Abstract

The detection and identification of nanoparticles is of growing interest in atmospheric monitoring, medicine, and semiconductor manufacturing. While elastic light scattering with interferometric detection provides good sensitivity to single particles, active optical components prevent scalability of realistic sizes for deployment in the field or clinic. Here, we report on a simple phase-sensitive nanoparticle detection scheme with no active optical elements. Two measurements are taken simultaneously, allowing the amplitude and phase to be decoupled. We demonstrate the detection of 25nm Au particles in liquid in Δt1ms with a signal-to-noise ratio of 37. Such performance makes it possible to detect nanoscale contaminants or larger proteins in real time without the need of artificial labeling.

© 2010 Optical Society of America

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References

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2010 (1)

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

2008 (2)

V. Ramanathan and G. Carmichael, “Global and regional climate changes due to black carbon,” Nature Geosci. 1, 221–227 (2008).
[CrossRef]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nature Methods 5, 591–596 (2008).
[CrossRef] [PubMed]

2006 (2)

Y. J. Kaufman and I. Koren, “Smoke and pollution aerosol effect on cloud cover,” Science 313, 655–658 (2006).
[CrossRef] [PubMed]

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

2005 (2)

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

S. B. Ippolito, B. B. Goldberg, and M. S. Ünlü, “Theoretical analysis of numerical aperture increasing lens microscopy,” J. Appl. Phys. 97, 053105 (2005).
[CrossRef]

2004 (2)

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

2003 (1)

F. V. Ignatovich and L. Novotny, “Experimental study of nanoparticle detection by optical gradient forces,” Rev. Sci. Instr. 74, 5231–5235 (2003).
[CrossRef]

2002 (2)

M. R. Hillman, “Overview: Cause and prevention in biowarfare and bioterrorism,” Vaccine 20, 3055–3067 (2002).
[CrossRef]

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

1993 (1)

1988 (1)

K. Creath, “Phase measurement interferometry techniques,” Prog. Opt. 26, 349–393 (1988).
[CrossRef]

1974 (1)

Al-Hajj, A.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

Arnold, S.

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nature Methods 5, 591–596 (2008).
[CrossRef] [PubMed]

Barton, J.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Brangaccio, D. J.

Brock, N.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Bruning, J.

J. Bruning, “Phase measurement interferometry,” in Optical Shop Testing, D.Malacara, ed. (Wiley, 1987), p. 414.

Bruning, J. H.

Carmichael, G.

V. Ramanathan and G. Carmichael, “Global and regional climate changes due to black carbon,” Nature Geosci. 1, 221–227 (2008).
[CrossRef]

Creath, K.

K. Creath, “Phase measurement interferometry techniques,” Prog. Opt. 26, 349–393 (1988).
[CrossRef]

Deutsch, B.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

Drezek, R.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Dykes, C.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

Gallagher, D. P.

Gao, X.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

Goldberg, B. B.

S. B. Ippolito, B. B. Goldberg, and M. S. Ünlü, “Theoretical analysis of numerical aperture increasing lens microscopy,” J. Appl. Phys. 97, 053105 (2005).
[CrossRef]

Halas, N.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Hansen, J.

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

Hayes, J.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Hecht, B.

L. Novotny and B. Hecht, Principles of Nano-Optics(Cambridge University Press, 2006), p. 404.

Herriott, D. R.

Hillman, M. R.

M. R. Hillman, “Overview: Cause and prevention in biowarfare and bioterrorism,” Vaccine 20, 3055–3067 (2002).
[CrossRef]

Hirsch, L.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Ignatovich, F.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

Ignatovich, F. V.

F. V. Ignatovich and L. Novotny, “Experimental study of nanoparticle detection by optical gradient forces,” Rev. Sci. Instr. 74, 5231–5235 (2003).
[CrossRef]

Ippolito, S. B.

S. B. Ippolito, B. B. Goldberg, and M. S. Ünlü, “Theoretical analysis of numerical aperture increasing lens microscopy,” J. Appl. Phys. 97, 053105 (2005).
[CrossRef]

Kaufman, Y. J.

Y. J. Kaufman and I. Koren, “Smoke and pollution aerosol effect on cloud cover,” Science 313, 655–658 (2006).
[CrossRef] [PubMed]

Kimbrough, B.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Koren, I.

Y. J. Kaufman and I. Koren, “Smoke and pollution aerosol effect on cloud cover,” Science 313, 655–658 (2006).
[CrossRef] [PubMed]

Lee, M. H.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Lin, A.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Loo, C.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Luo, Y.

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

Malek, F.

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

McCarry, B. E.

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

Menon, S.

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

Millerd, J.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Mitra, A.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

Nazarenko, L.

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

Nie, S.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

North-Morris, M.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Novak, M.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Novotny, L.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

F. V. Ignatovich and L. Novotny, “Experimental study of nanoparticle detection by optical gradient forces,” Rev. Sci. Instr. 74, 5231–5235 (2003).
[CrossRef]

L. Novotny and B. Hecht, Principles of Nano-Optics(Cambridge University Press, 2006), p. 404.

O’Regan, R. M.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

Quinn, J. S.

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

Ramanathan, V.

V. Ramanathan and G. Carmichael, “Global and regional climate changes due to black carbon,” Nature Geosci. 1, 221–227 (2008).
[CrossRef]

Somers, C. M.

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

Surrel, Y.

Ünlü, M. S.

S. B. Ippolito, B. B. Goldberg, and M. S. Ünlü, “Theoretical analysis of numerical aperture increasing lens microscopy,” J. Appl. Phys. 97, 053105 (2005).
[CrossRef]

Vollmer, F.

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nature Methods 5, 591–596 (2008).
[CrossRef] [PubMed]

West, J.

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

White, A. D.

Wyand, J. C.

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Xing, Y.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

Yezhelyev, M. V.

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

ACS Nano (1)

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[CrossRef] [PubMed]

Appl. Opt. (2)

J. Appl. Phys. (1)

S. B. Ippolito, B. B. Goldberg, and M. S. Ünlü, “Theoretical analysis of numerical aperture increasing lens microscopy,” J. Appl. Phys. 97, 053105 (2005).
[CrossRef]

Lancet Oncol. (1)

M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan, “Emerging use of nanoparticles in diagnosis and treatment of breast cancer,” Lancet Oncol. 7, 657–667(2006).
[CrossRef] [PubMed]

Nature Geosci. (1)

V. Ramanathan and G. Carmichael, “Global and regional climate changes due to black carbon,” Nature Geosci. 1, 221–227 (2008).
[CrossRef]

Nature Methods (1)

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nature Methods 5, 591–596 (2008).
[CrossRef] [PubMed]

Proc. SPIE (1)

J. Millerd, N. Brock, J. Hayes, B. Kimbrough, M. Novak, M. North-Morris, and J. C. Wyand, “Modern approaches in phase measuring metrology,” Proc. SPIE 5856, 14–22 (2005).
[CrossRef]

Prog. Opt. (1)

K. Creath, “Phase measurement interferometry techniques,” Prog. Opt. 26, 349–393 (1988).
[CrossRef]

Rev. Sci. Instr. (1)

F. V. Ignatovich and L. Novotny, “Experimental study of nanoparticle detection by optical gradient forces,” Rev. Sci. Instr. 74, 5231–5235 (2003).
[CrossRef]

Science (3)

S. Menon, J. Hansen, L. Nazarenko, and Y. Luo, “Climate effects of black carbon aerosols in China and India,” Science 297, 2250–2253 (2002).
[CrossRef] [PubMed]

Y. J. Kaufman and I. Koren, “Smoke and pollution aerosol effect on cloud cover,” Science 313, 655–658 (2006).
[CrossRef] [PubMed]

C. M. Somers, B. E. McCarry, F. Malek, and J. S. Quinn, “Reduction of particulate air pollution lowers the risk of heritable mutations in mice,” Science 304, 1008–1010 (2004).
[CrossRef] [PubMed]

Technol. Cancer Res. Treat. (1)

C. Loo, A. Lin, L. Hirsch, M. H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3, 33–40 (2004).
[PubMed]

Vaccine (1)

M. R. Hillman, “Overview: Cause and prevention in biowarfare and bioterrorism,” Vaccine 20, 3055–3067 (2002).
[CrossRef]

Other (3)

S.T.Holgate, J.M.Samet, H.S.Koren, and R.L.Maynard, eds., Air Pollution and Health (Academic, 1999).

J. Bruning, “Phase measurement interferometry,” in Optical Shop Testing, D.Malacara, ed. (Wiley, 1987), p. 414.

L. Novotny and B. Hecht, Principles of Nano-Optics(Cambridge University Press, 2006), p. 404.

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Figures (3)

Fig. 1
Fig. 1

Dual-phase detection apparatus. (a) Configuration for immobilized particles. A 1.4 NA oil-immersion objective is used to focus light on a particle, and the particle is scanned through the focus. (b) Nanoscale channel configuration. Particles in solution are loaded into reservoirs at the ends of a 15 μm channel of cross-section 500 nm by 400 nm , and a microscope objective focuses light on the channel. The black arrow indicates the direction of electro-osmotic flow. (c) Numerical aperture increasing lens (NAIL) configuration. A NAIL is water-bonded to a coverslip and is used to focus light on an immobilized particle, which is scanned through the focus. (d) Schematic of dual-phase interferometer. A linear polarizer sets the polarization state of the signal beam to 45 ° , and a combination of a polarizer and quarter-wave plate (QWP) sets the reference polarization to be circular. After reference and signal are combined with a nonpolarizing beam splitter (NPBS), a polarizing beam splitter (PBS) sends the two orthogonal polarization states to detectors. The difference in relative phase between signal and reference at the two detectors is π / 2 .

Fig. 2
Fig. 2

Immobilized particle detection using dual-phase interferometry. (a) Time series of a detection event for a 30 nm radius immobilized Au particle in water. The event time is determined by the particle speed and the size of the laser focus, and the time resolution is determined by the data acquisition speed ( 50 k samples/sec). (b), (c) Histograms of signals for 20 nm (blue), 25 nm (pink), and 30 nm (yellow) radius Au nanoparticles immobilized on glass and immersed in water. In (a), the dual-phase scheme is used, and the signal is the area under the particle event peak. In (c), the intensity from a single detector is taken after background subtraction for the same data set, and the histogram is constructed from the maxima of the peaks, imitating homodyne interferometry. The inherent phase dependence leads to wider peaks and causes the distribution from the largest particle to overlap significantly with the others in this case. Scott’s choice was used to determine bin widths for all histograms.

Fig. 3
Fig. 3

Particle detection in nanoscale channels and in NAIL configuration. (a) Background-subtracted time series of a particle detection event for a 25 nm radius Au particle in the nanoscale channel configuration from Fig. 1b. (b) Histogram of signals from 3000 such events. (c) Background-subtracted time series of a particle detection event for a 50 nm radius Au particle using the NAIL configuration from Fig. 1c. (d) Histogram of signals from 3000 such events. Scott’s choice was used to determine bin widths for the histograms.

Equations (12)

Equations on this page are rendered with MathJax. Learn more.

E s k 3 α E 0 ,
α ( ω ) = 4 π ϵ 0 R 3 ϵ p ( ω ) ϵ m ϵ p ( ω ) + 2 ϵ m .
I = | E s | 2 + | E r | 2 + 2 | E s | | E r | cos ( ϕ ) ,
I i = | E s | 2 + | E r | 2 + 2 | E s | | E r | cos ( ϕ + δ i ) ,
I 1 = | E s | 2 + | E r | 2 + 2 | E s | | E r | cos ( ϕ )
I 2 = | E s | 2 + | E r | 2 + 2 | E s | | E r | sin ( ϕ ) .
I X = I 1 | E r | 2
I Y = I 2 | E r | 2
( I X 2 + I Y 2 ) 1 / 2 = 2 | E s | | E r |
tan 1 ( I Y / I X ) = ϕ .
| E s | 2 = 1 2 [ I 1 + I 2 + ( 4 | E r | 2 ( I 1 + I 2 ) ( I 1 I 2 ) 2 4 | E r | 4 ) 1 / 2 ] .
I = | E s | 2 + | E r | 2 + | E b | 2 + 2 | E s | | E r | cos ( ϕ ) + 2 | E s | | E b | cos ( ϕ s b ) + 2 | E r | | E b | cos ( ϕ r b ) ,

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