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Ion concentration polarization (ICP) of proteins at silicon micropillar nanogaps


Autoři: Bochao Lu aff001;  Michel M. Maharbiz aff001
Působiště autorů: UC Berkeley-UCSF Graduate Program in Bioengineering, University of California–Berkeley, Berkeley, California, United States of America aff001;  Electrical Engineering and Computer Science Department, University of California–Berkeley, Berkeley, California, United States of America aff002;  Chan Zuckerberg Biohub, San Francisco, California, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0223732

Souhrn

Fast detection of low-abundance protein remains a challenge because detection speed is limited by analyte transport to the detection site of a biosensor. In this paper, we demonstrate a scalable fabrication process for producing vertical nanogaps between micropillars which enable ion concentration polarization (ICP) enrichment for fast analyte detection. Compared to horizontal nanochannels, massively paralleled vertical nanogaps not only provide comparable electrokinetics, but also significantly reduce fluid resistance, enabling microbead-based assays. The channels on the device are straightforward to fabricate and scalable using conventional lithography tools. The device is capable of enriching protein molecules by >1000 fold in 10 min. We demonstrate fast detection of IL6 down to 7.4 pg/ml with only a 10 min enrichment period followed by a 5 min incubation. This is a 162-fold enhancement in sensitivity compared to that without enrichment. Our results demonstrate the possibility of using silicon/silica based vertical nanogaps to mimic the function of polymer membranes for the purpose of protein enrichment.

Klíčová slova:

Immunoassays – Fluorescence imaging – Manufacturing processes – Cations – Chemical deposition – Microfluidics – Microbeads – Bionanotechnology


Zdroje

1. Bange A, Halsall HB, Heineman WR. Microfluidic immunosensor systems. Biosens Bioelectron. 2005;20: 2488–2503. doi: 10.1016/j.bios.2004.10.016 15854821

2. Wu G, Datar RH, Hansen KM, Thundat T, Cote RJ, Majumdar A. Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nat Biotechnol. 2001;19: 856–860. doi: 10.1038/nbt0901-856 11533645

3. Kurita R, Yokota Y, Sato Y, Mizutani F, Niwa O. On-chip enzyme immunoassay of a cardiac marker using a microfluidic device combined with a portable surface plasmon resonance system. Anal Chem. 2006;78: 5525–5531. doi: 10.1021/ac060480y 16878891

4. Zheng G, Patolsky F, Cui Y, Wang WU, Lieber CM. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol. 2005;23: 1294–1301. doi: 10.1038/nbt1138 16170313

5. Wang YC, Han J. Pre-binding dynamic range and sensitivity enhancement for immuno-sensors using nanofluidic preconcentrator. Lab Chip. 2008;8: 392–394. doi: 10.1039/b717220f 18305855

6. Nair PR, Alam MA. Performance limits of nanobiosensors. Appl Phys Lett. 2006;88: 9–11. doi: 10.1063/1.2211310

7. Sparreboom W, van den Berg a, Eijkel JCT. Principles and applications of nanofluidic transport. Nat Nanotechnol. Nature Publishing Group; 2009;4: 713–720. doi: 10.1038/nnano.2009.332 19898499

8. Sheehan PE, Whitman LJ. Detection Limits for Nanoscale Biosensors. Nano Lett. 2005;5: 803–807. doi: 10.1021/nl050298x 15826132

9. Cohen AE, Fields AP. The cat that caught the canary: What to do with single-molecule trapping. ACS Nano. 2011;5: 5296–5299. doi: 10.1021/nn202313g 21710977

10. Cesaro-Tadic S, Dernick G, Juncker D, Buurman G, Kropshofer H, Michel B, et al. High-sensitivity miniaturized immunoassays for tumor necrosis factor a using microfluidic systems. Lab Chip. 2004;4: 563–569. doi: 10.1039/b408964b 15570366

11. Grilli S, Miccio L, Gennari O, Coppola S, Vespini V, Battista L, et al. Active accumulation of very diluted biomolecules by nano-dispensing for easy detection below the femtomolar range. Nat Commun. Nature Publishing Group; 2014;5: 1–6. doi: 10.1038/ncomms6314 25408128

12. Jaffrin MY. Hydrodynamic Techniques to Enhance Membrane Filtration. Annu Rev Fluid Mech. 2011;44: 77–96. doi: 10.1146/annurev-fluid-120710-101112

13. Van Der Bruggen B, Vandecasteele C, Van Gestel T, Doyen W, Leysen R. A review of pressure-driven membrane processes in wastewater treatment and drinking water production. Environ Prog. 2003;22: 46–56. doi: 10.1002/ep.670220116

14. Chen JZ, Balgley BM, DeVoe DL, Lee CS. Capillary isoelectric focusing-based multidimensional concentration. Anal Chem. 2003;75: 3145–3152. doi: 10.1021/ac034014+ 12964763

15. Herr AE, Molho JI, Drouvalakis KA, Mikkelsen JC, Utz PJ, Santiago JG, et al. On-chip coupling of isoelectric focusing and free solution electrophoresis for multidimensional separations. Anal Chem. 2003;75: 1180–1187. doi: 10.1021/ac026239a 12641239

16. Cui H, Horiuchi K, Dutta P, Ivory CF. Multistage isoelectric focusing in a polymeric microfluidic chip. Anal Chem. 2005;77: 7878–7886. doi: 10.1021/ac050781s 16351133

17. Cui H, Horiuchi K, Dutta P, Ivory CF. Isoelectric focusing in a poly(dimethylsiloxane) microfluidic chip. Anal Chem. 2005;77: 1303–9. doi: 10.1021/ac048915+ 15732911

18. Jung B, Bharadwaj R, Santiago JG. On-chip millionfold sample stacking using transient isotachophoresis. Anal Chem. 2006;78: 2319–2327. doi: 10.1021/ac051659w 16579615

19. Wei W, Xue G, Yeung ES. One-step concentration of analytes based on dynamic change in pH in capillary zone electrophoresis. Anal Chem. 2002;74: 934–940. doi: 10.1021/ac015617t 11924995

20. Arnett SD, Lunte CE. Investigation of the mechanism of pH-mediated stacking of anions for the analysis of physiological samples by capillary electrophoresis. Electrophoresis. 2003;24: 1745–1752. doi: 10.1002/elps.200305399 12783451

21. Beard NP, Zhang C-X, DeMello AJ. In-column field-amplified sample stacking of biogenic amines on microfabricated ellectrophoresis devices. Electrophoresis. 2003;24: 732–739. doi: 10.1002/elps.200390088 12601745

22. Lichtenberg J, Verpoorte E, de Rooij NF. Sample preconcentration by field amplication stacking for microchip-based capillary electrophoresis. Electrophoresis. 2001. pp. 258–271. doi: 10.1002/1522-2683(200101)22:2<258::AID-ELPS258>3.0.CO;2-4 11288893

23. Liao KT, Chou CF. Nanoscale molecular traps and dams for ultrafast protein enrichment in high-conductivity buffers. J Am Chem Soc. 2012;134: 8742–8745. doi: 10.1021/ja3016523 22594700

24. Sanghavi BJ, Varhue W, Rohani A, Liao K-T, Bazydlo LAL, Chou C-F, et al. Ultrafast immunoassays by coupling dielectrophoretic biomarker enrichment in nanoslit channel with electrochemical detection on graphene. Lab Chip. 2015;15: 4563–4570. doi: 10.1039/c5lc00840a 26496877

25. Sanghavi BJ, Varhue W, Chávez JL, Chou CF, Swami NS. Electrokinetic preconcentration and detection of neuropeptides at patterned graphene-modified electrodes in a nanochannel. Anal Chem. 2014;86: 4120–4125. doi: 10.1021/ac500155g 24697740

26. Liao KT, Tsegaye M, Chaurey V, Chou CF, Swami NS. Nano-constriction device for rapid protein preconcentration in physiological media through a balance of electrokinetic forces. Electrophoresis. 2012;33: 1958–1966. doi: 10.1002/elps.201100707 22806460

27. Fu LM, Hou HH, Chiu PH, Yang RJ. Sample preconcentration from dilute solutions on micro/nanofluidic platforms: A review. Electrophoresis. 2018;39: 289–310. doi: 10.1002/elps.201700340 28960423

28. Kim SJ, Song YA, Han J. Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: Theory, fabrication, and applications. Chem Soc Rev. 2010;39: 912–922. doi: 10.1039/b822556g 20179814

29. Cheow LF, Han J. Continuous Signal Enhancement for Sensitive Aptamer Affinity Probe Electrophoresis Assay Using Electrokinetic Concentration. Anal Chem. 2011;83: 7086–7093. doi: 10.1021/ac201307d 21809885

30. Choi J, Huh K, Moon DJ, Chae JH, Kim HC, Hong JW, et al. AN ELECTROKINETIC DEVICE FOR SELECTIVE PRECONCENTRATION AND ONLINE COLLECTION BASED ON ION CONCENTRATION POLARIZATION. Transducers. 2015. pp. 228–231. doi: 10.1109/TRANSDUCERS.2015.7180903

31. Lee JH, Song Y, Tannenbaum SR, Han J. Increase of Reaction Rate and Sensitivity of Low-Abundance Enzyme Assay Using Micro/ Nanofluidic Preconcentration Chip. Lab Chip. 2008;80: 6592–6598. doi: 10.1039/B717900F.Analytical

32. Ouyang W, Ko SH, Wu D, Wang AY, Barone PW, Hancock WS, et al. Rapid Assessment of Therapeutic Proteins Using Molecular Charge Modulation Enhanced Electrokinetic Concentration Assays. Anal Chem. 2016;88: 9669–9677. doi: 10.1021/acs.analchem.6b02517 27624735

33. Wang YC, Stevens AL, Han J. Million-fold preconcentration of proteins and peptides by nanofluidic filter. Anal Chem. 2005;77: 4293–4299. doi: 10.1021/ac050321z 16013838

34. Pu Q, Yun J, Temkin H, Liu S. Ion-enrichment and ion-depletion effect of nanochannel structures. Nano Lett. 2004;4: 1099–1103. doi: 10.1021/nl0494811

35. Yossifon G, Mushenheim P, Chang YC, Chang HC. Eliminating the limiting-current phenomenon by geometric field focusing into nanopores and nanoslots. Phys Rev E—Stat Nonlinear, Soft Matter Phys. 2010;81: 1–13. doi: 10.1103/PhysRevE.81.046301 20481821

36. Chung PS, Fan YJ, Sheen HJ, Tian WC. Real-time dual-loop electric current measurement for label-free nanofluidic preconcentration chip. Lab Chip. Royal Society of Chemistry; 2015;15: 319–330. doi: 10.1039/c4lc01143k 25372369

37. Kim SJ, Wang YC, Lee JH, Jang H, Han J. Concentration polarization and nonlinear electrokinetic flow near a nanofluidic channel. Phys Rev Lett. 2007;99: 1–4. doi: 10.1103/PhysRevLett.99.044501 17678369

38. Lee JH, Han J. Concentration-enhanced rapid detection of human chorionic gonadotropin as a tumor marker using a nanofluidic preconcentrator. Microfluid Nanofluidics. 2010;9: 973–979. doi: 10.1007/s10404-010-0598-z 20953263

39. Ko SH, Kim SJ, Cheow LF, Li LD, Kang KH, Han J. Massively parallel concentration device for multiplexed immunoassays. Lab Chip. 2011;11: 1351–1358. doi: 10.1039/c0lc00349b 21321747

40. Ko SH, Song Y-AA, Kim SJ, Kim M, Han J, Kang KH. Nanofluidic preconcentration device in a straight microchannel using ion concentration polarization. Lab Chip. 2012;12: 4472. doi: 10.1039/c2lc21238b 22907316

41. Chao CC, Chiu PH, Yang RJ. Preconcentration of diluted biochemical samples using microchannel with integrated nanoscale Nafion membrane. Biomed Microdevices. 2015;17. doi: 10.1007/s10544-015-9940-2 25681049

42. Kwak R, Kang JY, Kim TS. Spatiotemporally Defining Biomolecule Preconcentration by Merging Ion Concentration Polarization. Anal Chem. 2016;88: 988–996. doi: 10.1021/acs.analchem.5b03855 26642086

43. Yoo YK, Yoon DS, Kim G, Kim J, Han S Il, Lee J, et al. An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator. Sci Rep. Springer US; 2017;7: 1–8. doi: 10.1038/s41598-016-0028-x 28127051

44. Fan YJ, Deng CZ, Chung PS, Tian WC, Sheen HJ. A high sensitivity bead-based immunoassay with nanofluidic preconcentration for biomarker detection. Sensors Actuators, B Chem. Elsevier; 2018;272: 502–509. doi: 10.1016/j.snb.2018.05.141

45. Lee JH, Song Y-A, Han J. Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. Lab Chip. 2008;8: 596–601. doi: 10.1039/b717900f 18369515

46. Leinweber FC, Tallarek U. Nonequilibrium electrokinetic effects in beds of ion-permselective particles. Langmuir. 2004;20: 11637–11648. doi: 10.1021/la048408n 15595793

47. Rubinstein SM, Manukyan G, Staicu A, Rubinstein I, Zaltzman B, Lammertink RGH, et al. Direct observation of a nonequilibrium electro-osmotic instability. Phys Rev Lett. 2008;101: 1–4. doi: 10.1103/PhysRevLett.101.236101 19113567

48. Qiu B, Gong L, Li Z, Han J. Electrokinetic flow in the U-shaped micro-nanochannels. Theor Appl Mech Lett. The Authors. Published by Elsevier Ltd on behalf of The Chinese Society of Theoretical and Applied Mechanics; 2019;9: 36–42. doi: 10.1016/j.taml.2019.01.006

49. Gong L, Ouyang W, Li Z, Han J. Force fields of charged particles in micro-nanofluidic preconcentration systems. AIP Adv. 2017;7. doi: 10.1063/1.5008365 29308297

50. Ouyang W, Ye X, Li Z, Han J. Deciphering ion concentration polarization-based electrokinetic molecular concentration at the micro-nanofluidic interface: theoretical limits and scaling laws. Nanoscale. Royal Society of Chemistry; 2018;10: 15187–15194. doi: 10.1039/c8nr02170h 29790562

51. DAMA P, LEDOUX D, NYS M, VRINDTS Y, GROOTE D DE, FRANCHIMONT P, et al. Cytokine Serum Level During Severe Sepsis in Human IL-6 as a Marker of Severity. Ann Surg. 1992;215: 356–362. doi: 10.1097/00000658-199204000-00009 1558416

52. Hou T, Huang D, Zeng R, Ye Z, Zhang Y. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: a systematic review and meta-analysis. Int J Clin Exp Med. 2015;8: 15238–15245. Available: http://www.ncbi.nlm.nih.gov/pubmed/26629009%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4658898 26629009

53. Takahashi W, Watanabe E, Fujimura L, Watanabe-Takano H, Yoshidome H, Swanson PE, et al. Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. Crit Care. 2013;17. doi: 10.1186/cc12839 23883625

54. Kleiner G, Marcuzzi A, Zanin V, Monasta L, Zauli G. Cytokine Levels in the Serum of Healthy Subjects. Mediat Inflamm. 2013;2013. doi: 10.1155/2013/434010 23533306

55. Chaudhry H, Zhou J, Zhong Y, Ali MM, Mcguire F, Nagarkatti PS, et al. Role of cytokines as a double-edged sword in sepsis. In Vivo (Brooklyn). 2013;27: 669–684.

56. Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: A novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. Elsevier Ltd; 2013;13: 260–268. doi: 10.1016/S1473-3099(13)70001-X 23427891

57. Leichlé T, Lin YL, Chiang PC, Hu SM, Liao KT, Chou CF. Biosensor-compatible encapsulation for pre-functionalized nanofluidic channels using asymmetric plasma treatment. Sensors Actuators, B Chem. Elsevier B.V.; 2012;161: 805–810. doi: 10.1016/j.snb.2011.11.036

58. Gu J, Gupta R, Chou CF, Wei Q, Zenhausern F. A simple polysilsesquioxane sealing of nanofluidic channels below 10 nm at room temperature. Lab Chip. 2007;7: 1198–1201. doi: 10.1039/b704851c 17713620

59. Tang KC, Liao E, Ong WL, Wong JDS, Agarwal A, Nagarajan R, et al. Evaluation of bonding between oxygen plasma treated polydimethyl siloxane and passivated silicon. J Phys Conf Ser. 2006;34: 155–161. doi: 10.1088/1742-6596/34/1/026

60. Erickson HP. Size and shape of protein molecules at the nanometer level determined by sedimentation, gel filtration, and electron microscopy. Biol Proced Online. 2009;11: 32–51. doi: 10.1007/s12575-009-9008-x 19495910

61. Reverberi R, Reverberi L. Factors affecting the antigen-antibody reaction. Blood Transfus. 2007;5: 227–240. doi: 10.2450/2007.0047-07 19204779

62. Kwak R, Kim SJ, Han J. Continuous-flow biomolecule and cell concentrator by ion concentration polarization. Anal Chem. 2011;83: 7348–7355. doi: 10.1021/ac2012619 21854051

63. Hecht AH, Sommer GJ, Durland RH, Yang X, Singh AK, Hatch A V. Aptamers as affinity reagents in an integrated electrophoretic lab-on-a-chip platform. Anal Chem. 2010;82: 8813–8820. doi: 10.1021/ac101106m 20945866

64. Liu YF, Oey I, Bremer P, Carne A, Silcock P. Effects of pH, temperature and pulsed electric fields on the turbidity and protein aggregation of ovomucin-depleted egg white. Food Res Int. Elsevier Ltd; 2017;91: 161–170. doi: 10.1016/j.foodres.2016.12.005 28290320

65. Borzova VA, Markossian KA, Chebotareva NA, Kleymenov SY, Poliansky NB, Muranov KO, et al. Kinetics of thermal denaturation andaggregation of bovine serum albumin. PLoS One. 2016;11: 1–29. doi: 10.1371/journal.pone.0153495 27101281

66. Pereira RN, Souza BWS, Cerqueira MA, Teixeira JA, Vicente AA. Effects of electric fields on protein unfolding and aggregation: Influence on edible films formation. Biomacromolecules. 2010;11: 2912–2918. doi: 10.1021/bm100681a 20873858

67. Wei Z, Ruijin Y, Yali T, Wenbin Z, Xiao H. Investigation of the protein-protein aggregation of egg white proteins under pulsed electric fields. J Agric Food Chem. 2009;57: 3571–3577. doi: 10.1021/jf803900f 19309077

68. Bekard I, Dunstan DE. Electric field induced changes in protein conformation. Soft Matter. 2014;10: 431–437. doi: 10.1039/c3sm52653d 24652412

69. Dittmer J, Dittmer A, Bruna RD, Kasche V. A native, affinity‐based protein blot for the analysis of streptavidin heterogeneity: Consequences for the specificity of streptavidin mediated binding assays. Electrophoresis. 1989;10: 762–765. doi: 10.1002/elps.1150101106 2612477

70. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2015 43:D512–20. In: 2014. 2014. doi: 10.1093/nar/gku1267 25514926

71. Behrens SH, Grier DG. The charge of glass and silica surfaces. J Chem Phys. 2001;115: 6716–6721. doi: 10.1063/1.1404988


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