12):8447–80.

    Article  CAS  PubMed  Google Scholar 

  64. Yang YY, Noviana E, Nguyen MP, Geiss BJ, Dandy DS, Henry CS. Paper-based microfluidic devices: emerging themes and applications. Anal Chem. 2017;89(1):71–91.

    Article  CAS  PubMed  Google Scholar 

  65. Song YZ, Zhang XX, Liu JJ, Fang F, Wu ZY. Electrokinetic stacking of electrically neutral analytes with paper-based analytical device. Talanta. 2018;182:247–52.

    Article  CAS  PubMed  Google Scholar 

  66. Gong MM, Nosrati R, San Gabriel MC, Zini A, Sinton D. Direct DNA analysis with paper-based ion concentration polarization. J Am Chem Soc. 2015;137(43):13913–9.

    Article  CAS  PubMed  Google Scholar 

  67. Yeh SH, Chou KH, Yang RJ. Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices. Lab Chip. 2016;16(5):925–31.

    Article  CAS  PubMed  Google Scholar 

  68. Hong S, Kwak R, Kim W. Paper-based flow fractionation system applicable to preconcentration and field-flow separation. Anal Chem. 2016;88(3):1682–7.

    Article  CAS  PubMed  Google Scholar 

  69. Han SI, Hwang KS, Kwak R, Lee JH. Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization. Lab Chip. 2016;16(12):2219–27.

    Article  CAS  PubMed  Google Scholar 

  70. Yang RJ, Pu HH, Wang HL. Ion concentration polarization on paper-based microfluidic devices and its application to preconcentrate dilute sample solutions. Biomicrofluid. 2015;9(1):014122.

    Article  CAS  Google Scholar 

  71. Gong MM, Zhang P, MacDonald BD, Sinton D. Nanoporous membranes enable concentration and transport in fully wet paper-based assays. Anal Chem. 2014;86(16):8090–7.

    Article  CAS  PubMed  Google Scholar 

  72. Li X, Luo L, Crooks RM. Faradaic ion concentration polarization on a paper fluidic platform. Anal Chem. 2017;89(7):4294–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Phana DT, Shaeghb SAM, Yanga C, Nguyenc NT. Sample concentration in a microfluidic paper-based analytical device using ion concentration polarization. Sensors Actuators B Chem. 2016;222:735–40.

    Article  CAS  Google Scholar 

  74. Gao H, Xie MR, Liu JJ, Fang F, Wu ZY. Electrokinetic stacking on paper-based analytical device by ion concentration polarization with ion exchange membrane interface. Microfluid Nanofluid. 2018;22:50.

    Article  CAS  Google Scholar 

  75. Wang C, Li SJ, Wu ZQ, Xu JJ, Chen HY, Xia XH. Study on the kinetics of homogeneous enzyme reactions in a micro/nanofluidics device. Lab Chip. 2010;10(5):639–46.

    Article  CAS  PubMed  Google Scholar 

  76. Wang C, Sheng ZH, Ouyang J, Xu JJ, Chen HY, Xia XH. Nanoconfinement effects: glucose oxidase reaction kinetics in nanofluidics. Chem Phys Chem. 2012;13(3):762–8.

    Article  CAS  PubMed  Google Scholar 

  77. Wang C, Ouyang J, Ye DK, Xu JJ, Chen HY, Xia XH. Rapid protein concentration, efficient fluorescence labeling and purification on a micro/nanofluidics chip. Lab Chip. 2012;12(15):2664–71.

    Article  CAS  PubMed  Google Scholar 

  78. Wang C, Ye DK, Wang YY, Lu T, Xia XH. Insights into the “free state”enzyme reaction kinetics in nanoconfinement. Lab Chip. 2013;13(8):1546–53.

    Article  CAS  PubMed  Google Scholar 

  79. Wang C, Xu JJ, Chen HY, Xia XH. Mass transport in nanofluidic devices. Sci China Chem. 2012;55(4):453–68.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the grants from the National Key R&D Program of China (2017YFA0700500), the National Natural Science Foundation of China (21874155, 21635004, 21575163), the Qing-Lan Project of Jiangsu Province (2019), and “Double First-Class” University project (CPU2018GY25).

Author information

Authors and Affiliations

  1. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, Jiangsu, China

    Chen Wang, Yang Wang, Yue Zhou, Zeng-Qiang Wu & Xing-Hua Xia

  2. Key Laboratory of Biomedical Functional Materials, School of Science, China Pharmaceutical University, Nanjing, 211198, Jiangsu, China

    Chen Wang

Authors
  1. Chen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeng-Qiang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xing-Hua Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xing-Hua Xia.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Published in the topical collection New Insights into Analytical Science in China with guest editors Lihua Zhang, Hua Cui, and Qiankun Zhuang.

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, C., Wang, Y., Zhou, Y. et al. High-performance bioanalysis based on ion concentration polarization of micro-/nanofluidic devices. Anal Bioanal Chem 411, 4007–4016 (2019). https://doi.org/10.1007/s00216-019-01756-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01756-8

Keywords

Search

Navigation