Impact of Microfluidic Chip Electrophoresis in Modern Analysis: An
Update on Recent Trends

Sumit      Pasricha; Rohit      Bhatia; Preeti      Patel; Bhupinder      Kumar
Abstract

The recent development of microfluidics and lab-on-a-chip technology has substantially raised interest in analytical chemistry. Since, they have demonstrated to be extraordinarily adept at precise fluid control, cell manipulation, and signal output, microfluidic chips are a useful tool for quick and in-depth single-cell investigation. This technique is cost-effective, less time-consuming, automatic, high mobility, and fast separation technique. Due to the internal chip sizes, which range from micrometers to millimeters, consumption of the samples and reagents occurs at the nanoliter and picoliter levels. The microfluidic device can fit a variety of functions onto a few centimeter-long chips. In this article, we discussed numerous preparations of microfluidic chip electrophoresis and its recent advancements. This method is useful for the detection of various small amounts of content with less time and greater efficacy. It is also useful in cancer studies, 3D inkjet printing, immunoassay investigation in cell-cell interactions, analysis of nanoparticles, dielectrophoretic particle separation, plant alkaloids, and forensic science applications. This review, therefore, examines the use of various microfluidic chips in electrophoretic separation during 2017–2022. There are various papers found by search, indicating continuous activity in the research area along with studies to explain its material, method, and its efficacy.
Graphical Abstract

[1]
Papadimitriou, V.A.; Segerink, L.I.; Eijkel, J.C.T. Continuous focusing, fractionation and extraction of anionic analytes in a microfluidic chip. Lab Chip,  2019, 19(19), 3238-3248.
 [http://dx.doi.org/10.1039/C9LC00434C] [PMID:  31475716]

[2]
Harrison, D.J.; Fluri, K.; Seiler, K.; Fan, Z.; Effenhauser, C.S.; Manz, A. Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science,  1993, 261(5123), 895-897.
 [http://dx.doi.org/10.1126/science.261.5123.895] [PMID:  17783736]

[3]
Duarte, L.M.; Moreira, R.C.; Coltro, W.K.T. Nonaqueous electrophoresis on microchips: A review. Electrophoresis,  2020, 41(7-8), 434-448.
 [http://dx.doi.org/10.1002/elps.201900238] [PMID:  31793007]

[4]
Castro, E.R.; Manz, A. Present state of microchip electrophoresis: State of the art and routine applications. J. Chromatogr. A,  2015, 1382, 66-85.
 [http://dx.doi.org/10.1016/j.chroma.2014.11.034] [PMID:  25529267]

[5]
Zhang, W.; He, Z.; Yi, L.; Mao, S.; Li, H.; Lin, J.M. A dual-functional microfluidic chip for on-line detection of interleukin-8 based on rolling circle amplification. Biosens. Bioelectron.,  2018, 102, 652-660.
 [http://dx.doi.org/10.1016/j.bios.2017.12.017] [PMID:  29268188]

[6]
Ou, X.; Chen, P.; Huang, X.; Li, S.; Liu, B.F. Microfluidic chip electrophoresis for biochemical analysis. J. Sep. Sci.,  2020, 43(1), 258-270.
 [http://dx.doi.org/10.1002/jssc.201900758] [PMID:  31654552]

[7]
Liu, B.F.; Hisamoto, H.; Terabe, S. Subsecond separation of cellular flavin coenzymes by microchip capillary electrophoresis with laser-induced fluorescence detection. J. Chromatogr. A,  2003, 1021(1-2), 201-207.
 [http://dx.doi.org/10.1016/j.chroma.2003.09.012] [PMID:  14735989]

[8]
Fan, Y.; Dong, D.; Li, Q.; Si, H.; Pei, H.; Li, L.; Tang, B. Fluorescent analysis of bioactive molecules in single cells based on microfluidic chips. Lab Chip,  2018, 18(8), 1151-1173.
 [http://dx.doi.org/10.1039/C7LC01333G] [PMID:  29541737]

[9]
Gabriel, E.F.M.; Lucca, B.G.; Duarte, G.R.M.; Coltro, W.K.T. Recent advances in toner-based microfluidic devices for bioanalytical applications. Anal. Methods,  2018, 10(25), 2952-2962.
 [http://dx.doi.org/10.1039/C8AY01095A]

[10]
Jiang, B.; Zhu, L.; Min, L.; Li, X.; Zhai, Z.; Drummer, D. Characterization of microchannel replicability of injection molded electrophoresis microfluidic chips. Polymers,  2019, 11(4), 608.
 [http://dx.doi.org/10.3390/polym11040608] [PMID:  30960592]

[11]
Kraly, J.R.; Holcomb, R.E.; Guan, Q.; Henry, C.S. Review: Microfluidic applications in metabolomics and metabolic profiling. Anal. Chim. Acta,  2009, 653(1), 23-35.
 [http://dx.doi.org/10.1016/j.aca.2009.08.037] [PMID:  19800473]

[12]
Faure, K. Liquid chromatography on chip. Electrophoresis,  2010, 31(15), 2499-2511.
 [http://dx.doi.org/10.1002/elps.201000051] [PMID:  20603823]

[13]
Cui, P.; Wang, S. Application of microfluidic chip technology in pharmaceutical analysis: A review. J. Pharm. Anal.,  2019, 9(4), 238-247.
 [http://dx.doi.org/10.1016/j.jpha.2018.12.001] [PMID:  31452961]

[14]
Ribeiro da Silva, M.; Zaborowska, I.; Carillo, S.; Bones, J. A rapid, simple and sensitive microfluidic chip electrophoresis mass spectrometry method for monitoring amino acids in cell culture media. J. Chromatogr. A,  2021, 1651, 462336.
 [http://dx.doi.org/10.1016/j.chroma.2021.462336] [PMID:  34153732]

[15]
Sonker, M.; Sahore, V.; Woolley, A.T. Recent advances in microfluidic sample preparation and separation techniques for molecular biomarker analysis: A critical review. Anal. Chim. Acta,  2017, 986, 1-11.
 [http://dx.doi.org/10.1016/j.aca.2017.07.043] [PMID:  28870312]

[16]
Kašička, V. From micro to macro: Conversion of capillary electrophoretic separations of biomolecules and bioparticles to preparative free-flow electrophoresis scale. Electrophoresis,  2009, 30(S1)(Suppl. 1), S40-S52.
 [http://dx.doi.org/10.1002/elps.200900156] [PMID:  19517515]

[17]
Xie, L.; Cao, Y.; Hu, F.; Li, T.; Wang, Q.; Gan, N. Microfluidic chip electrophoresis for simultaneous fluorometric aptasensing of alpha-fetoprotein, carbohydrate antigen 125 and carcinoembryonic antigen by applying a catalytic hairpin assembly. Mikrochim. Acta,  2019, 186(6), 547.

[18]
Abou-Hassan, A.; Sandre, O.; Cabuil, V. Microfluidics in inorganic chemistry. Angew. Chem. Int. Ed.,  2010, 49(36), 6268-6286.
 [http://dx.doi.org/10.1002/anie.200904285] [PMID:  20677292]

[19]
Cong, H.; Xu, X.; Yu, B.; Yuan, H.; Peng, Q.; Tian, C. Recent progress in preparation and application of microfluidic chip electrophoresis. J. Micromech. Microeng.,  2015, 25(5), 053001.
 [http://dx.doi.org/10.1088/0960-1317/25/5/053001]

[20]
Wang, R.; Wang, X. Sensing of inorganic ions in microfluidic devices. Sens. Actuators B Chem.,  2021, 329, 129171.
 [http://dx.doi.org/10.1016/j.snb.2020.129171]

[21]
Olney, D.; Fuller, L.; Santhanam, K.S.V. A greenhouse gas silicon microchip sensor using a conducting composite with single walled carbon nanotubes. Sens. Actuators B Chem.,  2014, 191, 545-552.
 [http://dx.doi.org/10.1016/j.snb.2013.10.039]

[22]
Pinheiro, K.M.P.; Duarte, L.M.; Duarte-Junior, G.F.; Coltro, W.K.T. Chip-based separation of organic and inorganic anions and multivariate analysis of wines according to grape varieties. Talanta,  2021, 231, 122381.
 [http://dx.doi.org/10.1016/j.talanta.2021.122381] [PMID:  33965044]

[23]
Bai, Z.; He, Q.; Huang, S.; Hu, X.; Chen, H. Preparation of hybrid soda-lime/quartz glass chips with wettability-patterned channels for manipulation of flow profiles in droplet-based analytical systems. Anal. Chim. Acta,  2013, 767, 97-103.
 [http://dx.doi.org/10.1016/j.aca.2013.01.008] [PMID:  23452792]

[24]
Fu, J.L.; Fang, Q.; Zhang, T.; Jin, X.H.; Fang, Z.L. Laser-induced fluorescence detection system for microfluidic chips based on an orthogonal optical arrangement. Anal. Chem.,  2006, 78(11), 3827-3834.
 [http://dx.doi.org/10.1021/ac060153q] [PMID:  16737244]

[25]
Effenhauser, C.S.; Manz, A.; Widmer, H.M. Glass chips for high-speed capillary electrophoresis separations with submicrometer plate heights. Anal. Chem.,  1993, 65(19), 2637-2642.
 [http://dx.doi.org/10.1021/ac00067a015]

[26]
Bhansali, S.; Vasudev, A. MEMS for biomedical applications; Elsevier, 2012. 
 [http://dx.doi.org/10.1533/9780857096272]

[27]
Lobo-Júnior, E.O.; Chagas, C.L.S.; Duarte, L.C.; Cardoso, T.M.G.; Souza, F.R.; Lima, R.S.; Coltro, W.K.T. Inexpensive and nonconventional fabrication of microfluidic devices in PMMA based on a soft‐embossing protocol. Electrophoresis,  2020, 41(18-19), 1641-1650.
 [http://dx.doi.org/10.1002/elps.202000131] [PMID:  32726462]

[28]
Muluneh, M.; Issadore, D. A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics. Lab Chip,  2014, 14(23), 4552-4558.
 [http://dx.doi.org/10.1039/C4LC00869C] [PMID:  25284502]

[29]
Nandi, P.; Scott, D.E.; Desai, D.; Lunte, S.M. Development and optimization of an integrated PDMS based-microdialysis microchip electrophoresis device with on-chip derivatization for continuous monitoring of primary amines. Electrophoresis,  2013, 34(6), 895-902.
 [http://dx.doi.org/10.1002/elps.201200454] [PMID:  23335091]

[30]
Júnior, E.d.O.L.; da Costa Duarte, L.; de Paula Braga, L.E.; Gobbi, Â.L.; de Jesus, D.P.; Coltro, W.K.T. >High fidelity prototyping of PDMS electrophoresis microchips using laser-printed masters. Microsyst. Technol.,  2014, 21(16), 1-9.

[31]
Khizar, S.; Zine, N.; Errachid, A.; Jaffrezic-Renault, N.; Elaissari, A. Microfluidic‐based nanoparticle synthesis and their potential applications. Electrophoresis,  2022, 43(7-8), 819-838.
 [http://dx.doi.org/10.1002/elps.202100242] [PMID:  34758117]

[32]
Khizar, S.; Ben Halima, H.; Ahmad, N.M.; Zine, N.; Errachid, A.; Elaissari, A. Magnetic nanoparticles in microfluidic and sensing: From transport to detection. Electrophoresis,  2020, 41(13-14), 1206-1224.
 [http://dx.doi.org/10.1002/elps.201900377] [PMID:  32347555]

[33]
Pattanayak, P.; Singh, S.K.; Gulati, M.; Vishwas, S.; Kapoor, B.; Chellappan, D.K.; Anand, K.; Gupta, G.; Jha, N.K.; Gupta, P.K.; Prasher, P.; Dua, K.; Dureja, H.; Kumar, D.; Kumar, V. Microfluidic chips: Recent advances, critical strategies in design, applications and future perspectives. Microfluid. Nanofluidics,  2021, 25(12), 99.
 [http://dx.doi.org/10.1007/s10404-021-02502-2] [PMID:  34720789]

[34]
Liang, R.; Hu, P.; Gan, G.; Qiu, J. Deoxyribonucleic acid modified poly(dimethylsiloxane) microfluidic channels for the enhancement of microchip electrophoresis. Talanta,  2009, 77(5), 1647-1653.
 [http://dx.doi.org/10.1016/j.talanta.2008.09.056] [PMID:  19159778]

[35]
Rehmani, M.A.A.; Jaywant, S.A.; Arif, K.M. Study of microchannels fabricated using desktop fused deposition modeling systems. Micromachines,  2020, 12(1), 14.
 [http://dx.doi.org/10.3390/mi12010014] [PMID:  33375727]

[36]
Liu, X.; Sanner, N.; Sentis, M.; Stoian, R.; Zhao, W.; Cheng, G.; Utéza, O. Front-surface fabrication of moderate aspect ratio micro-channels in fused silica by single picosecond Gaussian–Bessel laser pulse. Appl. Phys., A Mater. Sci. Process.,  2018, 124(2), 206.
 [http://dx.doi.org/10.1007/s00339-018-1634-1]

[37]
Felhofer, J.L.; Blanes, L.; Garcia, C.D. Recent developments in instrumentation for capillary electrophoresis and microchip-capillary electrophoresis. Electrophoresis,  2010, 31(15), 2469-2486.
 [http://dx.doi.org/10.1002/elps.201000203] [PMID:  20665910]

[38]
Quero, R.F.; Bressan, L.P.; da Silva, J.A.F.; de Jesus, D.P. A novel thread-based microfluidic device for capillary electrophoresis with capacitively coupled contactless conductivity detection. Sens. Actuators B Chem.,  2019, 286, 301-305.
 [http://dx.doi.org/10.1016/j.snb.2019.01.168]

[39]
Collins, G.E.; Wu, P.; Lu, Q.; Ramsey, J.D.; Bromund, R.H. Compact, high voltage power supply for the lab-on-a-chip. Lab Chip,  2004, 4(4), 408-411.
 [http://dx.doi.org/10.1039/b314349j] [PMID:  15269813]

[40]
Pan, Q.; Yamauchi, K.A.; Herr, A.E. Controlling dispersion during single-cell polyacrylamide-gel electrophoresis in open microfluidic devices. Anal. Chem.,  2018, 90(22), 13419-13426.
 [http://dx.doi.org/10.1021/acs.analchem.8b03233] [PMID:  30346747]

[41]
Li, Q.; Zhang, H.; Wang, Y.; Tang, B.; Liu, X.; Gong, X. Versatile programmable eight-path-electrode power supply for automatic manipulating microfluids of a microfluidic chip. Sens. Actuators B Chem.,  2009, 136(1), 265-274.
 [http://dx.doi.org/10.1016/j.snb.2008.10.066]

[42]
Tamdoğan, E. Immersion cooling of suspended and coated nano-phosphor particles for extending the limits of optical extraction of light emitting diodes. J. Heat Transfer,  2017, 144(12), 12250.

[43]
Khandekar, S.; Sahu, G.; Muralidhar, K.; Gatapova, E.Y.; Kabov, O.A.; Hu, R.; Luo, X.; Zhao, L. Cooling of high-power LEDs by liquid sprays: Challenges and prospects. Appl. Therm. Eng.,  2021, 184, 115640.
 [http://dx.doi.org/10.1016/j.applthermaleng.2020.115640]

[44]
Dolník, V.; Liu, S.; Jovanovich, S. Capillary electrophoresis on microchip. Electrophoresis,  2000, 21(1), 41-54.
 [http://dx.doi.org/10.1002/(SICI)1522-2683(20000101)21:1<41:AID-ELPS41>3.0.CO;2-7] [PMID:  10634469]

[45]
Becker, H.; Gärtner, C. Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis,  2000, 21(1), 12-26.
 [http://dx.doi.org/10.1002/(SICI)1522-2683(20000101)21:1<12:AID-ELPS12>3.0.CO;2-7] [PMID:  10634467]

[46]
Li, W.; Zhang, L.; Ge, X.; Xu, B.; Zhang, W.; Qu, L.; Choi, C.H.; Xu, J.; Zhang, A.; Lee, H.; Weitz, D.A. Microfluidic fabrication of microparticles for biomedical applications. Chem. Soc. Rev.,  2018, 47(15), 5646-5683.
 [http://dx.doi.org/10.1039/C7CS00263G] [PMID:  29999050]

[47]
Gale, B.; Jafek, A.; Lambert, C.; Goenner, B.; Moghimifam, H.; Nze, U.; Kamarapu, S. A review of current methods in microfluidic device fabrication and future commercialization prospects. Inventions,  2018, 3(3), 60.
 [http://dx.doi.org/10.3390/inventions3030060]

[48]
Becker, H.; Locascio, L.E. Polymer microfluidic devices. Talanta,  2002, 56(2), 267-287.
 [http://dx.doi.org/10.1016/S0039-9140(01)00594-X] [PMID:  18968500]

[49]
Kaur, G.; Tomar, M.; Gupta, V. Development of a microfluidic electrochemical biosensor: Prospect for point-of-care cholesterol monitoring. Sens. Actuators B Chem.,  2018, 261, 460-466.
 [http://dx.doi.org/10.1016/j.snb.2018.01.144]

[50]
Zhang, M.; Wu, J.; Wang, L.; Xiao, K.; Wen, W. A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips. Lab Chip,  2010, 10(9), 1199-1203.
 [http://dx.doi.org/10.1039/b923101c] [PMID:  20390140]

[51]
Beauchamp, M.J.; Nielsen, A.V.; Gong, H.; Nordin, G.P.; Woolley, A.T. 3D printed microfluidic devices for microchip electrophoresis of preterm birth biomarkers. Anal. Chem.,  2019, 91(11), 7418-7425.
 [http://dx.doi.org/10.1021/acs.analchem.9b01395] [PMID:  31056901]

[52]
Beauchamp, M.J.; Nordin, G.P.; Woolley, A.T. Moving from millifluidic to truly microfluidic sub-100-μm cross-section 3D printed devices. Anal. Bioanal. Chem.,  2017, 409(18), 4311-4319.
 [http://dx.doi.org/10.1007/s00216-017-0398-3] [PMID:  28612085]

[53]
Zhang, L.; Chen, Q.; Ma, Y.; Sun, J. Microfluidic methods for fabrication and engineering of nanoparticle drug delivery systems. ACS Appl. Bio Mater.,  2020, 3(1), 107-120.
 [http://dx.doi.org/10.1021/acsabm.9b00853] [PMID:  35019430]

[54]
Catarino, S.O.; Rodrigues, R.O.; Pinho, D.; Miranda, J.M.; Minas, G.; Lima, R. Blood cells separation and sorting techniques of passive microfluidic devices: From fabrication to applications. Micromachines,  2019, 10(9), 593.
 [http://dx.doi.org/10.3390/mi10090593] [PMID:  31510012]

[55]
Han, H.; Zheng, Z.; Pan, D.; Wang, C.; Hu, X.; Wang, Y. Portable microfluidic chip electrophoresis device with integrated Pt electrodes for the analysis of AgNPs. Micro & Nano Lett.,  2018, 13(3), 302-305.
 [http://dx.doi.org/10.1049/mnl.2017.0515]

[56]
Li, Z.; Ju, R.; Sekine, S.; Zhang, D.; Zhuang, S.; Yamaguchi, Y. All-in-one microfluidic device for on-site diagnosis of pathogens based on an integrated continuous flow PCR and electrophoresis biochip. Lab Chip,  2019, 19(16), 2663-2668.
 [http://dx.doi.org/10.1039/C9LC00305C] [PMID:  31273367]

[57]
Zhao, Y.; Hu, X.; Hu, S.; Peng, Y. Applications of fiber-optic biochemical sensor in microfluidic chips: A review. Biosens. Bioelectron.,  2020, 166, 112447.
 [http://dx.doi.org/10.1016/j.bios.2020.112447] [PMID:  32738649]

[58]
Liu, J.; Zhang, Y.; Jiang, M.; Tian, L.; Sun, S.; Zhao, N.; Zhao, F.; Li, Y. Electrochemical microfluidic chip based on molecular imprinting technique applied for therapeutic drug monitoring. Biosens. Bioelectron.,  2017, 91, 714-720.
 [http://dx.doi.org/10.1016/j.bios.2017.01.037] [PMID:  28126661]

[59]
Jie, M.; Mao, S.; Li, H.; Lin, J.M. Multi-channel microfluidic chip-mass spectrometry platform for cell analysis. Chin. Chem. Lett.,  2017, 28(8), 1625-1630.
 [http://dx.doi.org/10.1016/j.cclet.2017.05.024]

[60]
Liao, Z.; Zhang, Y.; Li, Y.; Miao, Y.; Gao, S.; Lin, F.; Deng, Y.; Geng, L. Microfluidic chip coupled with optical biosensors for simultaneous detection of multiple analytes: A review. Biosens. Bioelectron.,  2019, 126, 697-706.
 [http://dx.doi.org/10.1016/j.bios.2018.11.032] [PMID:  30544083]

[61]
Liu, Y.; Li, C.; Li, Z.; Chan, S.D.; Eto, D.; Wu, W.; Zhang, J.P.; Chien, R.L.; Wada, H.G.; Greenstein, M.; Satomura, S. On-chip quantitative PCR using integrated real-time detection by capillary electrophoresis. Electrophoresis,  2016, 37(3), 545-552.
 [http://dx.doi.org/10.1002/elps.201500298] [PMID:  26456095]

[62]
Zhang, K.; Gan, N.; Shen, Z.; Cao, J.; Hu, F.; Li, T. Microchip electrophoresis based aptasensor for multiplexed detection of antibiotics in foods via a stir-bar assisted multi-arm junctions recycling for signal amplification. Biosens. Bioelectron.,  2019, 130, 139-146.
 [http://dx.doi.org/10.1016/j.bios.2019.01.044] [PMID:  30735947]

[63]
Kamruzzaman, M.; Alam, A.M.; Kim, K.M.; Lee, S.H.; Kim, Y.H.; Kim, G.M.; Dang, T.D. Microfluidic chip based chemiluminescence detection of L-phenylalanine in pharmaceutical and soft drinks. Food Chem.,  2012, 135(1), 57-62.
 [http://dx.doi.org/10.1016/j.foodchem.2012.04.062]

[64]
Mitchell, K.R.; Esene, J.E.; Woolley, A.T. Advances in multiplex electrical and optical detection of biomarkers using microfluidic devices. Anal. Bioanal. Chem.,  2022, 414(1), 167-180.
 [http://dx.doi.org/10.1007/s00216-021-03553-8] [PMID:  34345949]

[65]
Scholl, T.; Dietze, C.; Schmidt, M.; Ohla, S.; Belder, D. Sheathless coupling of microchip electrophoresis to ESI-MS utilising an integrated photo polymerised membrane for electric contacting. Anal. Bioanal. Chem.,  2018, 410(23), 5741-5750.
 [http://dx.doi.org/10.1007/s00216-018-1226-0] [PMID:  29974150]

[66]
Caxico de Abreu, F.; Costa, E.E.M. Electrochemical detection using an engraved microchip–capillary electrophoresis Platform. Electroanalysis,  2016, 28(9), 2104-2108.
 [http://dx.doi.org/10.1002/elan.201600033]

[67]
Costa, B.M.C.; Griveau, S.; Bedioui, F.; d’Orlye, F.; da Silva, J.A.F.; Varenne, A. Stereolithography based 3D-printed microfluidic device with integrated electrochemical detection. Electrochim. Acta,  2022, 407, 407139888.

[68]
Issaeva, N.; Bozko, P.; Enge, M.; Protopopova, M.; Verhoef, L.G.G.C.; Masucci, M.; Pramanik, A.; Selivanova, G. Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors. Nat. Med.,  2004, 10(12), 1321-1328.
 [http://dx.doi.org/10.1038/nm1146] [PMID:  15558054]

[69]
Li, J.; Richards, J.C. Application of capillary electrophoresis mass spectrometry to the characterization of bacterial lipopolysaccharides. Mass Spectrom. Rev.,  2007, 26(1), 35-50.
 [http://dx.doi.org/10.1002/mas.20105] [PMID:  16967446]

[70]
Khatri, K.; Klein, J.A.; Haserick, J.R.; Leon, D.R.; Costello, C.E.; McComb, M.E.; Zaia, J. Microfluidic capillary electrophoresis–mass spectrometry for analysis of monosaccharides, oligosaccharides, and glycopeptides. Anal. Chem.,  2017, 89(12), 6645-6655.
 [http://dx.doi.org/10.1021/acs.analchem.7b00875] [PMID:  28530388]

[71]
Mao, S.; Li, W.; Zhang, Q.; Zhang, W.; Huang, Q.; Lin, J-M. Cell analysis on chip-mass spectrometry. Trends Analyt. Chem.,  2018, 10743-10759.

[72]
Dabighi, A.; Toghraie, D. A new microfluidic device for separating circulating tumor cells based on their physical properties by using electrophoresis and dielectrophoresis forces within an electrical field. Comput. Methods Programs Biomed.,  2020, 185, 105147.
 [http://dx.doi.org/10.1016/j.cmpb.2019.105147] [PMID:  31669960]

[73]
Bhattacharjee, N.; Urrios, A.; Kang, S.; Folch, A. The upcoming 3D-printing revolution in microfluidics. Lab Chip,  2016, 16(10), 1720-1742.
 [http://dx.doi.org/10.1039/C6LC00163G] [PMID:  27101171]

[74]
Au, A.K.; Lee, W.; Folch, A. Mail-order microfluidics: Evaluation of stereolithography for the production of microfluidic devices. Lab Chip,  2014, 14(7), 1294-1301.
 [http://dx.doi.org/10.1039/C3LC51360B] [PMID:  24510161]

[75]
Walczak, R.; Adamski, K.; Kubicki, W. Inkjet 3D printed modular microfluidic chips for on-chip gel electrophoresis. J. Micromech. Microeng.,  2019, 29(5), 057001.
 [http://dx.doi.org/10.1088/1361-6439/ab0e64]

[76]
Ji, Q.; Zhang, J.M.; Liu, Y.; Li, X.; Lv, P.; Jin, D.; Duan, H. A modular microfluidic device via multimaterial 3D printing for emulsion generation. Sci. Rep.,  2018, 8(1), 4791.
 [http://dx.doi.org/10.1038/s41598-018-22756-1] [PMID:  29556013]

[77]
Munge, B.S.; Stracensky, T.; Gamez, K.; DiBiase, D.; Rusling, J.F. Multiplex immunosensor arrays for electrochemical detection of cancer biomarker proteins. Electroanalysis,  2016, 28(11), 2644-2658.
 [http://dx.doi.org/10.1002/elan.201600183] [PMID:  28592919]

[78]
Cappello, F.; Logozzi, M.; Campanella, C.; Bavisotto, C.C.; Marcilla, A.; Properzi, F.; Fais, S. Exosome levels in human body fluids: A tumor marker by themselves? Eur. J. Pharm. Sci.,  2017, 9693-9698.

[79]
Xie, L.; Li, T.; Hu, F.; Jiang, Q.; Wang, Q.; Gan, N. A novel microfluidic chip and antibody-aptamer based multianalysis method for simultaneous determination of several tumor markers with polymerization nicking reactions for homogenous signal amplification. Microchem. J.,  2019, 147, 454-462.
 [http://dx.doi.org/10.1016/j.microc.2019.03.028]

[80]
Sackmann, E.K.; Fulton, A.L.; Beebe, D.J. The present and future role of microfluidics in biomedical research. Nature,  2014, 507(7491), 181-189.
 [http://dx.doi.org/10.1038/nature13118] [PMID:  24622198]

[81]
Meng, H.L.; Chen, G.H.; Guo, X.; Chen, P.; Cai, Q.H.; Tian, Y.F. Determination of five quinolone antibiotic residues in foods by micellar electrokinetic capillary chromatography with quantum dot indirect laser-induced fluorescence. Anal. Bioanal. Chem.,  2014, 406(13), 3201-3208.
 [http://dx.doi.org/10.1007/s00216-014-7730-y] [PMID:  24633513]

[82]
Zhou, L.; Gan, N.; Zhou, Y.; Li, T.; Cao, Y.; Chen, Y. A label-free and universal platform for antibiotics detection based on microchip electrophoresis using aptamer probes. Talanta,  2017, 167, 544-549.
 [http://dx.doi.org/10.1016/j.talanta.2017.02.061] [PMID:  28340759]

[83]
He, L.; Shen, Z.; Cao, Y.; Li, T.; Wu, D.; Dong, Y.; Gan, N. A microfluidic chip based ratiometric aptasensor for antibiotic detection in foods using stir bar assisted sorptive extraction and rolling circle amplification. Analyst,  2019, 144(8), 2755-2764.
 [http://dx.doi.org/10.1039/C9AN00106A] [PMID:  30869681]

[84]
Song, W.; Zhu, K.; Cao, Z.; Lau, C.; Lu, J. Hybridization chain reaction-based aptameric system for the highly selective and sensitive detection of protein. Analyst,  2012, 137(6), 1396-1401.
 [http://dx.doi.org/10.1039/c2an16232f] [PMID:  22318238]

[85]
Stejskal, D.; Fiala, R.R. Evaluation of serum and urine clusterin as a potential tumor marker for urinary bladder cancer. Neoplasma,  2006, 53(4), 343-346.
 [PMID:  16830064]

[86]
Fan, Q.; Li, C.; Tao, Y.; Mao, X.; Li, G. Simple and fast screening of G-quadruplex ligands with electrochemical detection system. Talanta,  2016, 160, 144-147.
 [http://dx.doi.org/10.1016/j.talanta.2016.07.009] [PMID:  27591598]

[87]
Murat, P.; Singh, Y.; Defrancq, E. Methods for investigating G-quadruplex DNA/ligand interactions. Chem. Soc. Rev.,  2011, 40(11), 5293-5307.
 [http://dx.doi.org/10.1039/c1cs15117g] [PMID:  21720638]

[88]
Schilling, E.A.; Kamholz, A.E.; Yager, P. Cell lysis and protein extraction in a microfluidic device with detection by a fluorogenic enzyme assay. Anal. Chem.,  2002, 74(8), 1798-1804.
 [http://dx.doi.org/10.1021/ac015640e] [PMID:  11985310]

[89]
Tetala, K.K.R.; Swarts, J.W.; Chen, B.; Janssen, A.E.M.; van Beek, T.A. A three-phase microfluidic chip for rapid sample clean-up of alkaloids from plant extracts. Lab Chip,  2009, 9(14), 2085-2092.
 [http://dx.doi.org/10.1039/b822106e] [PMID:  19568679]

[90]
Cai, Q.; Meng, J.; Ge, Y.; Gao, Y.; Zeng, Y.; Li, H.; Sun, Y. Fishing antitumor ingredients by G-quadruplex affinity from herbal extract on a three-phase-laminar-flow microfluidic chip. Talanta,  2020, 220, 121368.
 [http://dx.doi.org/10.1016/j.talanta.2020.121368] [PMID:  32928397]

[91]
Huh, D.; Hamilton, G.A.; Ingber, D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol.,  2011, 21(12), 745-754.
 [http://dx.doi.org/10.1016/j.tcb.2011.09.005] [PMID:  22033488]

[92]
Sung, J.H.; Shuler, M.L. A micro cell culture analog (µCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip,  2009, 9(10), 1385-1394.
 [http://dx.doi.org/10.1039/b901377f] [PMID:  19417905]

[93]
Lu, S.; Dugan, C.E.; Kennedy, R.T. Microfluidic chip with integrated electrophoretic immunoassay for investigating cell–cell interactions. Anal. Chem.,  2018, 90(8), 5171-5178.
 [http://dx.doi.org/10.1021/acs.analchem.7b05304] [PMID:  29578696]

[94]
Wright, L.M.; Kreikemeier, J.T.; Fimmel, C.J. A concise review of serum markers for hepatocellular cancer. Cancer Detect. Prev.,  2007, 31(1), 35-44.
 [http://dx.doi.org/10.1016/j.cdp.2006.11.003] [PMID:  17293059]

[95]
Yu, H.; Yan, F.; Dai, Z.; Ju, H. A disposable amperometric immunosensor for α-1-fetoprotein based on enzyme-labeled antibody/chitosan-membrane-modified screen-printed carbon electrode. Anal. Biochem.,  2004, 331(1), 98-105.
 [http://dx.doi.org/10.1016/S0003-2697(04)00294-5] [PMID:  15246001]

[96]
Chen, Z.; Li, Q.; Sun, Q.; Chen, H.; Wang, X.; Li, N.; Yin, M.; Xie, Y.; Li, H.; Tang, B. Simultaneous determination of reactive oxygen and nitrogen species in mitochondrial compartments of apoptotic HepG2 cells and PC12 cells based on microchip electrophoresis-laser-induced fluorescence. Anal. Chem.,  2012, 84(11), 4687-4694.
 [http://dx.doi.org/10.1021/ac300255n] [PMID:  22551384]

[97]
Gan, N.; Xie, L.; Zhang, K.; Cao, Y.; Hu, F.; Li, T. An endonuclease-linked multiplex immunoassay for tumor markers detection based on microfluidic chip electrophoresis for DNA analysis. Sens. Actuators B Chem.,  2018, 272, 526-533.
 [http://dx.doi.org/10.1016/j.snb.2018.05.071]

[98]
Chong, W.P.K.; Goh, L.T.; Reddy, S.G.; Yusufi, F.N.K.; Lee, D.Y.; Wong, N.S.C.; Heng, C.K.; Yap, M.G.S.; Ho, Y.S. Metabolomics profiling of extracellular metabolites in recombinant Chinese Hamster Ovary fed-batch culture. Rapid Commun. Mass Spectrom.,  2009, 23(23), 3763-3771.
 [http://dx.doi.org/10.1002/rcm.4328] [PMID:  19902412]

[99]
Xing, Z.; Kenty, B.; Koyrakh, I.; Borys, M.; Pan, S.H.; Li, Z.J. Optimizing amino acid composition of CHO cell culture media for a fusion protein production. Process Biochem.,  2011, 46(7), 1423-1429.
 [http://dx.doi.org/10.1016/j.procbio.2011.03.014]

[100]
Najjar, A.; Karaman, R. The prodrug approach in the era of drug design. Expert Opin. Drug Deliv.,  2019, 16(1), 1-5.
 [http://dx.doi.org/10.1080/17425247.2019.1553954] [PMID:  30558447]

[101]
Solá, R.J.; Griebenow, K. Effects of glycosylation on the stability of protein pharmaceuticals. J. Pharm. Sci.,  2009, 98(4), 1223-1245.
 [http://dx.doi.org/10.1002/jps.21504] [PMID:  18661536]

[102]
Mellors, J.S.; Black, W.A.; Chambers, A.G.; Starkey, J.A.; Lacher, N.A.; Ramsey, J.M. Hybrid capillary/microfluidic system for comprehensive online liquid chromatography-capillary electrophoresis-electrospray ionization-mass spectrometry. Anal. Chem.,  2013, 85(8), 4100-4106.
 [http://dx.doi.org/10.1021/ac400205a] [PMID:  23477683]

[103]
Deyanova, E.G.; Huang, R.Y.C.; Madia, P.A.; Nandi, P.; Gudmundsson, O.; Chen, G. Rapid fingerprinting of a highly glycosylated fusion protein by microfluidic chip‐based capillary electrophoresis–mass spectrometry. Electrophoresis,  2021, 42(4), 460-464.
 [http://dx.doi.org/10.1002/elps.202000132] [PMID:  32885501]

[104]
Zeid, A.M.; Nasr, J.J.M.; Belal, F.; Walash, M.I.; Baba, Y.; Kaji, N. Determination of three antiepileptic drugs in pharmaceutical formulations using microfluidic chips coupled with light-emitting diode induced fluorescence detection. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2021, 246, 119021.
 [http://dx.doi.org/10.1016/j.saa.2020.119021] [PMID:  33045480]

[105]
Quist, J.; Janssen, K.G.H.; Vulto, P.; Hankemeier, T.; van der Linden, H.J. Single-electrolyte isotachophoresis using a nanochannel-induced depletion zone. Anal. Chem.,  2011, 83(20), 7910-7915.
 [http://dx.doi.org/10.1021/ac2018348] [PMID:  21861489]

[106]
Li, D.; Yu, W.; Zhou, T.; Li, M.; Song, Y.; Li, D. Conductivity-difference-enhanced DC dielectrophoretic particle separation in a microfluidic chip. Analyst,  2022, 147(6), 1106-1116.
 [http://dx.doi.org/10.1039/D1AN02196F] [PMID:  35225995]

[107]
Lv, D.; Zhang, X.; Xu, M.; Cao, W.; Liu, X.; Deng, J.; Yang, J.; Hu, N. Trapping and releasing of single microparticles and cells in a microfluidic chip. Electrophoresis,  2022, 43(21-22), 2165-2174.
 [http://dx.doi.org/10.1002/elps.202200091] [PMID:  35730632]

[108]
Dittrich, P.S.; Tachikawa, K.; Manz, A. Micro total analysis systems. Latest advancements and trends. Anal. Chem.,  2006, 78(12), 3887-3908.
 [http://dx.doi.org/10.1021/ac0605602] [PMID:  16771530]

[109]
Fernández-la-Villa, A.; Sánchez-Barragán, D.; Pozo-Ayuso, D.F.; Castaño-Álvarez, M. Smart portable electrophoresis instrument based on multipurpose microfluidic chips with electrochemical detection. Electrophoresis,  2012, 33(17), 2733-2742.
 [http://dx.doi.org/10.1002/elps.201200236] [PMID:  22965719]

[110]
Ruitberg, C.M.; Reeder, D.J.; Butler, J.M. STRBase: A short tandem repeat DNA database for the human identity testing community. Nucleic Acids Res.,  2001, 29(1), 320-322.
 [http://dx.doi.org/10.1093/nar/29.1.320] [PMID:  11125125]

[111]
Butler, J.M. Short tandem repeat typing technologies used in human identity testing. Biotechniques,  2007, 43(4), 2-5.
 [http://dx.doi.org/10.2144/000112582]

[112]
Han, J.P.; Sun, J.; Wang, L.; Liu, P.; Zhuang, B.; Zhao, L.; Liu, Y.; Li, C.X. The optimization of electrophoresis on a glass microfluidic chip and its application in forensic science. J. Forensic Sci.,  2017, 62(6), 1603-1612.
 [http://dx.doi.org/10.1111/1556-4029.13408] [PMID:  28168694]

[113]
Manz, A.; Graber, N.; Widmer, H.M. Miniaturized total chemical analysis systems: A novel concept for chemical sensing. Sens. Actuators B Chem.,  1990, 1(1-6), 244-248.
 [http://dx.doi.org/10.1016/0925-4005(90)80209-I]

[114]
Shinohara, K.; Sugii, Y.; Aota, A.; Hibara, A.; Tokeshi, M.; Kitamori, T.; Okamoto, K. High-speed micro-PIV measurements of transient flow in microfluidic devices. Meas. Sci. Technol.,  2004, 15(10), 1965-1970.
 [http://dx.doi.org/10.1088/0957-0233/15/10/003]

[115]
Toh, Y.C.; Zhang, C.; Zhang, J.; Khong, Y.M.; Chang, S.; Samper, V.D.; van Noort, D.; Hutmacher, D.W.; Yu, H. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip,  2007, 7(3), 302-309.
 [http://dx.doi.org/10.1039/b614872g] [PMID:  17330160]

[116]
Tokeshi, M.; Minagawa, T.; Uchiyama, K.; Hibara, A.; Sato, K.; Hisamoto, H.; Kitamori, T. Continuous-flow chemical processing on a microchip by combining microunit operations and a multiphase flow network. Anal. Chem.,  2002, 74(7), 1565-1571.
 [http://dx.doi.org/10.1021/ac011111z] [PMID:  12033246]

[117]
Hu, Y.; Peng, H.; Yan, Y.; Guan, S.; Wang, S.; Li, P.C.H.; Sun, Y. Integration of laminar flow extraction and capillary electrophoretic separation in one microfluidic chip for detection of plant alkaloids in blood samples. Anal. Chim. Acta,  2017, 985, 121-128.
 [http://dx.doi.org/10.1016/j.aca.2017.05.036] [PMID:  28864182]
Cite As
Current Analytical Chemistry

Impact of Microfluidic Chip Electrophoresis in Modern Analysis: An Update on Recent Trends

Abstract

Graphical Abstract
