Optical microscopy system

About

Background: Researchers in Prof. Karl Deisseroth’s laboratory have developed an optical imaging and optogenetics two photon laser system that uses a single beam to illuminate many sites in three-dimensions. The invention employs a low repetition rate, high peak energy laser with a programmable diffractive element to precisely deliver femtosecond pulsed laser light to cellular-sized regions under a microscope. This technology enables all optical closed loop observations and control of neural activity.   Stage of Research: The inventors were able to sample calcium signals at 10 Hz from 104 locations spanning 200 microns in depth through a cranial window over S1 barrel cortex in head-fixed mice (N=2) virally transduced with GCaMP6m (AAVdj-Camk2a-GCaMP6m) undergoing whisker stimulation.   Applications: Optical imaging - including 3D calcium or voltage imaging in rodent in vivo applications Optogenetic control - 3D control, possibly in a closed loop configuration which would enable end users to perform circuit screening in animal models for neuropsychiatric disease   Advantages: Structured 3D illumination - can illuminate many more sites, over a much larger 3D field of view than previous systems Two photon excitation - can generate more signal than previous systems, with longer dwell times than scanning-based systems Precise - femtosecond pulsed laser enables spatially precise delivery of light using two photon excitation to achieve a greater penetration depth in scattering tissue   Publications: PCT Published Patent WO 2016209654 A1, "Methods and devices for imaging and/or optogenetic control of light-responsive neurons". Samuel J. Yang, William E. Allen, Isaac Kauvar, Aaron S. Andalman, Noah P. Young, Christina K. Kim, James H. Marshel, Gordon Wetzstein, and Karl Deisseroth, "Extended field-of-view and increased-signal 3D holographic illumination with time-division multiplexing,". Optics Express Vol. 23, Issue 25, pp. 32573-32581 (2015).