Abstract
We report on electrokinetic manipulation of submicron particles in a device with microfabricated Si electrodes featuring segmented sidewalls acting as tracks guiding particles under hydrodynamic drag. Electrohydrodynamic drag, both AC electroosmosis in low-conductive medium and electrothermal flow in high-conductive medium, gives rise to fluid rolls that deliver particles to tracks where they are held under the influence of dielectrophoretic forces. Particles are being railed along tracks under pressure-driven flow to a downstream junction where tracks act as bridges, keeping particles on course within the main channel causing their post-junction enrichment. This outcome, however, is strongly coupled to electrode sidewall contours as demonstrated here. We also report on particle oscillations under strong AC electroosmosis. Specifically, particles in deionized water can be seen bouncing off tracks or circulating with convective rolls in and out of space beneath tracks at an oscillation frequency and amplitude depending on the activation frequency. These results collectively draw attention to the functional use of electrode sidewall contours for continuous-flow manipulation of particles, which are rarely explored in microfluidics and yet could lead to more effective designs for particle separation and enrichment.
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The data generated and analysed during this study are available from the corresponding author on reasonable request.
References
Bazant MZ, Kilic MS, Storey BD, Ajdari A (2009) Nonlinear electrokinetics at large voltages. New J Phys 11:075016. https://doi.org/10.1088/1367-2630/11/7/075016
Bertrand N, Wu J, Xu X et al (2014) Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66:2–25. https://doi.org/10.1016/j.addr.2013.11.009
Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2009) Inertial microfluidics for continuous particle filtration and extraction. Microfluid Nanofluidics 7:217–226. https://doi.org/10.1007/s10404-008-0377-2
Chang DK, Chiu CY, Kuo SY et al (2009) Antiangiogenic targeting liposomes increase therapeutic efficacy for solid tumors. J Biol Chem 284:12905–12916. https://doi.org/10.1074/jbc.M900280200
Chen GD, Alberts CJ, Rodriguez W, Toner M (2010) Concentration and purification of human immunodeficiency virus type 1 virions by microfluidic separation of superparamagnetic nanoparticles. Anal Chem 82:723–728. https://doi.org/10.1021/ac9024522
Davis JA, Inglis DW, Morton KJ et al (2006) Deterministic hydrodynamics: taking blood apart. Proc Natl Acad Sci USA 103:14779–14784. https://doi.org/10.1073/pnas.0605967103
Destgeer G, Ha BH, Jung JH, Sung HJ (2014) Submicron separation of microspheres via travelling surface acoustic waves. Lab Chip 14:4665–4672. https://doi.org/10.1039/c4lc00868e
Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. ACS Nano 3:16–20. https://doi.org/10.1021/nn900002m
Goddard G, Brown LO, Habbersett R et al (2010) High-resolution spectral analysis of individual sers-active nanoparticles in flow. J Am Chem Soc 132:6081–6090. https://doi.org/10.1021/ja909850s
Gonzales PA, Pisitkun T, Hoffert JD et al (2009) Large-scale proteomics and phosphoproteomics of urinary exosomes. J Am Soc Nephrol 20:363–379. https://doi.org/10.1681/ASN.2008040406
Gou Y, Jia Y, Wang P, Sun C (2018) Progress of inertial microfluidics in principle and application. Sensors 18:1762
Hainfeld JF, Smilowitz HM, Oconnor MJ et al (2013) Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine 8:1601–1609. https://doi.org/10.2217/nnm.12.165
Hou HW, Bhagat AAS, Lin Chong AG et al (2010) Deformability based cell margination—A simple microfluidic design for malaria-infected erythrocyte separation. Lab Chip 10:2605–2613. https://doi.org/10.1039/c003873c
Huang LR, Cox EC, Austin RH, Sturm JC (2004) Continuous particle separation through deterministic lateral displacement. Science 304:987–990. https://doi.org/10.1126/science.1094567
Inglis DW, Herman N, Vesey G (2010) Highly accurate deterministic lateral displacement device and its application to purification of fungal spores. Biomicrofluidics 4:024109. https://doi.org/10.1063/1.3430553
Jalalian SH, Ramezani M, Jalalian SA et al (2019) Exosomes, new biomarkers in early cancer detection. Anal Biochem 571:1–13. https://doi.org/10.1016/J.AB.2019.02.013
Lamparski HG, Metha-Damani A, Yao JY et al (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226. https://doi.org/10.1016/S0022-1759(02)00330-7
Lee SHS, Hatton TA, Khan SA (2011) Microfluidic continuous magnetophoretic protein separation using nanoparticle aggregates. Microfluid Nanofluidics 11:429–438. https://doi.org/10.1007/s10404-011-0808-3
Lee K, Shao H, Weissleder R, Lee H (2015) Acoustic purification of extracellular microvesicles. ACS Nano 9:2321–2327. https://doi.org/10.1021/nn506538f
Lewpiriyawong N, Yang C (2012) AC-dielectrophoretic characterization and separation of submicron and micron particles using sidewall AgPDMS electrodes. Biomicrofluidics 6:1–9. https://doi.org/10.1063/1.3682049
Liu FK, Lin YY, Wu CH (2005) Highly efficient approach for characterizing nanometer-sized gold particles by capillary electrophoresis. Anal Chim Acta 528:249–254. https://doi.org/10.1016/j.aca.2004.08.052
Liu C, Guo J, Tian F et al (2017) Field-free isolation of exosomes from extracellular vesicles by microfluidic viscoelastic flows. ACS Nano 11:6968–6976. https://doi.org/10.1021/acsnano.7b02277
Luo T, Fan L, Zhu R, Sun D (2019) Microfluidic single-cell manipulation and analysis: methods and applications. Micromachines 10:1–31. https://doi.org/10.3390/mi10020104
Manzoor AA, Lindner LH, Landon CD et al (2012) Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res 72:5566–5575. https://doi.org/10.1158/0008-5472.CAN-12-1683
Miyabe H, Hyodo M, Nakamura T et al (2014) A new adjuvant delivery system “cyclic di-GMP/YSK05 liposome” for cancer immunotherapy. J Control Release 184:20–27. https://doi.org/10.1016/j.jconrel.2014.04.004
Morgan H, Hughes MP, Green NG (1999) Separation of submicron bioparticles by dielectrophoresis. Biophys J 77:516–525. https://doi.org/10.1016/S0006-3495(99)76908-0
Nikpoor AR, Tavakkol-Afshari J, Sadri K et al (2017) Improved tumor accumulation and therapeutic efficacy of CTLA-4-blocking antibody using liposome-encapsulated antibody: in vitro and in vivo studies. Nanomed Nanotechnol Biol Med 13:2671–2682. https://doi.org/10.1016/j.nano.2017.08.010
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383. https://doi.org/10.1083/jcb.201211138
Raposo G, Nijman HW, Stoorvogel W et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172. https://doi.org/10.1084/jem.183.3.1161
Romero-Creel MF, Goodrich E, Polniak DV, Lapizco-Encinas BH (2017) Assessment of sub-micron particles by exploiting charge differences with dielectrophoresis. Micromachines 8:239. https://doi.org/10.3390/mi8080239
Salafi T, Zeming KK, Zhang Y (2017) Advancements in microfluidics for nanoparticle separation. Lab Chip 17:11–33. https://doi.org/10.1039/C6LC01045H
Shafiee H, Caldwell JL, Sano MB, Davalos RV (2009) Contactless dielectrophoresis: a new technique for cell manipulation. Biomed Microdev 11:997–1006. https://doi.org/10.1007/s10544-009-9317-5
Shi L, Rana A, Esfandiari L (2018) A low voltage nanopipette dielectrophoretic device for rapid entrapment of nanoparticles and exosomes extracted from plasma of healthy donors. Sci Rep 8:1–12. https://doi.org/10.1038/s41598-018-25026-2
Sun X, Tabakman SM, Seo WS et al (2009) Separation of nanoparticles in a density gradient: FeCo@C and gold nanocrystals. Angew Chemie Int Ed 48:939–942. https://doi.org/10.1002/anie.200805047
Wu Z, Willing B, Bjerketorp J et al (2009) Soft inertial microfluidics for high throughput separation of bacteria from human blood cells. Lab Chip 9:1193–1199. https://doi.org/10.1039/b817611f
Wunsch BH, Smith JT, Gifford SM et al (2016) Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20nm. Nat Nanotechnol 11:936–940. https://doi.org/10.1038/nnano.2016.134
Xing X, Yobas L (2015) Dielectrophoretic isolation of cells using 3D microelectrodes featuring castellated blocks. Analyst 140:3397–3405. https://doi.org/10.1039/c5an00167f
Xing X, Zhang M, Yobas L (2013) Interdigitated 3-D silicon ring microelectrodes for DEP-based particle manipulation. J Microelectromech Syst 22:363–371. https://doi.org/10.1109/JMEMS.2012.2224641
Xing X, Poon RYC, Wong CSC, Yobas L (2014) Label-free enumeration of colorectal cancer cells from lymphocytes performed at a high cell-loading density by using interdigitated ring-array microelectrodes. Biosens Bioelectron 61:434–442. https://doi.org/10.1016/j.bios.2014.05.054
Xing X, He M, Qiu H, Yobas L (2016) Continuous-flow electrokinetic-assisted plasmapheresis by using three-dimensional microelectrodes featuring sidewall undercuts. Anal Chem 88:5197–5204. https://doi.org/10.1021/acs.analchem.6b00215
Xing X, Ng CN, Chau ML, Yobas L (2018) Railing cells along 3D microelectrode tracks for continuous-flow dielectrophoretic sorting. Lab Chip 18:3760–3769. https://doi.org/10.1039/c8lc00805a
Xu X, Caswell KK, Tucker E et al (2007) Size and shape separation of gold nanoparticles with preparative gel electrophoresis. J Chromatogr A 1167:35–41. https://doi.org/10.1016/j.chroma.2007.07.056
Zhao K, Li D (2017) Continuous separation of nanoparticles by type via localized DC-dielectrophoresis using asymmetric nano-orifice in pressure-driven flow. Sensors Actuators B Chem 250:274–284. https://doi.org/10.1016/j.snb.2017.04.184
Acknowledgements
Device fabrication was carried out at the Nanosystem Fabrication Facility (NFF) of the HKUST.
Funding
This project was supported financially by the Research Grant Council (RGC) of Hong Kong under grant 16200719.
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Conceptualization and methodology, LY; Validation, SDK, YB, and ZT; Formal analysis, SDK, YB, and ZT; Writing—original draft, review & editing, LY, SDK, YB, and ZT; Funding acquisition, LY; Supervision, LY.
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Kushigbor, S.D., Tang, Z., Bu, Y. et al. Electrokinetic oscillation, railing, and enrichment of submicron particles along 3D microelectrode tracks. Microfluid Nanofluid 25, 37 (2021). https://doi.org/10.1007/s10404-021-02439-6
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DOI: https://doi.org/10.1007/s10404-021-02439-6