Implantable photonic neural probes with 3D-printed microfluidics and applications to uncaging.

Advances in chip-scale photonic-electronic integration are enabling a new generation of foundry-manufacturable implantable silicon neural probes incorporating nanophotonic waveguides and microelectrodes for optogenetic stimulation and electrophysiological recording in neuroscience research. Further extending neural probe functionalities with integrated microfluidics is a direct approach to achieve neurochemical injection and sampling capabilities. In this work, we use two-photon polymerization 3D printing to integrate microfluidic channels onto photonic neural probes, which include silicon nitride nanophotonic waveguides and grating emitters. The customizability of 3D printing enables a unique geometry of microfluidics that conforms to the shape of each neural probe, enabling integration of microfluidics with a variety of existing neural probes while avoiding the complexities of monolithic microfluidics integration. We demonstrate the photonic and fluidic functionalities of the neural probes via fluorescein injection in agarose gel and photoloysis of caged fluorescein in solution and in fixed brain tissue.

3D printed neural tissues with in situ optical dopamine sensors.

Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO could sense DA in the 3D printed neural network with a detection limit of 0.137 µM. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.