Overcoming the tradeoff between confinement and focal distance using virtual ultrasonic optical waveguides

Optogenetics has become a widely used technique in neuroscience research, capable of controlling neuronal activity with high spatiotemporal precision and cell‐type specificity. Expressing exogenous opsins in the selected cells can induce neuronal activation upon light irradiation, and the activation depends on the power of incident light. However, high optical power can also lead to off‐target neuronal activation or even cell damage. Limiting the incident power, but enhancing power distribution to the targeted neurons, can improve optogenetic efficiency and reduce off‐target effects. Here, the use of optical lenses made of polystyrene microspheres is demonstrated to achieve effective focusing of the incident light of relatively low power to neighboring neurons via photonic jets. The presence of microspheres significantly localizes and enhances the power density to the target neurons both in vitro and ex vivo, resulting in increased inward current and evoked action potentials. In vivo results show optogenetic stimulation with microspheres that can evoke significantly more motor behavior and neuronal activation at lowered power density. In all, a proof‐of‐concept of a strategy is demonstrated to increase the efficacy of optogenetic neuromodulation using pulses of reduced optical power.

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Section: Resultsmentioning

confidence: 99%

Photonic Nanojet‐Mediated Optogenetics

Guo

Gong

et al. 2022

Advanced Science

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“…Therefore, other strategies for light delivery, such as focused ultrasound to guide the propagation and emission of light in the local brain tissue noninvasively can become complementary to the nanoject based optogenetics in the future studies. [30,31] Using microspheres for the formation of PNJs offer the possibility of tailoring their physical properties depending upon the intended application. Opsins that have been applied in optogenetics can be activated by light at different wavelengths.…”

Section: Discussionmentioning

confidence: 99%

Photonic Nanojet‐Mediated Optogenetics

Guo¹,

Wu²,

Gong³

et al. 2022

Advanced Science

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In the original published article, there was a mistake in Figure 2I. Please find the correct Figure 2 below.Figure 2. PS microsphere enhances light-evoked neuron activity via ChR2. A) Schematic configuration for in vitro experiment. Whole-cell patch clamp recording was conducted in ChR2-expressed cells stimulated by blue light in the presence of PS (PS(+)) or not (PS(−)). B) Inward currents induced by a 100 ms light pulse with or without PS in 293T cell with ChR2. C) The curve between input power density and inward currents induced by light with PS or without PS in 293T cells, n = 5, *p < 0.05, **p < 0.01, ***p < 0.001, unpaired two-tailed t-test. D) Inward currents of the target neurons as a function of the input power density. E) Primary hippocampal neurons expressing ChR2-mCherry in bright filed and 488 nm excitation without PS or with PS (scale bar 100 μm). F) Inward currents induced by 20 ms light pulse with or without PS in primary hippocampus neuron with ChR2. n = 10, ***p < 0.001 unpaired two-tailed t-test. G) The curve between input power density and inward currents induced by light with PS or without PS in primary hippocampus neuron. H) Inward currents of the target neurons as a function of the input power density. I) Current clamp recording of hippocampus neuron stimulated with 20 ms pulse light without or with PS. J) Success rate of generation of action potential evoked by light pulse in different power density. n = 3, **p < 0.01, unpaired two-tailed t-test.

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“…In particular, as ultrasonic pressure waves are applied to the medium, they modulate its local refractive index, creating continuously-varying refractive index profiles analogous to those in gradient-index (GRIN) optical waveguides. Depending on the sculpted profile, the resulting virtual optical waveguides can steer light to produce focused spots [1] and complex spatio-temporal patterns [2] inside the medium, or relay images through the medium [3].…”

Section: Introductionmentioning

confidence: 99%

“…For example, virtual optical waveguides can potentially be used in biomedical applications, to enable light delivery and confinement through absorptive and scattering biological tissue for optogenetic stimulation of cells, fluorescence imaging, calcium imaging, photodynamic and photothermal therapy [6,7,8,9,10,11]. More generally, virtual optical waveguides can improve the performance and flexibility of the methods and processes for light manipulation in clear and turbid compressible media [12].…”

Section: Introductionmentioning

confidence: 99%

Optimized Virtual Optical Waveguides Enhance Light Throughput in Scattering Media

Pediredla

Scopelliti

Narasimhan

et al. 2021

Preprint

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Ultrasonically sculpted gradient-index optical waveguides make it possible to non-invasively steer and confine light inside scattering media. This confinement capability has applications in tissue and brain imaging, where virtual optical waveguides can be used on their own or cascaded with physical optical elements. The level of light confinement strongly depends on ultrasound parameters such as modulation pattern, frequency, and amplitude, as well as the material parameters of the scattering medium such as the refractive index, scattering coefficient, and phase function. We provide a characterization of these dependencies for a radially symmetric virtual optical waveguide. To this end, we develop a physically-accurate simulator, and use it to quantify how different ultrasound and material parameters affect light confinement. We explain our observations through a qualitative analysis of the behavior of multiply scattered light. We use the results of this analysis to demonstrate that, by properly designing ultrasound parameters, we can achieve a fourfold improvement in light confinement compared to previous virtual optical waveguide designs. We additionally show that virtual optical waveguides can achieve up to 50% light throughput enhancement compared to an ideal external lens, in a medium that mimics the scattering properties of human bladder, and at an optical thickness of one transport mean free path. Lastly, we show experimental results that corroborate the simulation predictions. In particular, we demonstrate for the first time that virtual optical waveguides effectively recycle scattered light in turbid media, and can achieve a 15% light throughput enhancement at five transport mean free paths.

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Overcoming the tradeoff between confinement and focal distance using virtual ultrasonic optical waveguides

Cited by 10 publications

References 30 publications

Photonic Nanojet‐Mediated Optogenetics

Photonic Nanojet‐Mediated Optogenetics

Photonic Nanojet‐Mediated Optogenetics

Optimized Virtual Optical Waveguides Enhance Light Throughput in Scattering Media

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