Low-cost dual-channel random-access fluorescence sensor for high spatiotemporal resolution neural recording

Hyejin Yoo¹Mark T Scimone¹Jeffery L Campbell¹Gopi Maguluri¹Nolan D Hartley²Zhanyan Fu²Aman Aberra³Michael Blake Hoppa³Nicusor V. Iftimia¹Youbo Zhao^1*

• ¹Physical Sciences Inc., ANDOVER, MA, United States
• ²Broad Institute of MIT and Harvard, Cambridge, MA, United States
• ³Dartmouth College, Hanover, NH, United States

High spatiotemporal resolution recording of neuronal dynamics is central to fundamental neuroscience, facilitating the investigation of normal brain functions and neurodegenerative pathologies. Fluorescence microscopy is widely employed for recording of neuronal activity across a wide range of temporal and spatial scales. However, existing fluorescence neural imaging technologies face limitations related to imaging speed, spatial resolution, complexity, and/or system cost. Thus, there is significant demand for simple yet effective solutions capable of achieving high spatiotemporal neuronal imaging. Here, we demonstrate a simple and effective fluorescence neural imaging sensor for recording of membrane potentials from multiple neurons with high spatiotemporal resolution. The selfcontained sensor combines two complementary detection channels, enabling neuronal recording with sub-micron spatial resolution and sub-millisecond temporal resolution. Sub-micron resolution imaging is achieved using a consumer-grade camera sensor, while sub-millisecond resolution is accomplished through a high-sensitivity single-point detector combined with a high-speed spatial light modulator. Compared to conventional scientific CMOS cameras, our approach offers increased temporal resolution, lower noise levels, improved data efficiency, and cost-effectiveness. We validated the capability of the prototype instrument through high spatiotemporal recordings of membrane dynamics and action potentials from cultured primary neurons and acute brain slices using fluorescent calcium and membrane voltage indicators. These results illustrate the potential of our technology as a low-cost, high-performance solution for non-invasive recording of neuronal kinetics with exceptional spatiotemporal resolution.