MEMS Enabled Miniature Two-Photon Microscopy for Biomedical Imaging

Over the last decade, two-photon microscopy (TPM) has been the technique of choice for in vivo noninvasive optical brain imaging for neuroscientific study or intra-vital microendoscopic imaging for clinical diagnosis or surgical guidance because of its intrinsic capability of optical sectioning for imaging deeply below the tissue surface with sub-cellular resolution. However, most of these research activities and clinical applications are constrained by the bulky size of traditional TMP systems. An attractive solution is to develop miniaturized TPMs, but this is challenged by the difficulty of the integration of dynamically scanning optical and mechanical components into a small space. Fortunately, microelectromechanical systems (MEMS) technology, together with other emerging micro-optics techniques, has offered promising opportunities in enabling miniaturized TPMs. In this paper, the latest advancements in both lateral scan and axial scan techniques and the progress of miniaturized TPM imaging will be reviewed in detail. Miniature TPM probes with lateral 2D scanning mechanisms, including electrostatic, electromagnetic, and electrothermal actuation, are reviewed. Miniature TPM probes with axial scanning mechanisms, such as MEMS microlenses, remote-focus, liquid lenses, and deformable MEMS mirrors, are also reviewed.