Next-gen optical systems for disease diagnosis and drug discovery

Image courtesy: Partha Pratim Mondal

Disease diagnosis requires understanding biological processes over extensive length scales. Specifically, this requires investigation both at a single macromolecule or protein level and at a large cell or tissue level, thereby calling for imaging techniques that are scalable as well as precise.

Two recent technologies encompassing these length scales are single molecule-based super-resolution microscopy (SMLM) and iLIFE light sheet imaging cytometry. While SMLM-based techniques can determine biological mechanisms with single molecule precision, iLIFE Lightsheet Cytometry can interrogate cells and tissues at high throughput with sub-cellular resolution.

Over the past year, research in the lab of Partha Pratim Mondal, Professor at the Department of Instrumentation and Applied Physics (IAP), IISc, has led to a series of inventions and techniques that demonstrate such capabilities.

In one study, the team has developed a single molecule-based super-resolution microscopy system, which employs 4f detection for rapid volume imaging by leveraging the use of a flexible electrically-tunable lens to reconstructure the entire cell volume being analysed.

In second study, they report the development of a new system called M3IC (Multichannel, Multi sheet and Multicolour light sheet Imaging flow Cytometry). This technique uses a sheet of light to illuminate the inner organelles of the cell. The technique also allows rapid scanning of thousands of cells simultaneously.

In a more recent study, the team developed a technique to improve the quality of the reconstructed images in single-molecule based super resolution microscopy, to rule out false detection due to random background noise.

The researchers suggest that a futuristic optical system combining these advanced technologies offers great promise for disease and cell biology, taking scientists closer to precision drug discovery.

REFERENCES:
1. Basumatary J, Baro N, Joshi P, Modal PP, Scanning single molecule localization microscopy (scanSMLM) for super-resolution volume imaging, Communications Biology (2023).
https://www.nature.com/articles/s42003-023-05364-2

2. Aravinth S, Zanacchi FC, Mondal PP, Fortunate molecules boost signal to background ratio and localization precision in correlation based single molecule localization microscopy, Communications Biology (2024)
https://www.nature.com/articles/s42003-024-07153-x

3. Joshi P, Kumar P, Aravinth S, Varghese JM, Mondal PP, Fluorescence-based multifunctional light sheet imaging flow cytometry for high-throughput optical interrogation of live cells, Communications Physics (2024).
https://www.nature.com/articles/s42005-024-01522-y

LAB WEBSITE:
http://iap.iisc.ac.in/~partha/