Repetitive and intensive training is necessary to develop the required fine motor skills and competencies for residents to become proficient in microsurgery. Historically, surgical training has employed a “see one, do one, teach one,” approach, though there has been an increased interest in using simulation for training in recent years, in particular with respect to microsurgery, where there is little room for error. The majority of simulation training in microsurgery currently uses both live and cadaveric animal models. However, several financial, practical, ethical, and accessibility issues persist with animal model use, particularly in low-resource settings.

Proposing a move to non-biological models for simulation training

A recent study, published in the journal Plastic and Reconstructive Surgery led by Dr. Stephanie Thibaudeau, Assistant Professor of Surgery at McGill University, and Division of Plastic and Reconstructive Surgery Program Director at the McGill University Health Centre, puts forward the notion that non-biologic simulators could prove to be a better alternative when it comes to training future surgeons.

“Our paper provides a comprehensive summary of all non-biologic simulators in use for microsurgery training in plastic surgery, and reports on the demonstrated efficacy of non-biologic simulators for the acquisition and retention of microsurgical skills,” explains Jad Abi-Rafeh, a medical student at McGill and the paper’s first author.

“In contrast to animal model training, which requires expensive labs, the advantages of non-biologic simulators include increased availability, ease of set-up, flexibility (accommodating interrupted practice), low cost, low maintenance, lack of biological hazards, portability, potential for repeated use, and easy storage. It also reduces animal use and is overall more ethical.”

The researchers showed that using basic sewing needles led to a 48 percent decrease in the number of animals needed for microsurgery training, resulting in an equivalent performance on animal models compared with animal model training alone. Supplementing an animal-based training course with practice card exercises led to a 50 percent reduction in costs associated with microsurgical training, decreased animal use and death, and improved performance on animal models later on.

Silicone tubing yielded equivalent outcomes as animal model training on rat anastomosis assessment exercises, and skills learned were retained over the next four months.

Moving towards implementation

“The findings of our study bring us one step closer towards a new standardized, ethical, accessible, and objectively measurable microsurgery training curriculum to train the modern-day surgical resident in the practice of microsurgery,” the authors claim. “The next steps would be to develop a training curriculum employing various non-biologic simulators that would leverage the use of different models of increasing complexity to teach growing microsurgical skills in a stepwise fashion. It would also leverage exciting emerging technologies to further narrow the gap between biologic and non-biologic simulators, such as the heart-like ‘micro-pump’, which drives pulsatile and dynamic circulation through simulated non-biologic vessels.”

The researchers note that once this curriculum is developed, it would then need to be validated and compared to animal-based training models presently available, and, if demonstrated to be as effective, may considerably reduce, if not by-pass completely, animal model use in microsurgery training.

“It is such a privilege for a medical student like myself to be working with such a talented team of plastic surgery residents under the supervision of Dr. Thibaudeau,” adds Jad. “All co-authors on this study have such notable experience in simulation research; Dr. Zammit and Dr. Jaberi are CIHR-funded researchers currently obtaining their masters in experimental surgery and simulation, while Dr. Al-Halabi is a PhD candidate with interests in surgical education. Without their guidance and supervision, this study would not have been possible.”

The origin story of the tiny rockets began with a fundamental scientific question: Could scientists design nano- and microscale vessels that use chemicals for fuel to travel through the human body? Fifteen years of research by Mallouk and others showed that the short answer was “yes,” but researchers faced significant barriers for using these vessels in biomedical applications because the chemicals they used for fuel, like hydrogen peroxide, were toxic.

An “accidental” discovery led Mallouk and his group to focus on the use of a completely different type of fuel: sound waves. While trying to move their rockets with acoustic levitation, a process used to lift particles off a microscope slide with high-frequency sound waves, the group was surprised to find that ultrasound made the robots move at very fast speeds. Mallouk and his team decided to investigate this phenomenon further to see if they could use high-frequency sound waves to power their tiny vessels.

The group’s latest paper details the design of the microscale rockets, resembling a round-bottomed cup 10 microns in length and 5 microns wide, or about the size of a particle of dust. The rounded cups are 3D printed using laser lithography and contain an outer layer of gold and inner layers of nickel and a polymer. Treatment with a hydrophobic chemical after the gold is cast causes an air bubble to form and become trapped inside the rocket’s cavity.

In the presence of ultrasound waves, the bubble inside the rocket is excited by high-frequency oscillation at the water-air interface, which turns the bubble into an onboard motor. The rocket can then be steered using an external magnetic field. Each individual rocket has its own resonant frequency, meaning that each member of a fleet can be driven independently from the others. The tiny rockets are also incredibly adept, able to travel up microscopic staircases and swim freely in three dimensions with the help of special fins.

One of the rocket’s most unique features is their ability to move other particles and cells with sharp precision, even in crowded environments. The robotic vessels can either push particles in the desired direction or use a “tractor beam” approach to pull objects with an attractive force. Mallouk says the ability to push objects without disturbing the environment “wasn’t available on a larger scale,” adding that the tractor beam approach used by larger-sized vessels isn’t as good at precise movements. “There’s a lot of control you can do at this length scale,” he adds.

At this particular size, the rockets are large enough not to be impacted by Brownian motion, the random and erratic movements experienced by particles in the nanometer size range, but are small enough to move objects without disturbing the environment around them. “At this particular length scale, we’re right at the crossover point between when the power is enough to affect other particles,” says Mallouk.

By increasing or decreasing the amount of acoustic “fuel” the researchers provide the rockets, they can also control the speed of the tiny vessels. “If I want it to go slow, I can turn the power down, and if I want it to go really fast, I can turn the power up,” explains Jeff McNeill, a graduate student who works on nano- and microscale motor projects. “That’s a really useful tool.”

Mallouk and his lab are already exploring a number of possible areas of further research, including ways to actuate the rockets with light, and making even smaller rockets that would be faster and stronger for their size. Future collaborations with engineers and roboticists at Penn, including Dan Hammer, Marc Miskin, Vijay Kumar, James Pikul, and Kathleen Stebe, could help make the rockets “smart” by allowing them to outfit the vessels with computer chips and sensors to give them autonomy and intelligence.

As the group considers the micro-rocket’s broad medical potential from medical imaging to nano-robotics Mallouk says, “We’d like to have controllable robots that can do tasks inside the body: Deliver medicine, rotor rooter arteries, diagnostic snooping.”

This research was supported by National Science Foundation Grant DMR-1420620, which funds the Penn State Center for Nanoscale Science, a Materials Research Science and Engineering Center that supports collaborative, interdisciplinary research in the area of nanoscale materials.

Thomas Mallouk is the Vagelos Professor in Energy Research in the Department of Chemistry in the School of Arts and Sciences at the University of Pennsylvania.

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Materials provided by University of Pennsylvania. Original written by Erica K Brockmeier. Note: Content may be edited for style and length.

Most methods of removing carbon dioxide from a stream of gas require higher concentrations, such as those found in the flue emissions from fossil fuel-based power plants. A few variations have been developed that can work with the low concentrations found in air, but the new method is significantly less energy-intensive and expensive, the researchers say.

The technique, based on passing air through a stack of charged electrochemical plates, is described in a new paper in the journal Energy and Environmental Science, by MIT postdoc Sahag Voskian, who developed the work during his PhD, and T. Alan Hatton, the Ralph Landau Professor of Chemical Engineering.

The device is essentially a large, specialized battery that absorbs carbon dioxide from the air (or other gas stream) passing over its electrodes as it is being charged up, and then releases the gas as it is being discharged. In operation, the device would simply alternate between charging and discharging, with fresh air or feed gas being blown through the system during the charging cycle, and then the pure, concentrated carbon dioxide being blown out during the discharging.

As the battery charges, an electrochemical reaction takes place at the surface of each of a stack of electrodes. These are coated with a compound called polyanthraquinone, which is composited with carbon nanotubes. The electrodes have a natural affinity for carbon dioxide and readily react with its molecules in the airstream or feed gas, even when it is present at very low concentrations. The reverse reaction takes place when the battery is discharged — during which the device can provide part of the power needed for the whole system — and in the process ejects a stream of pure carbon dioxide. The whole system operates at room temperature and normal air pressure.

“The greatest advantage of this technology over most other carbon capture or carbon absorbing technologies is the binary nature of the adsorbent’s affinity to carbon dioxide,” explains Voskian. In other words, the electrode material, by its nature, “has either a high affinity or no affinity whatsoever,” depending on the battery’s state of charging or discharging. Other reactions used for carbon capture require intermediate chemical processing steps or the input of significant energy such as heat, or pressure differences.

“This binary affinity allows capture of carbon dioxide from any concentration, including 400 parts per million, and allows its release into any carrier stream, including 100 percent CO2,” Voskian says. That is, as any gas flows through the stack of these flat electrochemical cells, during the release step the captured carbon dioxide will be carried along with it. For example, if the desired end-product is pure carbon dioxide to be used in the carbonation of beverages, then a stream of the pure gas can be blown through the plates. The captured gas is then released from the plates and joins the stream.

In some soft-drink bottling plants, fossil fuel is burned to generate the carbon dioxide needed to give the drinks their fizz. Similarly, some farmers burn natural gas to produce carbon dioxide to feed their plants in greenhouses. The new system could eliminate that need for fossil fuels in these applications, and in the process actually be taking the greenhouse gas right out of the air, Voskian says. Alternatively, the pure carbon dioxide stream could be compressed and injected underground for long-term disposal, or even made into fuel through a series of chemical and electrochemical processes.

The process this system uses for capturing and releasing carbon dioxide “is revolutionary” he says. “All of this is at ambient conditions — there’s no need for thermal, pressure, or chemical input. It’s just these very thin sheets, with both surfaces active, that can be stacked in a box and connected to a source of electricity.”

“In my laboratories, we have been striving to develop new technologies to tackle a range of environmental issues that avoid the need for thermal energy sources, changes in system pressure, or addition of chemicals to complete the separation and release cycles,” Hatton says. “This carbon dioxide capture technology is a clear demonstration of the power of electrochemical approaches that require only small swings in voltage to drive the separations.”

In a working plant — for example, in a power plant where exhaust gas is being produced continuously — two sets of such stacks of the electrochemical cells could be set up side by side to operate in parallel, with flue gas being directed first at one set for carbon capture, then diverted to the second set while the first set goes into its discharge cycle. By alternating back and forth, the system could always be both capturing and discharging the gas. In the lab, the team has proven the system can withstand at least 7,000 charging-discharging cycles, with a 30 percent loss in efficiency over that time. The researchers estimate that they can readily improve that to 20,000 to 50,000 cycles.

The electrodes themselves can be manufactured by standard chemical processing methods. While today this is done in a laboratory setting, it can be adapted so that ultimately they could be made in large quantities through a roll-to-roll manufacturing process similar to a newspaper printing press, Voskian says. “We have developed very cost-effective techniques,” he says, estimating that it could be produced for something like tens of dollars per square meter of electrode.

Compared to other existing carbon capture technologies, this system is quite energy efficient, using about one gigajoule of energy per ton of carbon dioxide captured, consistently. Other existing methods have energy consumption which vary between 1 to 10 gigajoules per ton, depending on the inlet carbon dioxide concentration, Voskian says.

The researchers have set up a company called Verdox to commercialize the process, and hope to develop a pilot-scale plant within the next few years, he says. And the system is very easy to scale up, he says: “If you want more capacity, you just need to make more electrodes.”

Just before the Big Bang launched the universe onto its ever-expanding course, physicists believe, there was another, more explosive phase of the early universe at play: cosmic inflation, which lasted less than a trillionth of a second. During this period, matter — a cold, homogeneous goop — inflated exponentially quickly before processes of the Big Bang took over to more slowly expand and diversify the infant universe.

Recent observations have independently supported theories for both the Big Bang and cosmic inflation. But the two processes are so radically different from each other that scientists have struggled to conceive of how one followed the other.

Now physicists at MIT, Kenyon College, and elsewhere have simulated in detail an intermediary phase of the early universe that may have bridged cosmic inflation with the Big Bang. This phase, known as “reheating,” occurred at the end of cosmic inflation and involved processes that wrestled inflation’s cold, uniform matter into the ultrahot, complex soup that was in place at the start of the Big Bang.

“The postinflation reheating period sets up the conditions for the Big Bang, and in some sense puts the ‘bang’ in the Big Bang,” says David Kaiser, the Germeshausen Professor of the History of Science and professor of physics at MIT. “It’s this bridge period where all hell breaks loose and matter behaves in anything but a simple way.”

Kaiser and his colleagues simulated in detail how multiple forms of matter would have interacted during this chaotic period at the end of inflation. Their simulations show that the extreme energy that drove inflation could have been redistributed just as quickly, within an even smaller fraction of a second, and in a way that produced conditions that would have been required for the start of the Big Bang.

The team found this extreme transformation would have been even faster and more efficient if quantum effects modified the way that matter responded to gravity at very high energies, deviating from the way Einstein’s theory of general relativity predicts matter and gravity should interact.

“This enables us to tell an unbroken story, from inflation to the postinflation period, to the Big Bang and beyond,” Kaiser says. “We can trace a continuous set of processes, all with known physics, to say this is one plausible way in which the universe came to look the way we see it today.”

The team’s results appear today in Physical Review Letters. Kaiser’s co-authors are lead author Rachel Nguyen, and John T. Giblin, both of Kenyon College, and former MIT graduate student Evangelos Sfakianakis and Jorinde van de Vis, both of Leiden University in the Netherlands.

“In sync with itself”

The theory of cosmic inflation, first proposed in the 1980s by MIT’s Alan Guth, the V.F. Weisskopf Professor of Physics, predicts that the universe began as an extremely small speck of matter, possibly about a hundred-billionth the size of a proton. This speck was filled with ultra-high-energy matter, so energetic that the pressures within generated a repulsive gravitational force — the driving force behind inflation. Like a spark to a fuse, this gravitational force exploded the infant universe outward, at an ever-faster rate, inflating it to nearly an octillion times its original size (that’s the number 1 followed by 26 zeroes), in less than a trillionth of a second.

Kaiser and his colleagues attempted to work out what the earliest phases of reheating — that bridge interval at the end of cosmic inflation and just before the Big Bang — might have looked like.

“The earliest phases of reheating should be marked by resonances. One form of high-energy matter dominates, and it’s shaking back and forth in sync with itself across large expanses of space, leading to explosive production of new particles,” Kaiser says. “That behavior won’t last forever, and once it starts transferring energy to a second form of matter, its own swings will get more choppy and uneven across space. We wanted to measure how long it would take for that resonant effect to break up, and for the produced particles to scatter off each other and come to some sort of thermal equilibrium, reminiscent of Big Bang conditions.”

The team’s computer simulations represent a large lattice onto which they mapped multiple forms of matter and tracked how their energy and distribution changed in space and over time as the scientists varied certain conditions. The simulation’s initial conditions were based on a particular inflationary model — a set of predictions for how the early universe’s distribution of matter may have behaved during cosmic inflation.

The scientists chose this particular model of inflation over others because its predictions closely match high-precision measurements of the cosmic microwave background — a remnant glow of radiation emitted just 380,000 years after the Big Bang, which is thought to contain traces of the inflationary period.

A universal tweak

The simulation tracked the behavior of two types of matter that may have been dominant during inflation, very similar to a type of particle, the Higgs boson, that was recently observed in other experiments.

Before running their simulations, the team added a slight “tweak” to the model’s description of gravity. While ordinary matter that we see today responds to gravity just as Einstein predicted in his theory of general relativity, matter at much higher energies, such as what’s thought to have existed during cosmic inflation, should behave slightly differently, interacting with gravity in ways that are modified by quantum mechanics, or interactions at the atomic scale.

In Einstein’s theory of general relativity, the strength of gravity is represented as a constant, with what physicists refer to as a minimal coupling, meaning that, no matter the energy of a particular particle, it will respond to gravitational effects with a strength set by a universal constant.

However, at the very high energies that are predicted in cosmic inflation, matter interacts with gravity in a slightly more complicated way. Quantum-mechanical effects predict that the strength of gravity can vary in space and time when interacting with ultra-high-energy matter — a phenomenon known as nonminimal coupling.

Kaiser and his colleagues incorporated a nonminimal coupling term to their inflationary model and observed how the distribution of matter and energy changed as they turned this quantum effect up or down.

In the end they found that the stronger the quantum-modified gravitational effect was in affecting matter, the faster the universe transitioned from the cold, homogeneous matter in inflation to the much hotter, diverse forms of matter that are characteristic of the Big Bang.

By tuning this quantum effect, they could make this crucial transition take place over 2 to 3 “e-folds,” referring to the amount of time it takes for the universe to (roughly) triple in size. In this case, they managed to simulate the reheating phase within the time it takes for the universe to triple in size two to three times. By comparison, inflation itself took place over about 60 e-folds.

“Reheating was an insane time, when everything went haywire,” Kaiser says. “We show that matter was interacting so strongly at that time that it could relax correspondingly quickly as well, beautifully setting the stage for the Big Bang. We didn’t know that to be the case, but that’s what’s emerging from these simulations, all with known physics. That’s what’s exciting for us.”

The married couple’s step-by-step approach has revealed a new way to detect and attack cancer cells using technology traditionally reserved for solar power. The results, published in the current issue of Scientific Reports, showcases dramatic improvements in light-activated fluorescent dyes for disease diagnosis, image-guided surgery and site-specific tumor treatment.

“We’ve tested this concept in breast, lung cancer and skin cancer cell lines and mouse models, and so far it’s all looking remarkably promising,” said Sophia, MSU biochemistry and molecular biologist.

While the cancer applications hold the most possibility, their findings have potential beyond the field of oncology, said Richard, the Johansen Crosby Endowed Professor of chemical engineering and materials science.

“This work has the potential to transform fluorescent probes for broad societal impact through applications ranging from biomedicine to photocatalysis — the acceleration of chemical reactions with light,” he said. “Our solar research inspired this cancer project, and in turn, focusing on cancer cells has advanced our solar cell research; it’s been an amazing feedback loop.”

Prior to the Lunts’ combined effort, fluorescent dyes used for therapeutics and diagnostics, aka “theranostics,” had shortcomings, such as low brightness, high toxicity to cells, poor tissue penetration and unwanted side effects.

By optoelectronically tuning organic salt nanoparticles used as theranostics, the Lunts were able to control them in a range of cancer studies. Coaxing the nanoparticles into the nontoxic zone resulted in enhanced imaging, while pushing them into the phototoxic — or light-activated — range produced effective on-site tumor treatment.

The key was learning to control the electronics of their photoactive molecules independently from their optical properties and then making the leap to apply this understanding in a new way to a seemingly unrelated field.

Richard had recently discovered the ability to electronically tune these salts from his work in converting photovoltaics into solar glass. Sophia had long studied metabolic pathways unique to cancer cells. It was when the Lunts were discussing solar glass during a walk that they made the connection: Molecules active in the solar cells might also be used to more effectively target and kill cancer cells.

A journey of 1,000 miles

Their walks had rather unscientific beginnings. Shortly after the Lunts met at Princeton University, Richard moved to another university. To maintain their long-distance relationship, they scheduled daily phone calls. Upon their arrival at MSU, individual academic career demands replaced geographic distance as a challenge to their busy lives.

To connect daily, they take CEO-style walks together every evening. The two-mile saunters take place rain or shine, and they often engage in scientific discussions. The three keys to their walks are intentional curiosity, perseverance and the merging of different fields and perspectives, Sophia said.

“We talk science, strategic plans for our careers and our various grants,” she said. “We ping ideas off each other. Our continual conversations brainstorming ideas on a particular topic or challenge often lead to those exciting ‘aha’ moments.”

Their walks have helped them push through many challenges.

“Our first experiments did not turn out as expected; I’m surprised that we didn’t give up given how crazy the idea seemed at first,” Richard said. “Figuring out how to do this research took many walks.”

Obviously, the results were worth the hike. Today, Richard designs the molecules; Babak Borhan, MSU chemist, synthesizes and improves them; and Sophia tests their photoactive inventions in cancer cell lines and mouse models.

Future research will work to improve the theranostics’ effectiveness, decrease toxicity and reduce side effects. The Lunts have applied for a patent for their work, and they’re looking forward to eventually pushing their photoactive molecule findings through clinical trials.

“Though that will take many more walks,” Richard said with a smile.

The benefits of a diet high in fiber and yogurt have already been established for cardiovascular disease and gastrointestinal cancer. The new findings based on an analysis of data from studies involving 1.4 million adults in the United States, Europe and Asia suggest this diet may also protect against lung cancer.

Participants were divided into five groups, according to the amount of fiber and yogurt they consumed. Those with the highest yogurt and fiber consumption had a 33% reduced lung cancer risk as compared to the group who did not consume yogurt and consumed the least amount of fiber.

“Our study provides strong evidence supporting the U.S. 2015-2020 Dietary Guideline recommending a high fiber and yogurt diet,” said senior author Xiao-Ou Shu, MD, PhD, MPH, Ingram Professor of Cancer Research, associate director for Global Health and co-leader of the Cancer Epidemiology Research Program at Vanderbilt-Ingram Cancer Center.

“This inverse association was robust, consistently seen across current, past and never smokers, as well as men, women and individuals with different backgrounds,” she added.

Shu said the health benefits may be rooted in their prebiotic (nondigestible food that promotes growth of beneficial microorganisms in the intestines) and probiotic properties. The properties may independently or synergistically modulate gut microbiota in a beneficial way.

The study’s lead authors are Jae Jeong Yang, PhD, a visiting research fellow from the Seoul National University, South Korea, and Danxia Yu, PhD, assistant professor of Medicine at Vanderbilt.

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Materials provided by Vanderbilt University Medical Center. Note: Content may be edited for style and length.