Abstract

Mass transport of analyte to surface-immobilized affinity reagents is the fundamental bottleneck for sensitive detection in solid-support microarrays and biosensors. Analyte depletion in the volume adjacent to the sensor causes deviation from ideal association, significantly slows down reaction kinetics, and causes inhomogeneous binding across the sensor surface. In this paper we use high-resolution molecular interferometric imaging (MI2), a label-free optical interferometry technique for direct detection of molecular films, to study the inhomogeneous distribution of intra-spot binding across 100 micron-diameter protein spots. By measuring intra-spot binding inhomogeneity, reaction kinetics can be determined accurately when combined with a numerical three-dimensional finite element model. To ensure homogeneous binding across a spot, a critical flow rate is identified in terms of the association rate ka and the spot diameter. The binding inhomogeneity across a spot can be used to distinguish high-affinity low-concentration specific reactions from low-affinity high-concentration non-specific binding of background proteins.

© 2010 OSA

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    [PubMed]
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2010 (1)

P. R. Nair and M. A. Alam, “Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective,” J. Appl. Phys. 107(6), 064701 (2010).
[CrossRef] [PubMed]

2009 (2)

D. D. Nolte, “Invited Review Article: Review of centrifugal microfluidic and bio-optical disks,” Rev. Sci. Instrum. 80(10), 101101 (2009).
[CrossRef] [PubMed]

E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

2008 (5)

J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, “Biosensing with plasmonic nanosensors,” Nat. Mater. 7(6), 442–453 (2008).
[CrossRef] [PubMed]

N. Ramachandran, S. Srivastava, and J. LaBaer, “Applications of protein microarrays for biomarker discovery,” Proteom. Clin. Appl. 2(10–11), 1444–1459 (2008).
[CrossRef]

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[CrossRef] [PubMed]

X. F. Wang, M. Zhao, and D. D. Nolte, “Area-scaling of interferometric and fluorescent detection of protein on antibody microarrays,” Biosens. Bioelectron. 24(4), 981–993 (2008).
[CrossRef] [PubMed]

M. Zhao, X. F. Wang, and D. D. Nolte, “Molecular interferometric imaging,” Opt. Express 16(10), 7102–7118 (2008).
[CrossRef] [PubMed]

2007 (5)

X. F. Wang, M. Zhao, and D. D. Nolte, “Common-path interferometric detection of protein monolayer on the BioCD,” Appl. Opt. 46(32), 7836–7849 (2007).
[CrossRef] [PubMed]

M. Zhao, X. F. Wang, G. M. Lawrence, P. Espinoza, and D. D. Nolte, “Molecular interferometric imaging for biosensor applications,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1680–1690 (2007).
[CrossRef]

L. L. Lv and B. C. Liu, “High-throughput antibody microarrays for quantitative proteomic analysis,” Expert Rev. Proteomics 4(4), 505–513 (2007).
[CrossRef] [PubMed]

S. L. Seurynck-Servoss, A. M. White, C. L. Baird, K. D. Rodland, and R. C. Zangar, “Evaluation of surface chemistries for antibody microarrays,” Anal. Biochem. 371(1), 105–115 (2007).
[CrossRef] [PubMed]

G. Q. Hu, Y. L. Gao, and D. Q. Li, “Modeling micropatterned antigen-antibody binding kinetics in a microfluidic chip,” Biosens. Bioelectron. 22(7), 1403–1409 (2007).
[CrossRef] [PubMed]

2006 (9)

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

G. Shekhawat, S. H. Tark, and V. P. Dravid, “MOSFET-Embedded microcantilevers for measuring deflection in biomolecular sensors,” Science 311(5767), 1592–1595 (2006).
[CrossRef] [PubMed]

L. Rindorf, J. B. Jensen, M. Dufva, L. H. Pedersen, P. E. Høiby, and O. Bang, “Photonic crystal fiber long-period gratings for biochemical sensing,” Opt. Express 14(18), 8224–8231 (2006).
[CrossRef] [PubMed]

S. F. Kingsmore, “Multiplexed protein measurement: technologies and applications of protein and antibody arrays,” Nat. Rev. Drug Discov. 5(4), 310–321 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
[CrossRef] [PubMed]

M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
[CrossRef] [PubMed]

P. R. Nair and M. A. Alam, “Performance limits of nanobiosensors,” Appl. Phys. Lett. 88(23), 233120 (2006).
[CrossRef]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

2005 (4)

P. E. Sheehan and L. J. Whitman, “Detection limits for nanoscale biosensors,” Nano Lett. 5(4), 803–807 (2005).
[CrossRef] [PubMed]

G. Gauglitz, “Direct optical sensors: principles and selected applications,” Anal. Bioanal. Chem. 381(1), 141–155 (2005).
[CrossRef] [PubMed]

B. B. Haab, “Antibody arrays in cancer research,” Mol. Cell. Proteomics 4(4), 377–383 (2005).
[CrossRef] [PubMed]

P. Angenendt, “Progress in protein and antibody microarray technology,” Drug Discov. Today 10(7), 503–511 (2005).
[CrossRef] [PubMed]

2004 (1)

U. B. Nielsen and B. H. Geierstanger, “Multiplexed sandwich assays in microarray format,” J. Immunol. Methods 290(1-2), 107–120 (2004).
[CrossRef] [PubMed]

2003 (2)

W. Kusnezow and J. D. Hoheisel, “Solid supports for microarray immunoassays,” J. Mol. Recognit. 16(4), 165–176 (2003).
[CrossRef] [PubMed]

H. Zhu and M. Snyder, “Protein chip technology,” Curr. Opin. Chem. Biol. 7(1), 55–63 (2003).
[CrossRef] [PubMed]

2002 (2)

M. A. Cooper, “Optical biosensors in drug discovery,” Nat. Rev. Drug Discov. 1(7), 515–528 (2002).
[CrossRef] [PubMed]

G. MacBeath, “Protein microarrays and proteomics,” Nat. Genet. 32(Suppl), 526–532 (2002).
[CrossRef] [PubMed]

1999 (1)

K. P. S. Dancil, D. P. Greiner, and M. J. Sailor, “A porous silicon optical biosensor: Detection of reversible binding of IgG to a protein A-modified surface,” J. Am. Chem. Soc. 121(34), 7925–7930 (1999).
[CrossRef]

1998 (1)

R. P. Ekins, “Ligand assays: from electrophoresis to miniaturized microarrays,” Clin. Chem. 44(9), 2015–2030 (1998).
[PubMed]

1996 (2)

P. Schuck and A. P. Minton, “Analysis of mass transport-limited binding kinetics in evanescent wave biosensors,” Anal. Biochem. 240(2), 262–272 (1996).
[CrossRef] [PubMed]

P. Schuck, “Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport,” Biophys. J. 70(3), 1230–1249 (1996).
[CrossRef] [PubMed]

1995 (1)

A. Brecht and G. Gauglitz, “Optical probes and transducers,” Biosens. Bioelectron. 10(9-10), 923–936 (1995).
[CrossRef] [PubMed]

1988 (2)

M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

T. Jøssang, J. Feder, and E. Rosenqvist, “Photon correlation spectroscopy of human IgG,” J. Protein Chem. 7(2), 165–171 (1988).
[CrossRef] [PubMed]

Alam, M. A.

P. R. Nair and M. A. Alam, “Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective,” J. Appl. Phys. 107(6), 064701 (2010).
[CrossRef] [PubMed]

P. R. Nair and M. A. Alam, “Performance limits of nanobiosensors,” Appl. Phys. Lett. 88(23), 233120 (2006).
[CrossRef]

Aldridge, J. C.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Angenendt, P.

P. Angenendt, “Progress in protein and antibody microarray technology,” Drug Discov. Today 10(7), 503–511 (2005).
[CrossRef] [PubMed]

Anker, J. N.

J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, “Biosensing with plasmonic nanosensors,” Nat. Mater. 7(6), 442–453 (2008).
[CrossRef] [PubMed]

Anthes-Washburn, M. S.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Baird, C. L.

S. L. Seurynck-Servoss, A. M. White, C. L. Baird, K. D. Rodland, and R. C. Zangar, “Evaluation of surface chemistries for antibody microarrays,” Anal. Biochem. 371(1), 105–115 (2007).
[CrossRef] [PubMed]

Bang, O.

Baudenstiel, N.

W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

Bergstein, D. A.

E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

Brecht, A.

A. Brecht and G. Gauglitz, “Optical probes and transducers,” Biosens. Bioelectron. 10(9-10), 923–936 (1995).
[CrossRef] [PubMed]

Chbouki, N.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Chiari, M.

E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

Cho, W. R.

M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
[CrossRef] [PubMed]

Cooper, M. A.

M. A. Cooper, “Optical biosensors in drug discovery,” Nat. Rev. Drug Discov. 1(7), 515–528 (2002).
[CrossRef] [PubMed]

Cretich, M.

E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

Dancil, K. P. S.

K. P. S. Dancil, D. P. Greiner, and M. J. Sailor, “A porous silicon optical biosensor: Detection of reversible binding of IgG to a protein A-modified surface,” J. Am. Chem. Soc. 121(34), 7925–7930 (1999).
[CrossRef]

Desai, T. A.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Dravid, V. P.

G. Shekhawat, S. H. Tark, and V. P. Dravid, “MOSFET-Embedded microcantilevers for measuring deflection in biomolecular sensors,” Science 311(5767), 1592–1595 (2006).
[CrossRef] [PubMed]

Dufva, M.

Ekins, R. P.

R. P. Ekins, “Ligand assays: from electrophoresis to miniaturized microarrays,” Clin. Chem. 44(9), 2015–2030 (1998).
[PubMed]

Eliasson, M.

M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

Espinoza, P.

M. Zhao, X. F. Wang, G. M. Lawrence, P. Espinoza, and D. D. Nolte, “Molecular interferometric imaging for biosensor applications,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1680–1690 (2007).
[CrossRef]

Fan, X. D.

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[CrossRef] [PubMed]

Feder, J.

T. Jøssang, J. Feder, and E. Rosenqvist, “Photon correlation spectroscopy of human IgG,” J. Protein Chem. 7(2), 165–171 (1988).
[CrossRef] [PubMed]

Gao, Y. L.

G. Q. Hu, Y. L. Gao, and D. Q. Li, “Modeling micropatterned antigen-antibody binding kinetics in a microfluidic chip,” Biosens. Bioelectron. 22(7), 1403–1409 (2007).
[CrossRef] [PubMed]

Gauer, C.

W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

Gauglitz, G.

G. Gauglitz, “Direct optical sensors: principles and selected applications,” Anal. Bioanal. Chem. 381(1), 141–155 (2005).
[CrossRef] [PubMed]

A. Brecht and G. Gauglitz, “Optical probes and transducers,” Biosens. Bioelectron. 10(9-10), 923–936 (1995).
[CrossRef] [PubMed]

Geierstanger, B. H.

U. B. Nielsen and B. H. Geierstanger, “Multiplexed sandwich assays in microarray format,” J. Immunol. Methods 290(1-2), 107–120 (2004).
[CrossRef] [PubMed]

Gill, M.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
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E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
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A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
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W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
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K. P. S. Dancil, D. P. Greiner, and M. J. Sailor, “A porous silicon optical biosensor: Detection of reversible binding of IgG to a protein A-modified surface,” J. Am. Chem. Soc. 121(34), 7925–7930 (1999).
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M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
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W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
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Hryniewicz, J.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
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G. Q. Hu, Y. L. Gao, and D. Q. Li, “Modeling micropatterned antigen-antibody binding kinetics in a microfluidic chip,” Biosens. Bioelectron. 22(7), 1403–1409 (2007).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
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W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
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W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
[CrossRef] [PubMed]

W. Kusnezow and J. D. Hoheisel, “Solid supports for microarray immunoassays,” J. Mol. Recognit. 16(4), 165–176 (2003).
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N. Ramachandran, S. Srivastava, and J. LaBaer, “Applications of protein microarrays for biomarker discovery,” Proteom. Clin. Appl. 2(10–11), 1444–1459 (2008).
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Lawrence, G. M.

M. Zhao, X. F. Wang, G. M. Lawrence, P. Espinoza, and D. D. Nolte, “Molecular interferometric imaging for biosensor applications,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1680–1690 (2007).
[CrossRef]

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G. Q. Hu, Y. L. Gao, and D. Q. Li, “Modeling micropatterned antigen-antibody binding kinetics in a microfluidic chip,” Biosens. Bioelectron. 22(7), 1403–1409 (2007).
[CrossRef] [PubMed]

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M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
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A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
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L. L. Lv and B. C. Liu, “High-throughput antibody microarrays for quantitative proteomic analysis,” Expert Rev. Proteomics 4(4), 505–513 (2007).
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E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
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L. L. Lv and B. C. Liu, “High-throughput antibody microarrays for quantitative proteomic analysis,” Expert Rev. Proteomics 4(4), 505–513 (2007).
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J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, “Biosensing with plasmonic nanosensors,” Nat. Mater. 7(6), 442–453 (2008).
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P. Schuck and A. P. Minton, “Analysis of mass transport-limited binding kinetics in evanescent wave biosensors,” Anal. Biochem. 240(2), 262–272 (1996).
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P. R. Nair and M. A. Alam, “Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective,” J. Appl. Phys. 107(6), 064701 (2010).
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X. F. Wang, M. Zhao, and D. D. Nolte, “Area-scaling of interferometric and fluorescent detection of protein on antibody microarrays,” Biosens. Bioelectron. 24(4), 981–993 (2008).
[CrossRef] [PubMed]

M. Zhao, X. F. Wang, and D. D. Nolte, “Molecular interferometric imaging,” Opt. Express 16(10), 7102–7118 (2008).
[CrossRef] [PubMed]

X. F. Wang, M. Zhao, and D. D. Nolte, “Common-path interferometric detection of protein monolayer on the BioCD,” Appl. Opt. 46(32), 7836–7849 (2007).
[CrossRef] [PubMed]

M. Zhao, X. F. Wang, G. M. Lawrence, P. Espinoza, and D. D. Nolte, “Molecular interferometric imaging for biosensor applications,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1680–1690 (2007).
[CrossRef]

M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
[CrossRef] [PubMed]

Oliver King, V.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

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M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

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E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

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M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

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M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
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Popat, K. C.

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
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N. Ramachandran, S. Srivastava, and J. LaBaer, “Applications of protein microarrays for biomarker discovery,” Proteom. Clin. Appl. 2(10–11), 1444–1459 (2008).
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M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
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Rodland, K. D.

S. L. Seurynck-Servoss, A. M. White, C. L. Baird, K. D. Rodland, and R. C. Zangar, “Evaluation of surface chemistries for antibody microarrays,” Anal. Biochem. 371(1), 105–115 (2007).
[CrossRef] [PubMed]

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T. Jøssang, J. Feder, and E. Rosenqvist, “Photon correlation spectroscopy of human IgG,” J. Protein Chem. 7(2), 165–171 (1988).
[CrossRef] [PubMed]

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W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
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A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

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K. P. S. Dancil, D. P. Greiner, and M. J. Sailor, “A porous silicon optical biosensor: Detection of reversible binding of IgG to a protein A-modified surface,” J. Am. Chem. Soc. 121(34), 7925–7930 (1999).
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P. Schuck and A. P. Minton, “Analysis of mass transport-limited binding kinetics in evanescent wave biosensors,” Anal. Biochem. 240(2), 262–272 (1996).
[CrossRef] [PubMed]

Sebald, W.

W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
[CrossRef] [PubMed]

Seurynck-Servoss, S. L.

S. L. Seurynck-Servoss, A. M. White, C. L. Baird, K. D. Rodland, and R. C. Zangar, “Evaluation of surface chemistries for antibody microarrays,” Anal. Biochem. 371(1), 105–115 (2007).
[CrossRef] [PubMed]

Shah, N. C.

J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, “Biosensing with plasmonic nanosensors,” Nat. Mater. 7(6), 442–453 (2008).
[CrossRef] [PubMed]

Sheehan, P. E.

P. E. Sheehan and L. J. Whitman, “Detection limits for nanoscale biosensors,” Nano Lett. 5(4), 803–807 (2005).
[CrossRef] [PubMed]

Shekhawat, G.

G. Shekhawat, S. H. Tark, and V. P. Dravid, “MOSFET-Embedded microcantilevers for measuring deflection in biomolecular sensors,” Science 311(5767), 1592–1595 (2006).
[CrossRef] [PubMed]

Shopova, S. I.

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
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H. Zhu and M. Snyder, “Protein chip technology,” Curr. Opin. Chem. Biol. 7(1), 55–63 (2003).
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Srivastava, S.

N. Ramachandran, S. Srivastava, and J. LaBaer, “Applications of protein microarrays for biomarker discovery,” Proteom. Clin. Appl. 2(10–11), 1444–1459 (2008).
[CrossRef]

Sun, Y. Z.

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[CrossRef] [PubMed]

Suter, J. D.

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[CrossRef] [PubMed]

Syagailo, Y. V.

W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

W. Kusnezow, Y. V. Syagailo, S. Rüffer, K. Klenin, W. Sebald, J. D. Hoheisel, C. Gauer, and I. Goychuk, “Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface,” Proteomics 6(3), 794–803 (2006).
[CrossRef] [PubMed]

Tark, S. H.

G. Shekhawat, S. H. Tark, and V. P. Dravid, “MOSFET-Embedded microcantilevers for measuring deflection in biomolecular sensors,” Science 311(5767), 1592–1595 (2006).
[CrossRef] [PubMed]

Uhlén, M.

M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

Unlu,

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Unlü, M. S.

E. Özkumur, A. Yalçin, M. Cretich, C. A. Lopez, D. A. Bergstein, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Quantification of DNA and protein adsorption by optical phase shift,” Biosens. Bioelectron. 25(1), 167–172 (2009).
[CrossRef] [PubMed]

Van,

A. Yalcin, K. C. Popat, J. C. Aldridge, T. A. Desai, J. Hryniewicz, N. Chbouki, B. E. Little, V. Oliver King, Van, D. Sai Chu, M. Gill, M. S. Anthes-Washburn, Unlu, and B. B. Goldberg, “Optical sensing of biomolecules using microring resonators,” IEEE J. Sel. Top. Quantum Electron. 12(1), 148–155 (2006).
[CrossRef]

Van Duyne, R. P.

J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, “Biosensing with plasmonic nanosensors,” Nat. Mater. 7(6), 442–453 (2008).
[CrossRef] [PubMed]

Varma, M.

M. Zhao, D. D. Nolte, W. R. Cho, F. Regnier, M. Varma, G. Lawrence, and J. Pasqua, “High-speed interferometric detection of label-free immunoassays on the biological compact disc,” Clin. Chem. 52(11), 2135–2140 (2006).
[CrossRef] [PubMed]

Wang, X. F.

M. Zhao, X. F. Wang, and D. D. Nolte, “Molecular interferometric imaging,” Opt. Express 16(10), 7102–7118 (2008).
[CrossRef] [PubMed]

X. F. Wang, M. Zhao, and D. D. Nolte, “Area-scaling of interferometric and fluorescent detection of protein on antibody microarrays,” Biosens. Bioelectron. 24(4), 981–993 (2008).
[CrossRef] [PubMed]

M. Zhao, X. F. Wang, G. M. Lawrence, P. Espinoza, and D. D. Nolte, “Molecular interferometric imaging for biosensor applications,” IEEE J. Sel. Top. Quantum Electron. 13(6), 1680–1690 (2007).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, “Common-path interferometric detection of protein monolayer on the BioCD,” Appl. Opt. 46(32), 7836–7849 (2007).
[CrossRef] [PubMed]

White, A. M.

S. L. Seurynck-Servoss, A. M. White, C. L. Baird, K. D. Rodland, and R. C. Zangar, “Evaluation of surface chemistries for antibody microarrays,” Anal. Biochem. 371(1), 105–115 (2007).
[CrossRef] [PubMed]

White, I. M.

X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[CrossRef] [PubMed]

Whitman, L. J.

P. E. Sheehan and L. J. Whitman, “Detection limits for nanoscale biosensors,” Nano Lett. 5(4), 803–807 (2005).
[CrossRef] [PubMed]

Wiberg, K.

M. Eliasson, A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganäs, B. Guss, M. Lindberg, and M. Uhlén, “Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G,” J. Biol. Chem. 263(9), 4323–4327 (1988).
[PubMed]

Wild, D.

W. Kusnezow, Y. V. Syagailo, S. Rüffer, N. Baudenstiel, C. Gauer, J. D. Hoheisel, D. Wild, and I. Goychuk, “Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment,” Mol. Cell. Proteomics 5(9), 1681–1696 (2006).
[CrossRef] [PubMed]

Wild, D. G.

W. Kusnezow, Y. V. Syagailo, I. Goychuk, J. D. Hoheisel, and D. G. Wild, “Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity,” Expert Rev. Mol. Diagn. 6(1), 111–124 (2006).
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Supplementary Material (2)

» Media 1: AVI (8913 KB)     
» Media 2: AVI (8391 KB)     

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Figures (9)

Fig. 1
Fig. 1

(Media 1) Movie of 200 ng/mL rabbit IgG binding against protein A/G under different flow rates of: top-left 5 μm/sec; top-right 10 μm/sec; bottom-left 20 μm/sec; bottom-right 50 μm/sec. Pronounced edge binding due to mass transport is observed at low flow velocities. The flow direction is from the upper right to lower left.

Fig. 2
Fig. 2

Height increase of the protein spots at different flow rates (a) averaged over the full spot, large deviations occur at low flow rates; (b) from only the leading edges of the protein spots.

Fig. 3
Fig. 3

Association rate ka from fits to ideal association for the full-spot average compared with signals taken only from the leading edge of the spots.

Fig. 4
Fig. 4

Binding inhomogeneity in (a) 1 μg/mL streptavidin binding to immobilized biotinylated anti-rabbit IgG, (b) 1 μg/mL rabbit IgG binding to immobilized protein A/G, and (c) 200 μg/mL BSA binding non-specifically to protein A/G. The flow velocity for all experiments was 50 μm/sec. The mass-transport effect is more obvious in larger ka reactions because of faster analyte depletion.

Fig. 5
Fig. 5

Comparison of experimental and numerical simulation results. (a) (Media 2) A movie comparing experimental data and simulation of rabbit IgG binding against protein A/G. (b) Cross sections of the experimental and numerical data after 2 hour incubation.

Fig. 6
Fig. 6

(a) The normalized protein binding height at different concentrations across a spot. Except at the highest concentration, the others have similar normalized concentration profile. (b) Effect of active flow on the inhomogeneous binding profile of a protein spot after 1000 seconds incubation.

Fig. 7
Fig. 7

Binding kinetics at different flow rates for 5 μg/mL. (a) The average response over a protein spot as a function of time (dashed curves) and at the leading edge of a protein spot as a function of time (solid curves). (b) Effective ka for the average responses and the leading edge responses. The leading edge shows less deviation from ideal association, but is still strongly skewed from the ideal value at low flow rates.

Fig. 8
Fig. 8

Average protein height of protein spots with different sizes after 1000 second incubation at different flow rates for (a) electrokinetically driven flow and (b) pressure driven flow.

Fig. 9
Fig. 9

(a) Binding profile within a protein spot and (b) binding kinetics at different kinetic association rates for ka [C] = 0.005 sec−1. High association rate leads to larger inhomogeneity which can be easily distinguished from low association rate non-specific binding.

Equations (19)

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Δ I I = C ( λ , d ) ( g 2 ( x , y ) h ( x , y ) )
C ( λ , d ) = 8 π n p λ Im ( ( r p r ) ( 1 r r p ) 1 r p 2 )
D i j ( t ) = 2 I i j ( t ) I i j ( 0 ) I i j ( t ) + I i j ( 0 ) = C ( λ , d ) ( h i j ( t ) h i j ( 0 ) )
d H d t = k a C ( H max H ) k d H
H ( t ) = k a C k a C + k d H max [ 1 exp ( ( k d + k a C ) t ) ]
C t = v C + D 2 C
D C z = ρ d H d t
Δ C Δ t = v C + D 2 C R Δ H Δ t
R = Δ C Δ H = ρ Δ l = ρ D
v ( z ) = 6 v m ( z / h ) ( 1 z / h )
C t = v C + D 2 C R ( k a C ( H max H ) k d H )
C t = D 2 C R k a C H max
D d 2 C d x 2 R k a C H max = 0
D C w D 2 R k a C H max = 0
w D = D R k a H max
v d C d x + D d 2 C d x 2 R k a C H max = 0
v C w F + D C w D 2 R k a C H max = 0
w F v / R k a H max
v c r i t w F R k a H max

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