Abstract
The transport of molecules and inorganic ions across the plasma membrane results in chemical fluxes that reflect cellular function in healthy and diseased states. Measurement of these chemical fluxes enables the characterization of protein function and transporter stoichiometry, characterization of the viability of single cells and embryos prior to implantation, and screening of pharmaceutical agents. Electrochemical sensors are sensitive and noninvasive tools for measuring chemical fluxes immediately outside the cells in the boundary layer, that are capable of monitoring a diverse range of transported analytes including inorganic ions, gases, neurotransmitters, hormones, and pharmaceutical agents. Used on their own or in combination with other methods, these sensors continue to expand our understanding of the function of rare cells and small tissues. Advances in sensor construction and detection strategies continue to improve sensitivity under physiological conditions, diversify analyte detection, and increase throughput. These advances will be discussed in the context of addressing technical challenges to measuring in the boundary layer of cells and measuring the resultant changes to the chemical concentration in the bulk media.
Keywords: Electrochemistry, molecular physiology, transmembrane flux, drug detection, electrochemical sensors, chemical flux.
[http://dx.doi.org/10.1074/jbc.M804916200] [PMID: 18782776]
[http://dx.doi.org/10.1110/ps.051528905] [PMID: 16131665]
[http://dx.doi.org/10.1126/science.aaf7066] [PMID: 27338706]
[http://dx.doi.org/10.1038/nature10257] [PMID: 21785437]
[http://dx.doi.org/10.1038/nature17656] [PMID: 27135929]
[http://dx.doi.org/10.1016/S0014-5793(97)01246-5] [PMID: 9426218]
[http://dx.doi.org/10.1016/S0006-291X(03)01342-1] [PMID: 12890493]
[http://dx.doi.org/10.1016/S0014-5793(00)01333-8] [PMID: 10745077]
[http://dx.doi.org/10.2174/157340611794072698] [PMID: 21235516]
[http://dx.doi.org/10.1371/journal.pone.0028111] [PMID: 22140516]
[http://dx.doi.org/10.1371/journal.pone.0018414] [PMID: 21494599]
[http://dx.doi.org/10.1371/journal.pone.0038546] [PMID: 22685582]
[http://dx.doi.org/10.1016/j.bbrc.2009.06.016] [PMID: 19523442]
[http://dx.doi.org/10.1021/pr049931q] [PMID: 15359741]
[http://dx.doi.org/10.1016/j.bbrc.2004.05.016] [PMID: 15178425]
[http://dx.doi.org/10.1021/pr050145a] [PMID: 16212421]
[http://dx.doi.org/10.1021/pr049905s] [PMID: 15473697]
[http://dx.doi.org/10.2174/092986612800494066] [PMID: 22519536]
[http://dx.doi.org/10.1016/j.ygeno.2017.10.002] [PMID: 28989035]
[http://dx.doi.org/10.1039/C7MB00267J] [PMID: 28702580]
[http://dx.doi.org/10.1093/bioinformatics/btx476] [PMID: 29036535]
[http://dx.doi.org/10.1016/j.gene.2017.07.036] [PMID: 28728979]
[http://dx.doi.org/10.1016/j.ygeno.2017.08.005] [PMID: 28818512]
[http://dx.doi.org/10.1093/bioinformatics/btx711] [PMID: 29106451]
[http://dx.doi.org/10.1016/j.ygeno.2018.08.007] [PMID: 30179658]
[http://dx.doi.org/10.1093/bioinformatics/bty628] [PMID: 30010789]
[http://dx.doi.org/10.1042/bj1870829] [PMID: 7188428]
[http://dx.doi.org/10.1042/bj2220169] [PMID: 6477507]
[http://dx.doi.org/10.1006/abio.1994.1405] [PMID: 7529005]
[PMID: 2745429]
[http://dx.doi.org/10.1016/0301-4622(90)80056-D] [PMID: 2183882]
[http://dx.doi.org/10.1155/2013/485034] [PMID: 24078917]
[PMID: 7681060]
[PMID: 7686907]
[http://dx.doi.org/10.1016/0006-2952(94)90077-9] [PMID: 7516658]
[http://dx.doi.org/10.1021/bi00077a008] [PMID: 7687145]
[http://dx.doi.org/10.2174/0929867043364667] [PMID: 15279552]
[http://dx.doi.org/10.1016/S0065-7743(08)61100-8]
[http://dx.doi.org/10.18632/oncotarget.19757] [PMID: 29050302]
[http://dx.doi.org/10.1016/j.ymben.2011.07.002] [PMID: 21821143]
[http://dx.doi.org/10.1016/j.aca.2015.11.023] [PMID: 26709297]
[http://dx.doi.org/10.1039/C3LC50759A] [PMID: 24217869]
[http://dx.doi.org/10.1039/C5LC01046B] [PMID: 26732665]
[http://dx.doi.org/10.2147/JPR.S59144] [PMID: 24966693]
[http://dx.doi.org/10.1016/j.aca.2009.07.064] [PMID: 19733728]
[http://dx.doi.org/10.1089/neu.2014.3473] [PMID: 25019674]
[http://dx.doi.org/10.1089/adt.2004.2.543] [PMID: 15671652]
[http://dx.doi.org/10.1016/B978-0-12-374841-6.00004-9]
[http://dx.doi.org/10.1021/ac00091a600] [PMID: 7978299]
[http://dx.doi.org/10.1007/s00216-007-1804-z] [PMID: 18193410]
[PMID: 10212144]
[http://dx.doi.org/10.1007/s00232-005-0735-x] [PMID: 15981714]
[http://dx.doi.org/10.1111/j.1365-313X.2004.02252.x] [PMID: 15546362]
[http://dx.doi.org/10.1038/nm0496-470] [PMID: 8597961]
[http://dx.doi.org/10.1152/ajpcell.1998.275.4.C1134] [PMID: 9755067]
[http://dx.doi.org/10.1186/s12899-016-0024-1] [PMID: 27515813]
[http://dx.doi.org/10.1371/journal.pone.0017411] [PMID: 21364900]
[http://dx.doi.org/10.1152/jn.00409.2017] [PMID: 28855292]
[http://dx.doi.org/10.1371/journal.pone.0190893] [PMID: 29466379]
[http://dx.doi.org/10.1073/pnas.0403930101] [PMID: 15240890]
[http://dx.doi.org/10.1085/jgp.200810016] [PMID: 18824592]
[http://dx.doi.org/10.1152/ajpcell.00143.2013] [PMID: 23804202]
[http://dx.doi.org/10.1002/bies.200900173] [PMID: 20486138]
[http://dx.doi.org/10.1038/nature02271] [PMID: 14765196]
[http://dx.doi.org/10.1113/jphysiol.2008.162453] [PMID: 19064619]
[http://dx.doi.org/10.1016/j.ceca.2011.03.004] [PMID: 21466891]
[http://dx.doi.org/10.1021/ac403808f] [PMID: 24283934]
[http://dx.doi.org/10.1016/j.bioelechem.2017.06.007] [PMID: 28633068]
[http://dx.doi.org/10.1007/s00249-010-0636-5] [PMID: 20976596]
[http://dx.doi.org/10.1007/s00249-007-0226-3] [PMID: 17968537]
[http://dx.doi.org/10.1021/ac061984z] [PMID: 17411008]
[http://dx.doi.org/10.1021/ac061878x] [PMID: 17370998]
[http://dx.doi.org/10.1529/biophysj.106.102947] [PMID: 17259274]
[http://dx.doi.org/10.1016/j.bpj.2008.11.025] [PMID: 19217875]
[http://dx.doi.org/10.1002/elan.200904618]
[http://dx.doi.org/10.1016/j.bbrc.2004.02.098] [PMID: 15033447]
[http://dx.doi.org/10.2174/157340609788185909] [PMID: 19442215]
[http://dx.doi.org/10.1016/j.jtbi.2013.08.013] [PMID: 23988798]
[http://dx.doi.org/10.1155/2014/286419] [PMID: 24991545]
[http://dx.doi.org/10.1038/nature12283] [PMID: 23739335]
[http://dx.doi.org/10.1038/nature06531] [PMID: 18235503]
[http://dx.doi.org/10.1038/nsmb.1707] [PMID: 19898475]
[http://dx.doi.org/10.1073/pnas.0902548106] [PMID: 19383794]
[http://dx.doi.org/10.1007/s13238-010-0025-y] [PMID: 21203971]
[http://dx.doi.org/10.1016/j.jtbi.2009.03.003] [PMID: 19285514]
[http://dx.doi.org/10.1017/S000711451100376X] [PMID: 21767446]
[http://dx.doi.org/10.1073/pnas.1222142110] [PMID: 23716681]
[PMID: 24778671]
[http://dx.doi.org/10.1371/journal.pone.0151089] [PMID: 26986722]
[http://dx.doi.org/10.1038/nrn1671] [PMID: 15891778]
[http://dx.doi.org/10.1007/s10534-011-9451-4] [PMID: 21479832]
[http://dx.doi.org/10.1016/j.cub.2011.09.040] [PMID: 22075424]
[http://dx.doi.org/10.1016/j.snb.2005.07.039]
[http://dx.doi.org/10.2478/s11532-013-0390-5]
[http://dx.doi.org/10.1080/00032719208016108]
[http://dx.doi.org/10.1007/s10008-012-1759-7]
[http://dx.doi.org/10.1021/ja011774y] [PMID: 11817952]
[http://dx.doi.org/10.1016/S0003-2670(99)00396-7]
[http://dx.doi.org/10.1021/ac010094a] [PMID: 11569816]
[http://dx.doi.org/10.1021/ac034335l]
[http://dx.doi.org/10.1080/00032716908051343]
[http://dx.doi.org/10.1021/cr970113+] [PMID: 11848943]
[http://dx.doi.org/10.1016/j.talanta.2016.06.050] [PMID: 27591587]
[http://dx.doi.org/10.1021/ac00168a016] [PMID: 3232811]
[http://dx.doi.org/10.1021/cr400546e] [PMID: 24588137]
[http://dx.doi.org/10.1038/s41467-017-01615-z] [PMID: 29127288]
[http://dx.doi.org/10.2174/1573406411666141229162618] [PMID: 25548926]
[http://dx.doi.org/10.2174/1568026617666170414145508] [PMID: 28413951]
[http://dx.doi.org/10.2174/1573406411666141229162834] [PMID: 25548930]
[http://dx.doi.org/10.18632/oncotarget.7815] [PMID: 26942877]
[http://dx.doi.org/10.1371/journal.pone.0018476] [PMID: 21533231]
[http://dx.doi.org/10.1016/j.ab.2013.01.019] [PMID: 23395824]
[PMID: 22591473]
[http://dx.doi.org/10.2174/157489312800604426]
[http://dx.doi.org/10.1371/journal.pone.0105018] [PMID: 25121969]
[http://dx.doi.org/10.18632/oncotarget.10027] [PMID: 27322424]
[http://dx.doi.org/10.1080/07391102.2011.672629] [PMID: 22545996]
[http://dx.doi.org/10.2174/1568026615666150819110421] [PMID: 26286211]
[http://dx.doi.org/10.1093/bioinformatics/btw387] [PMID: 27354696]
[http://dx.doi.org/10.1371/journal.pone.0072234] [PMID: 24015221]
[http://dx.doi.org/10.1016/j.bbrc.2005.06.087] [PMID: 16002049]
[http://dx.doi.org/10.1007/s10930-005-7592-4] [PMID: 16323044]
[http://dx.doi.org/10.2174/092986608785849308] [PMID: 18991767]
[http://dx.doi.org/10.1016/j.jtbi.2005.08.016] [PMID: 16197963]
[http://dx.doi.org/10.1016/j.jtbi.2011.06.006] [PMID: 21718705]
[http://dx.doi.org/10.1007/s00726-006-0439-2] [PMID: 17031474]
[http://dx.doi.org/10.1016/j.bbrc.2004.12.069] [PMID: 15649422]
[http://dx.doi.org/10.4236/ns.2009.12011]
[http://dx.doi.org/10.1002/minf.201600010] [PMID: 28488814]
[http://dx.doi.org/10.2174/1573406413666170419150052] [PMID: 28425870]
[http://dx.doi.org/10.2174/1573406415666181218102517] [PMID: 30569871]
[http://dx.doi.org/10.4236/ns.2011.310111]
[http://dx.doi.org/10.1016/j.jelechem.2016.11.006]
[http://dx.doi.org/10.1016/j.elecom.2008.09.027]
[http://dx.doi.org/10.1016/j.bios.2010.06.030] [PMID: 20630738]
[http://dx.doi.org/10.1002/anie.201800954] [PMID: 29431913]
[http://dx.doi.org/10.1016/j.aca.2004.10.061]
[http://dx.doi.org/10.1002/elan.1140091411]
[http://dx.doi.org/10.1021/ac010339j] [PMID: 11510844]
[http://dx.doi.org/10.1093/humrep/der324] [PMID: 21972254]
[http://dx.doi.org/10.1017/S0967199400000782] [PMID: 10840870]
[http://dx.doi.org/10.1007/s00411-014-0574-1] [PMID: 25335641]
[http://dx.doi.org/10.1038/ncb2330] [PMID: 21926988]
[http://dx.doi.org/10.1016/0022-0728(93)80483-X]
[http://dx.doi.org/10.2307/1543355] [PMID: 11687412]
[http://dx.doi.org/10.1152/ajpcell.00308.2004] [PMID: 15342341]
[http://dx.doi.org/10.1016/j.ab.2010.12.019] [PMID: 21167120]
[http://dx.doi.org/10.1002/mc.22079] [PMID: 24000146]
[http://dx.doi.org/10.1016/j.jsbmb.2013.03.012] [PMID: 23619337]
[http://dx.doi.org/10.1016/j.jneumeth.2010.03.001] [PMID: 20298719]
[http://dx.doi.org/10.1021/acs.analchem.7b02074] [PMID: 28876053]
[http://dx.doi.org/10.1039/b608202e] [PMID: 17066165]
[http://dx.doi.org/10.1146/annurev-anchem-071114-040426] [PMID: 25939038]
[http://dx.doi.org/10.1080/00032719.2011.553010]
[http://dx.doi.org/10.1021/ac3006878] [PMID: 22900668]
[http://dx.doi.org/10.1016/S0006-3495(98)77670-2] [PMID: 9788921]
[http://dx.doi.org/10.1021/ac9811773] [PMID: 10424170]
[PMID: 2570070]
[http://dx.doi.org/10.1007/s00216-011-5589-8] [PMID: 22169951]
[http://dx.doi.org/10.1016/j.talanta.2014.12.020] [PMID: 25702993]
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[http://dx.doi.org/10.1021/acs.langmuir.5b03123] [PMID: 26474107]
[http://dx.doi.org/10.1021/acs.accounts.6b00331] [PMID: 27622924]
[http://dx.doi.org/10.1073/pnas.1605002113] [PMID: 27217569]
[http://dx.doi.org/10.2174/156652406779010777] [PMID: 17168740]
[http://dx.doi.org/10.1073/pnas.97.18.9855] [PMID: 10963658]
[http://dx.doi.org/10.1007/s10911-004-1407-7] [PMID: 15838606]
[http://dx.doi.org/10.1038/srep05216] [PMID: 24910017]
[http://dx.doi.org/10.1073/pnas.0407613101] [PMID: 15601769]
[http://dx.doi.org/10.1073/pnas.0402556101] [PMID: 15148374]
[http://dx.doi.org/10.1039/B911763F] [PMID: 20024047]
[http://dx.doi.org/10.1016/j.trac.2015.11.004]
[http://dx.doi.org/10.1007/s10008-008-0608-1]