Optical Microscopy

Neuroscience requires microscopes to volumetrically image neural activity with high temporal resolution. My lab’s optical microscopes significantly increased the imaging metrics of multiple forms of microscopes that image volumes of neural tissue. We combined light-sheet microscopy, structured illumination, and light-field microscopy to enhance the contrast of light-field microscopy by an order of magnitude and the resolution by a factor of two. Another approach in our lab is to use a form of oblique light-sheet microscopy (SCAPE). This microscope scans an oblique light-sheet pattern and de-scans the light-sheet fluorescence to a fixed plane, thus removing limitations imposed by scanning mechanics in the system. However, this microscope design suffers from low light transmission due to the two-objective turn that rotates the oblique light-sheet toward the camera. We designed a water coupling between those two objectives, supporting the use of high numerical aperture objectives in the SCAPE turn that tripled the transmission and doubled resolution of the microscope. We used this microscope to examine neural activity from live zebrafish as well. My optical microscopes will impact neuroscience by increasing the signal fidelity and expanding the volume recorded from live brain tissue; such enhancements will increase the accuracy and the explanatory power of the captured neural activity.

Left: Our new our oblique light-sheet microscope used a water-coupling between the final two objectives to increase resolution and light transmission efficiency. Right: This microscope can image neural activity from zebrafish at high speed.

Key papers