Synthesis and Luminescence Investigation of Nano-Scintillators As Next Generation Tools for Optogenetics

Currently, the visible light sources used for optogenetics are surgically implanted into the brain tissue, but this harmful and invasive technique may be avoided if suitable scintillating nanoparticles can be inserted via injection. The proposed nano-scintillator particles must adhere to rigorous parameters including being under 100nm, uniform, nontoxic, and dispersible to be successful in this biological system. The phase, crystallinity, and dopant concentration must be optimized to absorb X-ray radiation and emit photons of the desired energy necessary to activate the selected neurons.

We began a synthesis program to prepare suitable cerium doped gadolinium silicate nanoparticles to pair with blue absorbing opsins, such as channelrhodopsin-2. This produced several phases including Ce:Gd_4.67(SiO₄)₃O (Ce:GSAP), Ce:Gd₂SiO₅ (Ce:GSO), and Ce:Gd₂Si₂O_7, (Ce:GPS) nano-scintillators. In our modified core-shell synthesis the silica core served as both a template to ensure uniformity in size and shape, and could be manipulated to elicit different silicate phases. The addition of lutetium into the gadolinium silicate nanoparticles was also investigated. The mixed gadolinium/lutetium materials could also be engineered to produce different silicate phases and showed enhanced light output under X-ray stimulation.

Next, europium doped rare earth oxide (Eu:RE₂O₃, RE = Y, Gd, Lu) nanospheres were targeted as light sources for inhibitory opsins, such as the red-shifted cruxhalorhodopsin, Jaws. Monodispersed, spherical RE₂O₃ nanoparticles were produced via an urea assisted homogenous precipitation followed by annealing. We were able to obtain systematic increases in the radioluminescence intensity from our base Eu:RE₂O₃ nanoparticles by applying two different synthetic strategies.

MTS assays were ran on human embryonic kidney (HEK) cells incubated with the nanoparticles as an early cytotoxicity assessment. The ability to produce these particles in a straightforwardly, uniform, and dispersible manner as well as their relative chemical and biological inertness make them exciting candidates for the optogenetics toolbelt.