Title: Adaptive Optics Microscopy Using Direct Wavefront Sensing for Deep Tissue Imaging Xiaodong Tao, UCSC Abstract: Optical aberrations due to the inhomogeneous refractive index of tissue degrade the resolution and brightness of images in deep tissue imaging. We introduce a confocal fluorescence microscope with Adaptive Optics (AO) for high-speed and high-performance wavefront correction. The wavefront is measured directly by a Shack-Hartmann wavefront sensor using a fluorescent microsphere embedded in the sample as a reference beacon. We have also recently used fluorescent proteins labeled in sub-cellular structures for reference beacons, which generalizes the technique to many different samples. Our recent results have shown a 4.3x improvement in the image quality (Strehl ratio) and a 2.4x improvement in the signal intensity for fixed mouse brain tissues at depths of up to 100 µm. Results from live Drosophila (fruit fly) embryo shows the ability to improve the intensity and resolution to depth of 120µm. The interferometric focusing applied in wavefront sensing to suppress scattering will be also discussed.