Tag Archives: James L. Hedrick

Ultimate discovery tool?

For anyone familiar with the US nanomedicine scene, Chad Mirkin’s appearance in this announcement from Northwestern University isn’t much of a surprise.  From a June 23, 2016 news item on ScienceDaily,

The discovery power of the gene chip is coming to nanotechnology. A Northwestern University research team is developing a tool to rapidly test millions and perhaps even billions or more different nanoparticles at one time to zero in on the best particle for a specific use.

When materials are miniaturized, their properties—optical, structural, electrical, mechanical and chemical—change, offering new possibilities. But determining what nanoparticle size and composition are best for a given application, such as catalysts, biodiagnostic labels, pharmaceuticals and electronic devices, is a daunting task.

“As scientists, we’ve only just begun to investigate what materials can be made on the nanoscale,” said Northwestern’s Chad A. Mirkin, a world leader in nanotechnology research and its application, who led the study. “Screening a million potentially useful nanoparticles, for example, could take several lifetimes. Once optimized, our tool will enable researchers to pick the winner much faster than conventional methods. We have the ultimate discovery tool.”

A June 23, 2016 Northwestern University news release (also on EurekAlert), which originated the news item, describes the work in more detail,

Using a Northwestern technique that deposits materials on a surface, Mirkin and his team figured out how to make combinatorial libraries of nanoparticles in a very controlled way. (A combinatorial library is a collection of systematically varied structures encoded at specific sites on a surface.) Their study will be published June 24 by the journal Science.

The nanoparticle libraries are much like a gene chip, Mirkin says, where thousands of different spots of DNA are used to identify the presence of a disease or toxin. Thousands of reactions can be done simultaneously, providing results in just a few hours. Similarly, Mirkin and his team’s libraries will enable scientists to rapidly make and screen millions to billions of nanoparticles of different compositions and sizes for desirable physical and chemical properties.

“The ability to make libraries of nanoparticles will open a new field of nanocombinatorics, where size — on a scale that matters — and composition become tunable parameters,” Mirkin said. “This is a powerful approach to discovery science.”

“I liken our combinatorial nanopatterning approach to providing a broad palette of bold colors to an artist who previously had been working with a handful of dull and pale black, white and grey pastels,” said co-author Vinayak P. Dravid, the Abraham Harris Professor of Materials Science and Engineering in the McCormick School of Engineering.

Using five metallic elements — gold, silver, cobalt, copper and nickel — Mirkin and his team developed an array of unique structures by varying every elemental combination. In previous work, the researchers had shown that particle diameter also can be varied deliberately on the 1- to 100-nanometer length scale.

Some of the compositions can be found in nature, but more than half of them have never existed before on Earth. And when pictured using high-powered imaging techniques, the nanoparticles appear like an array of colorful Easter eggs, each compositional element contributing to the palette.

To build the combinatorial libraries, Mirkin and his team used Dip-Pen Nanolithography, a technique developed at Northwestern in 1999, to deposit onto a surface individual polymer “dots,” each loaded with different metal salts of interest. The researchers then heated the polymer dots, reducing the salts to metal atoms and forming a single nanoparticle. The size of the polymer dot can be varied to change the size of the final nanoparticle.

This control of both size and composition of nanoparticles is very important, Mirkin stressed. Having demonstrated control, the researchers used the tool to systematically generate a library of 31 nanostructures using the five different metals.

To help analyze the complex elemental compositions and size/shape of the nanoparticles down to the sub-nanometer scale, the team turned to Dravid, Mirkin’s longtime friend and collaborator. Dravid, founding director of Northwestern’s NUANCE Center, contributed his expertise and the advanced electron microscopes of NUANCE to spatially map the compositional trajectories of the combinatorial nanoparticles.

Now, scientists can begin to study these nanoparticles as well as build other useful combinatorial libraries consisting of billions of structures that subtly differ in size and composition. These structures may become the next materials that power fuel cells, efficiently harvest solar energy and convert it into useful fuels, and catalyze reactions that take low-value feedstocks from the petroleum industry and turn them into high-value products useful in the chemical and pharmaceutical industries.

Here’s a diagram illustrating the work,

 Caption: A combinatorial library of polyelemental nanoparticles was developed using Dip-Pen Nanolithography. This novel nanoparticle library opens up a new field of nanocombinatorics for rapid screening of nanomaterials for a multitude of properties. Credit: Peng-Cheng Chen/James Hedrick

Caption: A combinatorial library of polyelemental nanoparticles was developed using Dip-Pen Nanolithography. This novel nanoparticle library opens up a new field of nanocombinatorics for rapid screening of nanomaterials for a multitude of properties. Credit: Peng-Cheng Chen/James Hedrick

Here’s a link to and a citation for the paper,

Polyelemental nanoparticle libraries by Peng-Cheng Chen, Xiaolong Liu, James L. Hedrick, Zhuang Xie, Shunzhi Wang, Qing-Yuan Lin, Mark C. Hersam, Vinayak P. Dravid, Chad A. Mirkin. Science  24 Jun 2016: Vol. 352, Issue 6293, pp. 1565-1569 DOI: 10.1126/science.aaf8402

This paper is behind a paywall.

Fungal infections, begone!

A May 7, 2014 news item on Nanowerk highlights some antifungal research at A*STAR (Singapore’s Agency for Science, Technology and Research),

Pathogenic fungi like Candida albicans can cause oral, skin, nail and genital infections. While exposure to pathogenic fungi is generally not life-threatening, it can be deadly to immunocompromised patients with AIDS or cancer. A variety of antifungal medications, such as triazoles and polyenes, are currently used for treating fungal infections. The range of these antifungal medications, however, is extremely limited, with some fungal species developing resistance to these drugs.

Yi Yan Yang at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and co-workers, in collaboration with IBM Almaden Research Center in the United States, have discovered four cationic terephthalamide-bisurea compounds with strong antifungal activity, excellent microbial selectivity and low host toxicity …

A May 7, 2018 A*STAR news release, which originated the news item, describes the research in detail (Note: A link has been removed),

Conformational analysis revealed that the terephthalamide-bisurea compounds have a Z-shaped structure: the terephthalamide sits in the middle, urea groups on both sides of the terephthalamide, and cationic charges at both ends. The researchers prepared compounds with different spacers — ethyl, butyl, hexyl or benzyl amine — in-between the urea group and the cationic charge.

When dissolved in water, the terephthalamide-bisurea compounds aggregate to form fibers with lengths ranging from a few hundred nanometers to several micrometers. Some of the compounds form fibers with high flexibility and others with high rigidity.

The researchers evaluated the antifungal activity of their terephthalamide-bisurea compounds against C. albicans. They found that all of the cationic compounds effectively inhibited fungal growth, even when the fungal concentration increased from 102 to 105 colony-forming units per milliliter.

The researchers believe that the potent antifungal activity is largely due to the formation of fibers with extremely small diameters in the order of 5 to 10 nanometers, which facilitates the rupture of fungal membranes. “This is particularly important because the fungal membrane of C. albicans is multilayered and has low negative charges,” explains Yang. “It also helps explain why cationic terephthalamide-bisurea compounds could easily penetrate the fungal membrane.”

The terephthalamide-bisurea compounds also eradicated clinically isolated drug-resistant C. albicans. The compounds prevent the development of drug resistance by rupturing the fungal membrane of C. albicans and disrupting the biofilm (see image).

Additionally, cytotoxicity tests showed that the cationic terephthalamide-bisurea compounds exhibit low toxicity toward mammalian cells and in a mouse model, revealing that the compounds “are relatively safe for preventing and treating fungal infections,” says Yang. [emphasis mine]

It’s nice to see that this potential anti-fungal treatment isn’t damaging to one’s cells.

Here’s a link to and a citation for the paper,

Supramolecular high-aspect ratio assemblies with strong antifungal activity by Kazuki Fukushima, Shaoqiong Liu, Hong Wu, Amanda C. Engler, Daniel J. Coady, Hareem Maune, Jed Pitera, Alshakim Nelson, Nikken Wiradharma, Shrinivas Venkataraman, Yuan Huang, Weimin Fan, Jackie Y. Ying, Yi Yan Yang, & James L. Hedrick. Nature Communications 4, Article number: 286 doi:10.1038/ncomms3861 Published 09 December 2013

This article is behind a paywall.