Abstract

We present a fast, wide-field holography system for detecting photothermally excited gold nanospheres with combined quantitative phase imaging. An interferometric photothermal optical lock-in approach (POLI) is shown to improve SNR for detecting nanoparticles (NPs) on multiple substrates, including a monolayer of NPs on a silanized coverslip, and NPs bound to live cells. Furthermore, the set up allowed for co-registered quantitative phase imaging (QPI) to be acquired in an off-axis holographic set-up. An SNR of 103 was obtained for NP-tagging of epidermal growth factor receptor (EGFR) in live cells with a 3 second acquisition, while an SNR of 47 was seen for 20 ms acquisition. An analysis of improvements in SNR due to averaging multiple frames is presented, which suggest that residual photothermal signal can be a limiting factor. The combination of techniques allows for high resolution imaging of cell structure via QPI with the ability to identify receptor expression via POLI.

© 2014 Optical Society of America

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References

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    [CrossRef] [PubMed]
  2. A. Wax, A. Meiri, S. Arumugam, and M. T. Rinehart, “Comparative review of interferometric detection of plasmonic nanoparticles,” Biomed. Opt. Express4(10), 2166–2178 (2013).
    [CrossRef] [PubMed]
  3. A. Curry, W. L. Hwang, and A. Wax, “Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture,” Opt. Express14(14), 6535–6542 (2006).
    [CrossRef] [PubMed]
  4. N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).
  5. C. Pache, N. L. Bocchio, A. Bouwens, M. Villiger, C. Berclaz, J. Goulley, M. I. Gibson, C. Santschi, and T. Lasser, “Fast three-dimensional imaging of gold nanoparticles in living cells with photothermal optical lock-in Optical Coherence Microscopy,” Opt. Express20(19), 21385–21399 (2012).
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    [CrossRef] [PubMed]
  7. A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
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    [CrossRef] [PubMed]
  9. D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
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    [CrossRef] [PubMed]
  14. K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
    [CrossRef] [PubMed]
  15. M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
    [CrossRef] [PubMed]
  16. A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).
  17. M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
    [CrossRef] [PubMed]
  18. M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
    [CrossRef] [PubMed]
  19. M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
    [CrossRef] [PubMed]
  20. M. Atlan, M. Gross, P. Desbiolles, É. Absil, G. Tessier, and M. Coppey-Moisan, “Heterodyne holographic microscopy of gold particles,” Opt. Lett.33(5), 500–502 (2008).
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2013

A. Wax, A. Meiri, S. Arumugam, and M. T. Rinehart, “Comparative review of interferometric detection of plasmonic nanoparticles,” Biomed. Opt. Express4(10), 2166–2178 (2013).
[CrossRef] [PubMed]

N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

2012

2011

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

2010

2009

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

2008

M. Atlan, M. Gross, P. Desbiolles, É. Absil, G. Tessier, and M. Coppey-Moisan, “Heterodyne holographic microscopy of gold particles,” Opt. Lett.33(5), 500–502 (2008).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).

2006

S. Eustis and M. A. el-Sayed, “Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes,” Chem. Soc. Rev.35(3), 209–217 (2006).
[CrossRef] [PubMed]

A. Curry, W. L. Hwang, and A. Wax, “Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture,” Opt. Express14(14), 6535–6542 (2006).
[CrossRef] [PubMed]

2004

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

2002

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Absil, E.

Absil, É.

Albanese, A.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Arumugam, S.

Atlan, M.

Berciaud, S.

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

Berclaz, C.

Blab, G. A.

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

Bocchio, N. L.

Bouwens, A.

Boyer, D.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Chan, W. C. W.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Chilkoti, A.

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Cognet, L.

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

Cook, J. M.

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

Coppey-Moisan, M.

Crow, M. J.

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Crow, M.J.

A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).

Curry, A.

Curry, A.C.

A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).

Desbiolles, P.

el-Sayed, M. A.

S. Eustis and M. A. el-Sayed, “Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes,” Chem. Soc. Rev.35(3), 209–217 (2006).
[CrossRef] [PubMed]

Eustis, S.

S. Eustis and M. A. el-Sayed, “Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes,” Chem. Soc. Rev.35(3), 209–217 (2006).
[CrossRef] [PubMed]

Fournier, D.

Gaiduk, A.

A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
[CrossRef]

Gibson, M. I.

Goulley, J.

Grant, G.

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

Gross, M.

Hwang, W. L.

Izatt, J. A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Lam, A. K.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Lasser, T.

Lounis, B.

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Maali, A.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Marinakos, S.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Marinakos, S. M.

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

Meiri, A.

Orrit, M.

A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
[CrossRef]

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Ostrander, J.

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

Ostrander, J. H.

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

Pache, C.

Peled, A.

N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).

Price, H.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

Provenzale, J. M.

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

Rinehart, M. T.

Rocheleau, J. V.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Ruijgrok, P. V.

A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
[CrossRef]

Santschi, C.

Seekell, K.

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

Shaked, N. T.

N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).

Skala, M. C.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Suck, S.

Sykes, E. A.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Tamarat, P.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Tessier, G.

Turko, N. A.

N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).

Villiger, M.

Warnasooriya, N.

Wax, A.

A. Wax, A. Meiri, S. Arumugam, and M. T. Rinehart, “Comparative review of interferometric detection of plasmonic nanoparticles,” Biomed. Opt. Express4(10), 2166–2178 (2013).
[CrossRef] [PubMed]

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).

A. Curry, W. L. Hwang, and A. Wax, “Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture,” Opt. Express14(14), 6535–6542 (2006).
[CrossRef] [PubMed]

Yorulmaz, M.

A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
[CrossRef]

ACS Nano

M. J. Crow, K. Seekell, J. H. Ostrander, and A. Wax, “Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles,” ACS Nano5(11), 8532–8540 (2011).
[CrossRef] [PubMed]

AJR Am. J. Roentgenol.

M. J. Crow, G. Grant, J. M. Provenzale, and A. Wax, “Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles,” AJR Am. J. Roentgenol.192(4), 1021–1028 (2009).
[CrossRef] [PubMed]

Biomed. Opt. Express

Chem. Sci.

A. Gaiduk, P. V. Ruijgrok, M. Yorulmaz, and M. Orrit, “Detection limits in photothermal microscopy,” Chem. Sci.1(3), 343–350 (2010).
[CrossRef]

Chem. Soc. Rev.

S. Eustis and M. A. el-Sayed, “Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes,” Chem. Soc. Rev.35(3), 209–217 (2006).
[CrossRef] [PubMed]

Cytometry A

M. J. Crow, S. M. Marinakos, J. M. Cook, A. Chilkoti, and A. Wax, “Plasmonic flow cytometry by immunolabeled nanorods,” Cytometry A79A(1), 57–65 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt.

A.C. Curry, M.J. Crow, and A. Wax, “Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles,” J. Biomed. Opt.13(1), 014022 (2008).

K. Seekell, M. J. Crow, S. Marinakos, J. Ostrander, A. Chilkoti, and A. Wax, “Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles,” J. Biomed. Opt.16(11), 116003 (2011).
[CrossRef] [PubMed]

N. A. Turko, A. Peled, and N. T. Shaked, “Wide-field interferometric phase microscopy with molecular specificity using plasmonic nanoparticles,” J. Biomed. Opt.18(11), 111414 (2013).

Methods

K. Seekell, H. Price, S. Marinakos, and A. Wax, “Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis,” Methods56(2), 310–316 (2012).
[CrossRef] [PubMed]

Nano Lett.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Nat. Comm.

A. Albanese, A. K. Lam, E. A. Sykes, J. V. Rocheleau, and W. C. W. Chan, “Tumour-on-a-chip provides an optical window into nanoparticle tissue transport,” Nat. Comm.4, 1–8 (2013).

Opt. Express

Opt. Lett.

Phys. Rev. Lett.

S. Berciaud, L. Cognet, G. A. Blab, and B. Lounis, “Photothermal heterodyne imaging of individual nonfluorescent nanoclusters and nanocrystals,” Phys. Rev. Lett.93(25), 257402 (2004).
[CrossRef] [PubMed]

Science

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

Other

A. Datta, Biological and Bioenvironmental Heat and Mass Transfer (Marcel Dekker, 2002).

J. E. Mark, “Poly(dimethylsiloxane),” in Polymer Data Handbook (Oxford University Press, 1998).

J. D. Hoffman, Numerical Methods for Engineers and Scientists, 2nd ed. (McGraw-Hill, 2001).

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Figures (5)

Fig. 1
Fig. 1

Optical setup for the wide field optical lock-in detection scheme of gold NP labeled samples.

Fig. 2
Fig. 2

(a) SNR of photothermal optical lock-in (POLI) signal averaged over 10 frames as a function of frequency for NPs in solution: experimental results (blue markers) and fit to the exponential decay of the thermally modulated refractive index profile, with r = 10μm (red dotted line). Inset: POLI signal for modulation frequency of 100Hz. (b) SNR as a function of number of averaged frames: modulation frequency of 100Hz at 30ms (red) and 35ms (black) integration times and 200Hz at 35 ms integration time (blue). For comparison, shot-noise limited √N dependence also shown (green dotted line), scaled to the first frame SNR value for the 200 Hz curve. (c) Noise as function of frames averaged for 100 Hz modulation frequency at different exposure times. The dotted lines show expected shot noise limited behavior. Inset: Modulated heat image minus no-heat image at 50ms exposure time and averaged over 50 frames, red rectangle marks the area taken for noise calculation. (d) POLI signal for a monolayer of NPs with a modulation of 100 Hz. The SNR obtained in this frame was 120.

Fig. 3
Fig. 3

(a) Photothermal optical lock-in (POLI) signal for a NP solution in a PDMS microchannel at a modulation frequency of 100Hz. (b) FDTD simulation of the change in the refractive index for a PDMS microchannel. (c) POLI signal for NPs solution in a glass microchannel (red dotted lines mark the channel edges, based on the phase image).

Fig. 4
Fig. 4

MDA-MB-468 cell images. (a) Overlay of wide field POLI (green) and QPI grayscale) images of NP tagged cell. The two images were normalized to 1 and then thresholded with values of 0.5, 0.3 for the POLI and QPI images respectively. Red circles mark the excitation beam location. (b) QPI image of the cell from (a). (c) and (d) Overlay image and QPI image of a negative control cell. (e) Overlay of POLI and QPI images for 20 ms total integration time. (f) QPI Image of the same cell in (e).

Fig. 5
Fig. 5

Noise in POLI image as a function of frames averaged N for 100 Hz modulation frequency, with 50 ms integration time, using the data set seen in Fig. 4(a). The dotted line shows expected shot noise limited behavior.

Equations (6)

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Δn( r,t )= n T P abs 4πκr [ 1+cos( Ωt r r th ) e r/ r th ]
I(k,t)= E i 2 T n T r * e i(2k z n +Ωt) e i2k z r + E i 2 T np T r * e i2k z r e i[k(2 z np +αcos(Ωt))+Ωt]
I(k,t) =i E i 2 T np T r * e i2k( z np z r ) Δt J 1 (αk)
N(k,t) = I(k,t) = E i T np T r * Δt J 1 (αk) .
SNR= I(k,t) / N(k,t) = I(k,t) = E i T np T r * Δt J 1 (αk) .
B N (k,t)=Re{ E i 2 T n T r e i2k( z n z r ) T 0 N T 0 N+Δt e iΩt dt } 2 Ω cos[ Ω( δ+Δ t N )N+Ωδ/2 ]sin( Ωδ 2 )

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