Tag Archives: David A. Muller

An exoskeleton for a cell-sized robot

A January 3, 2018 news item on phys.org announces work on cell-sized robots,

An electricity-conducting, environment-sensing, shape-changing machine the size of a human cell? Is that even possible?

Cornell physicists Paul McEuen and Itai Cohen not only say yes, but they’ve actually built the “muscle” for one.

With postdoctoral researcher Marc Miskin at the helm, the team has made a robot exoskeleton that can rapidly change its shape upon sensing chemical or thermal changes in its environment. And, they claim, these microscale machines – equipped with electronic, photonic and chemical payloads – could become a powerful platform for robotics at the size scale of biological microorganisms.

“You could put the computational power of the spaceship Voyager onto an object the size of a cell,” Cohen said. “Then, where do you go explore?”

“We are trying to build what you might call an ‘exoskeleton’ for electronics,” said McEuen, the John A. Newman Professor of Physical Science and director of the Kavli Institute at Cornell for Nanoscale Science. “Right now, you can make little computer chips that do a lot of information-processing … but they don’t know how to move or cause something to bend.”

Cornell University has produced a video of the researchers discussing their work (about 3 mins. running time)

For those who prefer text or need it to reinforce their understanding, there’s a January 2, 2018 Cornell University news release (also on EurekAlert but dated Jan. 3, 2018) by Tom Fleischman, which originated the news item,

The machines move using a motor called a bimorph. A bimorph is an assembly of two materials – in this case, graphene and glass – that bends when driven by a stimulus like heat, a chemical reaction or an applied voltage. The shape change happens because, in the case of heat, two materials with different thermal responses expand by different amounts over the same temperature change.

As a consequence, the bimorph bends to relieve some of this strain, allowing one layer to stretch out longer than the other. By adding rigid flat panels that cannot be bent by bimorphs, the researchers localize bending to take place only in specific places, creating folds. With this concept, they are able to make a variety of folding structures ranging from tetrahedra (triangular pyramids) to cubes.

In the case of graphene and glass, the bimorphs also fold in response to chemical stimuli by driving large ions into the glass, causing it to expand. Typically this chemical activity only occurs on the very outer edge of glass when submerged in water or some other ionic fluid. Since their bimorph is only a few nanometers thick, the glass is basically all outer edge and very reactive.

“It’s a neat trick,” Miskin said, “because it’s something you can do only with these nanoscale systems.”

The bimorph is built using atomic layer deposition – chemically “painting” atomically thin layers of silicon dioxide onto aluminum over a cover slip – then wet-transferring a single atomic layer of graphene on top of the stack. The result is the thinnest bimorph ever made. One of their machines was described as being “three times larger than a red blood cell and three times smaller than a large neuron” when folded. Folding scaffolds of this size have been built before, but this group’s version has one clear advantage.

“Our devices are compatible with semiconductor manufacturing,” Cohen said. “That’s what’s making this compatible with our future vision for robotics at this scale.”

And due to graphene’s relative strength, Miskin said, it can handle the types of loads necessary for electronics applications. “If you want to build this electronics exoskeleton,” he said, “you need it to be able to produce enough force to carry the electronics. Ours does that.”

For now, these tiniest of tiny machines have no commercial application in electronics, biological sensing or anything else. But the research pushes the science of nanoscale robots forward, McEuen said.

“Right now, there are no ‘muscles’ for small-scale machines,” he said, “so we’re building the small-scale muscles.”

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

Graphene-based bimorphs for micron-sized, autonomous origami machines by Marc Z. Miskin, Kyle J. Dorsey, Baris Bircan, Yimo Han, David A. Muller, Paul L. McEuen, and Itai Cohen. PNAS [Proceedings of the National Academy of Sciences] 2018 doi: 10.1073/pnas.1712889115 published ahead of print January 2, 2018

This paper is behind a paywall.

Nanopatch more effective with poliovirus

No more needles or syringes that’s the Nanopatch promise and its one I’ve been writing about since 2009. It seems 2017 marks another step closer to seeing this idea become a product. From an Oct. 5, 2017 news item on ScienceDaily,

Efforts to rid the world of polio have taken another significant step, thanks to research led by University of Queensland [UQ] bioscience experts and funding from the World Health Organisation (WHO).

A fresh study of the Nanopatch — a microscopic vaccine delivery platform first developed by UQ researchers — has shown the device more effectively combats poliovirus than needles and syringes.

Here’s a prototype,

Caption: This is an image of the intended commercial product. Credit: Courtesy Vaxxas Pty Ltd

An Oct. 5, 2017 University of Queensland press release (also on EurekAlert), which originated the news item, provides more detail (Note: Links have been removed),

Head of UQ’s School of Chemistry and Molecular Biosciences Professor Paul Young said the breakthrough provided the next step in consigning polio to history.

“Polio was one of the most dreaded childhood diseases of the 20th century, resulting in limb disfigurement and irreversible paralysis in tens of millions of cases,” Professor Young said.

“This most recent study showed the Nanopatch enhanced responses to all three types of inactivated poliovirus vaccines (IPV) – a necessary advancement from using the current live oral vaccine.

“We are extremely grateful to the WHO for providing funding to Vaxxas Pty Ltd, the biotechnology company commercialising the Nanopatch.

“The support specifically assists pre-clinical studies and good manufacturing practices.”

Patch inventor Professor Mark Kendall said the study exhibited a key advantage of the Nanopatch.

“It targets the abundant immune cell populations in the skin’s outer layers, rather than muscle, resulting in a more efficient vaccine delivery system,” Professor Kendall said.

“The ease of administration, coupled with dose reduction observed in this study suggests that the Nanopatch could facilitate inexpensive vaccination of inactivated poliovirus vaccines.”

UQ Australian Institute for Biotechnology and Nanotechnology researcher Dr David Muller said effectively translating the dose could dramatically reduce the cost.

“A simple, easy-to-administer polio Nanopatch vaccine could increase the availability of the IPV vaccine and facilitate its administration in door-to-door and mass vaccination campaigns,” said Dr Muller.

“As recently as 1988, more than 350,000 cases occurred every year in more than 125 endemic countries.

“Concerted efforts to eradicate the disease have reduced incidence by more than 99 per cent.”

“Efforts are being intensified to eradicate the remaining strains of transmission once and for all.”

Data from the study encourages efforts by Vaxxas – established by UQ’s commercialisation company UniQuest – to bring the technology to use for human vaccinations.

“The research we are undertaking in conjunction with UQ and WHO can improve the reach of life-saving vaccines to children everywhere,” Vaxxas chief executive officer David Hoey said.

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

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses by David A. Muller, Germain J. P. Fernando, Nick S. Owens, Christiana Agyei-Yeboah, Jonathan C. J. Wei, Alexandra C. I. Depelsenaire, Angus Forster, Paul Fahey, William C. Weldon, M. Steven Oberste, Paul R. Young, & Mark A. F. Kendall. Scientific Reports 7, Article number: 12644 (2017) doi:10.1038/s41598-017-13011-0 Published online: 03 October 2017

This paper is open access.

Should you be interested in seeing previous posts, just use ‘Nanopatch’ as your search term in the blog search engine.

Australia’s nanopatch: a way to eliminate needle vaccinations

Tristan Clemons has written a Nov. 9, 2016 essay for The Conversation on one of my favourite stories, the nanopatch,

Who likes getting a needle? I know I definitely don’t.

Someone else who doesn’t is Mark Kendall from the University of Queensland, winner of the Young Florey Medal 2016.

Mark’s work in developing the nanopatch has provided a clear pathway for vaccine delivery science to move beyond 160 year-old needle and syringe technology.

… There are approximately 20,000 projections per square centimeter on each patch, each around 60 to 100 micrometres in length. One micrometre is one million times smaller than a metre, so the height of these tiny spikes is approximately the width of a human hair.

The nanopatch is produced using a technique known as “deep reactive ion etching”, which essentially makes use of ions (charged atoms) in an electric field to selectively etch the surface of a material away. Controlling the electric field and the ions allows a high degree of control, so the microprojections are regularly spaced and of similar dimensions.

An added advantage of this approach is it has been used in the electronic circuit and solar energy industries for many years, and has the potential for increasing the scale of production.

The tiny projections on each nanopatch are invisible to the naked eye, but are long enough to breach the outermost skin layer, the stratum corneum. The stratum corneum is a layer of dead skin cells which acts as the first barrier in protecting us from infection and skin water loss.

The nanopatch projections penetrate through the stratum corneum to reach the living skin layers directly below, the epidermis and the dermis. In the epidermis are several types of immune cells that are vital for the vaccine to work.

Hence the nanopatch is well suited to the delivery of vaccines where targeting immune cells is vital for vaccination success. Examples include influenza, polio and cholera.

Mark Kendall and his colleagues have shown they are able to coat nanopatch microprojections with a vaccine, apply the nanopatch to the skin and achieve vaccination with one tenth to one thirtieth of the dose required using traditional needle and syringe approaches.

… it’s more than just a good idea. Mark Kendall and his colleagues are now running human clinical trials of nanopatches in Brisbane, and the WHO is planning a polio vaccine trial in Cuba in 2017.

The latest information I have about this research is from a Feb. 26, 2016 University of Queensland press release,

Needle-free Nanopatch technology developed at The University of Queensland has been used to successfully deliver an inactivated poliovirus vaccine.

Delivery of a polio vaccine with the Nanopatch was demonstrated by UQ’s Professor Mark Kendall and his research team at UQ’s Australian Institute for Bioengineering and Nanotechnology, in collaboration with the World Health Organisation, the US Centres for Disease Control and Prevention, and vaccine technology company Vaxxas.

Professor Kendall said the Nanopatch had been used to administer an inactivated Type 2 poliovirus vaccine in a rat model.

“We compared the Nanopatch to the traditional needle and syringe, and found that there is about a 40-fold improvement in delivered dose-sparing,” Professor Kendall said.

“This means about 40 times less polio vaccine was needed in Nanopatch delivery to generate a functional immune response as the needle and syringe.

“To our knowledge, this is the highest level of dose-sparing observed for an inactivated polio vaccine in rats achieved by any type of delivery technology, so this is a key breakthrough.”

The next step will be clinical testing.

Dr David Muller, first author of the research published in Scientific Reports, said the work demonstrated a key advantage of the Nanopatch.

“The Nanopatch targets the abundant immune cell populations in the skin’s outer layers; rather than muscle, resulting in a more efficient vaccine delivery system,” he said.

Clinical success and widespread use of the Nanopatch against polio could help in the current campaign to eradicate polio. It could be produced and distributed at a cheaper cost, and its ease of use would make it suitable for house-to-house vaccination efforts in endemic areas with only minimal training required.

World Health Organisation Global Polio Eradication Initiative Director Mr Michel Zaffran said only Afghanistan and Pakistan remained polio-endemic, but all countries were at risk until the disease was eradicated everywhere.

“Needle-free microneedle patches such as the Nanopatch offer great promise for reaching more children with polio vaccine as well as other antigens such as measles vaccine, particularly in hard-to-reach areas or areas with inadequate healthcare infrastructure,” Mr Zaffran said.

Nanopatch technology is being commercialised by Vaxxas Pty Ltd, which has scaled the Nanopatch from use in small models to prototypes for human use.

Vaxxas CEO Mr David Hoey said the first human vaccination studies are scheduled for this year [2016].

“Key attributes of the Nanopatch, including its ease of use and potential to not require refrigeration, could improve the reach and efficiency of vaccination campaigns in difficult-to-reach locations, including those where polio remains endemic,” Mr Hoey said.

The work was funded by the World Health Organisation, Vaxxas, Rotary District 9630 and the Rotary Foundation.

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

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses by David A. Muller, Frances E. Pearson, Germain J.P. Fernando, Christiana Agyei-Yeboah, Nick S. Owens, Simon R. Corrie, Michael L. Crichton, Jonathan C.J. Wei, William C. Weldon, M. Steven Oberste, Paul R. Young, & Mark A. F. Kendall. Scientific Reports 6, Article number: 22094 (2016) doi:10.1038/srep22094 Published online: 25 February 2016

This paper is open access.

As befitting a ‘favourite story’, I’ve been following it for a number of years starting with this April 23, 2009 posting (scroll down about 25% of the way) although you might prefer to read this more substantive July 26, 2010 posting. The last time (Aug. 3, 2011 posting) I featured the story, it was to announce an investment of AUD $15M in Vaxxas (Kendall is not listed as member of the company) in order to bring the nanopatch to market.

Clues as to how mother of pearl is made

Iridescence seems to fascinate scientists and a team at Cornell University is no exception (from a Dec. 4, 2015 news item on Nanowerk),

Mother nature has a lot to teach us about how to make things.

With that in mind, Cornell researchers have uncovered the process by which mollusks manufacture nacre – commonly known as “mother of pearl.” Along with its iridescent beauty, this material found on the insides of seashells is incredibly strong. Knowing how it’s made could lead to new methods to synthesize a variety of new materials with as yet unguessed properties.

“We have all these high-tech facilities to make new materials, but just take a walk along the beach and see what’s being made,” said postdoctoral research associate Robert Hovden, M.S. ’10, Ph.D. ’14. “Nature is doing incredible nanoscience, and we need to dig into it.”

A Dec. 4, 2015 Cornell University news release by Bill Steele, which originated the news item, expands on the theme,

Using a high-resolution scanning transmission electron microscope (STEM), the researchers examined a cross section of the shell of a large Mediterranean mollusk called the noble pen shell or fan mussel (Pinna nobilis). To make the observations possible they had to develop a special sample preparation process. Using a diamond saw, they cut a thin slice through the shell, then in effect sanded it down with a thin film in which micron-sized bits of diamond were embedded, until they had a sample less than 30 nanometers thick, suitable for STEM observation. As in sanding wood, they moved from heavier grits for fast cutting to a fine final polish to make a surface free of scratches that might distort the STEM image.

Images with nanometer-scale resolution revealed that the organism builds nacre by depositing a series of layers of a material containing nanoparticles of calcium carbonate. Moving from the inside out, these particles are seen coming together in rows and fusing into flat crystals laminated between layers of organic material. (The layers are thinner than the wavelengths of visible light, causing the scattering that gives the material its iridescence.)

Exactly what happens at each step is a topic for future research. For now, the researchers said in their paper, “We cannot go back in time” to observe the process. But knowing that nanoparticles are involved is a valuable insight for materials scientists, Hovden said.

Here’s an image from the researchers,

Electron microscope image of a cross-section of a mollusk shell. The organism builds its shell from the inside out by depositing layers of calcium carbonate nanoparticles. As the particle density increases over time they fuse into large flat crystals embedded in layers of organic material to form nacre. Courtesy: Cornell University

Electron microscope image of a cross-section of a mollusk shell. The organism builds its shell from the inside out by depositing layers of calcium carbonate nanoparticles. As the particle density increases over time they fuse into large flat crystals embedded in layers of organic material to form nacre. Courtesy: Cornell University

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

Nanoscale assembly processes revealed in the nacroprismatic transition zone of Pinna nobilis mollusc shells by Robert Hovden, Stephan E. Wolf, Megan E. Holtz, Frédéric Marin, David A. Muller, & Lara A. Estroff. Nature Communications 6, Article number: 10097 doi:10.1038/ncomms10097 Published 03 December 2015

This is an open access paper.