Abstract

We demonstrate optical trapping of red blood cells (RBCs) in living animals by using a water immersion objective. First, the cells within biological tissue are mimicked by the particles immersed in aqueous solutions of glycerol. The optical forces depending on trapping depth are investigated when a parallel laser beam enters the water immersion objective. The results show that the optical forces vary with trapping depth, and the optimal trapping depth in aqueous solutions of glycerol (n=1.39) is 50 μm. Second, the optimal trapping depth in aqueous solutions of glycerol can be changed by altering the actual tube length of the water immersion objective. Finally, we achieved optical trapping and manipulation of RBCs in living mice.

© 2013 Optical Society of America

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R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
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R. Skalak, N. Ozkaya, and T. Skalak, Annu. Rev. Fluid Mech. 21, 167 (1989).
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P. Barak, A. Rai, P. Rai, and R. Mallik, Nat. Methods 10, 68 (2013).
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Bjorkholm, J. E.

Block, S. M.

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
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Brenner, H.

J. Happel and H. Brenner, Low Reynolds Number Hydrodynamics (Martinus Nijhoff, 1983).

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I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
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Chu, S.

R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
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A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, Opt. Lett. 11, 288 (1986).
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T. Cizmar, M. Mazilu, and K. Dholakia, Nat. Photonics 4, 388 (2010).
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J. E. Curtis and D. G. Grier, Phys. Rev. Lett. 90, 133901 (2003).
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J. J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, J. Biomed. Opt. 10, 044014 (2005).
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T. Cizmar, M. Mazilu, and K. Dholakia, Nat. Photonics 4, 388 (2010).
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M. P. MacDonald, G. C. Spalding, and K. Dholakia, Nature 426, 421 (2003).
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Dirckx, J. J. J.

J. J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, J. Biomed. Opt. 10, 044014 (2005).
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Dziedzic, J. M.

Farge, G.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
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R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
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J. Happel and H. Brenner, Low Reynolds Number Hydrodynamics (Martinus Nijhoff, 1983).

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I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
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Heller, I.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
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Ivanov, C. D.

Ke, P. C.

P. C. Ke and M. Gu, J. Mod. Opt. 45, 2159 (1998).
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C. Veigel, J. E. Molloy, S. Schmitz, and J. Kendrick-Jones, Nat. Cell Biol. 5, 980 (2003).
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Khalesifard, H. R.

Kozma, I. Z.

Krok, P.

Kuypers, L. C.

J. J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, J. Biomed. Opt. 10, 044014 (2005).
[CrossRef]

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Ladavac, K.

Lagendijk, A.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, Nat. Photonics 4, 320 (2010).
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Lee, S.

Li, Y. M.

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
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M. C. Zhong, J. H. Zhou, Y. X. Ren, Y. M. Li, and Z. Wang, Appl. Opt. 48, 4397 (2009).
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Lieber, C.

Ma, L.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

MacDonald, M. P.

M. P. MacDonald, G. C. Spalding, and K. Dholakia, Nature 426, 421 (2003).
[CrossRef]

Mallik, R.

P. Barak, A. Rai, P. Rai, and R. Mallik, Nat. Methods 10, 68 (2013).
[CrossRef]

Mazilu, M.

T. Cizmar, M. Mazilu, and K. Dholakia, Nat. Photonics 4, 388 (2010).
[CrossRef]

Mehra, R.

R. Mehra, Proc. Indian Acad. Sci., Chem. Sci. 115, 147 (2003).
[CrossRef]

Menges, C.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

Molloy, J. E.

C. Veigel, J. E. Molloy, S. Schmitz, and J. Kendrick-Jones, Nat. Cell Biol. 5, 980 (2003).
[CrossRef]

Mosk, A. P.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, Nat. Photonics 4, 320 (2010).
[CrossRef]

I. Vellekoop and A. P. Mosk, Opt. Lett. 32, 2309 (2007).
[CrossRef]

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K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

Nikolov, I. D.

Ozkaya, N.

R. Skalak, N. Ozkaya, and T. Skalak, Annu. Rev. Fluid Mech. 21, 167 (1989).
[CrossRef]

Peterman, E. J. G.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

Polin, M.

Rai, A.

P. Barak, A. Rai, P. Rai, and R. Mallik, Nat. Methods 10, 68 (2013).
[CrossRef]

Rai, P.

P. Barak, A. Rai, P. Rai, and R. Mallik, Nat. Methods 10, 68 (2013).
[CrossRef]

Reihani, S. N. S.

Ren, Y. X.

Riedle, E.

Rohrbach, A.

Roichman, Y.

Rothman, J.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Schmidt, C. F.

Schmitz, S.

C. Veigel, J. E. Molloy, S. Schmitz, and J. Kendrick-Jones, Nat. Cell Biol. 5, 980 (2003).
[CrossRef]

Simmons, R. M.

R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
[CrossRef]

Sirinakis, G.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Sitters, G.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

Skalak, R.

R. Skalak, N. Ozkaya, and T. Skalak, Annu. Rev. Fluid Mech. 21, 167 (1989).
[CrossRef]

Skalak, T.

R. Skalak, N. Ozkaya, and T. Skalak, Annu. Rev. Fluid Mech. 21, 167 (1989).
[CrossRef]

Spalding, G. C.

M. P. MacDonald, G. C. Spalding, and K. Dholakia, Nature 426, 421 (2003).
[CrossRef]

Spudich, J. A.

R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
[CrossRef]

Stienen, G. J. M.

Torok, P.

Varga, P.

Veigel, C.

C. Veigel, J. E. Molloy, S. Schmitz, and J. Kendrick-Jones, Nat. Cell Biol. 5, 980 (2003).
[CrossRef]

Vellekoop, I.

Vellekoop, I. M.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, Nat. Photonics 4, 320 (2010).
[CrossRef]

Vermeulen, K. C.

Wang, Z.

Wang, Z. Q.

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
[CrossRef]

Wei, X. B.

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
[CrossRef]

Wende, W.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

Wuite, G. J. L.

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

K. C. Vermeulen, G. J. L. Wuite, G. J. M. Stienen, and C. F. Schmidt, Appl. Opt. 45, 1812 (2006).
[CrossRef]

Xi, Z.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Yu, G.

Zhang, Y.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Zhong, M. C.

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
[CrossRef]

M. C. Zhong, J. H. Zhou, Y. X. Ren, Y. M. Li, and Z. Wang, Appl. Opt. 48, 4397 (2009).
[CrossRef]

Zhou, J. H.

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
[CrossRef]

M. C. Zhong, J. H. Zhou, Y. X. Ren, Y. M. Li, and Z. Wang, Appl. Opt. 48, 4397 (2009).
[CrossRef]

Zorman, S.

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Annu. Rev. Fluid Mech. (1)

R. Skalak, N. Ozkaya, and T. Skalak, Annu. Rev. Fluid Mech. 21, 167 (1989).
[CrossRef]

Appl. Opt. (5)

Biophys. J. (1)

R. M. Simmons, J. T. Finer, S. Chu, and J. A. Spudich, Biophys. J. 70, 1813 (1996).
[CrossRef]

J. Biomed. Opt. (1)

J. J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, J. Biomed. Opt. 10, 044014 (2005).
[CrossRef]

J. Mod. Opt. (1)

P. C. Ke and M. Gu, J. Mod. Opt. 45, 2159 (1998).
[CrossRef]

J. Opt. Soc. Am. A (1)

J. Opt. Soc. Am. B (1)

Nat. Cell Biol. (1)

C. Veigel, J. E. Molloy, S. Schmitz, and J. Kendrick-Jones, Nat. Cell Biol. 5, 980 (2003).
[CrossRef]

Nat. Commun. (1)

M. C. Zhong, X. B. Wei, J. H. Zhou, Z. Q. Wang, and Y. M. Li, Nat. Commun. 4, 1768 (2013).
[CrossRef]

Nat. Methods (2)

P. Barak, A. Rai, P. Rai, and R. Mallik, Nat. Methods 10, 68 (2013).
[CrossRef]

I. Heller, G. Sitters, O. D. Broekmans, G. Farge, C. Menges, W. Wende, S. W. Hell, E. J. G. Peterman, and G. J. L. Wuite, Nat. Methods 10, 910 (2013).
[CrossRef]

Nat. Photonics (2)

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, Nat. Photonics 4, 320 (2010).
[CrossRef]

T. Cizmar, M. Mazilu, and K. Dholakia, Nat. Photonics 4, 388 (2010).
[CrossRef]

Nature (1)

M. P. MacDonald, G. C. Spalding, and K. Dholakia, Nature 426, 421 (2003).
[CrossRef]

Opt. Express (2)

Opt. Lett. (4)

Phys. Rev. Lett. (1)

J. E. Curtis and D. G. Grier, Phys. Rev. Lett. 90, 133901 (2003).
[CrossRef]

Proc. Indian Acad. Sci., Chem. Sci. (1)

R. Mehra, Proc. Indian Acad. Sci., Chem. Sci. 115, 147 (2003).
[CrossRef]

Rev. Sci. Instrum. (1)

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

Science (1)

Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. Rothman, and Y. Zhang, Science 337, 1340 (2012).
[CrossRef]

Other (1)

J. Happel and H. Brenner, Low Reynolds Number Hydrodynamics (Martinus Nijhoff, 1983).

Supplementary Material (1)

» Media 1: MOV (14625 KB)     

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Figures (4)

Fig. 1.
Fig. 1.

Optical tweezers setup. Instrument layout showing optical paths for 1064 nm trapping laser and halogen lamp for bright-field imaging. L1–L3, lens; Ltube, tube lens; M1 and M2, mirrors; MO, microscope objective; DM, dichroic mirror; PZT, piezoelectric transducer. The inset shows the geometric optics representation of the refraction of a light beam focused in vivo. NFP, nominal focal position; AFP, the actual focal position.

Fig. 2.
Fig. 2.

Escape velocities as a function of trapping depth for trapped particle immersion in different refractive indices medias. The escape velocities are normalized with their maximum velocities. The trapping laser beam is parallel at the BFP of the objective.

Fig. 3.
Fig. 3.

Escape velocities as a function of trapping depth for different actual tube length t. The trapped particles are immersed in aqueous solutions of glycerol. The actual tube lengths with values of negative, infinite, and finite represent the converging, parallel, and diverging laser beam hitting the BFP of the objective, respectively.

Fig. 4.
Fig. 4.

(Media 1) Optical manipulation of an RBC in three dimensions. (a) and (b) Longitudinal manipulation of an RBC. With the longitudinal movement of the optical trap, the (a) clear image of the surrounding tissue becomes (b) blurred, whereas the trapped RBC image is always clear, indicating that the trapped RBC is moving longitudinally with the optical trap. (c) and (d) Transversal manipulation of an RBC. With the transversal movement of the optical trap, the trapped RBC is gradually far away from the surrounding tissue. The cell moves with a transversal distance of about 4.2 μm. Scale bar, 10 μm; “+” indicates the optical trap center.

Equations (2)

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

ψ(θ1,θ2,d)=d(n1cosθ1n2cosθ2).
ψ=2k0s2Δll2×sin4(θ1/2)

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