Nanoscale technology could turbo-charge response to future pandemics

A new technique for synthesising and screening molecules developed by Danish researchers has been described in a paper published in Nature Chemistry.

The technique, dubbed “single particle combinatorial lipidic nanocontainer fusion based on DNA-mediated fusion” or SPARCLD, uses tiny soap-like “bubbles” to produce more than 40,000 different molecules on an area the size of a pinhead.

The bubbles form “nano-containers” inside which molecules can be produced using DNA nanotechnology. About 42,000 nano-containers can fit on one square millimetre.

The researchers are excited about the technology’s potential to allow extremely rapid and efficient screening of thousands of candidate molecules for applications such as vaccine and pharmaceutical production.

“This is an unprecedented save in effort, material, manpower, and energy,” says Nikos Hatzakis, an associate professor in chemistry at the University of Copenhagen and leader of the research project.

Such savings are “fundamentally important” for the synthesis, development and evaluation of new pharmaceuticals, adds Mette G. Malle, the article’s lead author now based at Harvard University.

The technology integrates aspects of nanotechnology, chemistry and machine learning. Some of the “bubbles”, also known as liposomes, are tethered to a surface, while others float around freely. Each bubble contains a different DNA sequence and fluorescent markers that can be detected by a special microscope.

As the bubbles float around and randomly fuse, many different combinations of DNA fragments can be created and detected in real time using the microscope. A machine learning algorithm decodes the microscopy images to classify distinct ‘fusion sequences’ created during this process.

According to Hatzakis, SPARCLD has numerous potential applications in both research and industry. For example, it could be used to synthesise and screen RNA molecules for use in CRISPR-mediated gene editing or future RNA vaccines.

“A safe bet would be that both industry and academic groups involved in synthesis of long molecules such as polymers could be among the first to adopt the method,” he says. “The same goes for ligands of relevance for pharmaceutical development.”