Chip-Based Fluorescence Optical Nanoscopy

Chip-Based Optical Nanoscopy

These studies showcase the development of a chip-based optical platform for super-resolution imaging of biological tissues, highlighting its potential for both histological investigations and nanoscale cellular analysis.

In one application, the chip-based system is used for super-resolution imaging of cryopreserved ultrathin tissue sections from human placenta, mouse kidney, pig heart, and zebrafish retina. By incorporating advanced modalities such as total internal reflection fluorescence microscopy (TIRFM), intensity fluctuation-based nanoscopy, single-molecule localization microscopy (dSTORM), and correlative light-electron microscopy, the system provides detailed structural insights beyond the diffraction limit—without the complexity or cost of conventional super-resolution setups.

In another application, the platform is extended to combine dSTORM with QPM for the 3D nanoscale imaging of liver sinusoidal endothelial cells (LSECs). These cells contain fenestrations and sieve plates that demand sub-100 nm resolution in both lateral and axial directions. The integrated setup, based on a Linnik-type interferometer, captures both fluorescence and label-free phase images, enabling quantification of fenestration diameter, membrane thickness, and cell height. Chemical treatments such as cytochalasin B further demonstrate the system’s sensitivity to morphological changes at the subcellular level.

Together, these chip-based imaging platforms offer a powerful and compact solution for super-resolution and phase-resolved imaging, addressing critical challenges in tissue pathology and subcellular structural biology with applications in both research and clinical diagnostics.

References:

1. Villegas-Hernández, Luis E., Vishesh Dubey, Mona Nystad, Jean-Claude Tinguely, David A. Coucheron, Firehun T. Dullo, Anish Priyadarshi et al. "Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections." Light: Science & Applications 11, no. 1 (2022): 43. Link 

2. Butola, Ankit, David A. Coucheron, Karolina Szafranska, Azeem Ahmad, Hong Mao, Jean-Claude Tinguely, Peter McCourt et al. "Multimodal on-chip nanoscopy and quantitative phase imaging reveals the nanoscale morphology of liver sinusoidal endothelial cells." Proceedings of the National Academy of Sciences 118, no. 47 (2021): e2115323118. Link 

3. Priyadarshi, Anish, Firehun Tsige Dullo, Deanna Lynn Wolfson, Azeem Ahmad, Nikhil Jayakumar, Vishesh Dubey, Jean-Claude Tinguely, Balpreet Singh Ahluwalia, and Ganapathy Senthil Murugan. "A transparent waveguide chip for versatile total internal reflection fluorescence-based microscopy and nanoscopy." Communications Materials 2, no. 1 (2021): 85. Link