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Drug Development Could Be Accelerated Using New Photonic Effect

Twisted semiconductor nanostructures turn red light into twisted blue light in minuscule volumes, which may help create chiral drugs.

Drug Development Could Be Accelerated Using New Photonic Effect.
The illustration shows a microplate well in the foreground, while in the background a tested sample receives red laser light and releases twisted blue light. (Image credit: Ventsislav Valev, Kylian Valev, and Lukas Ohnoutek, University of Bath).

Scientists at the University of Bath and the University of Michigan have demonstrated that twisted nanoscale semiconductors control light in a new manner. The effect could be utilized to quicken the discovery and creation of life-saving medicines as well as photonic technologies.

The photonic effect could aid in the swift development and screening of new antibiotics and other drugs through automation — basically, robotic chemists. It delivers a new analysis tool for high-throughput screening, a technique to examine huge libraries of chemical compounds.

A minute sample of each compound packs a well on a microplate. The wells can be as tiny as a cubic millimeter, and a plate the size of a chocolate bar can hold a thousand of them.

To meet the requirements of the emerging robotized chemistry, wells are getting really tiny—too small for current analytical methods. So, fundamentally new methods are needed to analyze would-be drugs.

Ventsislav Valev, Study Co-Corresponding Author and Professor of Physics, University of Bath

Details of the study have been reported in Nature Photonics.

One of the main measurements in drug exploration is chirality, or which way the molecule twists. Biological systems, such as the human body, usually favor one direction over the other - a left-handed or right-handed curl.

At best, a drug molecule with an erroneous twist does nothing, but at worst, it can result in harm. The effect revealed by the scientists permits chirality to be measured in volumes that are 10,000 times smaller than a cubic millimeter.

The small volumes possible for registration of these effects are the game-changing property that enables the researchers to use very small amounts of expensive drugs and collect thousands times more data.

Nicholas Kotov, Study Co-Corresponding Author and the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering, University of Michigan

The technique depends on a structure influenced by biological designs, formulated in Kotov’s lab. Cadmium telluride, a semiconductor widely used in solar cells, is engineered into nanoparticles that look like short segments of a twisted ribbon. These assemble into helices, imitating the way proteins assemble.

Being illuminated with red light, the small semiconductor helices generate new light that is blue and twisted. The blue light is also emitted in a specific direction, which makes it easy to collect and analyze. The trifecta of unusual optical effects drastically reduces the noise that other nanoscale molecules and particles in biological fluids may cause.

Nicholas Kotov, the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering, University of Michigan

To employ these effects in high-throughput screening for drug discovery, the nanoparticles assembling into helices may be combined with a drug candidate. When the nanohelices form a lock-and-key assembly with the drug, mimicking the drug target, the twist of the nanohelices will significantly change. This change in the twist can be computed via the blue light.

“Applications to drugs are now only a question of technological development. Our next step is to seek funding for this development,” said Valev, who headed the photonic experiments at Bath.

The formation of blue light from red is also useful in drug development in samples approaching the intricacy of biological tissues. The dividing of two colors of light is technically easy and helps decrease light noise, false negatives and false positives.

While the researchers tried out experiments testing the biological concept, COVID-19 closures and delays made the protein samples deform each time.

The postdoc on my side, Ji-Young Kim, and Ph.D. student Lukas Ohnoutek on the Bath side, they are heroes. They were trying to work in some night shifts, even when it was very restricted.

Nicholas Kotov, Study Co-Corresponding Author and the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering, University of Michigan

The study received funding from the Royal Society, Science and Technology Facilities Council and the Engineering and Physical Science Research Council in the U.K., and the U.S. Office of Naval Research.

Kotov is also the Joseph B. and Florence V. Cejka Professor of Engineering and professor of chemical engineering, materials science and engineering, and macromolecular science and engineering.

Patent protection has been filed by the University of Michigan. The university is also seeking partners to commercialize the new technology.

Journal Reference:

Ohnoutek, L., et al. (2022) Third-harmonic Mie scattering from semiconductor nanohelices. Nature Photonics.

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