Abstract

The continuous measurement of uptake or release of biomarkers provides invaluable information for understanding and monitoring the metabolism of cells. In this work, a multiscattering-enhanced optical biosensor for the multiplexed, non-invasive, and continuous detection of hydrogen peroxide (H2O2), lactate and glucose is presented. The sensing scheme is based on optical monitoring of the oxidation state of the metalloprotein cytochrome c (cyt c). The analyte of interest is enzymatically converted into H2O2 leading to an oxidation of the cyt c. Contact microspotting is used to prepare nanoliter-sized sensing spots containing either pure cyt c, a mixture of cyt c with glucose oxidase (GOx) to detect glucose, or a mixture of cyt c with lactate oxidase (LOx) to detect lactate. The sensing spots are embedded in a multiscattering porous medium that enhances the optical signal. We achieve limits of detection down to 240 nM and 110 nM for lactate and glucose, respectively. A microfluidic embodiment enables multiplexed and crosstalk-free experiments on living organisms. As an example, we study the uptake of exogenously supplied glucose by the green algae Chlamydomonas reinhardtii and simultaneously monitor the stress-related generation of H2O2. This multifunctional detection scheme provides a powerful tool to study biochemical processes at cellular level.

© 2015 Optical Society of America

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References

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2015 (2)

V. B. Koman, C. Santschi, and O. J. F. Martin, “Multiscattering-Enhanced Absorption Spectroscopy,” Anal. Chem. 87(3), 1536–1543 (2015).
[Crossref] [PubMed]

V. B. Koman, C. Santschi, N. R. von Moos, V. I. Slaveykova, and O. J. F. Martin, “Portable oxidative stress sensor: dynamic and non-invasive measurements of extracellular H₂O₂ released by algae,” Biosens. Bioelectron. 68, 245–252 (2015).
[Crossref] [PubMed]

2014 (1)

G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
[Crossref] [PubMed]

2013 (6)

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

G. Suárez, C. Santschi, V. I. Slaveykova, and O. J. F. Martin, “Sensing the dynamics of oxidative stress using enhanced absorption in protein-loaded random media,” Sci. Rep. 3, 3447 (2013).
[Crossref] [PubMed]

C. G. Pheeney, A. R. Arnold, M. A. Grodick, and J. K. Barton, “Multiplexed electrochemistry of DNA-bound metalloproteins,” J. Am. Chem. Soc. 135(32), 11869–11878 (2013).
[Crossref] [PubMed]

S. Govindarajan, C. J. McNeil, J. P. Lowry, C. P. McMahon, and R. D. O’Neill, “Highly selective and stable microdisc biosensors for l-glutamate monitoring,” Sens. Actuators B Chem. 178, 606–614 (2013).
[Crossref]

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
[Crossref] [PubMed]

W. Putzbach and N. J. Ronkainen, “Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review,” Sensors (Basel) 13(4), 4811–4840 (2013).
[Crossref] [PubMed]

2012 (6)

W. Chen, L. Hong, A.-L. Liu, J.-Q. Liu, X.-H. Lin, and X.-H. Xia, “Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal cupric oxide nanoparticles as peroxidase mimic,” Talanta 99, 643–648 (2012).
[Crossref] [PubMed]

D. C. Klonoff, “Overview of Fluorescence Glucose Sensing: A Technology with a Bright Future,” J. Diabetes Sci. Tech. 6(6), 1242–1250 (2012).
[Crossref] [PubMed]

B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
[Crossref] [PubMed]

G. Suarez, C. Santschi, S. Dutta-Gupta, L. Juillerat-Jeanneret, and O. J. F. Martin, “Biophotonic tool for sensing the dynamics of H2O2 extracellular release in stressed cells,” Proc. SPIE 8229, 822908 (2012).

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

P. Xie, I. Fujii, J. Zhao, M. Shinohara, and M. Matsukura, “A Novel Polysaccharide Compound Derived from Algae Extracts Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage in Vitro,” Biol. Pharm. Bull. 35(9), 1447–1453 (2012).
[PubMed]

2011 (3)

L. Michaelis, M. L. Menten, K. A. Johnson, and R. S. Goody, “The original Michaelis Constant: Translation of the 1913 Michaelis-Menten Paper,” Biochemistry 50(39), 8264–8269 (2011).
[Crossref] [PubMed]

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

T. Sikora, G. Istamboulie, E. Jubete, E. Ochoteco, J.-L. Marty, and T. Noguer, “Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene),” J. Sens. 2011, 1–7 (2011).
[Crossref]

2010 (2)

G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
[Crossref] [PubMed]

H. Chen, R. Li, L. Lin, G. Guo, and J.-M. Lin, “Determination of L-ascorbic acid in human serum by chemiluminescence based on hydrogen peroxide-sodium hydrogen carbonate-CdSe/CdS quantum dots system,” Talanta 81(4-5), 1688–1696 (2010).
[Crossref] [PubMed]

2009 (4)

Y.-S. Li, X. Ju, X.-F. Gao, and W. Yang, “A Novel Immobilization Enzyme Lactate Fluorescence Capillary Biosensor,” Chin. J. Anal. Chem. 37(5), 637–642 (2009).
[Crossref]

J. R. Henderson, H. Swalwell, S. Boulton, P. Manning, C. J. McNeil, and M. A. Birch-Machin, “Direct, real-time monitoring of superoxide generation in isolated mitochondria,” Free Radic. Res. 43(9), 796–802 (2009).
[Crossref] [PubMed]

J. R. Henderson, D. A. Fulton, C. J. McNeil, and P. Manning, “The development and in vitro characterisation of an intracellular nanosensor responsive to reactive oxygen species,” Biosens. Bioelectron. 24(12), 3608–3614 (2009).
[Crossref] [PubMed]

L. Huang, S. J. Maerkl, and O. J. Martin, “Integration of plasmonic trapping in a microfluidic environment,” Opt. Express 17(8), 6018–6024 (2009).
[Crossref] [PubMed]

2008 (2)

H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
[Crossref] [PubMed]

U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).
[Crossref] [PubMed]

2007 (1)

G. Suárez, R. J. Jackson, J. A. Spoors, and C. J. McNeil, “Chemical Introduction of Disulfide Groups on Glycoproteins: A Direct Protein Anchoring Scenario,” Anal. Chem. 79(5), 1961–1969 (2007).
[Crossref] [PubMed]

2006 (1)

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

2005 (1)

A. Liesener and U. Karst, “Monitoring enzymatic conversions by mass spectrometry: a critical review,” Anal. Bioanal. Chem. 382(7), 1451–1464 (2005).
[Crossref] [PubMed]

2004 (3)

L. B. Gladden, “Lactate metabolism: a new paradigm for the third millennium,” J. Physiol. 558(1), 5–30 (2004).
[Crossref] [PubMed]

Y. Lin, F. Lu, Y. Tu, and Z. Ren, “Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles,” Nano Lett. 4(2), 191–195 (2004).
[Crossref]

C. Boozer, J. Ladd, S. Chen, Q. Yu, J. Homola, and S. Jiang, “DNA Directed Protein Immobilization on Mixed ssDNA/Oligo(ethylene glycol) Self-Assembled Monolayers for Sensitive Biosensors,” Anal. Chem. 76(23), 6967–6972 (2004).
[Crossref] [PubMed]

2003 (2)

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

E. A. McGlynn, S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr, “The Quality of Health Care Delivered to Adults in the United States,” N. Engl. J. Med. 348(26), 2635–2645 (2003).
[Crossref] [PubMed]

2002 (3)

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

B. Ahrén and H. Larsson, “Quantification of Insulin Secretion in Relation to Insulin Sensitivity in Nondiabetic Postmenopausal Women,” Diabetes 51(Suppl 1), S202–S211 (2002).
[Crossref] [PubMed]

W. Dröge, “Free Radicals in the Physiological Control of Cell Function,” Physiol. Rev. 82(1), 47–95 (2002).
[PubMed]

2001 (4)

J. Homola, H. B. Lu, G. G. Nenninger, J. Dostálek, and S. S. Yee, “A novel multichannel surface plasmon resonance biosensor,” Sens. Actuators B Chem. 76(1-3), 403–410 (2001).
[Crossref]

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
[Crossref] [PubMed]

C. M. Masimirembwa, R. Thompson, and T. B. Andersson, “In Vitro High Throughput Screening of Compounds for Favorable Metabolic Properties in Drug Discovery,” Comb. Chem. High Throughput Screen. 4(3), 245–263 (2001).
[Crossref] [PubMed]

R. Garjonyte, Y. Yigzaw, R. Meskys, A. Malinauskas, and L. Gorton, “Prussian Blue- and lactate oxidase-based amperometric biosensor for lactic acid,” Sens. Actuators B Chem. 79(1), 33–38 (2001).
[Crossref]

2000 (1)

K. Sirkar, A. Revzin, and M. V. Pishko, “Glucose and Lactate Biosensors Based on Redox Polymer/Oxidoreductase Nanocomposite Thin Films,” Anal. Chem. 72(13), 2930–2936 (2000).
[Crossref] [PubMed]

1999 (2)

S. A. Gerber, C. R. Scott, F. Turecek, and M. H. Gelb, “Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass Spectrometry,” J. Am. Chem. Soc. 121(5), 1102–1103 (1999).
[Crossref]

C. A. Rowe, S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler, “An array immunosensor for simultaneous detection of clinical analytes,” Anal. Chem. 71(2), 433–439 (1999).
[Crossref] [PubMed]

1997 (2)

G. Kenausis, Q. Chen, and A. Heller, “Electrochemical Glucose and Lactate Sensors Based on “Wired” Thermostable Soybean Peroxidase Operating Continuously and Stably at 37 ° C,” Anal. Chem. 69(6), 1054–1060 (1997).
[Crossref] [PubMed]

O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, and S. Sampath, “Sol−Gel Materials in Electrochemistry,” Chem. Mater. 9(11), 2354–2375 (1997).
[Crossref]

1996 (1)

M.-C. Shin, H. C. Yoon, and H.-S. Kim, “In situ biochemical reduction of interference in an amperometric biosensor with a novel heterobilayer configuration of polypyrrole/glucose oxidase/horseradish peroxidase,” Anal. Chim. Acta 329(3), 223–230 (1996).
[Crossref]

1990 (1)

B. A. Gregg and A. Heller, “Cross-linked redox gels containing glucose oxidase for amperometric biosensor applications,” Anal. Chem. 62(3), 258–263 (1990).
[Crossref] [PubMed]

1984 (1)

M. R. Liebowitz, A. J. Fyer, J. M. Gorman, D. Dillon, I. L. Appleby, G. Levy, S. Anderson, M. Levitt, M. Palij, S. O. Davies, and et al.., “Lactate provocation of panic attacks. I. Clinical and behavioral findings,” Arch. Gen. Psychiatry 41(8), 764–770 (1984).
[Crossref] [PubMed]

1972 (1)

R. A. Pelroy, R. Rippka, and R. Y. Stanier, “Metabolism of glucose by unicellular blue-green algae,” Arch. Mikrobiol. 87(4), 303–322 (1972).
[Crossref] [PubMed]

1970 (1)

M. H. Weil and A. A. Afifi, “Experimental and Clinical Studies on Lactate and Pyruvate as Indicators of the Severity of Acute Circulatory Failure (Shock),” Circulation 41(6), 989–1001 (1970).
[Crossref] [PubMed]

1969 (1)

E. A. Drew, “Uptake and metabolism of exogenously supplied sugards by brown algae,” New Phytol. 68(1), 35–43 (1969).
[Crossref]

1962 (1)

W. D. Butt and D. Keilin, “Absorption spectra and some other properties of cytochrome c and of its compounds with ligands,” Proc. R. Soc. Lond. B Biol. Sci. 156(965), 429–458 (1962).
[Crossref] [PubMed]

1958 (1)

W. E. Huckabee, “Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation,” J. Clin. Invest. 37(2), 244–254 (1958).
[Crossref] [PubMed]

1949 (1)

G. Strom, “The Influence of Anoxia on Lactate Utilization in Man After Prolonged Muscular Work,” Acta Physiol. Scand. 17(4), 440–451 (1949).
[Crossref] [PubMed]

Adams, J.

E. A. McGlynn, S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr, “The Quality of Health Care Delivered to Adults in the United States,” N. Engl. J. Med. 348(26), 2635–2645 (2003).
[Crossref] [PubMed]

Afifi, A. A.

M. H. Weil and A. A. Afifi, “Experimental and Clinical Studies on Lactate and Pyruvate as Indicators of the Severity of Acute Circulatory Failure (Shock),” Circulation 41(6), 989–1001 (1970).
[Crossref] [PubMed]

Ahrén, B.

B. Ahrén and H. Larsson, “Quantification of Insulin Secretion in Relation to Insulin Sensitivity in Nondiabetic Postmenopausal Women,” Diabetes 51(Suppl 1), S202–S211 (2002).
[Crossref] [PubMed]

Aitken, R. J.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

Alexander, R. W.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Anderson, J. L.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Anderson, S.

M. R. Liebowitz, A. J. Fyer, J. M. Gorman, D. Dillon, I. L. Appleby, G. Levy, S. Anderson, M. Levitt, M. Palij, S. O. Davies, and et al.., “Lactate provocation of panic attacks. I. Clinical and behavioral findings,” Arch. Gen. Psychiatry 41(8), 764–770 (1984).
[Crossref] [PubMed]

Andersson, T. B.

C. M. Masimirembwa, R. Thompson, and T. B. Andersson, “In Vitro High Throughput Screening of Compounds for Favorable Metabolic Properties in Drug Discovery,” Comb. Chem. High Throughput Screen. 4(3), 245–263 (2001).
[Crossref] [PubMed]

Appleby, I. L.

M. R. Liebowitz, A. J. Fyer, J. M. Gorman, D. Dillon, I. L. Appleby, G. Levy, S. Anderson, M. Levitt, M. Palij, S. O. Davies, and et al.., “Lactate provocation of panic attacks. I. Clinical and behavioral findings,” Arch. Gen. Psychiatry 41(8), 764–770 (1984).
[Crossref] [PubMed]

Arnold, A. R.

C. G. Pheeney, A. R. Arnold, M. A. Grodick, and J. K. Barton, “Multiplexed electrochemistry of DNA-bound metalloproteins,” J. Am. Chem. Soc. 135(32), 11869–11878 (2013).
[Crossref] [PubMed]

Asch, S. M.

E. A. McGlynn, S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr, “The Quality of Health Care Delivered to Adults in the United States,” N. Engl. J. Med. 348(26), 2635–2645 (2003).
[Crossref] [PubMed]

Bandodkar, A. J.

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
[Crossref] [PubMed]

Barton, J. K.

C. G. Pheeney, A. R. Arnold, M. A. Grodick, and J. K. Barton, “Multiplexed electrochemistry of DNA-bound metalloproteins,” J. Am. Chem. Soc. 135(32), 11869–11878 (2013).
[Crossref] [PubMed]

Bharathi, S.

O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, and S. Sampath, “Sol−Gel Materials in Electrochemistry,” Chem. Mater. 9(11), 2354–2375 (1997).
[Crossref]

Birch-Machin, M. A.

J. R. Henderson, H. Swalwell, S. Boulton, P. Manning, C. J. McNeil, and M. A. Birch-Machin, “Direct, real-time monitoring of superoxide generation in isolated mitochondria,” Free Radic. Res. 43(9), 796–802 (2009).
[Crossref] [PubMed]

Boero, C.

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

Boozer, C.

C. Boozer, J. Ladd, S. Chen, Q. Yu, J. Homola, and S. Jiang, “DNA Directed Protein Immobilization on Mixed ssDNA/Oligo(ethylene glycol) Self-Assembled Monolayers for Sensitive Biosensors,” Anal. Chem. 76(23), 6967–6972 (2004).
[Crossref] [PubMed]

Borrisé, X.

G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
[Crossref] [PubMed]

Boulton, S.

J. R. Henderson, H. Swalwell, S. Boulton, P. Manning, C. J. McNeil, and M. A. Birch-Machin, “Direct, real-time monitoring of superoxide generation in isolated mitochondria,” Free Radic. Res. 43(9), 796–802 (2009).
[Crossref] [PubMed]

Brugger, J.

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

Butt, W. D.

W. D. Butt and D. Keilin, “Absorption spectra and some other properties of cytochrome c and of its compounds with ligands,” Proc. R. Soc. Lond. B Biol. Sci. 156(965), 429–458 (1962).
[Crossref] [PubMed]

Butz, T.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

Cadarso, V. J.

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

Calza, L.

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

Campbell, R. E.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Cannon, R. O.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Cao, Z.

H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
[Crossref] [PubMed]

Carrara, S.

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

Cavaliere-Jaricot, S.

U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).
[Crossref] [PubMed]

Cepaitis, Z.

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
[Crossref] [PubMed]

Chan, G.

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
[Crossref] [PubMed]

Chen, H.

H. Chen, R. Li, L. Lin, G. Guo, and J.-M. Lin, “Determination of L-ascorbic acid in human serum by chemiluminescence based on hydrogen peroxide-sodium hydrogen carbonate-CdSe/CdS quantum dots system,” Talanta 81(4-5), 1688–1696 (2010).
[Crossref] [PubMed]

Chen, Q.

G. Kenausis, Q. Chen, and A. Heller, “Electrochemical Glucose and Lactate Sensors Based on “Wired” Thermostable Soybean Peroxidase Operating Continuously and Stably at 37 ° C,” Anal. Chem. 69(6), 1054–1060 (1997).
[Crossref] [PubMed]

Chen, S.

C. Boozer, J. Ladd, S. Chen, Q. Yu, J. Homola, and S. Jiang, “DNA Directed Protein Immobilization on Mixed ssDNA/Oligo(ethylene glycol) Self-Assembled Monolayers for Sensitive Biosensors,” Anal. Chem. 76(23), 6967–6972 (2004).
[Crossref] [PubMed]

Chen, W.

W. Chen, L. Hong, A.-L. Liu, J.-Q. Liu, X.-H. Lin, and X.-H. Xia, “Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal cupric oxide nanoparticles as peroxidase mimic,” Talanta 99, 643–648 (2012).
[Crossref] [PubMed]

Cheng, G.

H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
[Crossref] [PubMed]

Colvin, V.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

Criqui, M.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Darley-Usmar, V.

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

Davies, K. J. A.

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

Davies, S. O.

M. R. Liebowitz, A. J. Fyer, J. M. Gorman, D. Dillon, I. L. Appleby, G. Levy, S. Anderson, M. Levitt, M. Palij, S. O. Davies, and et al.., “Lactate provocation of panic attacks. I. Clinical and behavioral findings,” Arch. Gen. Psychiatry 41(8), 764–770 (1984).
[Crossref] [PubMed]

De Micheli, G.

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

DeCristofaro, A.

E. A. McGlynn, S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr, “The Quality of Health Care Delivered to Adults in the United States,” N. Engl. J. Med. 348(26), 2635–2645 (2003).
[Crossref] [PubMed]

Del Vecchio, G.

C. Boero, S. Carrara, G. Del Vecchio, L. Calza, and G. De Micheli, “Highly Sensitive Carbon Nanotube-Based Sensing for Lactate and Glucose Monitoring in Cell Culture,” IEEE Trans. NanoBioscience, 10, 59–67 (2011).

Dennery, P. A.

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

Dillon, D.

M. R. Liebowitz, A. J. Fyer, J. M. Gorman, D. Dillon, I. L. Appleby, G. Levy, S. Anderson, M. Levitt, M. Palij, S. O. Davies, and et al.., “Lactate provocation of panic attacks. I. Clinical and behavioral findings,” Arch. Gen. Psychiatry 41(8), 764–770 (1984).
[Crossref] [PubMed]

Donaldson, K.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

Dostálek, J.

J. Homola, H. B. Lu, G. G. Nenninger, J. Dostálek, and S. S. Yee, “A novel multichannel surface plasmon resonance biosensor,” Sens. Actuators B Chem. 76(1-3), 403–410 (2001).
[Crossref]

Drew, E. A.

E. A. Drew, “Uptake and metabolism of exogenously supplied sugards by brown algae,” New Phytol. 68(1), 35–43 (1969).
[Crossref]

Dröge, W.

W. Dröge, “Free Radicals in the Physiological Control of Cell Function,” Physiol. Rev. 82(1), 47–95 (2002).
[PubMed]

Dutta-Gupta, S.

G. Suarez, C. Santschi, S. Dutta-Gupta, L. Juillerat-Jeanneret, and O. J. F. Martin, “Biophotonic tool for sensing the dynamics of H2O2 extracellular release in stressed cells,” Proc. SPIE 8229, 822908 (2012).

Entringer, S.

B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
[Crossref] [PubMed]

Eriksson, J. G.

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
[Crossref] [PubMed]

Fadl, Y. Y.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Feldstein, M. J.

C. A. Rowe, S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler, “An array immunosensor for simultaneous detection of clinical analytes,” Anal. Chem. 71(2), 433–439 (1999).
[Crossref] [PubMed]

Forman, H. J.

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

Fortmann, S. P.

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C. A. Rowe, S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler, “An array immunosensor for simultaneous detection of clinical analytes,” Anal. Chem. 71(2), 433–439 (1999).
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B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
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Lindström, J.

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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W. Chen, L. Hong, A.-L. Liu, J.-Q. Liu, X.-H. Lin, and X.-H. Xia, “Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal cupric oxide nanoparticles as peroxidase mimic,” Talanta 99, 643–648 (2012).
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W. Chen, L. Hong, A.-L. Liu, J.-Q. Liu, X.-H. Lin, and X.-H. Xia, “Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal cupric oxide nanoparticles as peroxidase mimic,” Talanta 99, 643–648 (2012).
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Louheranta, A.

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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S. Govindarajan, C. J. McNeil, J. P. Lowry, C. P. McMahon, and R. D. O’Neill, “Highly selective and stable microdisc biosensors for l-glutamate monitoring,” Sens. Actuators B Chem. 178, 606–614 (2013).
[Crossref]

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Y. Lin, F. Lu, Y. Tu, and Z. Ren, “Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles,” Nano Lett. 4(2), 191–195 (2004).
[Crossref]

Lu, H. B.

J. Homola, H. B. Lu, G. G. Nenninger, J. Dostálek, and S. S. Yee, “A novel multichannel surface plasmon resonance biosensor,” Sens. Actuators B Chem. 76(1-3), 403–410 (2001).
[Crossref]

Maerkl, S. J.

Malinauskas, A.

R. Garjonyte, Y. Yigzaw, R. Meskys, A. Malinauskas, and L. Gorton, “Prussian Blue- and lactate oxidase-based amperometric biosensor for lactic acid,” Sens. Actuators B Chem. 79(1), 33–38 (2001).
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B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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J. R. Henderson, D. A. Fulton, C. J. McNeil, and P. Manning, “The development and in vitro characterisation of an intracellular nanosensor responsive to reactive oxygen species,” Biosens. Bioelectron. 24(12), 3608–3614 (2009).
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J. R. Henderson, H. Swalwell, S. Boulton, P. Manning, C. J. McNeil, and M. A. Birch-Machin, “Direct, real-time monitoring of superoxide generation in isolated mitochondria,” Free Radic. Res. 43(9), 796–802 (2009).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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Martin, O. J. F.

V. B. Koman, C. Santschi, N. R. von Moos, V. I. Slaveykova, and O. J. F. Martin, “Portable oxidative stress sensor: dynamic and non-invasive measurements of extracellular H₂O₂ released by algae,” Biosens. Bioelectron. 68, 245–252 (2015).
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V. B. Koman, C. Santschi, and O. J. F. Martin, “Multiscattering-Enhanced Absorption Spectroscopy,” Anal. Chem. 87(3), 1536–1543 (2015).
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G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
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G. Suárez, C. Santschi, V. I. Slaveykova, and O. J. F. Martin, “Sensing the dynamics of oxidative stress using enhanced absorption in protein-loaded random media,” Sci. Rep. 3, 3447 (2013).
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V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

G. Suarez, C. Santschi, S. Dutta-Gupta, L. Juillerat-Jeanneret, and O. J. F. Martin, “Biophotonic tool for sensing the dynamics of H2O2 extracellular release in stressed cells,” Proc. SPIE 8229, 822908 (2012).

Marty, J.-L.

T. Sikora, G. Istamboulie, E. Jubete, E. Ochoteco, J.-L. Marty, and T. Noguer, “Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene),” J. Sens. 2011, 1–7 (2011).
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C. M. Masimirembwa, R. Thompson, and T. B. Andersson, “In Vitro High Throughput Screening of Compounds for Favorable Metabolic Properties in Drug Discovery,” Comb. Chem. High Throughput Screen. 4(3), 245–263 (2001).
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P. Xie, I. Fujii, J. Zhao, M. Shinohara, and M. Matsukura, “A Novel Polysaccharide Compound Derived from Algae Extracts Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage in Vitro,” Biol. Pharm. Bull. 35(9), 1447–1453 (2012).
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E. A. McGlynn, S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr, “The Quality of Health Care Delivered to Adults in the United States,” N. Engl. J. Med. 348(26), 2635–2645 (2003).
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S. Govindarajan, C. J. McNeil, J. P. Lowry, C. P. McMahon, and R. D. O’Neill, “Highly selective and stable microdisc biosensors for l-glutamate monitoring,” Sens. Actuators B Chem. 178, 606–614 (2013).
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S. Govindarajan, C. J. McNeil, J. P. Lowry, C. P. McMahon, and R. D. O’Neill, “Highly selective and stable microdisc biosensors for l-glutamate monitoring,” Sens. Actuators B Chem. 178, 606–614 (2013).
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G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
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J. R. Henderson, D. A. Fulton, C. J. McNeil, and P. Manning, “The development and in vitro characterisation of an intracellular nanosensor responsive to reactive oxygen species,” Biosens. Bioelectron. 24(12), 3608–3614 (2009).
[Crossref] [PubMed]

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G. Suárez, R. J. Jackson, J. A. Spoors, and C. J. McNeil, “Chemical Introduction of Disulfide Groups on Glycoproteins: A Direct Protein Anchoring Scenario,” Anal. Chem. 79(5), 1961–1969 (2007).
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T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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R. Garjonyte, Y. Yigzaw, R. Meskys, A. Malinauskas, and L. Gorton, “Prussian Blue- and lactate oxidase-based amperometric biosensor for lactic acid,” Sens. Actuators B Chem. 79(1), 33–38 (2001).
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L. Michaelis, M. L. Menten, K. A. Johnson, and R. S. Goody, “The original Michaelis Constant: Translation of the 1913 Michaelis-Menten Paper,” Biochemistry 50(39), 8264–8269 (2011).
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O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, and S. Sampath, “Sol−Gel Materials in Electrochemistry,” Chem. Mater. 9(11), 2354–2375 (1997).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
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T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).
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J. Homola, H. B. Lu, G. G. Nenninger, J. Dostálek, and S. S. Yee, “A novel multichannel surface plasmon resonance biosensor,” Sens. Actuators B Chem. 76(1-3), 403–410 (2001).
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U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).
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T. Sikora, G. Istamboulie, E. Jubete, E. Ochoteco, J.-L. Marty, and T. Noguer, “Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene),” J. Sens. 2011, 1–7 (2011).
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O’Neill, R. D.

S. Govindarajan, C. J. McNeil, J. P. Lowry, C. P. McMahon, and R. D. O’Neill, “Highly selective and stable microdisc biosensors for l-glutamate monitoring,” Sens. Actuators B Chem. 178, 606–614 (2013).
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Oberdörster, G.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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Ochoteco, E.

T. Sikora, G. Istamboulie, E. Jubete, E. Ochoteco, J.-L. Marty, and T. Noguer, “Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene),” J. Sens. 2011, 1–7 (2011).
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Ortiz, P.

G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
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B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
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T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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Pellerin, L.

B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
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Pelroy, R. A.

R. A. Pelroy, R. Rippka, and R. Y. Stanier, “Metabolism of glucose by unicellular blue-green algae,” Arch. Mikrobiol. 87(4), 303–322 (1972).
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Peters, A.

B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
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C. G. Pheeney, A. R. Arnold, M. A. Grodick, and J. K. Barton, “Multiplexed electrochemistry of DNA-bound metalloproteins,” J. Am. Chem. Soc. 135(32), 11869–11878 (2013).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
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K. Sirkar, A. Revzin, and M. V. Pishko, “Glucose and Lactate Biosensors Based on Redox Polymer/Oxidoreductase Nanocomposite Thin Films,” Anal. Chem. 72(13), 2930–2936 (2000).
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Plateel, G.

G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
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Putzbach, W.

W. Putzbach and N. J. Ronkainen, “Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review,” Sensors (Basel) 13(4), 4811–4840 (2013).
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O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, and S. Sampath, “Sol−Gel Materials in Electrochemistry,” Chem. Mater. 9(11), 2354–2375 (1997).
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W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
[Crossref] [PubMed]

Ren, Z.

Y. Lin, F. Lu, Y. Tu, and Z. Ren, “Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles,” Nano Lett. 4(2), 191–195 (2004).
[Crossref]

Resch-Genger, U.

U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).
[Crossref] [PubMed]

Revzin, A.

K. Sirkar, A. Revzin, and M. V. Pishko, “Glucose and Lactate Biosensors Based on Redox Polymer/Oxidoreductase Nanocomposite Thin Films,” Anal. Chem. 72(13), 2930–2936 (2000).
[Crossref] [PubMed]

Riediker, M.

G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
[Crossref] [PubMed]

Rifai, N.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
[Crossref] [PubMed]

Rippka, R.

R. A. Pelroy, R. Rippka, and R. Y. Stanier, “Metabolism of glucose by unicellular blue-green algae,” Arch. Mikrobiol. 87(4), 303–322 (1972).
[Crossref] [PubMed]

Roberts, L. J.

B. Kalyanaraman, V. Darley-Usmar, K. J. A. Davies, P. A. Dennery, H. J. Forman, M. B. Grisham, G. E. Mann, K. Moore, L. J. Roberts, and H. Ischiropoulos, “Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations,” Free Radic. Biol. Med. 52(1), 1–6 (2012).
[Crossref] [PubMed]

Ronkainen, N. J.

W. Putzbach and N. J. Ronkainen, “Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review,” Sensors (Basel) 13(4), 4811–4840 (2013).
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Ryan, J.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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Salminen, V.

J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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Sampath, S.

O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, and S. Sampath, “Sol−Gel Materials in Electrochemistry,” Chem. Mater. 9(11), 2354–2375 (1997).
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Santschi, C.

V. B. Koman, C. Santschi, N. R. von Moos, V. I. Slaveykova, and O. J. F. Martin, “Portable oxidative stress sensor: dynamic and non-invasive measurements of extracellular H₂O₂ released by algae,” Biosens. Bioelectron. 68, 245–252 (2015).
[Crossref] [PubMed]

V. B. Koman, C. Santschi, and O. J. F. Martin, “Multiscattering-Enhanced Absorption Spectroscopy,” Anal. Chem. 87(3), 1536–1543 (2015).
[Crossref] [PubMed]

G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
[Crossref] [PubMed]

G. Suárez, C. Santschi, V. I. Slaveykova, and O. J. F. Martin, “Sensing the dynamics of oxidative stress using enhanced absorption in protein-loaded random media,” Sci. Rep. 3, 3447 (2013).
[Crossref] [PubMed]

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

G. Suarez, C. Santschi, S. Dutta-Gupta, L. Juillerat-Jeanneret, and O. J. F. Martin, “Biophotonic tool for sensing the dynamics of H2O2 extracellular release in stressed cells,” Proc. SPIE 8229, 822908 (2012).

Scott, C. R.

S. A. Gerber, C. R. Scott, F. Turecek, and M. H. Gelb, “Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass Spectrometry,” J. Am. Chem. Soc. 121(5), 1102–1103 (1999).
[Crossref]

Scruggs, S. B.

C. A. Rowe, S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler, “An array immunosensor for simultaneous detection of clinical analytes,” Anal. Chem. 71(2), 433–439 (1999).
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Seaton, A.

A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
[Crossref] [PubMed]

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M.-C. Shin, H. C. Yoon, and H.-S. Kim, “In situ biochemical reduction of interference in an amperometric biosensor with a novel heterobilayer configuration of polypyrrole/glucose oxidase/horseradish peroxidase,” Anal. Chim. Acta 329(3), 223–230 (1996).
[Crossref]

Shinohara, M.

P. Xie, I. Fujii, J. Zhao, M. Shinohara, and M. Matsukura, “A Novel Polysaccharide Compound Derived from Algae Extracts Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage in Vitro,” Biol. Pharm. Bull. 35(9), 1447–1453 (2012).
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T. Sikora, G. Istamboulie, E. Jubete, E. Ochoteco, J.-L. Marty, and T. Noguer, “Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene),” J. Sens. 2011, 1–7 (2011).
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K. Sirkar, A. Revzin, and M. V. Pishko, “Glucose and Lactate Biosensors Based on Redox Polymer/Oxidoreductase Nanocomposite Thin Films,” Anal. Chem. 72(13), 2930–2936 (2000).
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Slaveykova, V. I.

V. B. Koman, C. Santschi, N. R. von Moos, V. I. Slaveykova, and O. J. F. Martin, “Portable oxidative stress sensor: dynamic and non-invasive measurements of extracellular H₂O₂ released by algae,” Biosens. Bioelectron. 68, 245–252 (2015).
[Crossref] [PubMed]

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

G. Suárez, C. Santschi, V. I. Slaveykova, and O. J. F. Martin, “Sensing the dynamics of oxidative stress using enhanced absorption in protein-loaded random media,” Sci. Rep. 3, 3447 (2013).
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T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
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G. Suárez, R. J. Jackson, J. A. Spoors, and C. J. McNeil, “Chemical Introduction of Disulfide Groups on Glycoproteins: A Direct Protein Anchoring Scenario,” Anal. Chem. 79(5), 1961–1969 (2007).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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G. Strom, “The Influence of Anoxia on Lactate Utilization in Man After Prolonged Muscular Work,” Acta Physiol. Scand. 17(4), 440–451 (1949).
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G. Suarez, C. Santschi, S. Dutta-Gupta, L. Juillerat-Jeanneret, and O. J. F. Martin, “Biophotonic tool for sensing the dynamics of H2O2 extracellular release in stressed cells,” Proc. SPIE 8229, 822908 (2012).

Suárez, G.

G. Suárez, C. Santschi, G. Plateel, O. J. F. Martin, and M. Riediker, “Absorbance enhancement in microplate wells for improved-sensitivity biosensors,” Biosens. Bioelectron. 56, 198–203 (2014).
[Crossref] [PubMed]

G. Suárez, C. Santschi, V. I. Slaveykova, and O. J. F. Martin, “Sensing the dynamics of oxidative stress using enhanced absorption in protein-loaded random media,” Sci. Rep. 3, 3447 (2013).
[Crossref] [PubMed]

V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

G. Suárez, N. Keegan, J. A. Spoors, P. Ortiz, R. J. Jackson, J. Hedley, X. Borrisé, and C. J. McNeil, “Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach,” Langmuir 26(8), 6071–6077 (2010).
[Crossref] [PubMed]

G. Suárez, R. J. Jackson, J. A. Spoors, and C. J. McNeil, “Chemical Introduction of Disulfide Groups on Glycoproteins: A Direct Protein Anchoring Scenario,” Anal. Chem. 79(5), 1961–1969 (2007).
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J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
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S. A. Gerber, C. R. Scott, F. Turecek, and M. H. Gelb, “Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass Spectrometry,” J. Am. Chem. Soc. 121(5), 1102–1103 (1999).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
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J. Tuomilehto, J. Lindström, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, A. Louheranta, M. Rastas, V. Salminen, M. Uusitupa, Z. Cepaitis, V. Moltchanov, M. Hakumäki, M. Mannelin, V. Martikkala, J. Sundvall, M. Uusitupa, and Finnish Diabetes Prevention Study Group, “Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle Among Subjects with Impaired Glucose Tolerance,” N. Engl. J. Med. 344(18), 1343–1350 (2001).
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Vinicor, F.

T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, N. Rifai, S. C. Smith, K. Taubert, R. P. Tracy, and F. Vinicor, “Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association,” Circulation 107(3), 499–511 (2003).
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V. Koman, G. Suárez, C. Santschi, V. J. Cadarso, J. Brugger, N. von Moos, V. I. Slaveykova, and O. J. F. Martin, “A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements,” Proc. SPIE 8572, 857218 (2013).

von Moos, N. R.

V. B. Koman, C. Santschi, N. R. von Moos, V. I. Slaveykova, and O. J. F. Martin, “Portable oxidative stress sensor: dynamic and non-invasive measurements of extracellular H₂O₂ released by algae,” Biosens. Bioelectron. 68, 245–252 (2015).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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Wang, J.

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
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A. D. Maynard, R. J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M. A. Philbert, J. Ryan, A. Seaton, V. Stone, S. S. Tinkle, L. Tran, N. J. Walker, and D. B. Warheit, “Safe handling of nanotechnology,” Nature 444(7117), 267–269 (2006).
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Xie, P.

P. Xie, I. Fujii, J. Zhao, M. Shinohara, and M. Matsukura, “A Novel Polysaccharide Compound Derived from Algae Extracts Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage in Vitro,” Biol. Pharm. Bull. 35(9), 1447–1453 (2012).
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Yang, Z.

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
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M.-C. Shin, H. C. Yoon, and H.-S. Kim, “In situ biochemical reduction of interference in an amperometric biosensor with a novel heterobilayer configuration of polypyrrole/glucose oxidase/horseradish peroxidase,” Anal. Chim. Acta 329(3), 223–230 (1996).
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C. Boozer, J. Ladd, S. Chen, Q. Yu, J. Homola, and S. Jiang, “DNA Directed Protein Immobilization on Mixed ssDNA/Oligo(ethylene glycol) Self-Assembled Monolayers for Sensitive Biosensors,” Anal. Chem. 76(23), 6967–6972 (2004).
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Zeiss, I.

B. Kubera, C. Hubold, S. Otte, A. S. Lindenberg, I. Zeiss, R. Krause, M. Steinkamp, J. Klement, S. Entringer, L. Pellerin, and A. Peters, “Rise in Plasma Lactate Concentrations with Psychosocial Stress: A Possible Sign of Cerebral Energy Demand,” Obesity Facts 5(3), 384–392 (2012).
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Zhang, J.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
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Zhang, Z.

H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
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Zhao, J.

P. Xie, I. Fujii, J. Zhao, M. Shinohara, and M. Matsukura, “A Novel Polysaccharide Compound Derived from Algae Extracts Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage in Vitro,” Biol. Pharm. Bull. 35(9), 1447–1453 (2012).
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V. B. Koman, C. Santschi, and O. J. F. Martin, “Multiscattering-Enhanced Absorption Spectroscopy,” Anal. Chem. 87(3), 1536–1543 (2015).
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[Crossref] [PubMed]

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H. Vaisocherová, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, “Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma,” Anal. Chem. 80(20), 7894–7901 (2008).
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[Crossref] [PubMed]

W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J. R. Windmiller, Z. Yang, J. Ramírez, G. Chan, and J. Wang, “Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration,” Anal. Chem. 85(14), 6553–6560 (2013).
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Figures (5)

Fig. 1
Fig. 1

(a) Solutions containing cyt c + enzyme mixtures in microliter well-plates are automatically spotted onto a porous membrane using a microarray robot. The resulting crosslinked spots have a diameter of approx. 600 µm and are spectrally analyzed in transmission. (b) Optical transmission of 20 pmol cyt c spots printed on glass (black) or on a porous membrane (red). The insets show schematic of light propagation (green arrow) through samples. The dashed line corresponds to the wavelength λ = 542 nm.

Fig. 2
Fig. 2

(a) Time evolution of the oxidation state coefficient φ(t) for a 20 pmol cyt c sensing spot exposed to water (Ref.), to a 440 µM glucose solution in water (Glucose), to a 500 U/ml GOx solution in water (GOx), or to a solution with 440 µM glucose and 500 U/ml GOx in water (Glucose + GOx). (b) Time evolution of the oxidation state coefficient φ(t) for a 20 pmol cyt c sensing spot exposed to water (Ref.), to a 24 µM lactate solution in water (Lactate), to a 2.5 U/ml LOx solution in water (LOx), or to a solution with 440 μM glucose and 2.5 U/ml LOx in water (Lactate + LOx). (c) Time evolution of the oxidation state coefficient φ(t) for a hybrid sensing spot containing 20 pmol cyt c and 0.01 U GOx exposed to water (Ref.) or to a 440 µM glucose solution in water (Glucose). (d) Time evolution of the oxidation state coefficient φ(t) for a hybrid sensing spot containing 20 pmol cyt c and 1.25 × 10−4 U LOx exposed to water (Ref.) or to a 24 μM lactate solution in water (Lactate). (e) Calibration curve: response of the hybrid sensing spot in (c) after 30 min. as a function of the glucose concentration, for two different concentrations of GOx in the sensing spot: 0.1 U and 0.01 U. (f) Calibration curve: response of the hybrid sensing spot in (d) after 30 min. as a function of the lactate concentration, for two different concentrations of LOx in the sensing spot: 1.25 × 10−4 U and 2.5 × 10−3 U. The error bars in (e) and (f) represent the standard deviation over 3 measurements.

Fig. 3
Fig. 3

Multiplexed measurements using different pairs of sensing spots in the O-ring measurement chamber (photo to the right of panel a, the distance between the spots is 1 mm and the scale bar is 0.5 mm): green: spot with 20 pmol cyt c; red: 20 pmol cyt c + 0.01 U GOx; blue: 20 pmol cyt c + 1.25 × 10−4 U LOx. Response after 30 min. of the three different pairs of sensing spots to (a) 800 nM H2O2, (b) 440 µM glucose and (c) 90 µM lactate. (d) Kinetics of the multiplexed oxidation state coefficient φ for a pair of spots (green and blue) exposed to 90 µM lactate. (e) Calibration curve: difference of the oxidation state coefficient after 30 min. Δφ for different amounts of GOx in hybrid spots containing 20 pmol cyt c + GOx, after exposure to 440 µM of glucose; the response of a spot containing only 20 pmol cyt c, 1 mm away from the hybrid spot is also shown (crosstalks). The error bars represent the standard deviation over 3 measurements.

Fig. 4
Fig. 4

(a) Schematic of the microfluidic chip consisting of a glass substrate, a bottom PDMS layer containing the sensing spots and a top PDMS layer with channels and cell chamber. (b) Comparison of crosstalks between two sensing spots, one with 20 pmol cyt c and another one with 20 pmol cyt c + 2.5 × 10−3 U LOx exposed to 850 µM lactate. The asterisks denote the experiment performed in the microfluidic chip with a 0.2 mm/sec flow; the other experiment is performed in the O-ring chamber. (c) Picture of a top layer with three microfluidic channels coming out of the cell chamber.

Fig. 5
Fig. 5

Glucose uptake (8 μM) and H2O2 release by C. reinhardtii (2 × 106 cells/ml). Multiplexed measurements in microfluidics using (a) a spot with 20 pmol cyt c and (b) a hybrid spot with 20 pmol cyt c + 0.01 U GOx. Calculated concentrations of (c) H2O2 and (d) glucose using Eqs. (2) and (3). The same symbols are used for all panels. Limit of detection (LOD) is 40 nM for cyt c spots (taken from [42]) and 1.1 μM for hybrid spots.

Tables (1)

Tables Icon

Table 1 Fitting coefficients for Eq. (3) of hybrid spots (only valid in the 0.1–1000 µM analyte range).

Equations (3)

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φ = A 550 / A 542 A 550 o x / A 542 * A 550 r e d / A 542 * A 550 o x / A 542 * ,
C H 2 O 2 = d φ d t k φ ,
C a = f 1 ( C H 2 O 2 ) = a C H 2 O 2 2 + b C H 2 O 2 + d .

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