Abstract

Within optogenetics there is a need for compact light sources that are capable of delivering light with excellent spatial, temporal, and spectral resolution to deep brain structures. Here, we demonstrate a custom GaN-based LED probe for such applications and the electrical, optical, and thermal properties are analyzed. The output power density and emission spectrum were found to be suitable for stimulating channelrhodopsin-2, one of the most common light-sensitive proteins currently used in optogenetics. The LED device produced high light intensities, far in excess of those required to stimulate the light-sensitive proteins within the neurons. Thermal performance was also investigated, illustrating that a broad range of operating regimes in pulsed mode are accessible while keeping a minimum increase in temperature for the brain (0.5°C). This type of custom device represents a significant step forward for the optogenetics community, allowing multiple bright excitation sites along the length of a minimally invasive neural probe.

© 2013 Optical Society of America

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References

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2012 (4)

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

E. Stark, T. Koos, and G. Buzsaki, J. Neurophysiol. 108, 349 (2012).
[CrossRef]

A. N. Zorzos, J. Scholvin, E. S. Boyden, and C. G. Fonstad, Opt. Lett. 37, 4841 (2012).
[CrossRef]

2010 (1)

K. Deisseroth, Nat. Methods 8, 26 (2010).
[CrossRef]

2008 (2)

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

H. X. Zhang, D. Massoubre, J. McKendry, Z. Gong, B. Guilhabert, C. Griffin, E. Gu, P. E. Jessop, J. M. Girkin, and M. D. Dawson, Opt. Express 16, 9918 (2008).
[CrossRef]

2006 (1)

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

1995 (1)

P. Andersen and E. I. Moser, Hippocampus 5, 491 (1995).
[CrossRef]

Andersen, P.

P. Andersen and E. I. Moser, Hippocampus 5, 491 (1995).
[CrossRef]

Bernstein, J. G.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Bikson, M.

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

Boyden, E. S.

A. N. Zorzos, J. Scholvin, E. S. Boyden, and C. G. Fonstad, Opt. Lett. 37, 4841 (2012).
[CrossRef]

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Buzsaki, G.

E. Stark, T. Koos, and G. Buzsaki, J. Neurophysiol. 108, 349 (2012).
[CrossRef]

Cho, I.-J.

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

Dawson, M. D.

Deisseroth, K.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

K. Deisseroth, Nat. Methods 8, 26 (2010).
[CrossRef]

Desimone, R.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Elwassif, M. M.

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

Fonstad, C. G.

Funabiki, K.

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Girkin, J. M.

Gong, Z.

Govindarajan, A.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Griffin, C.

Gu, E.

Guilhabert, B.

Han, X.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Hayashi, Y.

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Henninger, M. A.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Im, M.

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

Jessop, P. E.

Ko, E. Y.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Kong, Q.

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

Koos, T.

E. Stark, T. Koos, and G. Buzsaki, J. Neurophysiol. 108, 349 (2012).
[CrossRef]

Liu, X.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Massoubre, D.

McConnell, J. P.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

McKendry, J.

Moser, E. I.

P. Andersen and E. I. Moser, Hippocampus 5, 491 (1995).
[CrossRef]

Nakanishi, S.

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Pang, P. T.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Puryear, C. B.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Qian, X.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Ramirez, S.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Scholvin, J.

Stark, E.

E. Stark, T. Koos, and G. Buzsaki, J. Neurophysiol. 108, 349 (2012).
[CrossRef]

Stern, P.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Tagawa, Y.

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Talei Franzesi, G.

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Tonegawa, S.

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Vazguez, M.

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

Wise, K.

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

Wu, F.

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

Yawata, S.

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Yoon, E.

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

Zhang, H. X.

Zorzos, A. N.

Eur. J. Neurosci. (1)

Y. Hayashi, Y. Tagawa, S. Yawata, S. Nakanishi, and K. Funabiki, Eur. J. Neurosci. 36, 2722 (2012).
[CrossRef]

Hippocampus (1)

P. Andersen and E. I. Moser, Hippocampus 5, 491 (1995).
[CrossRef]

J. Neural Eng. (1)

M. M. Elwassif, Q. Kong, M. Vazguez, and M. Bikson, J. Neural Eng. 3, 306 (2006).
[CrossRef]

J. Neurophysiol. (1)

E. Stark, T. Koos, and G. Buzsaki, J. Neurophysiol. 108, 349 (2012).
[CrossRef]

Nat. Methods (1)

K. Deisseroth, Nat. Methods 8, 26 (2010).
[CrossRef]

Nature (1)

X. Liu, S. Ramirez, P. T. Pang, C. B. Puryear, A. Govindarajan, K. Deisseroth, and S. Tonegawa, Nature 484, 381 (2012).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

Proc. SPIE (1)

J. G. Bernstein, X. Han, M. A. Henninger, E. Y. Ko, X. Qian, G. Talei Franzesi, J. P. McConnell, P. Stern, R. Desimone, and E. S. Boyden, Proc. SPIE 6854, 68540H (2008).
[CrossRef]

Other (1)

M. Im, I.-J. Cho, F. Wu, K. Wise, and E. Yoon, in International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE, 2011), p. 5480.

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Figures (3)

Fig. 1.
Fig. 1.

(a) Layout of LED probe, showing the single n-contact and bonding pads linked with tracks to the p-contacts for each LED. (b) Schematic cross section of the fabricated devices, showing the quantum well (QW) LED structure. (c) Tip of the five-site LED probe, before final thinning, with a single LED switched on, emission is through the sapphire substrate. Scale bar is 200 μm.

Fig. 2.
Fig. 2.

(a) Irradiance-current response for an LED. (b) Emission spectra of the LED at various light irradiances showing overlap with the absorption spectrum of ChR2. (c), (d) The calculated light intensity at differing depths within the brain for various device irradiances. The data points in (d) are from transmission experiments through varying thicknesses of brain slices (error is SD). Optogenetic constructs require 110mW/mm2 [1].

Fig. 3.
Fig. 3.

(a) Measured temperature profile for a single 200 ms pulse at 350mW/mm2 and 600mW/mm2. (b) Measured peak temperature of a single pulse for various pulse widths. (c) Measured average temperature rise versus repetition rate for an LED operating at 600mW/mm2 with various pulse widths. (d) The maximum repetition rate that the device can be operated at and not rise 0.5°C above ambient for two irradiances. Also shown is the maximum frequency for a given pulse. At lower irradiances the temperature rise was insufficient to be accurately recorded with the thermal camera.

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