With a precise, controlled movement, microrobots cleared a glass plate of a biofilm, as shown in this time-lapse image.
Credit: Geelsu Hwang and Edward Steager/University of Pennsylvania
A visit to the dentist typically involves time-consuming and sometimes unpleasant scraping with mechanical tools to remove plaque from teeth. What if, instead, a dentist could deploy a small army of tiny robots to precisely and non-invasively remove that buildup?
A team of engineers, dentists, and biologists from the University of Pennsylvania developed a microscopic robotic cleaning crew. With two types of robotic systems -- one designed to work on surfaces and the other to operate inside confined spaces -- the scientists showed that robots with catalytic activity could ably destroy biofilms, sticky amalgamations of bacteria enmeshed in a protective scaffolding. Such robotic biofilm-removal systems could be valuable in a wide range of potential applications, from keeping water pipes and catheters clean to reducing the risk of tooth decay, endodontic infections, and implant contamination.
The work, published in Science Robotics, was led by Hyun (Michel) Koo of the School of Dental Medicine and Edward Steager of the School of Engineering and Applied Science.
"This was a truly synergistic and multidisciplinary interaction," says Koo. "We're leveraging the expertise of microbiologists and clinician-scientists as well as engineers to design the best microbial eradication system possible. This is important to other biomedical fields facing drug-resistant biofilms as we approach a post-antibiotic era."
"Treating biofilms that occur on teeth requires a great deal of manual labor, both on the part of the consumer and the professional," adds Steager. "We hope to improve treatment options as well as reduce the difficulty of care."
Biofilms can arise on biological surfaces, such as on a tooth or in a joint or on objects, like water pipes, implants, or catheters. Wherever biofilms form, they are notoriously difficult to remove, as the sticky matrix that holds the bacteria provides protection from antimicrobial agents.
In previous work, Koo and colleagues have made headway at breaking down the biofilm matrix with a variety of outside-the-box methods. One strategy has been to employ iron-oxide-containing nanoparticles that work catalytically, activating hydrogen peroxide to release free radicals that can kill bacteria and destroy biofilms in a targeted fashion.
Serendipitously, the Penn Dental Medicine team found that groups at Penn Engineering led by Steager, Vijay Kumar, and Kathleen Stebe were working with a robotic platform that used very similar iron-oxide nanoparticles as building blocks for microrobots. The engineers control the movement of these robots using a magnetic field, allowing a tether-free way to steer them.
Together, the cross-school team designed, optimized, and tested two types of robotic systems, which the group calls catalytic antimicrobial robots, or CARs, capable of degrading and removing biofilms. The first involves suspending iron-oxide nanoparticles in a solution, which can then be directed by magnets to remove biofilms on a surface in a plow-like manner. The second platform entails embedding the nanoparticles into gel molds in three-dimensional shapes. These were used to target and destroy biofilms clogging enclosed tubes.
Both types of CARs effectively killed bacteria, broke down the matrix that surrounds them, and removed the debris with high precision. After testing the robots on biofilms growing on either a flat glass surface or enclosed glass tubes, the researchers tried out a more clinically relevant application: Removing biofilm from hard-to-reach parts of a human tooth.
The CARs were able to degrade and remove bacterial biofilms not just from a tooth surface but from one of the most difficult-to-access parts of a tooth, the isthmus, a narrow corridor between root canals where biofilms commonly grow.
"Existing treatments for biofilms are ineffective because they are incapabale of simultaneously degrading the protective matrix, killing the embedded bacteria, and physically removing the biodegraded products," says Koo. "These robots can do all three at once very effectively, leaving no trace of biofilm whatsoever."
By plowing away the degraded remains of the biofilm, Koo says, the chance of it taking hold and re-growing decreases substantially. The researchers envision precisely directing these robots to wherever they need to go to remove biofilms, be it the inside of a cathether or a water line or difficult-to-reach tooth surfaces.
"We think about robots as automated systems that take actions based on actively gathered information," says Steager. In this case, he says, "the motion of the robot can be informed by images of the biofilm gathered from microcameras or other modes of medical imaging."
To move the innovation down the road to clinical application, the researchers are receiving support from the Penn Center for Health, Devices, and Technology, an initiative supported by Penn's Perelman School of Medicine, Penn Engineering, and the Office of the Vice Provost for Research. Penn Health-Tech, as it's known, awards select interdisciplinary groups with support to create new health technologies, and the robotic platforms project was one of those awarded support in 2018.
"The team has a great clinical background on the dental side and a great technical background on the engineering side," says Victoria Berenholz, executive director of Penn Health-Tech. "We're here to round them out on the business side. They have really done a fantastic job on the project."

Purdue University researchers have developed a process to use magnetics with brain-like networks to program and teach devices to better generalize about different objects.
Credit: Kaushik Roy/Purdue University
Computers and artificial intelligence continue to usher in major changes in the way people shop. It is relatively easy to train a robot's brain to create a shopping list, but what about ensuring that the robotic shopper can easily tell the difference between the thousands of products in the store?
Purdue University researchers and experts in brain-inspired computing think part of the answer may be found in magnets. The researchers have developed a process to use magnetics with brain-like networks to program and teach devices such as personal robots, self-driving cars and drones to better generalize about different objects.
"Our stochastic neural networks try to mimic certain activities of the human brain and compute through a connection of neurons and synapses," said Kaushik Roy, Purdue's Edward G. Tiedemann Jr. Distinguished Professor of Electrical and Computer Engineering. "This allows the computer brain to not only store information but also to generalize well about objects and then make inferences to perform better at distinguishing between objects."
Roy presented the technology during the annual German Physical Sciences Conference earlier this month in Germany. The work also appeared in the Frontiers in Neuroscience.
The switching dynamics of a nano-magnet are similar to the electrical dynamics of neurons. Magnetic tunnel junction devices show switching behavior, which is stochastic in nature.
The stochastic switching behavior is representative of a sigmoid switching behavior of a neuron. Such magnetic tunnel junctions can be also used to store synaptic weights.
The Purdue group proposed a new stochastic training algorithm for synapses using spike timing dependent plasticity (STDP), termed Stochastic-STDP, which has been experimentally observed in the rat's hippocampus. The inherent stochastic behavior of the magnet was used to switch the magnetization states stochastically based on the proposed algorithm for learning different object representations.
The trained synaptic weights, encoded deterministically in the magnetization state of the nano-magnets, are then used during inference. Advantageously, use of high-energy barrier magnets (30-40KT where K is the Boltzmann constant and T is the operating temperature) not only allows compact stochastic primitives, but also enables the same device to be used as a stable memory element meeting the data retention requirement. However, the barrier height of the nano-magnets used to perform sigmoid-like neuronal computations can be lowered to 20KT for higher energy efficiency.
"The big advantage with the magnet technology we have developed is that it is very energy-efficient," said Roy, who leads Purdue's Center for Brain-inspired Computing Enabling Autonomous Intelligence. "We have created a simpler network that represents the neurons and synapses while compressing the amount of memory and energy needed to perform functions similar to brain computations."
Roy said the brain-like networks have other uses in solving difficult problems as well, including combinatorial optimization problems such as the traveling salesman problem and graph coloring. The proposed stochastic devices can act as "natural annealer," helping the algorithms move out of local minimas.
Their work aligns with Purdue's Giant Leaps celebration, acknowledging the university's global advancements in artificial intelligence as part of Purdue's 150th anniversary. It is one of the four themes of the yearlong celebration's Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.
Roy has worked with the Purdue Research Foundation Office of Technology Commercialization on patented technologies that are providing the basis for some of the research at C-BRIC. They are looking for partners to license the technology.

Bioengineers at Boston Children's Hospital report the first demonstration of a robot able to navigate autonomously inside the body. In an animal model of cardiac valve repair, the team programmed a robotic catheter to find its way along the walls of a beating, blood-filled heart to a leaky valve -- without a surgeon's guidance. They report their work today in Science Robotics.
Surgeons have used robots operated by joysticks for more than a decade, and teams have shown that tiny robots can be steered through the body by external forces such as magnetism. However, senior investigator Pierre Dupont, PhD, chief of Pediatric Cardiac Bioengineering at Boston Children's, says that to his knowledge, this is the first report of the equivalent of a self-driving car navigating to a desired destination inside the body.
Dupont envisions autonomous robots assisting surgeons in complex operations, reducing fatigue and freeing surgeons to focus on the most difficult maneuvers, improving outcomes.
"The right way to think about this is through the analogy of a fighter pilot and a fighter plane," he says. "The fighter plane takes on the routine tasks like flying the plane, so the pilot can focus on the higher-level tasks of the mission."
Touch-guided vision, informed by AI
The team's robotic catheter navigated using an optical touch sensor developed in Dupont's lab, informed by a map of the cardiac anatomy and preoperative scans. The touch sensor uses artificial intelligence (AI) and image processing algorithms to enable the catheter to figure out where it is in the heart and where it needs to go.
For the demo, the team performed a highly technically demanding procedure known as paravalvular aortic leak closure, which repairs replacement heart valves that have begun leaking around the edges. (The team constructed its own valves for the experiments.) Once the robotic catheter reached the leak location, an experienced cardiac surgeon took control and inserted a plug to close the leak.
In repeated trials, the robotic catheter successfully navigated to heart valve leaks in roughly the same amount of time as the surgeon (using either a hand tool or a joystick-controlled robot).
Biologically inspired navigation
Through a navigational technique called "wall following," the robotic catheter's optical touch sensor sampled its environment at regular intervals, in much the way insects' antennae or the whiskers of rodents sample their surroundings to build mental maps of unfamiliar, dark environments. The sensor told the catheter whether it was touching blood, the heart wall or a valve (through images from a tip-mounted camera) and how hard it was pressing (to keep it from damaging the beating heart).
Data from preoperative imaging and machine learning algorithms helped the catheter interpret visual features. In this way, the robotic catheter advanced by itself from the base of the heart, along the wall of the left ventricle and around the leaky valve until it reached the location of the leak.
"The algorithms help the catheter figure out what type of tissue it's touching, where it is in the heart, and how it should choose its next motion to get where we want it to go," Dupont explains.
Though the autonomous robot took a bit longer than the surgeon to reach the leaky valve, its wall-following technique meant that it took the longest path.
"The navigation time was statistically equivalent for all, which we think is pretty impressive given that you're inside the blood-filled beating heart and trying to reach a millimeter-scale target on a specific valve," says Dupont.
He adds that the robot's ability to visualize and sense its environment could eliminate the need for fluoroscopic imaging, which is typically used in this operation and exposes patients to ionizing radiation.
A vision of the future?
Dupont says the project was the most challenging of his career. While the cardiac surgical fellow, who performed the operations on swine, was able to relax while the robot found the valve leaks, the project was taxing for Dupont's engineering fellows, who sometimes had to reprogram the robot mid-operation as they perfected the technology.
"I remember times when the engineers on our team walked out of the OR completely exhausted, but we managed to pull it off," says Dupont. "Now that we've demonstrated autonomous navigation, much more is possible."
Some cardiac interventionalists who are aware of Dupont's work envision using robots for more than navigation, performing routine heart-mapping tasks, for example. Some envision this technology providing guidance during particularly difficult or unusual cases or assisting in operations in parts of the world that lack highly experienced surgeons.
As the Food and Drug Administration begins to develop a regulatory framework for AI-enabled devices, Dupont envisions the possibility of autonomous surgical robots all over the world pooling their data to continuously improve performance over time -- much like self-driving vehicles in the field send their data back to Tesla to refine its algorithms.
"This would not only level the playing field, it would raise it," says Dupont. "Every clinician in the world would be operating at a level of skill and experience equivalent to the best in their field. This has always been the promise of medical robots. Autonomy may be what gets us there."
The study was funded by the National Institutes of Health (R01HL124020), with partial support from the ANR/Investissement d'avenir program. Dupont and several of his coauthors are inventors on U.S. patent application held by Boston Children's Hospital that covers the optical imaging technique.

(a) Light with a wavelength of 700 nm traveling from bottom to top is distorted when the radius of the cylinder (in the middle) is 175 nm. (b) There is hardly any distortion when the cylinder has a radius of 195 nm. These images correspond to the conditions for invisibility predicted by the theoretical calculation.
Credit: Applied Physics Express
A pair of researchers at Tokyo Institute of Technology (Tokyo Tech) describes a way of making a submicron-sized cylinder disappear without using any specialized coating. Their findings could enable invisibility of natural materials at optical frequency [1] and eventually lead to a simpler way of enhancing optoelectronic devices, including sensing and communication technologies.
Making objects invisible is no longer the stuff of fantasy but a fast-evolving science. 'Invisibility cloaks' using metamaterials[2] -- engineered materials that can bend rays of light around an object to make it undetectable -- now exist, and are beginning to be used to improve the performance of satellite antennas and sensors. Many of the proposed metamaterials, however, only work at limited wavelength ranges such as microwave frequencies.
Now, Kotaro Kajikawa and Yusuke Kobayashi of Tokyo Tech's Department of Electrical and Electronic Engineering report a way of making a cylinder invisible without a cloak for monochromatic illumination at optical frequency -- a broader range of wavelengths including those visible to the human eye.
They firstly explored what happens when a light wave hits an imaginary cylinder with an infinite length. Based on a classical electromagnetic theory called Mie scattering[3], they visualized the relationship between the light-scattering efficiency of the cylinder and the refractive index [4]. They looked for a region indicating very low scattering efficiency, which they knew would correspond to the cylinder's invisibility.
After identifying a suitable region, they determined that invisibility would occur when the refractive index of the cylinder ranges from 2.7 to 3.8. Some useful natural materials fall within this range, such as silicon (Si), aluminum arsenide (AlAs) and germanium arsenide (GaAs), which are commonly used in semiconductor technology.
Thus, in contrast to the difficult and costly fabrication procedures often associated with exotic metamaterial coatings, the new approach could provide a much simpler way to achieve invisibility.
The researchers used numerical modeling based on the Finite-Difference Time-Domain (FDTD) method to confirm the conditions for achieving invisibility.  By taking a close look at the magnetic field profiles, they inferred that "the invisibility stems from the cancellation of the dipoles generated in the cylinder."
Although rigorous calculations of the scattering efficiency have so far only been possible for cylinders and spheres, Kajikawa notes there are plans to test other structures, but these would require much more computing power.
To verify the current findings in practice, it should be relatively easy to perform experiments using tiny cylinders made of silicon and germanium arsenide. Kajikawa says: "We hope to collaborate with research groups who are now focusing on such nanostructures. Then, the next step would be to design novel optical devices."
Potential optoelectronic applications may include new kinds of detectors and sensors for the medical and aerospace industries.
[1] Optical frequency: A region of the electromagnetic spectrum that includesultraviolet, visible and infrared light.
[2] Metamaterials: Specially engineered materials designed to have advantageouselectromagnetic properties. Many recent advances in optical cloaking are based on John Pendry's pioneering work on metamaterials.
[3] Mie scattering: A description of the scattering of light particles that have adiameter larger than the wavelength of the incident light. It is named after Germanphysicist Gustav Mie (1868-1957), who published a seminal paper on the scatteringof light by gold colloids in 1908.
[4]Refractive index: A measure of how fast light propagates through a material.

Scientists at the University of Bristol have invented a new technology that could lead to the development of a new generation of smart surgical glues and dressings for chronic wounds. The new method, pioneered by Dr Adam Perriman and colleagues, involves re-engineering the membranes of stem cells to effectively "weld" the cells together.
Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows scientists to provide additional functions in the therapeutic cells, such as homing, adhesion or hypoxia (low oxygen) resistance. At the moment, there are few examples where the cell membrane is re-engineered to display active enzymes that drive extracellular matrix production, which is an essential process in wound healing.
In this research, published in Nature Communications today [Tuesday 23 April], the team modified the membrane of human mesenchymal stem cells (hMSCs) with an enzyme, known as thrombin, which is involved in the wound healing process. When the modified cells were placed in a solution containing the blood protein fibrinogen, they automatically welded together through the growth of a natural hydrogel from the surface of the cells. The researchers have also shown that the resulting 3D cellular structures could be used for tissue engineering.
Dr Adam Perriman, Associate Professor in Biomaterials in the School of Cellular and Molecular Medicine, said: "One of the biggest challenges in cell therapies is the need to protect the cells from aggressive environments after transplantation. We have developed a completely new technology that allows cells to grow their own artificial extracellular matrix, enabling cells to protect themselves and allowing them to thrive after transplantation."
The team's findings could increase the possibilities in tissue engineering for chronic wound healing, especially because the process uses fibrinogen, which is abundant in blood.
The researcher's new method of the conversion of natural enzymes into a membrane binding proteins, could pave the way for the development of a wide range of new biotechnologies.

This is a scanning electron microscopy (SEM) image ofBacillus timonensis.
Credit: Jinglin Hu/Northwestern University
Antimicrobial paints offer the promise of extra protection against bacteria. But Northwestern University researchers caution that these paints might be doing more harm than good.
In a new study, the researchers tested bacteria commonly found inside homes on samples of drywall coated with antimicrobial, synthetic latex paints. Within 24 hours, all bacteria died except for Bacillus timonensis, a spore-forming bacterium. Most bacilli are commonly inhabit soil, but many are found in indoor environments.
"If you attack bacteria with antimicrobial chemicals, then they will mount a defense," said Northwestern's Erica Hartmann, who led the study. "Bacillus is typically innocuous, but by attacking it, you might prompt it to develop more antibiotic resistance."
Bacteria thrive in warm, moist environments, so most die on indoor surfaces, which are dry and cold, anyway. This makes Hartmann question the need to use antimicrobial paints, which may only be causing bacteria to become stronger.
Spore-forming bacteria, such as Bacillus, protect themselves by falling dormant for a period of time. While dormant, they are highly resistant to even the harshest conditions. After those conditions improve, they reactivate.
"When it's in spore form, you can hit it with everything you've got, and it's still going to survive," said Hartmann, assistant professor of civil and environmental engineering in Northwestern's McCormick School of Engineering. "We should be judicious in our use of antimicrobial products to make sure that we're not exposing the more harmless bacteria to something that could make them harmful."
The study was published online on April 13 in the journal Indoor Air.
One problem with antimicrobial products -- such as these paints -- is that they are not tested against more common bacteria. Manufacturers test how well more pathogenic bacteria, such as E. coli or Staphylococcus, survive but largely ignore the bacteria that people (and the products they use) would more plausibly encounter.
"E. coli is like the 'lab rat' of the microbial world," Hartmann said. "It is way less abundant in the environment than people think. We wanted to see how the authentic indoor bacteria would respond to antimicrobial surfaces because they don't behave the same way as E. coli."

Network science is how mathematicians and software designers construct complicated social networks like Facebook. But a group of Florida State University researchers has found that these equations can tell engineers a lot about the composition of different materials.
Using network science -- part of a larger mathematical field called graph theory -- FAMU-FSU Professor of Mechanical Engineering William Oates, former graduate student Peter Woerner and Associate Professor Kunihiko "Sam" Taira mapped long range atomic forces onto an incredibly complex graph to simulate macroscopic material behavior.
The group then developed and applied a method that greatly simplifies the graph so that other researchers could replicate the process with other materials.
The work is published in the journal PLOS ONE.
Oates said using graph theory allows researchers to better understand how the molecules that compose a material work on a macroscopic level.
"All atoms have electrons and nuclei with positive charges, they create forces between the ions," Oates said. "Trying to describe that as a global structure is challenging. There are methods to model molecules, but the challenge is how to describe macroscopic behavior. Knowing how the molecules interact is only half of the problem. Network science provides a unique bridge that allows us to take molecule dynamics to the macroscopic world."
Ultimately, researchers want to understand all the atomic interactions in a given material so that they can understand how and why materials behave in certain ways, Oates said. But when you keep track of all the atomic interactions in a material, it becomes a huge problem to solve on a computer.
Oates' group worked to make it a much smaller problem.
In looking at a graph that shows the atoms in a material, Oates said to think of atoms and the forces between them as beads and springs. The atomic charges connect these beads, and they vibrate in complicated ways -- some faster and some slower.
For engineering purposes, it wasn't necessary to keep track of all the forces. So, the group applied a method to figure out how the forces in the graph could be reconnected without creating errors.
Using that knowledge, their algorithm deleted certain atomic forces within the graph and rewired it so they kept important information while making it easier to compute macroscopic behavior.
"You cut out the unimportant stuff and keep the important parts to make the simulations run substantially faster," Oates said. "That was really the goal -- to simplify it in order to accelerate computational materials research."
Oates' research is funded by the National Science Foundation's EAGER program, a one-year infusion of funding that allows a faculty member to pursue a high-risk but potentially transformative research idea.
This first study was more of a proof of concept, he said. He will now look at whether this graph theoretic method can tell researchers how to make a material more efficient or how it might transport energy faster.
"We might be able to use these network models to help facilitate that design process," Oates said.
Aditya Nair, a doctoral student in the FAMU-FSU College of Engineering, also contributed to this study.

Powered by Blogger.