Apparatus for Sensitive Fluorescence Optical Measurement of Biological Parameters in Freely Behaving Animals

Fiber photometry, a measurement technique that aggregates fluorescence signal using a fiber optic, is a highly pervasive approach in the field of systems neuroscience to study in vivo brain tissue dynamics during ecologically relevant behavior. Despite its common usage by researchers and companies alike, none of the state-of-the art fiber photometry device is capable of detecting small and fast signal changes in a low-light regime in freely behaving animals. Current technologies are benchmarked against cytosolic calcium indicators whose dynamic ranges far exceed that of the instrument and biological noises. Therefore, when used outside of this original configuration, i.e. with other fluorescent indicators (voltage, neuromodulator sensors…) with much weaker dynamic ranges, these instruments do not protect against unwanted noise sources which can lead to biological confounds, especially when the instrumental noise correlates with the animal motion.

Inventors at Stanford have developed a novel fiber-optic technology that achieves ~10 fold greater sensitivity than prior fiber photometry systems and is immune to optical artifacts induced by animal motions. The uSMAART (ultra-Sensitive Measurement of Aggregated Activity in Restricted cell-Types) technology tracks signals from up to 2 reporters from up to 2 different brain regions concurrently, with high sensitivity. The uSMAART system outperforms similar fiber photometry implementations in at least one of the three following aspects: (1) stability of illumination source, (2) immunity to fiber motion-induced illumination artefacts, and (3) detection sensitivity in the visible range. The novel technology offers a low-cost, flexible, and highly sensitive tool to decipher the precise temporal relationship of multiple physiological processes from multiple brain regions simultaneously.

Stage of Development
Research – in vivo – working prototype and proof-of-concept in mice

Related Technology
Stanford Docket: S23-493: Strategy and Technological Implementations for Concurrent Fluorescence Measurements of Multiple Biological Parameters in Behaving Animals