A short review on cell-based biosensing: challenges and breakthroughs in biomedical analysis

Gheorghiu Mihaela

doi:10.7555/JBR.34.20200128

Volume 35 Issue 4

Jul. 2021

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Gheorghiu Mihaela. A short review on cell-based biosensing: challenges and breakthroughs in biomedical analysis[J]. The Journal of Biomedical Research, 2021, 35(4): 255-263. doi: 10.7555/JBR.34.20200128

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Gheorghiu Mihaela. A short review on cell-based biosensing: challenges and breakthroughs in biomedical analysis[J]. The Journal of Biomedical Research, 2021, 35(4): 255-263. doi: 10.7555/JBR.34.20200128

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A short review on cell-based biosensing: challenges and breakthroughs in biomedical analysis

doi: 10.7555/JBR.34.20200128

Gheorghiu Mihaela^,

Biosensors Department, International Centre of Biodynamics, Bucharest 060101, Romania

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Corresponding author: Mihaela Gheorghiu, Biosensors Department, International Centre of Biodynamics, 1B Intrarea Portocalelor, Bucharest 060101, Romania. Tel: +40-21-3104354, E-mail: mgheorghiu@biodyn.ro
Received: 2020-07-31
Revised: 2020-10-13
Accepted: 2020-11-06

Published: 2020-12-25

Issue Date: 2021-07-28

Abstract

Abstract

Current cell-based biosensors have progressed substantially from mere alternatives to molecular bioreceptors into enabling tools for interfacing molecular machineries and gene circuits with microelectronics and for developing groundbreaking sensing and theragnostic platforms. The recent literature concerning whole-cell biosensors is reviewed with an emphasis on mammalian cells, and the challenges and breakthroughs brought along in biomedical analyses through novel biosensing concepts and the synthetic biology toolbox. These recent innovations allow development of cell-based biosensing platforms having tailored performances and capable to reach the levels of sensitivity, dynamic range, and stability suitable for high analytic/medical relevance. They also pave the way for the construction of flexible biosensing platforms with utility across biological research and clinical applications. The work is intended to stimulate interest in generation of cell-based biosensors and improve their acceptance and exploitation.
- biosensing,
- electro-optical assays,
- synthetic biology,
- cell dynamics,
- cell physiology,
- theranostics

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References(78)

References

[1]	Gui QY, Lawson T, Shan SY, et al. The application of whole cell-based biosensors for use in environmental analysis and in medical diagnostics[J]. Sensors, 2017, 17(7): 1623. doi: 10.3390/s17071623
[2]	Turner APF. Biosensors: sense and sensibility[J]. Chem Soc Rev, 2013, 42(8): 3184–3196. doi: 10.1039/c3cs35528d
[3]	Goode JA, Rushworth JVH, Millner PA. Biosensor regeneration: a review of common techniques and outcomes[J]. Langmuir, 2015, 31(23): 6267–6276. doi: 10.1021/la503533g
[4]	Liu QJ, Wu CS, Cai H, et al. Cell-based biosensors and their application in biomedicine[J]. Chem Rev, 2014, 114(12): 6423–6461. doi: 10.1021/cr2003129
[5]	Brown JP, Lynch BS, Curry-Chisolm IM, et al. Assaying spontaneous network activity and cellular viability using multi-well microelectrode arrays[J]. Methods Mol Biol, 2017, 1601: 153–170. doi: 10.1007/978-1-4939-6960-9_13
[6]	Xie MQ, Fussenegger M. Designing cell function: assembly of synthetic gene circuits for cell biology applications[J]. Nat Rev Mol Cell Biol, 2018, 19(8): 507–525. doi: 10.1038/s41580-018-0024-z
[7]	Sedlmayer F, Aubel D, Fussenegger M. Synthetic gene circuits for the detection, elimination and prevention of disease[J]. Nat Biomed Eng, 2018, 2(6): 399–415. doi: 10.1038/s41551-018-0215-0
[8]	Gupta N, Renugopalakrishnan V, Liepmann D, et al. Cell-based biosensors: recent trends, challenges and future perspectives[J]. Biosens Bioelectron, 2019, 141: 111435. doi: 10.1016/j.bios.2019.111435
[9]	Hicks M, Bachmann TT, Wang BJ. Synthetic biology enables programmable cell-based biosensors[J]. ChemPhysChem, 2020, 21(2): 131. doi: 10.1002/cphc.201901191
[10]	Wegener J, Keese CR, Giaever I. Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces[J]. Exp Cell Res, 2000, 259(1): 158–166. doi: 10.1006/excr.2000.4919
[11]	Hafner F. Cytosensor^® microphysiometer: technology and recent applications[J]. Biosens Bioelectron, 2000, 15(3-4): 149–158. doi: 10.1016/S0956-5663(00)00069-5
[12]	Asphahani F, Thein M, Veiseh O, et al. Influence of cell adhesion and spreading on impedance characteristics of cell-based sensors[J]. Biosens Bioelectron, 2008, 23(8): 1307–1313. doi: 10.1016/j.bios.2007.11.021
[13]	Ghenim L, Kaji H, Hoshino Y, et al. Monitoring impedance changes associated with motility and mitosis of a single cell[J]. Lab Chip, 2010, 10(19): 2546–2550. doi: 10.1039/c004115g
[14]	Giaever I, Keese CR. Micromotion of mammalian cells measured electrically[J]. Proc Natl Acad Sci USA, 1991, 88(17): 7896–7900. doi: 10.1073/pnas.88.17.7896
[15]	Han A, Yang L, Frazier AB. Quantification of the heterogeneity in breast cancer cell lines using whole-cell impedance spectroscopy[J]. Clin Cancer Res, 2007, 13(1): 139–143. doi: 10.1158/1078-0432.CCR-06-1346
[16]	Hong J, Jiang DM, Gu CL, et al. Electrical cell-substrate impedance sensing as a non-invasive tool for cancer cell study[J]. Analyst, 2011, 136(2): 237–245. doi: 10.1039/C0AN00560F
[17]	Gheorghiu M, Gersing E, Gheorghiu E. Quantitative analysis of impedance spectra of organs during ischemia[J]. Ann N Y Acad Sci, 1999, 873(1): 65–71. doi: 10.1111/j.1749-6632.1999.tb09450.x
[18]	Schwarz M, Jendrusch M, Constantinou I. Spatially resolved electrical impedance methods for cell and particle characterization[J]. Electrophoresis, 2020, 41(1–2): 65–80. doi: 10.1002/elps.201900286
[19]	Wei XW, Gu CL, Li HB, et al. Efficacy and cardiotoxicity integrated assessment of anticancer drugs by a dual functional cell-based biosensor[J]. Sens Actuators B: Chem, 2019, 283: 881–889. doi: 10.1016/j.snb.2018.12.085
[20]	Pan YX, Jiang DM, Gu CL, et al. 3D microgroove electrical impedance sensing to examine 3D cell cultures for antineoplastic drug assessment[J]. Microsyst Nanoeng, 2020, 6(1): 23. doi: 10.1038/s41378-020-0130-x
[21]	Stanica L, Rosu-Hamzescu M, Gheorghiu M, et al. Electric cell-substrate impedance sensing of cellular effects under hypoxic conditions and carbonic anhydrase inhibition[J]. J Sens, 2017, 2017: 9290478. doi: 10.1155/2017/9290478
[22]	Stanica L, Gheorghiu M, Stan M, et al. Quantitative assessment of specific carbonic anhydrase inhibitors effect on hypoxic cells using electrical impedance assays[J]. J Enzyme Inhib Med Chem, 2017, 32(1): 1079–1090. doi: 10.1080/14756366.2017.1355306
[23]	Munteanu RE, Stǎnicǎ L, Gheorghiu M, et al. Measurement of the extracellular pH of adherently growing mammalian cells with high spatial resolution using a voltammetric pH microsensor[J]. Anal Chem, 2018, 90(11): 6899–6905. doi: 10.1021/acs.analchem.8b01124
[24]	Bondarenko A, Cortés-Salazar F, Gheorghiu M, et al. Electrochemical push-pull probe: from scanning electrochemical microscopy to multimodal altering of cell microenvironment[J]. Anal Chem, 2015, 87(8): 4479–4486. doi: 10.1021/acs.analchem.5b00455
[25]	Gáspár S, David S, Polonschii C, et al. Simultaneous impedimetric and amperometric interrogation of renal cells exposed to a calculus-forming salt[J]. Anal Chim Acta, 2012, 713: 115–120. doi: 10.1016/j.aca.2011.11.031
[26]	Gheorghiu E. Characterizing cellular systems by means of dielectric spectroscopy[J]. Bioelectromagnetics, 1996, 17(6): 475–482. doi: 10.1002/(SICI)1521-186X(1996)17:6<475::AID-BEM7>3.0.CO;2-0
[27]	Asami K, Gheorghiu E, Yonezawa T. Real-time monitoring of yeast cell division by dielectric spectroscopy[J]. Biophys J, 1999, 76(6): 3345–3348. doi: 10.1016/S0006-3495(99)77487-4
[28]	Gheorghiu E, Balut C, Gheorghiu M. Dielectric behaviour of gap junction connected cells: a microscopic approach[J]. Phys Med Biol, 2002, 47(2): 341–348. doi: 10.1088/0031-9155/47/2/312
[29]	Gheorghiu M, David S, Polonschii C, et al. Label free sensing platform for amyloid fibrils effect on living cells[J]. Biosens Bioelectron, 2014, 52: 89–97. doi: 10.1016/j.bios.2013.08.028
[30]	Gheorghiu M, Enciu AM, Popescu BO, et al. Functional and molecular characterization of the effect of amyloid-β₄₂ on an in vitro epithelial barrier model[J]. J Alzheimers Dis, 2014, 38(4): 787–798. doi: 10.3233/JAD-122374
[31]	Peter B, Ungai-Salanki R, Szabó B, et al. High-resolution adhesion kinetics of EGCG-exposed tumor cells on biomimetic interfaces: comparative monitoring of cell viability using label-free biosensor and classic end-point assays[J]. ACS Omega, 2018, 3(4): 3882–3891. doi: 10.1021/acsomega.7b01902
[32]	Dinca V, Zaharie-Butucel D, Stanica L, et al. Functional Micrococcus lysodeikticus layers deposited by laser technique for the optical sensing of lysozyme[J]. Colloids Surf B, 2018, 162: 98–107. doi: 10.1016/j.colsurfb.2017.11.058
[33]	Cheng MS, Lau SH, Chan KP, et al. Impedimetric cell-based biosensor for real-time monitoring of cytopathic effects induced by dengue viruses[J]. Biosens Bioelectron, 2015, 70: 74–80. doi: 10.1016/j.bios.2015.03.018
[34]	Selvam AP, Wangzhou AD, Jacobs M, et al. Development and validation of an impedance biosensor for point-of-care detection of vascular cell adhesion molecule-1 toward lupus diagnostics[J]. Future Sci OA, 2017, 3(3): FSO224. doi: 10.4155/fsoa-2017-0047
[35]	Pan YX, Hu N, Wei XW, et al. 3D cell-based biosensor for cell viability and drug assessment by 3D electric cell/matrigel-substrate impedance sensing[J]. Biosens Bioelectron, 2019, 130: 344–351. doi: 10.1016/j.bios.2018.09.046
[36]	Mohammadi S, Nikkhah M, Hosseinkhani S. Investigation of the effects of carbon-based nanomaterials on A53T alpha-synuclein aggregation using a whole-cell recombinant biosensor[J]. Int J Nanomedicine, 2017, 12: 8831–8840. doi: 10.2147/IJN.S144764
[37]	Daniels JS, Pourmand N. Label-free impedance biosensors: opportunities and challenges[J]. Electroanalysis, 2007, 19(12): 1239–1257. doi: 10.1002/elan.200603855
[38]	Gheorghiu M, Stănică L, Tegla MGG, et al. Cellular sensing platform with enhanced sensitivity based on optogenetic modulation of cell homeostasis[J]. Biosens Bioelectron, 2020, 154: 112003. doi: 10.1016/j.bios.2019.112003
[39]	Gheorghiu M, Stanica L, Polonschii C, et al. Modulation of cellular reactivity for enhanced cell-based biosensing[J]. Anal Chem, 2020, 92(1): 806–814. doi: 10.1021/acs.analchem.9b03217
[40]	Airan RD, Thompson KR, Fenno LE, et al. Temporally precise in vivo control of intracellular signalling[J]. Nature, 2009, 458(7241): 1025–1029. doi: 10.1038/nature07926
[41]	Mattis J, Tye KM, Ferenczi EA, et al. Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins[J]. Nat Methods, 2012, 9(2): 159–172. doi: 10.1038/nmeth.1808
[42]	Tischer D, Weiner OD. Illuminating cell signalling with optogenetic tools[J]. Nat Rev Mol Cell Biol, 2014, 15(8): 551–558. doi: 10.1038/nrm3837
[43]	Zhang F, Vierock J, Yizhar O, et al. The microbial opsin family of optogenetic tools[J]. Cell, 2011, 147(7): 1446–1457. doi: 10.1016/j.cell.2011.12.004
[44]	Charlton FW, Pearson HM, Hover S, et al. Ion channels as therapeutic targets for viral infections: further discoveries and future perspectives[J]. Viruses, 2020, 12(8): 844. doi: 10.3390/v12080844
[45]	Nieva JL, Madan V, Carrasco L. Viroporins: structure and biological functions[J]. Nat Rev Microbiol, 2012, 10(8): 563–574. doi: 10.1038/nrmicro2820
[46]	Sundelacruz S, Levin M, Kaplan DL. Role of membrane potential in the regulation of cell proliferation and differentiation[J]. Stem Cell Rev Rep, 2009, 5(3): 231–246. doi: 10.1007/s12015-009-9080-2
[47]	Mavrikou S, Moschopoulou G, Tsekouras V, et al. Development of a portable, ultra-rapid and ultra-sensitive cell-based biosensor for the direct detection of the SARS-CoV-2 S1 spike protein antigen[J]. Sensors, 2020, 20(11): 3121. doi: 10.3390/s20113121
[48]	Ausländer S, Fussenegger M. Engineering gene circuits for mammalian cell-based applications[J]. Cold Spring Harb Perspect Biol, 2016, 8(7): a023895. doi: 10.1101/cshperspect.a023895
[49]	Derick S, Gironde C, Perio P, et al. LUCS (Light-Up Cell System), a universal high throughput assay for homeostasis evaluation in live cells[J]. Sci Rep, 2017, 7(1): 18069. doi: 10.1038/s41598-017-18211-2
[50]	Ambrosi CM, Boyle PM, Chen K, et al. Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability[J]. Sci Rep, 2015, 5(1): 17350. doi: 10.1038/srep17350
[51]	Hofmann U, Michaelis S, Winckler T, et al. A whole-cell biosensor as in vitro alternative to skin irritation tests[J]. Biosens Bioelectron, 2013, 39(1): 156–162. doi: 10.1016/j.bios.2012.07.075
[52]	Apostolou T, Moschopoulou G, Kolotourou E, et al. Assessment of in vitro dopamine-neuroblastoma cell interactions with a bioelectric biosensor: perspective for a novel in itro functional assay for dopamine agonist/antagonist activity[J]. Talanta, 2017, 170: 69–73. doi: 10.1016/j.talanta.2017.03.098
[53]	Kojima R, Aubel D, Fussenegger M. Building sophisticated sensors of extracellular cues that enable mammalian cells to work as "doctors" in the body[J]. Cell Mol Life Sci, 2020, 77(18): 3567–3581. doi: 10.1007/s00018-020-03486-y
[54]	Kelkar SS, Reineke TM. Theranostics: combining imaging and therapy[J]. Bioconjugate Chem, 2011, 22(10): 1879–1903. doi: 10.1021/bc200151q
[55]	Belkin S. Microbial whole-cell sensing systems of environmental pollutants[J]. Curr Opin Microbiol, 2003, 6(3): 206–212. doi: 10.1016/S1369-5274(03)00059-6
[56]	Banerjee P, Bhunia AK. Mammalian cell-based biosensors for pathogens and toxins[J]. Trends Biotechnol, 2009, 27(3): 179–188. doi: 10.1016/j.tibtech.2008.11.006
[57]	Yang XY, Her J, Bashor CJ. Mammalian signaling circuits from bacterial parts[J]. Nat Chem Biol, 2020, 16(2): 110–111. doi: 10.1038/s41589-019-0436-x
[58]	Schwarz KA, Daringer NM, Dolberg TB, et al. Rewiring human cellular input-output using modular extracellular sensors[J]. Nat Chem Biol, 2017, 13(2): 202–209. doi: 10.1038/nchembio.2253
[59]	Vasilescu A, Purcarea C, Popa E, et al. Versatile SPR aptasensor for detection of lysozyme dimer in oligomeric and aggregated mixtures[J]. Biosens Bioelectron, 2016, 83: 353–360. doi: 10.1016/j.bios.2016.04.080
[60]	Donahue PS, Draut JW, Muldoon JJ, et al. The COMET toolkit for composing customizable genetic programs in mammalian cells[J]. Nat Commun, 2020, 11(1): 779. doi: 10.1038/s41467-019-14147-5
[61]	Bakhshpour M, Piskin AK, Yavuz H, et al. Quartz crystal microbalance biosensor for label-free MDA MB 231 cancer cell detection via notch-4 receptor[J]. Talanta, 2019, 204: 840–845. doi: 10.1016/j.talanta.2019.06.060
[62]	Chiu CH, Lei KF, Yeh WL, et al. Comparison between xCELLigence biosensor technology and conventional cell culture system for real-time monitoring human tenocytes proliferation and drugs cytotoxicity screening[J]. J Orthop Surg Res, 2017, 12(1): 149. doi: 10.1186/s13018-017-0652-6
[63]	Siska EK, Weisman I, Romano J, et al. Generation of an immortalized mesenchymal stem cell line producing a secreted biosensor protein for glucose monitoring[J]. PLoS One, 2017, 12(9): e0185498. doi: 10.1371/journal.pone.0185498
[64]	Bernhard K, Stahl C, Martens R, et al. A novel genetically encoded single use sensory cellular test system measures bicarbonate concentration changes in living cells[J]. Sensors, 2020, 20(6): 1570. doi: 10.3390/s20061570
[65]	Ma RL, Zheng HZ, Liu Q, et al. Exploring the interactions between engineered nanomaterials and immune cells at 3D nano-bio interfaces to discover potent nano-adjuvants[J]. Nanomed Nanotechnol Biol Med, 2019, 21: 102037. doi: 10.1016/j.nano.2019.102037
[66]	Snyder RA, Ellison CK, Severin GB, et al. Surface sensing stimulates cellular differentiation in Caulobacter crescentus[J]. Proc Natl Acad Sci USA, 2020, 117(30): 17984–17991. doi: 10.1073/pnas.1920291117
[67]	Stanley SA, Sauer J, Kane RS, et al. Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles[J]. Nat Med, 2015, 21(1): 92–98. doi: 10.1038/nm.3730
[68]	Mansouri M, Strittmatter T, Fussenegger M. Light-controlled mammalian cells and their therapeutic applications in synthetic biology[J]. Adv Sci, 2019, 6(1): 1800952. doi: 10.1002/advs.201800952
[69]	Ye HF, Fussenegger M. Optogenetic medicine: synthetic therapeutic solutions precision-guided by light[J]. Cold Spring Harb Perspect Med, 2019, 9(9): a034371. doi: 10.1101/cshperspect.a034371
[70]	Shao JW, Xue S, Yu GL, et al. Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice[J]. Sci Transl Med, 2017, 9(387): eaal2298. doi: 10.1126/scitranslmed.aal2298
[71]	Li GX, Wang FF, Yang WG, et al. Development of an image biosensor based on an optogenetically engineered cell for visual prostheses[J]. Nanoscale, 2019, 11(28): 13213–13218. doi: 10.1039/C9NR01688K
[72]	Daringer NM, Dudek RM, Schwarz KA, et al. Modular extracellular sensor architecture for engineering mammalian cell-based devices[J]. ACS Synth Biol, 2014, 3(12): 892–902. doi: 10.1021/sb400128g
[73]	Jeon H, Lee E, Kim D, et al. Cell-based biosensors based on intein-mediated protein engineering for detection of biologically active signaling molecules[J]. Anal Chem, 2018, 90(16): 9779–9786. doi: 10.1021/acs.analchem.8b01481
[74]	Hoffman T, Antovski P, Tebon P, et al. Synthetic biology and tissue engineering: toward fabrication of complex and smart cellular constructs[J]. Adv Funct Mater, 2020, 30(26): 1909882. doi: 10.1002/adfm.201909882
[75]	Matsunaga S, Jeremiah SS, Miyakawa K, et al. Engineering cellular biosensors with customizable antiviral responses targeting hepatitis B virus[J]. iScience, 2020, 23(3): 100867. doi: 10.1016/j.isci.2020.100867
[76]	Xie MQ, Ye HF, Wang H, et al. β-cell-mimetic designer cells provide closed-loop glycemic control[J]. Science, 2016, 354(6317): 1296–1301. doi: 10.1126/science.aaf4006
[77]	Scheller L, Fussenegger M. From synthetic biology to human therapy: engineered mammalian cells[J]. Curr Opin Biotechnol, 2019, 58: 108–116. doi: 10.1016/j.copbio.2019.02.023
[78]	Wu CY, Roybal KT, Puchner EM, et al. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor[J]. Science, 2015, 350(6258): aab4077. doi: 10.1126/science.aab4077