Authors of the study believe their breakthrough modelling on ‘active matter’ could mark a turning point in the design of robots. With further development of the concept, it may be possible to determine the shape, movement and behaviour of a soft solid not by its natural elasticity but by human-controlled activity on its surface.

The surface of an ordinary soft material always shrinks into a sphere. Think of the way water beads into droplets: the beading occurs because the surface of liquids and other soft material naturally contracts into the smallest surface area possible — i.e. a sphere. But active matter can be designed to work against this tendency. An example of this in action would be a rubber ball that’s wrapped in a layer of nano-robots, where the robots are programmed to work in unison to distort the ball into a new, pre-determined shape (say, a star).

It is hoped that active matter will lead to a new generation of machines whose function will come from the bottom up. So, instead of being governed by a central controller (the way today’s robotic arms are controlled in factories), these new machines would be made from many individual active units that cooperate to determine the machine’s movement and function. This is akin to the workings of our own biological tissues, such as the fibres in heart muscle.

Using this idea, scientists could design soft machines with arms made of flexible materials powered by robots embedded in their surface. They could also tailor the size and shape of drug delivery capsules, by coating the surface of nanoparticles in a responsive, active material.. This in turn could have a dramatic effect on how a drug interacts with cells in the body.

Work on active matter challenges the assumption that the energetic cost of the surface of a liquid or soft solid must always be positive because a certain amount of energy is always necessary to create a surface.

Dr Jack Binysh, study first author, said: “Active matter makes us look at the familiar rules of nature — rules like the fact that surface tension has to be positive — in a new light. Seeing what happens if we break these rules, and how we can harness the results, is an exciting place to be doing research.”

Corresponding author Dr Anton Souslov added: “This study is an important proof of concept and has many useful implications. For instance, future technology could produce soft robots that are far squishier and better at picking up and manipulating delicate materials.”

For the study, the researchers developed theory and simulations that described a 3D soft solid whose surface experiences active stresses. They found that these active stresses expand the surface of the material, pulling the solid underneath along with it, and causing a global shape change. The researchers found that the precise shape adopted by the solid could then be tailored by altering the elastic properties of the material.

In the next phase of this work — which has already begun — the researchers will apply this general principle to design specific robots, such as soft arms or self-swimming materials. They will also look at collective behaviour — for example, what happens when you have many active solids, all packed together.

This work was a collaboration between the Universities of Bath and Birmingham. It was funded by the Engineering and Physical Sciences Research Council (EPSRC) through New Investigator Award no. EP/T000961/1.

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“I’m aware of no other documented case in which the invasion rate of a large aquatic system has been suppressed through a management intervention,”said Ricciardi. “This layer of protection is clearly beneficial. There are many highly invasive freshwater species in Europe, for example, that could be delivered in ballast water and would almost certainly proliferate in the Great Lakes. The regulation is likely preventing their introduction.”

The world’s most invaded freshwater ecosystem

No other freshwater ecosystem on Earth has been invaded as much, or as frequently, as the Great Lakes basin. Nearly 190 non-native species of fish, invertebrates, plants, plankton, and microbes have established populations in the basin over past two centuries. Nearly 65% of invaders recorded since the opening of the St Lawrence seaway in 1959 were transported to the Great Lakes in the ballast tanks of ships from overseas ports. These include notorious stowaways such as the zebra mussel, the quagga mussel, the spiny water flea, and the round goby — each among the most ecologically and economically damaging invaders in the basin.

Between 1959 and the mid-2000s, one new invader was discovered established in the Great Lakes every 6-7 months.

This onslaught prompted a move by Canada and the USA to harmonize regulations and mandate flushing saltwater through ballast tanks of all ships while they were still in open ocean, before entering the St Lawrence seaway bound for the Great Lakes. Saltwater flushing has been shown in experiments to cause a massive reduction in the abundance and variety of freshwater organisms carried in ballast tanks.

Empirical evidence of an abrupt reduction in invasion risk

The true test of such a regulation is its effect on the observed rate of species invasion. Since 2008, invasions reported in the Great Lakes basin have declined by 85% and are now at their lowest rate in two centuries. Other factors could have contributed to the abrupt decline in the invasion rate, but empirical evidence points to ballast water regulation as the overwhelming primary cause.

Although the Great Lakes remain vulnerable to invasions from poorly regulated sources, such as trade in living organisms (e.g. aquarium pets, live bait, ornamental garden plants, food markets), this study highlights the potential benefit of an internationally coordinated, evidence-based control strategy.

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The findings, detailed in a recent article in the journal Nature Electronics, show that neuromorphic simulations employing the statistical method called random walks can track X-rays passing through bone and soft tissue, disease passing through a population, information flowing through social networks and the movements of financial markets, among other uses, said Sandia theoretical neuroscientist and lead researcher James Bradley Aimone.

“Basically, we have shown that neuromorphic hardware can yield computational advantages relevant to many applications, not just artificial intelligence to which it’s obviously kin,” said Aimone. “Newly discovered applications range from radiation transport and molecular simulations to computational finance, biology modeling and particle physics.”

In optimal cases, neuromorphic computers will solve problems faster and use less energy than conventional computing, he said.

The bold assertions should be of interest to the high-performance computing community because finding capabilities to solve statistical problems is of increasing concern, Aimone said.

“These problems aren’t really well-suited for GPUs [graphics processing units], which is what future exascale systems are likely going to rely on,” Aimone said. “What’s exciting is that no one really has looked at neuromorphic computing for these types of applications before.”

Sandia engineer and paper author Brian Franke said, “The natural randomness of the processes you list will make them inefficient when directly mapped onto vector processors like GPUs on next-generation computational efforts. Meanwhile, neuromorphic architectures are an intriguing and radically different alternative for particle simulation that may lead to a scalable and energy-efficient approach for solving problems of interest to us.”

Franke models photon and electron radiation to understand their effects on components.

The team successfully applied neuromorphic-computing algorithms to model random walks of gaseous molecules diffusing through a barrier, a basic chemistry problem, using the 50-million-chip Loihi platform Sandia received approximately a year and a half ago from Intel Corp., said Aimone. “Then we showed that our algorithm can be extended to more sophisticated diffusion processes useful in a range of applications.”

The claims are not meant to challenge the primacy of standard computing methods used to run utilities, desktops and phones. “There are, however, areas in which the combination of computing speed and lower energy costs may make neuromorphic computing the ultimately desirable choice,” he said.

Unlike the difficulties posed by adding qubits to quantum computers — another interesting method of moving beyond the limitations of conventional computing — chips containing artificial neurons are cheap and easy to install, Aimone said.

There can still be a high cost for moving data on or off the neurochip processor. “As you collect more, it slows down the system, and eventually it won’t run at all,” said Sandia mathematician and paper author William Severa. “But we overcame this by configuring a small group of neurons that effectively computed summary statistics, and we output those summaries instead of the raw data.”

Severa wrote several of the experiment’s algorithms.

Like the brain, neuromorphic computing works by electrifying small pin-like structures, adding tiny charges emitted from surrounding sensors until a certain electrical level is reached. Then the pin, like a biological neuron, flashes a tiny electrical burst, an action known as spiking. Unlike the metronomical regularity with which information is passed along in conventional computers, said Aimone, the artificial neurons of neuromorphic computing flash irregularly, as biological ones do in the brain, and so may take longer to transmit information. But because the process only depletes energies from sensors and neurons if they contribute data, it requires less energy than formal computing, which must poll every processor whether contributing or not. The conceptually bio-based process has another advantage: Its computing and memory components exist in the same structure, while conventional computing uses up energy by distant transfer between these two functions. The slow reaction time of the artificial neurons initially may slow down its solutions, but this factor disappears as the number of neurons is increased so more information is available in the same time period to be totaled, said Aimone.

The process begins by using a Markov chain — a mathematical construct where, like a Monopoly gameboard, the next outcome depends only on the current state and not the history of all previous states. That randomness contrasts, said Sandia mathematician and paper author Darby Smith, with most linked events. For example, he said, the number of days a patient must remain in the hospital are at least partially determined by the preceding length of stay.

Beginning with the Markov random basis, the researchers used Monte Carlo simulations, a fundamental computational tool, to run a series of random walks that attempt to cover as many routes as possible.

“Monte Carlo algorithms are a natural solution method for radiation transport problems,” said Franke. “Particles are simulated in a process that mirrors the physical process.”

The energy of each walk was recorded as a single energy spike by an artificial neuron reading the result of each walk in turn. “This neural net is more energy efficient in sum than recording each moment of each walk, as ordinary computing must do. This partially accounts for the speed and efficiency of the neuromorphic process,” said Aimone. More chips will help the process move faster using the same amount of energy, he said.

The next version of Loihi, said Sandia researcher Craig Vineyard, will increase its current chip scale from 128,000 neurons per chip to up to one million. Larger scale systems then combine multiple chips to a board.

“Perhaps it makes sense that a technology like Loihi may find its way into a future high-performance computing platform,” said Aimone. “This could help make HPC much more energy efficient, climate-friendly and just all around more affordable.”

The work was funded under the NNSA Advanced Simulation and Computing program and Sandia’s Laboratory Directed Research and Development program.

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“Vascular diseases afflict hundreds of millions of people in the world,” said Chang-Hyun Gil, MS, PhD, a postdoctoral fellow in the Department of Surgery and co-first author of the study. “In this study, we focused on the retinal vessel in type 2 diabetes. Our results demonstrate the safe, efficient and robust derivation of hiPSC-derived specific mesoderm subset for use as a novel therapy to rescue ischemic tissues and repair blood vessels in individuals with vascular diseases. The results provide a foundation for an early phase clinical trial.”

In the multi-site, early phase study recently published in Science Advances, investigators genetically reprogrammed diabetic and non-diabetic peripheral blood cells into hiPSCs and matured the cells into special blood vessel reparative cells. Upon injection into animal models with type 2 diabetic murine (T2D) retinal dysfunction, results showed significant improvement in visual acuity and electroretinograms with restoration of vascular perfusion. They hypothesized hiPSC-derived vascular reparative cells may serve as a source of endothelial precursors that will display in vivo vessel reparative properties in these diabetic subjects.

“Unlike the use of embryonic stem cells (ESCs), genetically engineered hiPSCs do not carry the ethical challenges ESCs possess that limit their possible usage, and hiPSCs are being increasingly recognized as a viable alternative in study design and application as a cell therapy for human disorders,” Gil said.

According to the U.S. Centers for Disease Control and Prevention, more than 37 million people in the United States have diabetes-more than 11 percent of the U.S. population. What’s more, diabetes-related complications have risen among both young adults ages 18 to 44 years of age and adults ages 45 to 64. These complications cause major metabolic disturbances that damage the cardiovascular, visual, peripheral nerve and renal systems through harming small and large microvessels that feed these tissues. In 2019, more than 11 percent of adults ages 18 and older reported severe vision issues or blindness and more than 1.87 million adults were diagnosed with major cardiovascular disease.

“This work by Dr. Gil represents a monumental step forward in the application of induced pluripotent stem cells in treating the complications of diabetes,” said Michael P. Murphy, MD, the Cryptic Medical Research Foundation Professor of Vascular Biology Research at IU School of Medicine, a vascular surgeon at IU Health and Eskenazi Health and a coauthor of the study.

Researchers converted hiPSC into a specific mesoderm subset that was enriched to generate endothelial cells with vessel reparative properties similar to endothelial colony forming cells (ECFC). Endothelial cells are cells found in the inner lining of blood vessels, lymph vessels and the heart and are a major component in regulating vascular function and inflammatory reactions. Endothelial cells control blood flow and regulate the transfer of proteins from blood into tissues.

Gil said the specific mesoderm subset expressing KDR, NCAM1 and APLNR (KNA⁺ mesoderm) exhibits enhanced capacity to differentiate into ECFC and form functional blood vessels in vivo and that mesoderm populations correct vasodegeneration of injured retinal vessels. Electroretinograms indicate enhanced function of neural retina and optokinetic nystagmus studies show improved vision.

“The next translational step of the work is to transfer the research protocols reported for differentiation of the hiPSC into to S^–KNA⁺ cells into large scale manufacturing processes,” said Mervin C. Yoder, MD, distinguished professor emeritus and research advisor for the Indiana Center for Regenerative Medicine and Engineering. Yoder is another coauthor of the study and is the scientific founder of Vascugen, a company driven to advance treatments for life-threatening conditions caused by microvascular conditions. “Selected aspects of this work have been licensed by Vascugen, Inc., through the Indiana University Innovation and Commercialization Office, who are focused on developing vascular reparative cells from induced pluripotent stem cells.”

Another study coauthor is Maria B. Grant, MD, the former Marilyn Glick Professor of Ophthalmology at the IU School of Medicine Eugene and Marilyn Glick Eye Institute and current endowed chair of ophthalmology at UAB. Grant said this is a highly translational study that is a continuation of a grant she and Yoder have been working on for the last 20 years regarding stems cells and how they can be used to repair blood vessels in the eye. While hiPSCs can take a long time to grow, the study team simplified the process to shorten the time to grow them and make them more feasible to translate into a human therapy to repair blood vessels in the eye.

“At UAB, we took the stem cells and hiPSC cells and studied them,” she said. “Science is really team science. I bring all the eye experience and some stem cell experience, and Dr. Yoder brings a lot of stem cell experience. It’s a complementary collaboration.”

“I want to express my greatest thanks to Dr. Yoder, Dr. Grant and Dr. Murphy for their support,” Gil said. He will remember Yoder for “his dedication, passion, patience and kindness” and Murphy for supporting him in completing the study.