Abstract

In vivo photoacoustic (PA) flow cytometry (PAFC) has great potential for detecting disease-associated biomarkers in blood and lymph flow, as well as real-time control of the efficacy of photothermal (PT) and other therapies through the counting of circulating abnormal objects. We report on a high speed PAFC with a Yb-doped fiber laser having a 0.5-MHz pulse repetition rate at a wavelength of 1064 nm, pulse width of 10 ns, and energy up to 100 µJ. This is the first biomedical application of PA and PT techniques operating at the highest pulse repetition rate of nanosecond lasers that provide 100-fold enhancement in detection speed of carbon nanotube clusters, as well as real-time monitoring of the flow velocity of individual targets through the width of PA signals. The laser pulse rate limits for PT and PA techniques depending on the sizes of laser beam and targets and flow velocity are discussed. We propose time-overlapping mode and generation of periodic nano- and microbubbles as PA-signal and PT-therapy amplifiers, including discrimination of small absorbing targets among large ones. Taking into account the relatively low level of background signals from most biotissues at 1064 nm, our data suggest that a nanosecond Yb-doped fiber laser operating at high pulse repetition rate could be a promising optical source for time-resolved PA and PT cytometry, imaging, microscopy, and therapy, including detection of nanoparticles and cells flowing at velocities up to 2.5 m/s.

© 2010 OSA

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E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, J. W. Kim, and V. P. Zharov, “Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing circulating cancer stem cells,” J. Biophotonics 2(12), 725–735 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

I. Y. Petrova, Y. Y. Petrov, R. O. Esenaliev, D. J. Deyo, I. Cicenaite, and D. S. Prough, “Noninvasive monitoring of cerebral blood oxygenation in ovine superior sagittal sinus with novel multi-wavelength optoacoustic system,” Opt. Express 17(9), 7285–7294 (2009).
[CrossRef] [PubMed]

2008

S. H. Holan and J. A. Viator, “Automated wavelet denoising of photoacoustic signals for circulating melanoma cell detection and burn image reconstruction,” Phys. Med. Biol. 53(227–N), 236 (2008).
[CrossRef]

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

2007

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal flow cytometry in vitro for detection and imaging of individual moving cells,” Cytometry A 71A(4), 191–206 (2007).
[CrossRef]

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

H. P. Brecht, D. S. Prough, Y. Y. Petrov, I. Patrikeev, I. Y. Petrova, D. J. Deyo, I. Cicenaite, and R. O. Esenaliev, “In vivo monitoring of blood oxygenation in large veins with a triple-wavelength optoacoustic system,” Opt. Express 15(24), 16261–16269 (2007).
[CrossRef] [PubMed]

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler flow measurement in optically scattering media,” Appl. Phys. Lett. 91(26), 264103 (2007).
[CrossRef]

2006

2005

V. P. Zharov, R. R. Letfullin, and E. N. Galitovskaya, “Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters,” J. Phys. D Appl. Phys. 38(15), 2571–2581 (2005).
[CrossRef]

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Y. Y. Petrov, D. S. Prough, D. J. D. Deyo, M. M. Klasing, M. Motamedi, and R. O. Esenaliev, “Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep,” Anesthesiology 102(1), 69–75 (2005).
[CrossRef]

I. Y. Petrova, R. O. Esenaliev, Y. Y. Petrov, H. P. E. Brecht, C. H. Svensen, J. Olsson, D. J. Deyo, and D. S. Prough, “Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study,” Opt. Lett. 30(13), 1677–1679 (2005).
[CrossRef] [PubMed]

2004

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal imaging of moving cells in lymph and blood flow in vivo,” Proc. SPIE 5320, 256–263 (2004).

1973

Brecht, H. P.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

H. P. Brecht, D. S. Prough, Y. Y. Petrov, I. Patrikeev, I. Y. Petrova, D. J. Deyo, I. Cicenaite, and R. O. Esenaliev, “In vivo monitoring of blood oxygenation in large veins with a triple-wavelength optoacoustic system,” Opt. Express 15(24), 16261–16269 (2007).
[CrossRef] [PubMed]

Brecht, H. P. E.

Brown, L. O.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Caldwell, C. W.

Cheng, J. X.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

Cicenaite, I.

Conjusteau, A.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

Dale, P. S.

Deyo, D. J.

Deyo, D. J. D.

Y. Y. Petrov, D. S. Prough, D. J. D. Deyo, M. M. Klasing, M. Motamedi, and R. O. Esenaliev, “Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep,” Anesthesiology 102(1), 69–75 (2005).
[CrossRef]

Doorn, S. K.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Ermilov, S. A.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

Esenaliev, R. O.

Fang, H.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler flow measurement in optically scattering media,” Appl. Phys. Lett. 91(26), 264103 (2007).
[CrossRef]

Fornage, B. D.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Fronheiser, M.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

Galanzha, E. I.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, J. W. Kim, and V. P. Zharov, “Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing circulating cancer stem cells,” J. Biophotonics 2(12), 725–735 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal flow cytometry in vitro for detection and imaging of individual moving cells,” Cytometry A 71A(4), 191–206 (2007).
[CrossRef]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, N. G. Khlebtsov, and V. V. Tuchin, “In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents,” Opt. Lett. 31(24), 3623–3625 (2006).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal imaging of moving cells in lymph and blood flow in vivo,” Proc. SPIE 5320, 256–263 (2004).

Galitovskaya, E. N.

V. P. Zharov, R. R. Letfullin, and E. N. Galitovskaya, “Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters,” J. Phys. D Appl. Phys. 38(15), 2571–2581 (2005).
[CrossRef]

Gaskill, D. R.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

George, T. F.

R. R. Letfullin, C. Joenathan, T. F. George, and V. P. Zharov, “Laser-induced explosion of gold nanoparticles: potential role for nanophotothermolysis of cancer,” Nanomedicine (Lond) 1(4), 473–480 (2006).
[CrossRef]

Graves, S. W.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Hale, G. M.

Hartmann, L. C.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

He, W.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

Holan, S. H.

S. H. Holan and J. A. Viator, “Automated wavelet denoising of photoacoustic signals for circulating melanoma cell detection and burn image reconstruction,” Phys. Med. Biol. 53(227–N), 236 (2008).
[CrossRef]

Hunt, K. K.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Jin, X.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Joenathan, C.

R. R. Letfullin, C. Joenathan, T. F. George, and V. P. Zharov, “Laser-induced explosion of gold nanoparticles: potential role for nanophotothermolysis of cancer,” Nanomedicine (Lond) 1(4), 473–480 (2006).
[CrossRef]

Kelly, T.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

Khlebtsov, N. G.

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, N. G. Khlebtsov, and V. V. Tuchin, “In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents,” Opt. Lett. 31(24), 3623–3625 (2006).
[CrossRef] [PubMed]

Kim, J. W.

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, J. W. Kim, and V. P. Zharov, “Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing circulating cancer stem cells,” J. Biophotonics 2(12), 725–735 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

Kim, J.-W.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

Klasing, M. M.

Y. Y. Petrov, D. S. Prough, D. J. D. Deyo, M. M. Klasing, M. Motamedi, and R. O. Esenaliev, “Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep,” Anesthesiology 102(1), 69–75 (2005).
[CrossRef]

Kokoska, M. S.

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

Kotagiri, N.

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

Ku, G.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Letfullin, R. R.

R. R. Letfullin, C. Joenathan, T. F. George, and V. P. Zharov, “Laser-induced explosion of gold nanoparticles: potential role for nanophotothermolysis of cancer,” Nanomedicine (Lond) 1(4), 473–480 (2006).
[CrossRef]

V. P. Zharov, R. R. Letfullin, and E. N. Galitovskaya, “Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters,” J. Phys. D Appl. Phys. 38(15), 2571–2581 (2005).
[CrossRef]

Lisle, A. E.

Low, P. S.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

Maslov, K.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler flow measurement in optically scattering media,” Appl. Phys. Lett. 91(26), 264103 (2007).
[CrossRef]

Moon, H. M.

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

Motamedi, M.

Y. Y. Petrov, D. S. Prough, D. J. D. Deyo, M. M. Klasing, M. Motamedi, and R. O. Esenaliev, “Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep,” Anesthesiology 102(1), 69–75 (2005).
[CrossRef]

Naivar, M.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Nolan, J. P.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Olsson, J.

Oraevsky, A. A.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

Patrikeev, I.

Petrov, Y. Y.

Petrova, I. Y.

Prough, D. S.

Querry, M. R.

Shashkov, E. V.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, N. G. Khlebtsov, and V. V. Tuchin, “In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents,” Opt. Lett. 31(24), 3623–3625 (2006).
[CrossRef] [PubMed]

Spring, P. M.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Su, R.

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

Suen, J. Y.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Svensen, C. H.

Tuchin, V. V.

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal flow cytometry in vitro for detection and imaging of individual moving cells,” Cytometry A 71A(4), 191–206 (2007).
[CrossRef]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, N. G. Khlebtsov, and V. V. Tuchin, “In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents,” Opt. Lett. 31(24), 3623–3625 (2006).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal imaging of moving cells in lymph and blood flow in vivo,” Proc. SPIE 5320, 256–263 (2004).

Viator, J. A.

S. H. Holan and J. A. Viator, “Automated wavelet denoising of photoacoustic signals for circulating melanoma cell detection and burn image reconstruction,” Phys. Med. Biol. 53(227–N), 236 (2008).
[CrossRef]

R. M. Weight, J. A. Viator, P. S. Dale, C. W. Caldwell, and A. E. Lisle, “Photoacoustic detection of metastatic melanoma cells in the human circulatory system,” Opt. Lett. 31(20), 2998–3000 (2006).
[CrossRef] [PubMed]

Wang, H. F.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

Wang, L. V.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler flow measurement in optically scattering media,” Appl. Phys. Lett. 91(26), 264103 (2007).
[CrossRef]

M. Xu and L. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77(4), 041101 (2006).
[CrossRef]

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Watson, D. A.

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

Weight, R. M.

Xu, M.

M. Xu and L. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77(4), 041101 (2006).
[CrossRef]

Xu, M. H.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Yang, L.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

Zharov, V. P.

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, J. W. Kim, and V. P. Zharov, “Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing circulating cancer stem cells,” J. Biophotonics 2(12), 725–735 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal flow cytometry in vitro for detection and imaging of individual moving cells,” Cytometry A 71A(4), 191–206 (2007).
[CrossRef]

R. R. Letfullin, C. Joenathan, T. F. George, and V. P. Zharov, “Laser-induced explosion of gold nanoparticles: potential role for nanophotothermolysis of cancer,” Nanomedicine (Lond) 1(4), 473–480 (2006).
[CrossRef]

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, N. G. Khlebtsov, and V. V. Tuchin, “In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents,” Opt. Lett. 31(24), 3623–3625 (2006).
[CrossRef] [PubMed]

V. P. Zharov, R. R. Letfullin, and E. N. Galitovskaya, “Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters,” J. Phys. D Appl. Phys. 38(15), 2571–2581 (2005).
[CrossRef]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal imaging of moving cells in lymph and blood flow in vivo,” Proc. SPIE 5320, 256–263 (2004).

Anesthesiology

Y. Y. Petrov, D. S. Prough, D. J. D. Deyo, M. M. Klasing, M. Motamedi, and R. O. Esenaliev, “Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep,” Anesthesiology 102(1), 69–75 (2005).
[CrossRef]

Appl. Opt.

Appl. Phys. Lett.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler flow measurement in optically scattering media,” Appl. Phys. Lett. 91(26), 264103 (2007).
[CrossRef]

Cancer Res.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser,” Cancer Res. 69(20), 7926–7934 (2009).
[CrossRef] [PubMed]

Cytometry A

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal flow cytometry in vitro for detection and imaging of individual moving cells,” Cytometry A 71A(4), 191–206 (2007).
[CrossRef]

D. A. Watson, L. O. Brown, D. R. Gaskill, M. Naivar, S. W. Graves, S. K. Doorn, and J. P. Nolan, “A flow cytometer for the measurement of Raman spectra,” Cytometry A 73A(2), 119–128 (2008).
[CrossRef]

E. I. Galanzha, E. V. Shashkov, V. V. Tuchin, and V. P. Zharov, “In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes,” Cytometry A 73A(10), 884–894 (2008).
[CrossRef]

J Biophotonics

E. I. Galanzha, M. S. Kokoska, E. V. Shashkov, J. W. Kim, V. V. Tuchin, and V. P. Zharov, “In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles,” J Biophotonics 2(8-9), 528–539 (2009).
[CrossRef] [PubMed]

J. Biomed. Opt.

V. P. Zharov, E. I. Galanzha, E. V. Shashkov, J. W. Kim, N. G. Khlebtsov, and V. V. Tuchin, “Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo,” J. Biomed. Opt. 12(5), 051503 (2007).
[CrossRef] [PubMed]

H. P. Brecht, R. Su, M. Fronheiser, S. A. Ermilov, A. Conjusteau, and A. A. Oraevsky, “Whole-body three-dimensional optoacoustic tomography system for small animals,” J. Biomed. Opt. 14(6), 064007 (2009).
[CrossRef]

J. Biophotonics

E. I. Galanzha, J. W. Kim, and V. P. Zharov, “Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing circulating cancer stem cells,” J. Biophotonics 2(12), 725–735 (2009).
[CrossRef] [PubMed]

J. Phys. D Appl. Phys.

V. P. Zharov, R. R. Letfullin, and E. N. Galitovskaya, “Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters,” J. Phys. D Appl. Phys. 38(15), 2571–2581 (2005).
[CrossRef]

Lasers Surg. Med.

J.-W. Kim, E. V. Shashkov, E. I. Galanzha, N. Kotagiri, and V. P. Zharov, “Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters,” Lasers Surg. Med. 39(7), 622–634 (2007).
[CrossRef] [PubMed]

Nanomedicine (Lond)

R. R. Letfullin, C. Joenathan, T. F. George, and V. P. Zharov, “Laser-induced explosion of gold nanoparticles: potential role for nanophotothermolysis of cancer,” Nanomedicine (Lond) 1(4), 473–480 (2006).
[CrossRef]

Nat. Nanotechnol.

J. W. Kim, E. I. Galanzha, E. V. Shashkov, H. M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, T. Kelly, J.-W. Kim, L. Yang, and V. P. Zharov, “In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells,” Nat. Nanotechnol. 4(12), 855–860 (2009).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Med. Biol.

S. H. Holan and J. A. Viator, “Automated wavelet denoising of photoacoustic signals for circulating melanoma cell detection and burn image reconstruction,” Phys. Med. Biol. 53(227–N), 236 (2008).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A.

W. He, H. F. Wang, L. C. Hartmann, J. X. Cheng, and P. S. Low, “In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry,” Proc. Natl. Acad. Sci. U.S.A. 104(28), 11760–11765 (2007).
[CrossRef] [PubMed]

Proc. SPIE

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, “Photothermal imaging of moving cells in lymph and blood flow in vivo,” Proc. SPIE 5320, 256–263 (2004).

Rev. Sci. Instrum.

M. Xu and L. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77(4), 041101 (2006).
[CrossRef]

Technol. Cancer Res. Treat.

G. Ku, B. D. Fornage, X. Jin, M. H. Xu, K. K. Hunt, and L. V. Wang, “Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging,” Technol. Cancer Res. Treat. 4(5), 559–566 (2005).
[PubMed]

Other

W. G. Zijlstra, A. Buursma, and O. W. van Assendelft, Visible and Near Infrared Absorption Spectra of Human and Animal Haemoglobin (VSP, Utrecht 2000).

H. M. Shapiro, Practical Flow Cytometry (Wiley-Liss, New York, 2003).

V. P. Zharov, and V. S. Letokhov, Laser optoacoustic spectroscopy (New York: Springer-Verlag, 1986).

S. E. Bialkowski, Photothermal spectroscopy methods for chemical analysis (A Wiley-Interscience publication, New York, 1996).

L. Wang, ed., Photoacoustic Imaging and Spectroscopy (Taylor & Francis/CRC Press, 2009).

A. N. S. Institute, American National Standard for the Safe Use of Lasers, ANSI Z136.1–2000, (American National Standards Institute, Washington, DC, 2000).

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Figures (10)

Fig. 1
Fig. 1

PAFC. (a) Scheme of the microscope for in vitro and in vivo studies; (b) fiber delivery of laser radiation; (c) study of CNTs suspension in 120-µm slide; (d) 300-µm glass tube in glycerol bath; (e) in vivo PA detection of circulating CNTs.

Fig. 2
Fig. 2

Signal diagrams: (a) Time diagram of laser pulses; (b) successive PT thermal-lens signals (linear and nanobubbles related signals); (c) laser-induced acoustic waves. Blue signals (# 1, 2, and 5) are background signals from blood and red signals (# 3–5) are from samples in flow with higher local light absorption (CNTs); (d) resulting curve in coordinates of PA signal amplitude vs. pulse number (or time) and curve parameters used to characterize CNTs parameters.

Fig. 3
Fig. 3

PA signals from a CNT solution in vitro, static conditions: (a) PA signal amplitudes at different f rep for l.0 and 2.0 µJ laser pulse energy, laser spot 150 μm; (b) time-resolved PT thermal-lens signals after a single laser pulse (exact position of the laser pulse is denoted by arrow); (c) PT stationary thermal-lens signals at high f rep values after beginning of excitation (denoted by arrow); (d) PA signal shapes recorded by PAFC in oscilloscope mode for 1, 100, 200, and 400 kHz; laser pulse energy, 1 μJ. Arrows indicate laser pulse position.

Fig. 4
Fig. 4

Amplitudes of PA signals from mouse blood and 3 μm CNT aggregates in 120-μm slide, f rep ~10 kHz, laser spot 25 μm, laser pulse energy 0.5 µJ.

Fig. 5
Fig. 5

PA detection of CNTs flowing in a 50-µm tube in vitro. (a) Traces of PA signals at the initial concentration of CNTs of 5 µg/mL and at different dilutions. The duration of displayed data is 100 s, and f rep = 10 kHz; (b) calibration graph for different CNT solutions based on data presented in part a; (c) average peak widths with the highest signal amplitudes as a function of the laser PRR. The intervals shown are confidence intervals for each data point n=20, P=0.95. Conditions of all experiments: flow rate, 3.4 cm/s; laser pulse energy, 1.5 µJ; laser beam size area, 10×50 µm.

Fig. 6
Fig. 6

PA detection of CNTs in a 350-µm tube in vitro at f rep of 9 kHz and 24 kHz. Linear flow velocity, 2.5 m/s. Laser pulse energy, 30 µJ; excitation beam configuration in tube, 25×150 µm.

Fig. 7
Fig. 7

Spectral characteristics of living tissue components and CNTs in the near-infrared region. (a) Light-absorption spectra of water [25], blood [26], and CNTs, 0.1 mg/mL solution in water; (b) PA spectra of skin with large blood vessels and of skin whitout it; (c,d) temporal shapes of PA signals from skin (c) and skin with blood vessels (d) measured at 1064 nm.

Fig. 8
Fig. 8

In vivo PAFC. (a) Mouse on the microscopic stage; (b) photo of ear blood vessel and laser beam spot made in transmission mode by CCD camera.

Fig. 9
Fig. 9

Traces of PA signals from circulating CNTs in mouse blood: (a,b) Two experiments with different mice. Injection of 5 and 50-µL CNTs solutions in PBS. Conditions of experiment: f rep, 9 kHz; laser pulse energy, 30 μJ; laser beam shape, 20×100 μm.

Fig. 10
Fig. 10

Statistical analysis of in vivo PAFC data. (a) Histogram representing the rates of peak emergence during the experiment; bin width is 20 s; (b) distribution of peak widths; (c) histogram representing the distribution of peak amplitudes (in logarithmic scale). The histograms were calculated for the experimental data displayed in Fig. 9(b).

Metrics