The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.

Optical imaging and stimulation are widely used to study biological events. However, scattering processes limit the depth to which externally focused light can penetrate tissue. Optical fibers and waveguides are commonly inserted into tissue when delivering light deeper than a few millimeters. This approach, however, introduces complications arising from tissue damage. In addition, it makes it difficult to steer light. Here, we demonstrate that ultrasound can be used to define and steer the trajectory of light within scattering media by exploiting local pressure differences created by acoustic waves that result in refractive index contrasts. We show that virtual light pipes can be created deep into the tissue (>18 scattering mean free paths). We demonstrate the application of this technology in confining light through mouse brain tissue. This technology is likely extendable to form arbitrary light patterns within tissue, extending both the reach and the flexibility of light-based methods.

We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components. We show that a virtual optical graded-index (GRIN) lens can be sculpted in the medium using in situ reconfigurable ultrasonic interference patterns to relay images through the medium. Ultrasonic wave patterns change the local density of the medium to sculpt a graded refractive index pattern normal to the direction of light propagation, which modulates the phase front of light, causing it to focus within the medium and effectively creating a virtual relay lens. We demonstrate the in situ relay imaging and resolving of small features (22 µm) through a turbid medium (optical thickness = 5.7 times the scattering mean free path), which is normally opaque. The focal distance and the numerical aperture of the sculpted optical GRIN lens can be tuned by changing the ultrasonic wave parameters. As an example, we experimentally demonstrate that the axial focal distance can be continuously scanned over a depth of 5.4 mm in the modulated medium and that the numerical aperture can be tuned up to 21.5%. The interaction of ultrasonic waves and light can be mediated through different physical media, including turbid media, such as biological tissue, in which the ultrasonically sculpted GRIN lens can be used for relaying images of the underlying structures through the turbid medium, thus providing a potential alternative to implanting invasive endoscopes.

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