Abstract

A new photoacoustic flow cytometry was developed for real-time detection of circulating cells, nanoparticles, and contrast agents in vivo. Its capability, integrated with photothermal and optical clearing methods, was demonstrated using a near-infrared tunable laser to characterize the in vivo kinetics of Indocyanine Green alone and single cancer cells labeled with gold nanorods and Indocyanine Green in the vasculature of the mouse ear. In vivo applications are discussed, including selective nanophotothermolysis of metastatic squamous cells, label-free detection of melanoma cells, study of pharmokinetics, and immune response to apoptotic and necrotic cells, with potential translation to humans. The threshold sensitivity is estimated as one cancer cell in the background of 107 normal blood cells.

© 2006 Optical Society of America

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  1. J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, Opt. Lett. 29, 77 (2004).
    [CrossRef] [PubMed]
  2. V. Zharov, E. Galanzha, and V. Tuchin, in Proc. SPIE 5320, 256 (2004).
  3. V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
    [CrossRef] [PubMed]
  4. X. Wang, G. Ku, M. A. Wegiel, D. J. Bornhop, G. Stoica, and L. V. Wang, Opt. Lett. 29, 730 (2004).
    [CrossRef] [PubMed]
  5. X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
    [CrossRef]

2006 (1)

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
[CrossRef] [PubMed]

2004 (3)

2003 (1)

X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
[CrossRef]

Bornhop, D. J.

Galanzha, E.

V. Zharov, E. Galanzha, and V. Tuchin, in Proc. SPIE 5320, 256 (2004).

Galanzha, E. I.

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
[CrossRef] [PubMed]

Georgakoudi, I.

Ku, G.

Lin, C. P.

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, Opt. Lett. 29, 77 (2004).
[CrossRef] [PubMed]

X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
[CrossRef]

Novak, J.

Prossin, A.

Runnels, J. M.

X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
[CrossRef]

Stoica, G.

Tuchin, V.

V. Zharov, E. Galanzha, and V. Tuchin, in Proc. SPIE 5320, 256 (2004).

Tuchin, V. V.

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
[CrossRef] [PubMed]

Wang, L. V.

Wang, X.

Wegiel, M. A.

Wei, X.

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, Opt. Lett. 29, 77 (2004).
[CrossRef] [PubMed]

X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
[CrossRef]

Zharov, V.

V. Zharov, E. Galanzha, and V. Tuchin, in Proc. SPIE 5320, 256 (2004).

Zharov, V. P.

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
[CrossRef] [PubMed]

Invest. Ophthalmol. Visual Sci. (1)

X. Wei, J. M. Runnels, and C. P. Lin, Invest. Ophthalmol. Visual Sci. 44, 4489 (2003).
[CrossRef]

J. Cell. Biochem. (1)

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J. Cell. Biochem. 97, 916 (2006).
[CrossRef] [PubMed]

Opt. Lett. (2)

Proc. SPIE (1)

V. Zharov, E. Galanzha, and V. Tuchin, in Proc. SPIE 5320, 256 (2004).

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Figures (4)

Fig. 1
Fig. 1

Integrated PA/PT FC with near-IR laser.

Fig. 2
Fig. 2

(a) Mouse ear. Transmission image of ear (b) before and (c) after topical administration of an optical clearing agent, glycerol (magnification 10 × ). (d) High-resolution images of individual RBCs in a capillary (indicated by dashed curves; magnification 100 × ).

Fig. 3
Fig. 3

(a) PT and (b) PA signals from the same RBCs in a blood capillary of the mouse ear, (top) noncompressed and (bottom) compressed. (c) PA signal from blood flow in vessel with diameter 30 μ m . (d) PA signal from single cancer cell labeled with GNs in blood flow. Amplitude/time scale/(laser pump wavelength)/(laser fluence): (a, top) 20 mV div 4 μ s div 530 nm 0.3 J cm 2 , (a, bottom) 20 mV div 20 ms div 530 nm 0.3 J cm 2 ; (b, top) 20 mV div 4 μ s div 530 nm 0.3 J cm 2 ; (b, bottom) 20 mV div 4 μ s div 530 nm 0.3 J cm 2 ; (c) 20 mV div 4 μ s 840 nm 25 mJ cm 2 ; (d) 200 mV div 4 μ s div 840 nm 18 mJ cm 2 .

Fig. 4
Fig. 4

(a) PT spectra of single cancer cells labeled with ICG or GN and single RBCs in solution in vitro at laser fluences 0.1, 0.028, and 0.09 J cm 2 , respectively. The dashed line with open triangles shows PT spectra of GNs after laser exposure (1 pulse, 20 mJ cm 2 ). (b) Normalized number of circulating cancer cells labeled with GNs and ICG in blood flow as a function of time postinjection monitored at 840 and 805 nm , respectively. (c) PA monitoring of ICG in the blood flow at 805 nm (maximum ICG absorption in flow).

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