Current progress in long-term and continuous cell metabolite detection using microfluidics

Le, 2014, Sub-nanomolar detection of thrombin activity on a microfluidic chip, Biomicrofluidics, 8, 064110, 10.1063/1.4902908 Yap, 2017, Bifunctional plasmonic-magnetic particles for an enhanced microfluidic SERS immunoassay, Nanoscale, 9, 7822, 10.1039/C7NR01511A Chen, 2018, Multiplexed detection of cancer biomarkers using a microfluidic platform integrating single bead trapping and acoustic mixing techniques, Nanoscale, 10, 20196, 10.1039/C8NR06367B Yotter, 2004, Sensor technologies for monitoring metabolic activity in single cells – Part I: optical, methods, IEEE Sens. J., 4, 395, 10.1109/JSEN.2004.830952 Yotter, 2004, Sensor technologies for monitoring metabolic activity in single cells - Part II: nonoptical methods and applications, IEEE Sens. J., 4, 412, 10.1109/JSEN.2004.830954 Kraly, 2009, Review: microfluidic applications in metabolomics and metabolic profiling, Anal. Chim. Acta, 653, 23, 10.1016/j.aca.2009.08.037 Varghese, 2010, FRET for lab-on-a-chip devices - current trends and future prospects, Lab Chip, 10, 1355, 10.1039/b924271f Zenobi, 2013, Single-cell metabolomics: analytical and biological perspectives, Science, 342, 1243259, 10.1126/science.1243259 Vasdekis, 2015, Review of methods to probe single cell metabolism and bioenergetics, Metab. Eng., 27, 115, 10.1016/j.ymben.2014.09.007 Kieninger, 2018, Microsensor systems for cell metabolism – from 2D culture to organ-on-chip, Lab Chip, 18, 1274, 10.1039/C7LC00942A Kucherenko, 2019, Advances in the biosensors for lactate and pyruvate detection for medical applications: a review, Trac. Trends Anal. Chem., 110, 160, 10.1016/j.trac.2018.11.004 Liu, 2016, A review on microfluidic paper-based analytical devices for glucose detection, Sensors, 16, 17, 10.3390/s16122086 van Enter, 2018, Challenges and perspectives in continuous glucose monitoring, Chem. Comm., 54, 5032, 10.1039/C8CC01678J Weltin, 2014, Cell culture monitoring for drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem, Lab Chip, 14, 138, 10.1039/C3LC50759A Heo, 2012, Real time culture and analysis of embryo metabolism using a microfluidic device with deformation based actuation, Lab Chip, 12, 2240, 10.1039/c2lc21050a Prill, 2014, Long-term microfluidic glucose and lactate monitoring in hepatic cell culture, Biomicrofluidics, 8, 10.1063/1.4876639 Zhao, 2016, Microchip based electrochemical-piezoelectric integrated multi-mode sensing system for continuous glucose monitoring, Sens. Actuator. B Chem., 223, 83, 10.1016/j.snb.2015.09.022 Cerdeira Ferreira, 2013, Miniaturized flow system based on enzyme modified PMMA microreactor for amperometric determination of glucose, Biosens. Bioelectron., 47, 539, 10.1016/j.bios.2013.03.052 Kurita, 2002, Microfluidic device integrated with pre-reactor and dual enzyme-modified microelectrodes for monitoring in vivo glucose and lactate, Sens. Actuator. B Chem., 87, 296, 10.1016/S0925-4005(02)00249-6 Huang, 2007, Integrated microfluidic systems for automatic glucose sensing and insulin injection, Sens. Actuators B Chem., 122, 461, 10.1016/j.snb.2006.06.015 Pu, 2016, A continuous glucose monitoring device by graphene modified electrochemical sensor in microfluidic system, Biomicrofluidics, 10, 10.1063/1.4942437 Picher, 2013, Nanobiotechnology advanced antifouling surfaces for the continuous electrochemical monitoring of glucose in whole blood using a lab-on-a-chip, Lab Chip, 13, 1780, 10.1039/c3lc41308j Obeidat, 2019, A multi-sensor system for measuring bovine embryo metabolism, Biosens. Bioelectron., 126, 615, 10.1016/j.bios.2018.09.071 Vonau, 2010, Conception of a new technique in cell cultivation using a lab-on-chip aided miniaturised device with calibratable electrochemical sensors, Microchim. Acta., 171, 451, 10.1007/s00604-010-0427-9 Rodrigues, 2008, Cell-based microfluidic biochip for the electrochemical real-time monitoring of glucose and oxygen, Sens. Actuator. B Chem., 132, 608, 10.1016/j.snb.2007.12.025 Gu, 2014, A droplet-based microfluidic electrochemical sensor using platinum-black microelectrode and its application in high sensitive glucose sensing, Biosens. Bioelectron., 55, 106, 10.1016/j.bios.2013.12.002 Bavli, 2016, Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction, Proc. Natl. Acad. Sci. Unit. States Am., 113, E2231, 10.1073/pnas.1522556113 Benito-Pena, 2016, Fluorescence based fiber optic and planar waveguide biosensors. A review, Anal. Chim.Acta, 943, 17, 10.1016/j.aca.2016.08.049 Zhu, 2017, A dual enzyme-inorganic hybrid nanoflower incorporated microfluidic paper-based analytic device (mu PAD) biosensor for sensitive visualized detection of glucose, Nanoscale, 9, 5658, 10.1039/C7NR00958E Urbanski, 2008, Noninvasive metabolic profiling using microfluidics for analysis of single preimplantation embryos, Anal. Chem., 80, 6500, 10.1021/ac8010473 Nacht, 2015, Integrated catheter system for continuous glucose measurement and simultaneous insulin infusion, Biosens. Bioelectron., 64, 102, 10.1016/j.bios.2014.08.012 Mohammadi, 2012, A minimally invasive chip based near infrared sensor for continuous glucose monitoring Park, 2018, Smart fluorescent hydrogel glucose biosensing microdroplets with dual-mode fluorescence quenching and size reduction, ACS Appl. Mater. Interfaces, 10, 30172, 10.1021/acsami.8b10768 Piao, 2015, Enzyme incorporated microfluidic device for in-situ glucose detection in water-in-air microdroplets, Biosens. Bioelectron., 65, 220, 10.1016/j.bios.2014.10.032 Perkel, 2017, Spent culture medium analysis from individually cultured bovine embryos demonstrates metabolomic differences, Zygote, 25, 662, 10.1017/S0967199417000417 Agrawal, 2016, A microfluidic platform for glucose sensing using broadband ultrasound spectroscopy, 5 Wang, 2008, A MEMS thermal biosensor for metabolic monitoring applications, J. Microelectromech. Syst., 17, 318, 10.1109/JMEMS.2008.916357 Boss, 2011, A viscosity-dependent affinity sensor for continuous monitoring of glucose in biological fluids, Biosens. Bioelectron., 30, 223, 10.1016/j.bios.2011.09.016 Yesiloz, 2015, Label-free high-throughput detection and content sensing of individual droplets in microfluidic systems, Lab Chip, 15, 4008, 10.1039/C5LC00314H Yao, 2004, On-line microdialysis assay of L-lactate and pyruvate in vitro and in vivo by a flow-injection system with a dual enzyme electrode, Talanta, 63, 771, 10.1016/j.talanta.2003.11.033 Yao, 2004, Simultaneous in vivo monitoring of glucose, L-lactate, and pyruvate concentrations in rat brain by a flow-injection biosensor system with an on-line microdialysis sampling, Anal. Chim. Acta, 510, 53, 10.1016/j.aca.2003.12.062 Cordeiro, 2015, In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device, Biosens. Bioelectron., 67, 677, 10.1016/j.bios.2014.09.101 Zhang, 1997, Dual-enzyme fiber optic biosensor for pyruvate, Anal. Chim. Acta, 350, 59 Shi, 2012, A replaceable dual-enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate, Electrophoresis, 33, 2145, 10.1002/elps.201200090 Wu, 2010, A Clark-type oxygen chip for in situ estimation of the respiratory activity of adhering cells, Talanta, 81, 228, 10.1016/j.talanta.2009.11.062 Luo, 2017, A low temperature co-fired ceramic based microfluidic Clark-type oxygen sensor for real-time oxygen sensing, Sens. Actuator. B Chem., 240, 392, 10.1016/j.snb.2016.08.180 Date, 2011, Monitoring oxygen consumption of single mouse embryos using an integrated electrochemical microdevice, Biosens. Bioelectron., 30, 100, 10.1016/j.bios.2011.08.037 Kurosawa, 2016, Development of a new clinically applicable device for embryo evaluation which measures embryo oxygen consumption, Hum. Reprod., 31, 2321, 10.1093/humrep/dew187 van Rossem, 2017, Sensing oxygen at the millisecond time-scale using an ultra-microelectrode array (UMEA), Sens. Actuator. B Chem., 238, 1008, 10.1016/j.snb.2016.06.156 Kieninger, 2007, Amperometric oxygen sensor array with novel chronoamperometric protocols for hypoxic tumor cell cultures Lin, 2009, In-situ measurement of cellular microenvironments in a microfluidic device, Lab Chip, 9, 257, 10.1039/B806907G Zhu, 2012, High throughput micropatterning of optical oxygen sensor for single cell analysis, IEEE Sens. J., 12, 1668, 10.1109/JSEN.2011.2176930 Lam, 2009, Culturing aerobic and anaerobic bacteria and mammalian cells with a microfluidic differential oxygenator, Anal. Chem., 81, 5918, 10.1021/ac9006864 Rivera, 2018, Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems, Biosens. Bioelectron., 123, 131, 10.1016/j.bios.2018.07.035 Huang, 2012, Light-addressable measurements of cellular oxygen consumption rates in microwell arrays based on phase-based phosphorescence lifetime detection, Biomicrofluidics, 6, 1, 10.1063/1.4772604 Huang, 2013, Metabolic profile analysis of a single developing zebrafish embryo via monitoring of oxygen consumption rates within a microfluidic device, Biomicrofluidics, 7, 64107, 10.1063/1.4833256 Talaei, 2015, Enzyme SU-8 microreactors: simple tools for cell-culture monitoring, Microfluid. Nanofluidics, 19, 351, 10.1007/s10404-015-1562-8 Ges, 2010, Enzyme-coated microelectrodes to monitor lactate production in a nanoliter microfluidic cell culture device, Biosens. Bioelectron., 26, 828, 10.1016/j.bios.2010.05.030 Hammar, 2015, Single-cell screening of photosynthetic growth and lactate production by cyanobacteria, Biotechnol. Biofuels, 8, 10.1186/s13068-015-0380-2 Mongersun, 2016, Droplet microfluidic platform for the determination of single-cell lactate release, Anal. Chem., 88, 3257, 10.1021/acs.analchem.5b04681 Welch, 2014, Real-time feedback control of pH within microfluidics using integrated sensing and actuation, Lab Chip, 14, 1191, 10.1039/c3lc51205c Ges, 2005, Thin-film IrOx pH microelectrode for microfluidic-based microsystems, Biosens. Bioelectron., 21, 248, 10.1016/j.bios.2004.09.021 Ges, 2007, Differential pH measurements of metabolic cellular activity in nl culture volumes using microfabricated iridium oxide electrodes, Biosens. Bioelectron., 22, 1303, 10.1016/j.bios.2006.05.033 Ges, 2008, On-chip acidification rate measurements from single cardiac cells confined in sub-nanoliter volumes, Biomed. Microdevices, 10, 347, 10.1007/s10544-007-9142-7 Mani, 2017, ZnO-based microfluidic pH sensor: a versatile approach for quick recognition of circulating tumor cells in blood, ACS Appl. Mater. Interfaces, 9, 5193, 10.1021/acsami.6b16261 Lee, 2008, Measurement of pH and dissolved oxygen within cell culture media using a hydrogel microarray sensor, Sens. Actuator. B Chem., 128, 388, 10.1016/j.snb.2007.06.027 Shaegh, 2016, A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices, Biomicrofluidics, 10 Zhang, 2017, Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors, Proc. Natl. Acad. Sci. Unit. States Am., 114, E2293, 10.1073/pnas.1612906114 Huang, 2017, Simultaneous monitoring of oxygen consumption and acidification rates of a single zebrafish embryo during embryonic development within a microfluidic device, Microfluid. Nanofluidics, 21, 10.1007/s10404-016-1841-z Weltin, 2017, Accessing 3D microtissue metabolism: lactate and oxygen monitoring in hepatocyte spheroids, Biosens. Bioelectron., 87, 941, 10.1016/j.bios.2016.07.094 Cheng, 2006, Metabolic monitoring of the electrically stimulated single heart cell within a microfluidic platform, Lab Chip, 6, 1424, 10.1039/b608202e Bergmann, 1999, A bienzyme modified carbon paste electrode for amperometric detection of pyruvate, Anal. Chim. Acta, 394, 233, 10.1016/S0003-2670(99)00296-2 Akyilmaz, 2007, Construction of an amperometric pyruvate oxidase enzyme electrode for determination of pyruvate and phosphate, Electrochim. Acta, 52, 7972, 10.1016/j.electacta.2007.06.058 Cheng, 1999, Rapid on-line microdialysis hyphenated technique for the dynamic monitoring of extracellular pyruvate, lactic acid and ascorbic acid during cerebral ischemia, J. Chromatogr. B, 723, 31, 10.1016/S0378-4347(98)00532-5 Wu, 2001, Determination of pyruvate and lactate in primary liver cell culture medium during hypoxia by on-line microdialysis-liquid chromatography, J. Chromatogr. A, 913, 341, 10.1016/S0021-9673(00)01265-6 Tholance, 2011, Analytical validation of microdialysis analyzer for monitoring glucose, lactate and pyruvate in cerebral microdialysates, Clin. Chim. Acta, 412, 647, 10.1016/j.cca.2010.12.025 Li, 2017, Research on a new micro-volume fluorescence capillary biosensor assay for sequentially quantifying pyruvate and lactate, J. Fluoresc., 27, 883, 10.1007/s10895-017-2024-3 Kalfe, 2015, Looking into living cell systems: planar waveguide microfluidic NMR detector for in vitro metabolomics of tumor spheroids, Anal. Chem., 87, 7402, 10.1021/acs.analchem.5b01603 Ibanez, 2013, Mass spectrometry-based metabolomics of single yeast cells, Proc. Natl. Acad. Sci. Unit. States Am., 110, 8790, 10.1073/pnas.1209302110 Gatenby, 2004, Why do cancers have high aerobic glycolysis?, Nat. Rev. Cancer, 4, 891, 10.1038/nrc1478 Zheng, 2010, Optical detection of single cell lactate release for cancer metabolic analysis, Anal. Chem., 82, 5082, 10.1021/ac100074n Cai, 2002, Ultra-low-volume, real-time measurements of lactate from the single heart cell using microsystems technology, Anal. Chem., 74, 908, 10.1021/ac010941+ Wu, 2007, Study of on-line monitoring of lactate based on optical fibre sensor and in-channel mixing mechanism, Biomed. Microdevices, 9, 167, 10.1007/s10544-006-9018-2 Wang, 2014, Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption, Nat. Biotechnol., 32, 10.1038/nbt.2857 Ordeig, 2012, Dual photonic-electrochemical lab on a chip for online simultaneous absorbance and amperometric measurements, Anal. Chem., 84, 3546, 10.1021/ac203106x Liu, 2016, Online monitoring of lactate efflux by multi-channel microfluidic chip-mass spectrometry for rapid drug evaluation, ACS Sens., 1, 344, 10.1021/acssensors.5b00221 Krommenhoek, 2007, Integrated electrochemical sensor array for on-line monitoring of yeast fermentations, Anal. Chem., 79, 5567, 10.1021/ac0623078 Yamanaka, 2011, Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption, Hum. Reprod., 26, 3366, 10.1093/humrep/der324 Tredan, 2007, Drug resistance and the solid tumor microenvironment, J. Natl. Cancer. Inst., 99, 1441, 10.1093/jnci/djm135 Clark, 1962, Electrode systems for continuous monitoring in cardiovascular surgery, Ann. N. Y. Acad. Sci., 102, 29, 10.1111/j.1749-6632.1962.tb13623.x Suresh, 2009, Techniques for oxygen transfer measurement in bioreactors: a review, J. Chem. Technol. Biotechnol., 84, 1091, 10.1002/jctb.2154 Oomen, 2016, Implementing oxygen control in chip-based cell and tissue culture systems, Lab Chip, 16, 3394, 10.1039/C6LC00772D Wu, 2007, Microfluidic chip integrated with amperometric detector array for in situ estimating oxygen consumption characteristics of single bovine embryos, Sens. Actuator. B Chem., 125, 680, 10.1016/j.snb.2007.03.017 Ebbesen, 2009, Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies, J. Enzym. Inhib. Med. Chem., 24, 1, 10.1080/14756360902784425 Kieninger, 2014, Pericellular oxygen monitoring with integrated sensor chips for reproducible cell culture experiments, Cell Prolif., 47, 180, 10.1111/j.1365-2184.2013.12089.x Kieninger, 2018, Sensor access to the cellular microenvironment using the sensing cell culture flask, Biosensors, 8, 10.3390/bios8020044 Dmitriev, 2012, Optical probes and techniques for O2 measurement in live cells and tissue, Cell. Mol. Life Sci., 69, 2025, 10.1007/s00018-011-0914-0 Wang, 2014, Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications, Chem. Soc. Rev., 43, 3666, 10.1039/C4CS00039K Konig, 2005, Fabrication and test of sol–gel based planar oxygen optodes for use in aquatic sediments, Mar. Chem., 97, 262, 10.1016/j.marchem.2005.05.003 Wilson, 2003 Nock, 2009, In-situ optical oxygen sensing for bio-artificial liver bioreactors, 778 Thomas, 2009, A noninvasive thin film sensor for monitoring oxygen tension during in vitro cell culture, Anal. Chem., 81, 9239, 10.1021/ac9013379 Vollmer, 2005, Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium, Lab Chip, 5, 1059, 10.1039/b508097e Hou, 2017, Fluorescent bioimaging of pH: from design to applications, Chem. Soc. Rev., 46, 2076, 10.1039/C6CS00719H Zhan, 2002, Hydrogel-based microreactors as a functional component of microfluidic systems, Anal. Chem., 74, 4647, 10.1021/ac020340y Wu, 2011, The open container-used microfluidic chip using IrO(x) ultramicroelectrodes for the in situ measurement of extracellular acidification, Biosens. Bioelectron., 26, 4191, 10.1016/j.bios.2011.04.034 Lima, 2014, Multichamber multipotentiostat system for cellular microphysiometry, Sens. Actuator. B Chem., 204, 536, 10.1016/j.snb.2014.07.126 Khan, 2017, A review on pH sensitive materials for sensors and detection methods, Microsyst. Technol., 23, 4391, 10.1007/s00542-017-3495-5 Lowe, 2017, Field-effect sensors - from pH sensing to biosensing: sensitivity enhancement using streptavidin-biotin as a model system, Analyst, 142, 4173, 10.1039/C7AN00455A Lehmann, 2000, Non-invasive measurement of cell membrane associated proton gradients by ion-sensitive field effect transistor arrays for microphysiological and bioelectronical applications, Biosens. Bioelectron., 15, 117, 10.1016/S0956-5663(00)00065-8 Lehmann, 2001, Simultaneous measurement of cellular respiration and acidification with a single CMOS ISFET, Biosens. Bioelectron., 16, 195, 10.1016/S0956-5663(01)00123-3 Brischwein, 2003, Functional cellular assays with multiparametric silicon sensor chips, Lab Chip, 3, 234, 10.1039/b308888j Sakata, 2011, Real-time and noninvasive monitoring of respiration activity of fertilized ova using semiconductor-based biosensing devices, Eur. Biophys. J. Biophys., 40, 699, 10.1007/s00249-010-0653-4 Huang, 2011, A flexible pH sensor based on the iridium oxide sensing film, Sens. Actuator A Phys., 169, 1, 10.1016/j.sna.2011.05.016 Kaviyarasu, 2017, In vitro cytotoxicity effect and antibacterial performance of human lung epithelial cells A549 activity of Zinc oxide doped TiO 2 nanocrystals: investigation of bio-medical application by chemical method, Mat. Sci. Eng. C Mater., 74, 325, 10.1016/j.msec.2016.12.024 Santos, 2014, WO3 nanoparticle-based conformable pH sensor, ACS Appl. Mater. Interfaces, 6, 12226, 10.1021/am501724h Li, 1999, pH-response of nanosized MnO prepared with solid state reaction route at room temperature, Sens. Actuator. B Chem., 59, 42, 10.1016/S0925-4005(99)00189-6 Sardarinejad, 2015, The pH sensing properties of RF Sputtered RuO2 thin-film prepared using different Ar/O2 flow ratio, Materials, 8, 3352, 10.3390/ma8063352 Apel, 2004, Reactive oxygen species: metabolism, oxidative stress, and signal transduction, Annu. Rev. Plant Biol., 55, 373, 10.1146/annurev.arplant.55.031903.141701 Schieber, 2014, ROS function in redox signaling and oxidative stress, Curr. Biol., 24, 453, 10.1016/j.cub.2014.03.034 Bulua, 2011, Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS), J. Exp. Med., 208, 519, 10.1084/jem.20102049 Jarrett, 2012, Consequences of oxidative stress in age-related macular degeneration, Mol. Asp. Med., 33, 399, 10.1016/j.mam.2012.03.009 Bhattacharyya, 2014, Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases, Physiol. Rev., 94, 329, 10.1152/physrev.00040.2012 Ushio-Fukai, 2008, Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy, Cancer Lett., 266, 37, 10.1016/j.canlet.2008.02.044 Shah, 2016, Molecular and cellular mechanisms of cardiovascular disorders in diabetes, Circ. Res., 118, 1808, 10.1161/CIRCRESAHA.116.306923 Zhou, 2018, Identification of novel Nrf2 activators from Cinnamomum chartophyllum H.W. Li and their potential application of preventing oxidative insults in human lung epithelial cells, Redox. Biol., 14, 154, 10.1016/j.redox.2017.09.004 Liang, 2014, Stem cells, redox signaling and stem cell aging, Antioxidants Redox Signal., 20, 1902, 10.1089/ars.2013.5300 Wen, 2013, Deconvoluting the role of reactive oxygen species and autophagy in human diseases, Free Radic. Biol. Med., 65, 402, 10.1016/j.freeradbiomed.2013.07.013 Klaunig, 2010, Oxidative stress and oxidative damage in carcinogenesis, Toxicol. Pathol., 38, 96, 10.1177/0192623309356453 Gomes, 2005, Fluorescence probes used for detection of reactive oxygen species, J. Biochem. Biophys. Methods, 65, 45, 10.1016/j.jbbm.2005.10.003 Swanson, 2011, In vivo imaging of Ca2+, pH, and reactive oxygen species using fluorescent probes in plants, Annu. Rev. Plant Biol., 62, 273, 10.1146/annurev-arplant-042110-103832 Chen, 2016, Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species, Chem. Soc. Rev., 45, 2976, 10.1039/C6CS00192K Woolley, 2013, Recent advances in reactive oxygen species measurement in biological systems, Trends Biochem. Sci., 38, 556, 10.1016/j.tibs.2013.08.009 Chen, 2013, A dual-emission fluorescent nanocomplex of gold-cluster-decorated silica particles for live cell imaging of highly reactive oxygen species, J. Am. Chem. Soc., 135, 11595, 10.1021/ja4035939 Calas-Blanchard, 2014, Electrochemical sensor and biosensor strategies for ROS/RNS detection in biological systems, Electroanalysis, 26, 1277, 10.1002/elan.201400083 Liu, 2017, A review on nanomaterial-based electrochemical sensors for H2O2, H2S and NO inside cells or released by cells, Microchim. Acta, 184, 1267, 10.1007/s00604-017-2179-2 Mao, 2002, Continuous on-line measurement of cerebral hydrogen peroxide using enzyme-modified ring-disk plastic carbon film electrode, Anal. Chem., 74, 3684, 10.1021/ac011261+ Amatore, 2007, Electrochemical detection in a microfluidic device of oxidative stress generated by macrophage cells, Lab Chip, 7, 233, 10.1039/B611569A Flamm, 2015, Superoxide microsensor integrated into a Sensing Cell Culture Flask microsystem using direct oxidation for cell culture application, Biosens. Bioelectron., 65, 354, 10.1016/j.bios.2014.10.062 Yan, 2011, Electrochemical biosensors for on-chip detection of oxidative stress from immune cells, Biomicrofluidics, 5, 320081, 10.1063/1.3624739 Matharu, 2013, Miniature enzyme-based electrodes for detection of hydrogen peroxide release from alcohol-injured hepatocytes, Anal. Chem., 85, 932, 10.1021/ac3025619 Li, 2018, Downstream simultaneous electrochemical detection of primary reactive oxygen and nitrogen species released by cell populations in an integrated microfluidic device, Anal. Chem., 90, 9386, 10.1021/acs.analchem.8b02039 Cheah, 2010, Microfluidic perfusion system for maintaining viable heart tissue with real-time electrochemical monitoring of reactive oxygen species, Lab Chip, 10, 2720, 10.1039/c004910g Sun, 2005, Determination of reactive oxygen species in single human erythrocytes using microfluidic chip electrophoresis, Anal. Bioanal. Chem., 382, 1472, 10.1007/s00216-005-3352-8 Li, 2009, Simultaneous determination of superoxide and hydrogen peroxide in macrophage RAW 264.7 cell extracts by microchip electrophoresis with laser-induced fluorescence detection, Anal. Chem., 81, 2193, 10.1021/ac801777c Chen, 2010, Potent method for the simultaneous determination of glutathione and hydrogen peroxide in mitochondrial compartments of apoptotic cells with microchip electrophoresis-laser induced fluorescence, Anal. Chem., 82, 2006, 10.1021/ac902741r Zhang, 2011, Electrokinetic gated injection-based microfluidic system for quantitative analysis of hydrogen peroxide in individual HepG2 cells, Lab Chip, 11, 1144, 10.1039/c0lc00263a Li, 2016, Consecutive gated injection-based microchip electrophoresis for simultaneous quantitation of superoxide anion and nitric oxide in single PC-12 cells, Anal. Chem., 88, 930, 10.1021/acs.analchem.5b03664 Chin, 2011, Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations, Lab Chip, 11, 1856, 10.1039/c0lc00651c