Recording brain activity from the individual neuron scale to neural networks is required for fully understanding the pathology of neurological diseases and developing new treatments. Optical techniques show much promise for imaging over these length scales; however, current methods generally require genetic encoding, rely on fluorophores that blink and bleach over time, or render the brains fixed or dead. Here, we report a new platform using upconverting nanoparticles coupled to voltage sensitive dyes to overcome limitations of current technologies. Upconverting nanoparticles use long lived f-f transitions in lanthanide ions to absorb near infrared (NIR) light and emit visible light. Owing to their passive ceramic host lattice, upconverting nanoparticles typically do not respond to external fields. To confer electric field sensitivity, we have adopted a novel core-shell structure and we couple the nanoparticles to voltage sensitive dyes. The nanoparticle core is ~5 nm NaYbF4 to maximize NIR photon absorption. The optically excited Yb3+ transfers energy to emitters (e.g. Er3+) doped in the shell. These emitters are optically coupled to the voltage sensitive dye DI-2-ANEPEQ on the nanoparticle surface. By concentrating the emitters in the shell, they are closer to the surface dyes, increasing FRET between lanthanide and dye and thereby enhancing the voltage sensitivity. We vary the shell dimensions from 0.5 to 2 and doping concentrations from 1 to 20% to maximize brightness and voltage sensitivity, while maintaining the total system size &lt;13 nm. In the presence of an electric field, the electronic states of the dye shift and its emission intensity decreases. This shift in the electronic states changes the coupling between the upconverters and the dye leading to spectral and intensity changes in the upconverter emission when an electric field is applied. We have measured a decrease in the upconversion intensity of ~7% under an electric field of ~125 kV/cm, comparable to the ~1-10% emission intensity change isolated dye molecules undergo in electric fields. Moreover, we measure a spectro-ratiometric change (the ratio between the green and red emission in Er3+) in emission of ~9% in a 125 kV/cm electric field, highlighting the sensitivity of these nanoparticles as electric field sensors for in vivo electric fields. Finally, we highlight enhancements to biostability and targeting of our nanoparticles via surface-functionalization with polymer.

Electric field sensitive upconverting nanoparticles: Toward background free in vivo action potential imaging

256th National Meeting (2018)

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