Digging Deeper through Biological Specimens Using Adaptive Optics-Based Optical Microscopy

Optical microscopy is a vital tool for visualizing the cellular and sub-cellular structures of biological specimens. However, due to its limited penetration depth, its biological applicability has been hindered. The scattering and absorption of light by a wide array of biomolecules causes signal attenuation and restricted imaging depth in tissues. Researchers have put forth various approaches to address this, including designing novel probes for imaging applications and introducing adaptive optics (AO) technology. Various techniques, such as direct wavefront sensing to quickly detect and fix wavefront deformation and indirect wavefront sensing using modal and zonal methods to rectify complex aberrations, have been developed through AO paradigms. In addition, algorithmic post-processing without mechanical feedback has been utilized to correct the optical patterns using the matrix-based method. Hence, reliable optical imaging through thick biological tissue is made possible by sensorless AO. This review highlights the latest advancements in various AO-based optical microscopy techniques for depth-resolved imaging and briefly discusses their potential in various biomedical applications.