Abstract

The refractive index (RI) is a fundamental parameter of materials that can be used to distinguish and sort materials of different nature. Although the RI of a virus is required for many optics-based biosensing applications, RIs of animal viruses have never been measured. Here we have developed a technique that can measure the RI of individual viruses in aqueous media with high precision. This technique is based on optical trapping of single virions and works by relating the size and RI of a single virus to the stiffness of an optical trap. We have derived an analytic expression to quantitatively describe the optical trapping of these particles. We have validated this equation using nanoparticles of known RI, and measured the RI of individual human immunodeficiency viruses type-1, which yielded a value of 1.42 at 830 nm with less than 2% coefficient of variation. This value is much lower than the RI typically assumed for viruses, but very close to that of 2.0 M sucrose solution in water. To the best of our knowledge, this is the first report on the experimental measurement of the RI for a single animal virus in aqueous media. This technique does not require prior knowledge on the diameter of the nanoparticles, and can be applied to other viruses or nanoparticles for accurate measurement of RI that is critical for the label-free detection of these particles in various settings.

© 2016 Optical Society of America

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References

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2015 (1)

P. Kang, P. Schein, X. Serey, D. O’Dell, and D. Erickson, “Nanophotonic detection of freely interacting molecules on a single influenza virus,” Sci. Rep. 5, 12087 (2015).
[Crossref] [PubMed]

2014 (3)

S. Liu, Y. Zhao, J. W. Parks, D. W. Deamer, A. R. Hawkins, and H. Schmidt, “Correlated Electrical and Optical Analysis of Single Nanoparticles and Biomolecules on a Nanopore-Gated Optofluidic Chip,” Nano Lett. 14(8), 4816–4820 (2014).
[Crossref] [PubMed]

E. van der Pol, F. A. W. Coumans, A. Sturk, R. Nieuwland, and T. G. van Leeuwen, “Refractive Index Determination of Nanoparticles in Suspension Using Nanoparticle Tracking Analysis,” Nano Lett. 14(11), 6195–6201 (2014).
[Crossref] [PubMed]

Y. Pang, H. Song, J. H. Kim, X. Hou, and W. Cheng, “Optical trapping of individual human immunodeficiency viruses in culture fluid reveals heterogeneity with single-molecule resolution,” Nat. Nanotechnol. 9(8), 624–630 (2014).
[Crossref] [PubMed]

2013 (3)

Y. Zhang, H. X. Lei, and B. J. Li, “Refractive-Index-Based Sorting of Colloidal Particles Using a Subwavelength Optical Fiber in a Static Fluid,” Appl. Phys. Express 6(7), 072001 (2013).
[Crossref]

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

2012 (3)

O. Block, A. Mitra, L. Novotny, and C. Dykes, “A rapid label-free method for quantitation of human immunodeficiency virus type-1 particles by nanospectroscopy,” J. Virol. Methods 182(1-2), 70–75 (2012).
[Crossref] [PubMed]

F. Shen, J. Wang, Z. Xu, Y. Wu, Q. Chen, X. Li, X. Jie, L. Li, M. Yao, X. Guo, and T. Zhu, “Rapid Flu Diagnosis Using Silicon Nanowire Sensor,” Nano Lett. 12(7), 3722–3730 (2012).
[Crossref] [PubMed]

S. Kedenburg, M. Vieweg, T. Gissibl, and H. Giessen, “Linear refractive index and absorption measurements of nonlinear optical liquids in the visible and near-infrared spectral region,” Opt. Mater. Express 2(11), 1588–1611 (2012).
[Crossref]

2011 (4)

W. Cheng, S. G. Arunajadai, J. R. Moffitt, I. Tinoco, and C. Bustamante, “Single-Base Pair Unwinding and Asynchronous RNA Release by the Hepatitis C Virus NS3 Helicase,” Science 333(6050), 1746–1749 (2011).
[Crossref] [PubMed]

J. A. Arter, D. K. Taggart, J. E. Diaz, R. M. Penner, and G. A. Weiss, “Virus-PEDOT nanowires for biosensing,” Abstracts of Papers of the American Chemical Society 241, 1 (2011).

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

P. M. Bendix and L. B. Oddershede, “Expanding the Optical Trapping Range of Lipid Vesicles to the Nanoscale,” Nano Lett. 11(12), 5431–5437 (2011).
[Crossref] [PubMed]

2010 (5)

W. Cheng, X. Hou, and F. Ye, “Use of tapered amplifier diode laser for biological-friendly high-resolution optical trapping,” Opt. Lett. 35(17), 2988–2990 (2010).
[Crossref] [PubMed]

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic Detection of Single Viruses and Nanoparticles,” ACS Nano 4(3), 1305–1312 (2010).
[Crossref] [PubMed]

A. A. Yanik, M. Huang, O. Kamohara, A. Artar, T. W. Geisbert, J. H. Connor, and H. Altug, “An Optofluidic Nanoplasmonic Biosensor for Direct Detection of Live Viruses from Biological Media,” Nano Lett. 10(12), 4962–4969 (2010).
[Crossref] [PubMed]

S. Wang, X. Shan, U. Patel, X. Huang, J. Lu, J. Li, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107(37), 16028–16032 (2010).
[Crossref] [PubMed]

G. G. Daaboul, A. Yurt, X. Zhang, G. M. Hwang, B. B. Goldberg, and M. S. Ünlü, “High-Throughput Detection and Sizing of Individual Low-Index Nanoparticles and Viruses for Pathogen Identification,” Nano Lett. 10(11), 4727–4731 (2010).
[Crossref] [PubMed]

2009 (2)

J. J. Xiao, J. Ng, Z. F. Lin, and C. T. Chan, “Whispering gallery mode enhanced optical force with resonant tunneling excitation in the Kretschmann geometry,” Appl. Phys. Lett. 94(1), 011102 (2009).
[Crossref]

N. Sultanova, S. Kasarova, and I. Nikolov, “Dispersion Properties of Optical Polymers,” Acta Phys. Pol. A 116(4), 585–587 (2009).
[Crossref]

2008 (6)

A. B. Stilgoe, T. A. Nieminen, G. Knöener, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “The effect of Mie resonances on trapping in optical tweezers,” Opt. Express 16(19), 15039–15051 (2008).
[Crossref] [PubMed]

L. A. Carlson, J. A. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

L. A. Carlson, J. A. G. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-Dimensional Analysis of Budding Sites and Released Virus Suggests a Revised Model For HIV-1 Morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

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

H. Zhu, I. M. White, J. D. Suter, M. Zourob, and X. Fan, “Opto-fluidic micro-ring resonator for sensitive label-free viral detection,” Analyst (Lond.) 133(3), 356–360 (2008).
[Crossref] [PubMed]

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105(52), 20701–20704 (2008).
[Crossref] [PubMed]

2007 (4)

H. Ewers, V. Jacobsen, E. Klotzsch, A. E. Smith, A. Helenius, and V. Sandoghdar, “Label-free optical detection and tracking of single virions bound to their receptors in supported membrane bilayers,” Nano Lett. 7(8), 2263–2266 (2007).
[Crossref] [PubMed]

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, and J. S. Kanger, “Fast, ultrasensitive virus detection using a young interferometer sensor,” Nano Lett. 7(2), 394–397 (2007).
[Crossref] [PubMed]

J. Xu, D. Suarez, and D. S. Gottfried, “Detection of avian influenza virus using an interferometric biosensor,” Anal. Bioanal. Chem. 389(4), 1193–1199 (2007).
[Crossref] [PubMed]

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knoner, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A, Pure Appl. Opt. 9(8), S196–S203 (2007).
[Crossref]

2006 (5)

P. Stoller, V. Jacobsen, and V. Sandoghdar, “Measurement of the complex dielectric constant of a single gold nanoparticle,” Opt. Lett. 31(16), 2474–2476 (2006).
[Crossref] [PubMed]

P. Zhu, J. Liu, J. Bess, E. Chertova, J. D. Lifson, H. Grisé, G. A. Ofek, K. A. Taylor, and K. H. Roux, “Distribution and three-dimensional structure of AIDS virus envelope spikes,” Nature 441(7095), 847–852 (2006).
[Crossref] [PubMed]

S. F. Tolic-Norrelykke, E. Schaffer, J. Howard, F. S. Pavone, F. Julicher, and H. Flyvbjerg, “Calibration of optical tweezers with positional detection in the back focal plane,” Rev. Sci. Instrum. 77(10), 103101 (2006).
[Crossref]

G. Knöner, S. Parkin, T. A. Nieminen, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Measurement of the index of refraction of single microparticles,” Phys. Rev. Lett. 97(15), 157402 (2006).
[Crossref] [PubMed]

S. Shanmukh, L. Jones, J. Driskell, Y. Zhao, R. Dluhy, and R. A. Tripp, “Rapid and sensitive detection of respiratory virus molecular signatures using a silver nanorod array SERS substrate,” Nano Lett. 6(11), 2630–2636 (2006).
[Crossref] [PubMed]

2005 (1)

A. Ymeti, J. S. Kanger, J. Greve, G. A. J. Besselink, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Integration of microfluidics with a four-channel integrated optical Young interferometer immunosensor,” Biosens. Bioelectron. 20(7), 1417–1421 (2005).
[Crossref] [PubMed]

2003 (4)

A. Ymeti, J. S. Kanger, J. Greve, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Realization of a multichannel integrated Young interferometer chemical sensor,” Appl. Opt. 42(28), 5649–5660 (2003).
[Crossref] [PubMed]

M. P. MacDonald, G. C. Spalding, and K. Dholakia, “Microfluidic sorting in an optical lattice,” Nature 426(6965), 421–424 (2003).
[Crossref] [PubMed]

J. A. G. Briggs, T. Wilk, R. Welker, H. G. Kräusslich, and S. D. Fuller, “Structural organization of authentic, mature HIV-1 virions and cores,” EMBO J. 22(7), 1707–1715 (2003).
[Crossref] [PubMed]

C. M. Trubey, E. Chertova, L. V. Coren, J. M. Hilburn, C. V. Hixson, K. Nagashima, J. D. Lifson, and D. E. Ott, “Quantitation of HLA class II protein incorporated into human immunodeficiency type 1 virions purified by anti-CD45 immunoaffinity depletion of microvesicles,” J. Virol. 77(23), 12699–12709 (2003).
[Crossref] [PubMed]

2002 (1)

D. McDonald, M. A. Vodicka, G. Lucero, T. M. Svitkina, G. G. Borisy, M. Emerman, and T. J. Hope, “Visualization of the intracellular behavior of HIV in living cells,” J. Cell Biol. 159(3), 441–452 (2002).
[Crossref] [PubMed]

2000 (2)

W. M. Balch, J. Vaughn, J. Navotny, D. T. Drapeau, R. Vaillancourt, J. Lapierre, and A. Ashe, “Light scattering by viral suspensions,” Limnol. Oceanogr. 45(2), 492–498 (2000).
[Crossref]

B. M. McDermott, A. H. Rux, R. J. Eisenberg, G. H. Cohen, and V. R. Racaniello, “Two distinct binding affinities of poliovirus for its cellular receptor,” J. Biol. Chem. 275(30), 23089–23096 (2000).
[Crossref] [PubMed]

1998 (2)

T. Tlusty, A. Meller, and R. Bar-Ziv, “Optical gradient forces of strongly localized fields,” Phys. Rev. Lett. 81(8), 1738–1741 (1998).
[Crossref]

F. Gittes and C. F. Schmidt, “Interference model for back-focal-plane displacement detection in optical tweezers,” Opt. Lett. 23(1), 7–9 (1998).
[Crossref] [PubMed]

1997 (3)

J. W. Bess, R. J. Gorelick, W. J. Bosche, L. E. Henderson, and L. O. Arthur, “Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations,” Virology 230(1), 134–144 (1997).
[Crossref] [PubMed]

P. Gluschankof, I. Mondor, H. R. Gelderblom, and Q. J. Sattentau, “Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations,” Virology 230(1), 125–133 (1997).
[Crossref] [PubMed]

J. Rheims, J. Koser, and T. Wriedt, “Refractive-index measurements in the near-IR using an Abbe refractometer,” Meas. Sci. Technol. 8(6), 601–605 (1997).
[Crossref]

1996 (3)

Y. Harada and T. Asakura, “Radiation forces on a dielectric sphere in the Rayleigh scattering regime,” Opt. Commun. 124(5-6), 529–541 (1996).
[Crossref]

H. Li and S. Xie, “Measurement method of the refractive index of biotissue by total internal reflection,” Appl. Opt. 35(10), 1793–1795 (1996).
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J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41(3), 369–382 (1996).
[Crossref] [PubMed]

1992 (1)

A. Ashkin, “Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime,” Biophys. J. 61(2), 569–582 (1992).
[Crossref] [PubMed]

1991 (1)

1989 (1)

1986 (1)

1983 (1)

1945 (1)

M. C. Wang and G. E. Uhlenbeck, “On the Theory of the Brownian Motion-Ii,” Rev. Mod. Phys. 17(2-3), 323–342 (1945).
[Crossref]

Altug, H.

A. A. Yanik, M. Huang, O. Kamohara, A. Artar, T. W. Geisbert, J. H. Connor, and H. Altug, “An Optofluidic Nanoplasmonic Biosensor for Direct Detection of Live Viruses from Biological Media,” Nano Lett. 10(12), 4962–4969 (2010).
[Crossref] [PubMed]

Arnold, S.

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105(52), 20701–20704 (2008).
[Crossref] [PubMed]

Artar, A.

A. A. Yanik, M. Huang, O. Kamohara, A. Artar, T. W. Geisbert, J. H. Connor, and H. Altug, “An Optofluidic Nanoplasmonic Biosensor for Direct Detection of Live Viruses from Biological Media,” Nano Lett. 10(12), 4962–4969 (2010).
[Crossref] [PubMed]

Arter, J. A.

J. A. Arter, D. K. Taggart, J. E. Diaz, R. M. Penner, and G. A. Weiss, “Virus-PEDOT nanowires for biosensing,” Abstracts of Papers of the American Chemical Society 241, 1 (2011).

Arthur, L. O.

J. W. Bess, R. J. Gorelick, W. J. Bosche, L. E. Henderson, and L. O. Arthur, “Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations,” Virology 230(1), 134–144 (1997).
[Crossref] [PubMed]

Arunajadai, S. G.

W. Cheng, S. G. Arunajadai, J. R. Moffitt, I. Tinoco, and C. Bustamante, “Single-Base Pair Unwinding and Asynchronous RNA Release by the Hepatitis C Virus NS3 Helicase,” Science 333(6050), 1746–1749 (2011).
[Crossref] [PubMed]

Asakura, T.

Y. Harada and T. Asakura, “Radiation forces on a dielectric sphere in the Rayleigh scattering regime,” Opt. Commun. 124(5-6), 529–541 (1996).
[Crossref]

Ashe, A.

W. M. Balch, J. Vaughn, J. Navotny, D. T. Drapeau, R. Vaillancourt, J. Lapierre, and A. Ashe, “Light scattering by viral suspensions,” Limnol. Oceanogr. 45(2), 492–498 (2000).
[Crossref]

Ashkin, A.

A. Ashkin, “Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime,” Biophys. J. 61(2), 569–582 (1992).
[Crossref] [PubMed]

A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, “Observation of a Single-Beam Gradient Force Optical Trap for Dielectric Particles,” Opt. Lett. 11(5), 288–290 (1986).
[Crossref] [PubMed]

Austin, J. L.

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

Balch, W. M.

W. M. Balch, J. Vaughn, J. Navotny, D. T. Drapeau, R. Vaillancourt, J. Lapierre, and A. Ashe, “Light scattering by viral suspensions,” Limnol. Oceanogr. 45(2), 492–498 (2000).
[Crossref]

Bar-Ziv, R.

T. Tlusty, A. Meller, and R. Bar-Ziv, “Optical gradient forces of strongly localized fields,” Phys. Rev. Lett. 81(8), 1738–1741 (1998).
[Crossref]

Batchelder, J. S.

Bendix, P. M.

P. M. Bendix and L. B. Oddershede, “Expanding the Optical Trapping Range of Lipid Vesicles to the Nanoscale,” Nano Lett. 11(12), 5431–5437 (2011).
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Bess, J.

P. Zhu, J. Liu, J. Bess, E. Chertova, J. D. Lifson, H. Grisé, G. A. Ofek, K. A. Taylor, and K. H. Roux, “Distribution and three-dimensional structure of AIDS virus envelope spikes,” Nature 441(7095), 847–852 (2006).
[Crossref] [PubMed]

Bess, J. W.

J. W. Bess, R. J. Gorelick, W. J. Bosche, L. E. Henderson, and L. O. Arthur, “Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations,” Virology 230(1), 134–144 (1997).
[Crossref] [PubMed]

Besselink, G. A. J.

A. Ymeti, J. S. Kanger, J. Greve, G. A. J. Besselink, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Integration of microfluidics with a four-channel integrated optical Young interferometer immunosensor,” Biosens. Bioelectron. 20(7), 1417–1421 (2005).
[Crossref] [PubMed]

Beumer, T. A. M.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, and J. S. Kanger, “Fast, ultrasensitive virus detection using a young interferometer sensor,” Nano Lett. 7(2), 394–397 (2007).
[Crossref] [PubMed]

Beuthan, J.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41(3), 369–382 (1996).
[Crossref] [PubMed]

Bjorkholm, J. E.

Block, O.

O. Block, A. Mitra, L. Novotny, and C. Dykes, “A rapid label-free method for quantitation of human immunodeficiency virus type-1 particles by nanospectroscopy,” J. Virol. Methods 182(1-2), 70–75 (2012).
[Crossref] [PubMed]

Bolin, F. P.

Borisy, G. G.

D. McDonald, M. A. Vodicka, G. Lucero, T. M. Svitkina, G. G. Borisy, M. Emerman, and T. J. Hope, “Visualization of the intracellular behavior of HIV in living cells,” J. Cell Biol. 159(3), 441–452 (2002).
[Crossref] [PubMed]

Bosche, W. J.

J. W. Bess, R. J. Gorelick, W. J. Bosche, L. E. Henderson, and L. O. Arthur, “Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations,” Virology 230(1), 134–144 (1997).
[Crossref] [PubMed]

Branczyk, A. M.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knoner, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A, Pure Appl. Opt. 9(8), S196–S203 (2007).
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Briggs, J. A.

L. A. Carlson, J. A. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

Briggs, J. A. G.

L. A. Carlson, J. A. G. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-Dimensional Analysis of Budding Sites and Released Virus Suggests a Revised Model For HIV-1 Morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

J. A. G. Briggs, T. Wilk, R. Welker, H. G. Kräusslich, and S. D. Fuller, “Structural organization of authentic, mature HIV-1 virions and cores,” EMBO J. 22(7), 1707–1715 (2003).
[Crossref] [PubMed]

Bustamante, C.

W. Cheng, S. G. Arunajadai, J. R. Moffitt, I. Tinoco, and C. Bustamante, “Single-Base Pair Unwinding and Asynchronous RNA Release by the Hepatitis C Virus NS3 Helicase,” Science 333(6050), 1746–1749 (2011).
[Crossref] [PubMed]

Carlson, L. A.

L. A. Carlson, J. A. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

L. A. Carlson, J. A. G. Briggs, B. Glass, J. D. Riches, M. N. Simon, M. C. Johnson, B. Müller, K. Grünewald, and H. G. Kräusslich, “Three-Dimensional Analysis of Budding Sites and Released Virus Suggests a Revised Model For HIV-1 Morphogenesis,” Cell Host Microbe 4(6), 592–599 (2008).
[Crossref] [PubMed]

Chan, C. T.

J. J. Xiao, J. Ng, Z. F. Lin, and C. T. Chan, “Whispering gallery mode enhanced optical force with resonant tunneling excitation in the Kretschmann geometry,” Appl. Phys. Lett. 94(1), 011102 (2009).
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Chen, Q.

F. Shen, J. Wang, Z. Xu, Y. Wu, Q. Chen, X. Li, X. Jie, L. Li, M. Yao, X. Guo, and T. Zhu, “Rapid Flu Diagnosis Using Silicon Nanowire Sensor,” Nano Lett. 12(7), 3722–3730 (2012).
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Chen, T.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Cheng, W.

Y. Pang, H. Song, J. H. Kim, X. Hou, and W. Cheng, “Optical trapping of individual human immunodeficiency viruses in culture fluid reveals heterogeneity with single-molecule resolution,” Nat. Nanotechnol. 9(8), 624–630 (2014).
[Crossref] [PubMed]

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

J. H. Kim, H. Song, J. L. Austin, and W. Cheng, “Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells,” PLoS One 8(6), e67170 (2013).
[Crossref] [PubMed]

W. Cheng, S. G. Arunajadai, J. R. Moffitt, I. Tinoco, and C. Bustamante, “Single-Base Pair Unwinding and Asynchronous RNA Release by the Hepatitis C Virus NS3 Helicase,” Science 333(6050), 1746–1749 (2011).
[Crossref] [PubMed]

W. Cheng, X. Hou, and F. Ye, “Use of tapered amplifier diode laser for biological-friendly high-resolution optical trapping,” Opt. Lett. 35(17), 2988–2990 (2010).
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M. C. DeSantis and W. Cheng, “Label-free detection and manipulation of single biological nanoparticles,” Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. in press (2016).

Chertova, E.

P. Zhu, J. Liu, J. Bess, E. Chertova, J. D. Lifson, H. Grisé, G. A. Ofek, K. A. Taylor, and K. H. Roux, “Distribution and three-dimensional structure of AIDS virus envelope spikes,” Nature 441(7095), 847–852 (2006).
[Crossref] [PubMed]

C. M. Trubey, E. Chertova, L. V. Coren, J. M. Hilburn, C. V. Hixson, K. Nagashima, J. D. Lifson, and D. E. Ott, “Quantitation of HLA class II protein incorporated into human immunodeficiency type 1 virions purified by anti-CD45 immunoaffinity depletion of microvesicles,” J. Virol. 77(23), 12699–12709 (2003).
[Crossref] [PubMed]

Chu, S.

Cohen, G. H.

B. M. McDermott, A. H. Rux, R. J. Eisenberg, G. H. Cohen, and V. R. Racaniello, “Two distinct binding affinities of poliovirus for its cellular receptor,” J. Biol. Chem. 275(30), 23089–23096 (2000).
[Crossref] [PubMed]

Connor, J. H.

A. A. Yanik, M. Huang, O. Kamohara, A. Artar, T. W. Geisbert, J. H. Connor, and H. Altug, “An Optofluidic Nanoplasmonic Biosensor for Direct Detection of Live Viruses from Biological Media,” Nano Lett. 10(12), 4962–4969 (2010).
[Crossref] [PubMed]

Cooper, P. R.

Coren, L. V.

C. M. Trubey, E. Chertova, L. V. Coren, J. M. Hilburn, C. V. Hixson, K. Nagashima, J. D. Lifson, and D. E. Ott, “Quantitation of HLA class II protein incorporated into human immunodeficiency type 1 virions purified by anti-CD45 immunoaffinity depletion of microvesicles,” J. Virol. 77(23), 12699–12709 (2003).
[Crossref] [PubMed]

Coumans, F. A. W.

E. van der Pol, F. A. W. Coumans, A. Sturk, R. Nieuwland, and T. G. van Leeuwen, “Refractive Index Determination of Nanoparticles in Suspension Using Nanoparticle Tracking Analysis,” Nano Lett. 14(11), 6195–6201 (2014).
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Daaboul, G. G.

G. G. Daaboul, A. Yurt, X. Zhang, G. M. Hwang, B. B. Goldberg, and M. S. Ünlü, “High-Throughput Detection and Sizing of Individual Low-Index Nanoparticles and Viruses for Pathogen Identification,” Nano Lett. 10(11), 4727–4731 (2010).
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Deamer, D. W.

S. Liu, Y. Zhao, J. W. Parks, D. W. Deamer, A. R. Hawkins, and H. Schmidt, “Correlated Electrical and Optical Analysis of Single Nanoparticles and Biomolecules on a Nanopore-Gated Optofluidic Chip,” Nano Lett. 14(8), 4816–4820 (2014).
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DeSantis, M. C.

M. C. DeSantis and W. Cheng, “Label-free detection and manipulation of single biological nanoparticles,” Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. in press (2016).

Deutsch, B.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic Detection of Single Viruses and Nanoparticles,” ACS Nano 4(3), 1305–1312 (2010).
[Crossref] [PubMed]

Dholakia, K.

M. P. MacDonald, G. C. Spalding, and K. Dholakia, “Microfluidic sorting in an optical lattice,” Nature 426(6965), 421–424 (2003).
[Crossref] [PubMed]

Diaz, J. E.

J. A. Arter, D. K. Taggart, J. E. Diaz, R. M. Penner, and G. A. Weiss, “Virus-PEDOT nanowires for biosensing,” Abstracts of Papers of the American Chemical Society 241, 1 (2011).

Dluhy, R.

S. Shanmukh, L. Jones, J. Driskell, Y. Zhao, R. Dluhy, and R. A. Tripp, “Rapid and sensitive detection of respiratory virus molecular signatures using a silver nanorod array SERS substrate,” Nano Lett. 6(11), 2630–2636 (2006).
[Crossref] [PubMed]

Drapeau, D. T.

W. M. Balch, J. Vaughn, J. Navotny, D. T. Drapeau, R. Vaillancourt, J. Lapierre, and A. Ashe, “Light scattering by viral suspensions,” Limnol. Oceanogr. 45(2), 492–498 (2000).
[Crossref]

Driskell, J.

S. Shanmukh, L. Jones, J. Driskell, Y. Zhao, R. Dluhy, and R. A. Tripp, “Rapid and sensitive detection of respiratory virus molecular signatures using a silver nanorod array SERS substrate,” Nano Lett. 6(11), 2630–2636 (2006).
[Crossref] [PubMed]

Dykes, C.

O. Block, A. Mitra, L. Novotny, and C. Dykes, “A rapid label-free method for quantitation of human immunodeficiency virus type-1 particles by nanospectroscopy,” J. Virol. Methods 182(1-2), 70–75 (2012).
[Crossref] [PubMed]

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic Detection of Single Viruses and Nanoparticles,” ACS Nano 4(3), 1305–1312 (2010).
[Crossref] [PubMed]

Dziedzic, J. M.

Eisenberg, R. J.

B. M. McDermott, A. H. Rux, R. J. Eisenberg, G. H. Cohen, and V. R. Racaniello, “Two distinct binding affinities of poliovirus for its cellular receptor,” J. Biol. Chem. 275(30), 23089–23096 (2000).
[Crossref] [PubMed]

Emerman, M.

D. McDonald, M. A. Vodicka, G. Lucero, T. M. Svitkina, G. G. Borisy, M. Emerman, and T. J. Hope, “Visualization of the intracellular behavior of HIV in living cells,” J. Cell Biol. 159(3), 441–452 (2002).
[Crossref] [PubMed]

Erickson, D.

P. Kang, P. Schein, X. Serey, D. O’Dell, and D. Erickson, “Nanophotonic detection of freely interacting molecules on a single influenza virus,” Sci. Rep. 5, 12087 (2015).
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Ewers, H.

H. Ewers, V. Jacobsen, E. Klotzsch, A. E. Smith, A. Helenius, and V. Sandoghdar, “Label-free optical detection and tracking of single virions bound to their receptors in supported membrane bilayers,” Nano Lett. 7(8), 2263–2266 (2007).
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Fan, X.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
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H. Zhu, I. M. White, J. D. Suter, M. Zourob, and X. Fan, “Opto-fluidic micro-ring resonator for sensitive label-free viral detection,” Analyst (Lond.) 133(3), 356–360 (2008).
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Ference, R. J.

Flagan, R. C.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Flyvbjerg, H.

S. F. Tolic-Norrelykke, E. Schaffer, J. Howard, F. S. Pavone, F. Julicher, and H. Flyvbjerg, “Calibration of optical tweezers with positional detection in the back focal plane,” Rev. Sci. Instrum. 77(10), 103101 (2006).
[Crossref]

Fraser, S. E.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Fuller, S. D.

J. A. G. Briggs, T. Wilk, R. Welker, H. G. Kräusslich, and S. D. Fuller, “Structural organization of authentic, mature HIV-1 virions and cores,” EMBO J. 22(7), 1707–1715 (2003).
[Crossref] [PubMed]

Geisbert, T. W.

A. A. Yanik, M. Huang, O. Kamohara, A. Artar, T. W. Geisbert, J. H. Connor, and H. Altug, “An Optofluidic Nanoplasmonic Biosensor for Direct Detection of Live Viruses from Biological Media,” Nano Lett. 10(12), 4962–4969 (2010).
[Crossref] [PubMed]

Gelderblom, H. R.

P. Gluschankof, I. Mondor, H. R. Gelderblom, and Q. J. Sattentau, “Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations,” Virology 230(1), 125–133 (1997).
[Crossref] [PubMed]

Giessen, H.

Gissibl, T.

Gittes, F.

Glass, B.

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A. Ymeti, J. S. Kanger, J. Greve, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Realization of a multichannel integrated Young interferometer chemical sensor,” Appl. Opt. 42(28), 5649–5660 (2003).
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Wijn, R. R.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, and J. S. Kanger, “Fast, ultrasensitive virus detection using a young interferometer sensor,” Nano Lett. 7(2), 394–397 (2007).
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Wilk, T.

J. A. G. Briggs, T. Wilk, R. Welker, H. G. Kräusslich, and S. D. Fuller, “Structural organization of authentic, mature HIV-1 virions and cores,” EMBO J. 22(7), 1707–1715 (2003).
[Crossref] [PubMed]

Wink, T.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, and J. S. Kanger, “Fast, ultrasensitive virus detection using a young interferometer sensor,” Nano Lett. 7(2), 394–397 (2007).
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Figures (10)

Fig. 1
Fig. 1

BFP interferometry to determine nanoparticle radius and trap stiffness. (a) nanoparticles were delivered into a microfluidic chamber and trapped by the IR laser focused at the center of the chamber. The xyz dimensions are shown as indicated, with y perpendicular to the figure plane. (b) The laser deflection signal measured in real time using BFP interferometry for a polystyrene sphere. The signal shown was along y-axis. (c) The power spectrum of the trapped polystyrene sphere from (b) when the chamber was oscillated at 10 Hz with amplitude of 208 nm along y-axis of the sample plane. The red curve is fitting of the thermal noise background to aliased Lorentzian with Dvolt = 2.68 × 10−3 V2/s and fc = 1198 Hz [33].

Fig. 2
Fig. 2

Particle radius and trap stiffness measured for polystyrene and silica spheres using BFP interferometry. (a) and (b), distributions of particle radius and trap stiffness for polystyrene spheres (N = 66). (c) and (d), distributions of particle radius and trap stiffness for silica spheres (N = 101).

Fig. 3
Fig. 3

Schematic of the cylindrical coordinate system for computation of the trap stiffness as a function of particle radius. The origin of the system is located at the focal point of the beam. The z-axis points along the beam axis, consistent with the representation in Fig. 1(a); and ρ points along the transverse dimension, which is perpendicular to the beam axis z. The electric field of the beam before focusing is polarized in the direction where the azimuth angle θ = 0.

Fig. 4
Fig. 4

Validation of the paraxial approximation for the optical forces exerted by a highly focused TEM00 laser beam on a nanoparticle. (a – c) The x, y, and z components, and (d) the total intensities of the electric field of the photons at the focal plane for a fully vectorial, diffraction limited focal spot formed by an objective with numerical aperture (NA) = 1.2. (e) The transverse trap stiffness induced by the total field intensity (Ex2 + Ey2 + Ez2) as compared to that induced by Ex2 only. The value of ω, which is the radius of the beam waist, is set to 322 nm as calculated for the diffraction limited, vectorial field at the beam focus. (f) Percentage difference in the trap stiffness as shown in e.

Fig. 5
Fig. 5

Validation of the 3D Gaussian profile in lieu of an authentic Gaussian beam to represent the field energy density. The trap stiffness (a.u.) as a function of particle radius normalized to the radius of the beam waist is shown above. These simulations were done for polystyrene particles. For authentic Gaussian beam profile, we have numerically calculated trap stiffness as a function of particle radius using Eq. (1), Eq. (2), and Eq. (3), and the result is shown in black solid curve. For 3D Gaussian profile to represent the field energy density, we have calculated trap stiffness as a function of particle radius using Eq. (1), Eq. (2), and Eq. (4). We have tested different values of the eccentricity ε varying from 1.1 to 5, and the results are shown in dashed lines as indicated. The same beam parameters of I0 and ω0 were used for all these simulations.

Fig. 6
Fig. 6

Quantitative dependence of trap stiffness on particle radius. (a) The dependence of trap stiffness on particle radius for polystyrene spheres (N = 66). The experimental data are shown in grey spheres. (b) The dependence of trap stiffness on particle radius for silica spheres (N = 101). The experimental data are shown in light cyan spheres. For both panels, the red solid curves represent the results from nonlinear least squares fitting of the experimental data using Eq. (5), with a beam eccentricity ϵ=2 . The green dashed lines represent the results from nonlinear least squares fitting of the experimental data using Rayleigh scatterer (the cubic dependence).

Fig. 7
Fig. 7

The value of 3D Gaussian beam eccentricity has negligible effect on the fitting of the trap stiffness. The experimentally measured trap stiffness as a function of particle radius (blue triangles) for polystyrene spheres was fitted using a 3D Gaussian profile with different values of beam eccentricity ε. The resulting fits are shown in red solid curves for (a) ε = 2; (b) ε = 3; (c) ε = 4; and (d) ε = 5, respectively.

Fig. 8
Fig. 8

The impact of scattering force on the modeling of the transverse trap stiffness. Transverse trap stiffness as a function of the particle radius R normalized by the radius of the beam waist ω was analytically calculated using Eq. (6) at different axial displacement values. The displacement of the trapped particle Pz is chosen to be 0 (red), 50 (green), 100 (blue) and 150 (cyan) nm away from the Origin.

Fig. 9
Fig. 9

Measurement of HIV-1 to determine the RI of single virions. (a) Distribution of particle radius measured for HIV-1 virions using BFP interferometry (N = 97). The red solid curve is a fit to Gaussian distribution. (b) Distribution of trap stiffness measured for single HIV-1 virions (N = 89). (c) Distribution of RI calculated for single HIV-1 virions using Eq. (5) (N = 89).

Fig. 10
Fig. 10

Measurement of unilamellar liposomes encapsulating 2.0 M sucrose. (a) Distribution of particle radius measured for liposomes using BFP interferometry (N = 142). The red solid curve is a fit to Gaussian distribution. (b) Distribution of trap stiffness measured for single liposome particles (N = 124). (c) Distribution of RI calculated for single liposomes using Eq. (5) (N = 124).

Tables (3)

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Table 1 Summary of RI values assumed in various viral sensing studies.

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Table 2 Summary of parameters in the nonlinear least square fitting of trap stiffness as a function of radius for individual polystyrene and silica spheres, respectively.

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Table 3 Summary of fitted beam parameters and the goodness of fits for polystyrene spheres using 3D Gaussian approximation with different beam eccentricities.

Equations (6)

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W=-α I(ρ,z)dV
κ= 2 W ρ 2
I(ρ,z)= I 0 ( ω 0 2 ω (z) 2 )exp( 2 ρ 2 ω (z) 2 )
κ=α I 0 ω 0 2π ξ 3 [ 2π ( (ξa) 2 + 1 4 ) e 2 a 2 erfi( 2 aξ)ξa e 2 a 2 / ε 2 ]
κ=α I 0 ω 0 2π ξ 3 F(R, ω 0 ,ε)
κ=α I 0 ω 0 { 4π P z 9 [ e ( P z +a ) 2 /2 e ( P z a ) 2 /2 ]+ 4πa 3 [ e ( P z a ) 2 /2 + e ( P z +a ) 2 /2 ]+ 2 6 π 3 2 9 (1+3 a 2 + P z 2 3 ) e 2 P Z 2 3 e a 2 2 [ erfi( 6 P Z 6 6 a 2 )erfi( 6 P Z 6 + 6 a 2 ) ] }

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