Abstract
Micro-optics are increasingly used for minimally invasive in vivo imaging, in miniaturized microscopes and in lab-on-a-chip devices. Owing to optical aberrations and lower numerical apertures, a main class of microlens, gradient refractive index lenses, has not achieved resolution comparable to conventional microscopy. Here we describe high-resolution microlenses, and illustrate two-photon imaging of dendritic spines on hippocampal neurons and dual-color nonlinear optical imaging of neuromuscular junctions in live mice.
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References
Flusberg, B.A. et al. Nat. Methods 2, 941–950 (2005).
Levene, M.J., Dombeck, D.A., Kasischke, K.A., Molloy, R.P. & Webb, W.W. J. Neurophysiol. 91, 1908–1912 (2004).
Alencar, H., Mahmood, U., Kawano, Y., Hirata, T. & Weissleder, R. Neoplasia 7, 977–983 (2005).
Flusberg, B.A., Jung, J.C., Cocker, E.D., Anderson, E.P. & Schnitzer, M.J. Opt. Lett. 30, 2272–2274 (2005).
Engelbrecht, C.J., Johnston, R.S., Seibel, E.J. & Helmchen, F. Opt. Express 16, 5556–5564 (2008).
Flusberg, B.A. et al. Nat. Methods 5, 935–938 (2008).
Hsiung, P.L. et al. Nat. Med. 14, 454–458 (2008).
Llewellyn, M.E., Barretto, R.P., Delp, S.L. & Schnitzer, M.J. Nature 454, 784–788 (2008).
Lin, K.Y., Maricevich, M., Bardeesy, N., Weissleder, R. & Mahmood, U. Transl. Oncol. 1, 84–94 (2008).
Roulet, J.C. et al. Anal. Chem. 74, 3400–3407 (2002).
Messerschmidt, B., McIntyre, B.L. & Houde-Walter, S.N. Appl. Opt. 35, 5670–5676 (1996).
Sickenger, H., Falkenstoerfer, O.R., Lindlein, N. & Schwider, J. Opt. Eng. 33, 2680–2686 (1994).
Born, M. & Wolf, E. Principles of Optics (Cambridge University Press, Cambridge, UK, 1999).
Jung, J.C., Mehta, A.D., Aksay, E., Stepnoski, R. & Schnitzer, M.J. J. Neurophysiol. 92, 3121–3133 (2004).
Knott, G. & Holtmaat, A. Brain Res. Rev. 58, 282–289 (2008).
Jung, J.C. & Schnitzer, M.J. Opt. Lett. 28, 902–904 (2003).
Messerschmidt, B., Possner, U. & Houde-Walter, S.N. Appl. Opt. 36, 8145–8152 (1997).
Messerschmidt, B., Possner, T. & Goering, R. Appl. Opt. 34, 7825–7830 (1995).
Acknowledgements
We thank the US National Institute of Neurological Disorders and Stroke (M.J.S.), GRINTech GmbH (B.M.) and the Stanford Biophysics (R.P.J.B.) training grant from the US National Institutes of Health for support of our work. We thank A. Attardo, L.D. Burns, E. Ho, J. Kobelke, S. Plochowietz and D. Profitt for technical assistance.
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Barretto, R., Messerschmidt, B. & Schnitzer, M. In vivo fluorescence imaging with high-resolution microlenses. Nat Methods 6, 511–512 (2009). https://doi.org/10.1038/nmeth.1339
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DOI: https://doi.org/10.1038/nmeth.1339
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