Combining optical and mathematical systems to create a better nanoscope.
Lu Zhang, Kuiwen Xu, Yu Zhong, Krishna Agarwal
NanoRIP is pushing the limits of physics, engineering, mathematics, and biology to develop a new kind of scope that can see the nano-scale components of our cells change and react to disease and therapeutic drugs.
The most advanced versions of the microscopes you used in school can image objects down to 250 nanometer (nm), enough to magnify the organelles in a cell. However, many cells and their components are even smaller than this and are hard to see with these standard microscopes. In order to view these tiny structures, researchers need to chemically label the cell using fluorescent molecules to make them more visible. While these fluorescent labels make it easier to see the interiors of the cell and identify specific structures, they are foreign bodies that can interfere with cell function. The new nanoscope that nanoRIP is developing will remove the need to use fluorescent labels and allow researchers to see structures as small as 80 nm.
Using this new scope, researchers will be able to see life-critical events in living cells to gain new insight into the mechanisms that underlie disease and healing. This may eventually lead to new drug design based on the location of drugs in the cell and how they interact with components of the cell.
Until now, there has been little symbiosis between optics and algorithms: optical instruments aren’t being designed in a way that can take advantage of algorithms and algorithms are not designed to work with optical systems. NanoRIP is changing that by designing both new optical and mathematical systems symbiotically over the next few years that will come together to create a better microscope. Their team of physicists and mathematicians are also collaborating with biologists to study heart cells as a practical target application for their system.
A key feature of the nanoscope is better precision and signal-to-noise ratio, its ability to find image features among the background noise. Most super-resolution microscopes make first order approximations to simplify the math and reduce the computational demand, but nanoRIP is redesigning their optical instruments to collect more information. They are building an optical system and algorithm that takes advantage of the fact that different parts of the cell scatter laser light differently to create better reconstructions of the cell.
Many optical projects never make it out of the lab and into the hands of other researchers. As they develop their new scope, nanoRIP will share their data and invite other Norwegian researchers to collaborate. They expect that by the third year of the project, biologists will be able to send in samples for imaging. Since biologists rely on the fluorescent labels to identify structures in their samples nanoRIP’s team is also developing a reference image library and incorporating artificial intelligence to virtually label the images under a parallel, providing the advantages of both label-free images and fluorescent labeling.
NanoRIP is led by Krishna Agarwal and is excited to be part of Digital Life Norway where they can continue to "explore the richness of opportunities that open up when different disciplines collaborate"