KEYNOTE: Deep and High-Throughput Nonlinear Optical Microscopy

Live, label-free imaging is critical for biomedical discovery but is fundamentally challenged by weak intrinsic contrast and light scattering, limiting imaging depth and throughput. This talk presents recent work harnessing nonlinear effects in standard multimode fibers to create novel light sources for deep bio-imaging.

First, You introduces a deep and dynamic simultaneous metabolic and structural imaging, or deep simultaneous label-free autofluorescence multiharmonic (dSLAM) microscope. By employing multimode fiber-based three-photon excitation, dSLAM extends the depth for label-free metabolic imaging beyond 700 µm - more than double the previous limit - enabling dynamic visualization of cellular activities in thick, living microtissues.

Second, the talk will describe the discovery of a self-localized ultrafast pencil beam. Scientists demonstrated that self-focusing in multimode fibers, traditionally considered detrimental, can be balanced by the multimode waveguiding geometry to generate a stable, sidelobe-suppressed beam with enhance resilience to tissue-induced aberrations. This provides a simple yet robust method for high-throughput volumetric imaging.

About the presenter
Sixian You, Ph.D., is the Alfred Henry and Jean Morrison Hayes Career Development Assistant Professor in the MIT EECS department, and a Principal Investigator in the MIT Research Laboratory of Electronics. Sixian did her doctorate at University of Illinois at Urbana-Champaign (2019), obtained bacherlo’s from HUST (2013), and completed her postdoc at the University of California at Berkeley. (2021).

Her research interests are in biophotonics and microscopy, with an emphasis on developing hardware and algorithms to overcome longstanding imaging limitations for biomedical translation. She has been the recipient of NSF CAREER Award, SCIALOG (Advancing Bioimaging) Award, Amazon Research Award, Microscopy Innovation Award, McGinnis Medical Innovation Graduate Inaugural Fellowship, Computational Science and Engineering Fellowship (UIUC), and Nikon Photomicrography Competition Image of Distinction award. Her work has been featured on the Cancer Research Cover, PNAS Cover, and Nature Communications Editors’ Highlight.