Project Summary Over the decades, various neurotechnologies have made significant advancements to meet the highest priority goals enumerated in the BRAIN 2025 Report. However, each tool development has been driven by a certain type of specific modalities in the target brain region, cell type, and limited experiments and has focused on scaling in a narrow domain. While the utility of such tools has uniquely served one modality, neuroscience experiments are inherently limited by the breadth of observations available. It is known that brain activities and status are affected by biophysiological parameters such as metabolism, hormones, neurotransmitters, temperature regulation, etc. However, as of yet, neurotechnology tools have not been combined to simultaneously measure multiple signals in a single experiment. This grant application proposes a reconfigurable neural interface platform on which multi-modal probes can be seamlessly integrated on the same flexible substrate to substantially enhance observational breadth. The proposed tool offers multi-modal capabilities by adding physio-bio-chemical sensor modules to the basic key electrophysiological functions of high-density neural recording and target-specific modulation of neurons. Each sensor module can be easily integrated into the existing modalities as an “additive” option, not a “replacing” alternative. The proposed platform is highly reconfigurable to meet the needs by pick-and-choose the desired modality for target studies and experiments. By modularizing and combing single-modality flexible probes, the proposed scheme can provide a highly efficient solution to the challenges in the comprehensive integration of multi-modality on the same platform. Preliminary Data: The previous work has demonstrated the feasibility of neuron-sized μLEDs (15 μm x 10 μm) monolithically integrated on silicon recording probes, precisely positioned relative to the recording sites. Prototype probes incorporated 256 recording sites and 128 μLEDs. Recently, we integrated the μLEDs on a flexible polymer substrate and stacked them with a recording probe. Initial feasibility was demonstrated for sensing dopamine and local brain temperature in-vivo from the flexible probes. Specific Aims: In aim 1, self-aligned flexible 3D origami probes will be developed for diverse neural interfaces with multiple modalities. Two prototype platforms will be developed: One is planar, stacked multi-modal probes with all electrical interfaces, and the other is 3D origami probes wrapped around an optical fiber that will give additional opto-modality such as photometry. In aim 2, a modular, compact headstage will be developed utilizing an innovative adaptable cable-on-chip assembly with custom ICs as an interposer. In aim 3, validation of the proposed multi-modal origami probes will be conducted in chronic rodent experiments.

Project Narrative This project will develop and validate reconfigurable multi-modal neural interface platforms for analysis of the dynamic activity of neural circuits at cellular resolution in a behaving animal. Multiple functional neural probes will be directly integrated with other physical sensors on a flexible substrate for measuring dopamine and temperature. The developed platform will uniquely address the restrictions in our current technologies, allowing neuroscientists to access important physiological parameters while recording and modulating neural activities in longitudinal chronic experiments.