Drexel University’s MXene material is one step closer to transforming the lives of people suffering from end-stage kidney disease. Nephria Bio Inc., a U.S.-based spin-off of the South Korean medical device company EOFlow Co. Ltd., has signed a licensing agreement with the University to use the two-dimensional material, discovered at Drexel, as a filter in a wearable artificial kidney device it’s developing. The technology could allow many of the millions of people suffering from end-stage kidney disease worldwide to move more freely, without spending hours each week anchored to large dialysis machines.

© Drexel University | https://drexel.edu

“Our fundamental study of titanium carbide MXene supported by NSF showed that MXene is biocompatible, able of adsorbing a variety of small molecules, and holds a lot of promise in medical applications, so it is exciting to see it applied for improving and really changing dialysis – an area of need in health care that can help millions of people,” says Yury Gogotsi, PhD, Distinguished University and Bach professor in Drexel’s College of Engineering, who is a world leader in developing and studying MXenes.

In the late stages of kidney disease, the kidneys have trouble filtering fluids and small molecules, including urea, and some of these molecules become toxic in the body when they begin to accumulate. Dialysis supports the kidneys in filtering toxins and excess fluids from the blood, but the process is time-consuming and requires patients to remain attached to immobile dialysis machines.

“This work could give hundreds of thousands of people with kidney disease the ability to live life more freely and fully,” says Meera Harhay, MD, an associate professor of Medicine in Drexel’s College of Medicine, who has been working with Gogotsi to study MXene’s application in dialysis. “A wearable artificial kidney would allow people suffering from kidney disease to more easily work and travel and maintain a more active lifestyle, which has been associated with positive health outcomes.”

A single facility-based hemodialysis session can require up to 200 liters of purified water to clear the build-up of urea and other toxic molecules from a patient’s blood. Developing a portable dialysis machine means figuring out how to reduce the amount of water the wearer would have to carry with them.

MXene is the solution, according to Jesse Kim, founding CEO of Nephria Bio and its parent company, EOFlow, because it filters urea and other electrolytes well enough that a single liter of water could be quickly cleaned and reused for the entirety of the process.

TMD has covered - in print and online - a range of artifical kidney technologies in development - click to look through the archives.

“In order to develop a wearable dialysis device, you need a material that can filter urea, which is a very, very small molecule that is also very soluble, it dissolves in water so well that it’s really hard to filter,” Kim says. “It’s the most difficult toxin to filter. And that’s why dialysis takes so long. If you go to a dialysis center, it takes 4 to 6 hours per session.”

© Drexel University | https://drexel.edu/now/archive/2018/November/MXene-urea-wearable-kidney/

MXene is a two-dimensional material just a few atoms thick that has demonstrated a number exceptional abilities since its discovery in Drexel’s College of Engineering in 2011. Among them, the ability to filter tiny particles from liquid, which researchers in the Department Materials Science and Engineering identified several years ago, made it a prime candidate for use in dialysis.

"Two technologies are essential to develop wearable artificial kidneys; One is a small, light actuator with low power consumption, and the other is an efficient material for urea filtration. Nephria Bio secured them both – the proprietary electroosmotic pump technology from EOFlow, and the filter technology from Drexel University,” Kim says. “With the unique combination of these enabling technologies, Nephria Bio feels that it can substantially enhance dialysis therapy for kidney patients.”

Drexel researchers Gogotsi, who discovered MXenes along with fellow College of Engineering professor Michel Barsoum, PhD, and Harhay, a kidney disease specialist, have been working with Kim with support from the Coulter-Drexel Translational Research Partnership Program to combine MXene with EOFlow’s patented electrochemical actuator pump, to produce a lightweight-but-powerful filtration device that will enable portable dialysis.

The EOFlow pump is the key component of a disposable insulin patch, which recently entered the market. It launched Nephria Bio in January 2021 with the specific goal of exploring how it could be used in dialysis.

Nephria Bio’s plan is to use the pump and MXene material to produce a lightweight, highly efficient filtration system that would enable reuse and recycling of the filtration water, called dialysate. Putting the technology in a flexible, wearable, cartridge-based system, called EOPump-based Continuous Ambulatory Renal Replacement Therapy (EOCARRT™), will allow ambulatory dialysis. The system could supplement or bridge traditional dialysis therapy and, ultimately, supplant it – depending on the therapeutic needs and how the device performs, Kim says.

“Working with Nephria Bio through the Coulter program has revealed the promise of MXene materials in biomedical technology. This collaboration is taking the work of many Drexel researchers one step closer to realizing its potential as a medical application,” says Kathie Jordan, PhD, director of the Coulter-Drexel program.

Being unable to walk quickly can be frustrating and problematic, but it’s a common issue, especially as people age. Noting the pervasiveness of slower-than-desired walking, engineers at Stanford University have tested how well a prototype exoskeleton system they have developed – which attaches around the shin and into a running shoe – increased the self-selected walking speed of people in an experimental setting.

The exoskeleton is externally powered by motors and controlled by an algorithm. When the researchers optimized it for speed, participants walked, on average, 42% faster than when they were wearing normal shoes and no exoskeleton. The results of this study were published April 20 in IEEE Transactions on Neural Systems and Rehabilitation Engineering.

"We were hoping that we could increase walking speed with exoskeleton assistance, but we were really surprised to find such a large improvement," says Steve Collins, associate professor of mechanical engineering at Stanford and senior author of the paper. "40% is huge."

For this initial set of experiments, the participants were young, healthy adults. Given their impressive results, the researchers plan to run future tests with older adults and to look at other ways the exoskeleton design can be improved. They also hope to eventually create an exoskeleton that can work outside the lab, though that goal is still a way off.

"My research mission is to understand the science of biomechanics and motor control behind human locomotion and apply that to enhance the physical performance of humans in daily life," says Seungmoon Song, a postdoctoral fellow in mechanical engineering and lead author of the paper. "I think exoskeletons are very promising tools that could achieve that enhancement in physical quality of life."

Walking in the loop
The ankle exoskeleton system tested in this research is an experimental emulator that serves as a testbed for trying out different designs. It has a frame that fastens around the upper shin and into an integrated running shoe that the participant wears. It’s attached to large motors that sit beside the walking surface and pull a tether that runs up the length of the back of the exoskeleton. Controlled by an algorithm, the tether tugs the wearer's heel upward, helping them point their toe down as they push off the ground.

For this study, the researchers had 10 participants walk with five different modes of operation. They walked in normal shoes without the exoskeleton, with the exoskeleton turned off, and with the exoskeleton turned on with three different modes: optimized for speed, optimized for energy use, and a placebo mode adjusted to make them walk more slowly. In all the tests, participants walked on a treadmill that adapts to their speed.

The mode that was optimized for speed – which resulted in the 42% increase in walking pace – was created through a human-in-the-loop process. An algorithm repeatedly adjusted the exoskeleton settings while the user walked, with the goal of improving the user's speed with each adjustment. Finding the speed-optimized mode of operation took about 150 rounds of adjustment and two hours per person.

In addition to greatly increasing walking speed, the speed-optimized mode also reduced energy use, by about 2% per meter traveled. However, that result varied widely from person to person, which is somewhat expected, given that it was not an intentional feature of that exoskeleton mode.

"The study was designed to specifically answer the scientific question about increasing walking speed," Song said. "We didn't care too much about the other performance measures, like comfort or energy. However, 7 out of 10 participants not only walked faster but consumed less energy, which really shows how much potential exoskeletons have for helping people in an efficient way."

The settings that were optimized specifically for energy use were borrowed from a previous experiment. In the current study, this mode decreased energy use more than the speed-optimized settings but did not increase speed as much. As intended, the placebo mode both slowed down participants and boosted their energy use.

Better, faster, stronger
Now that the researchers have attained such significant speed assistance, they plan to focus future versions of the ankle exoskeleton emulator on reducing energy use consistently across users, while also being more comfortable.

In considering older adults specifically, Collins and his lab wonder whether future designs could reduce pain caused by weight on joints or improve balance. They plan to conduct similar walking tests with older adults and hope those provide encouraging results as well.

"A 40% increase in speed is more than the difference between younger adults and older adults," said Collins. "So, it's possible that devices like this could not only restore but enhance self-selected walking speed for older individuals and that's something that we're excited to test next."

A lobster’s underbelly is lined with a thin, translucent membrane that is both stretchy and surprisingly tough. This marine under-armor, as MIT engineers reported in 2019, is made from the toughest known hydrogel in nature, which also happens to be highly flexible. This combination of strength and stretch helps shield a lobster as it scrabbles across the seafloor, while also allowing it to flex back and forth to swim.

Now a separate MIT team has fabricated a hydrogel-based material that mimics the structure of the lobster’s underbelly. The researchers ran the material through a battery of stretch and impact tests, and showed that, similar to the lobster underbelly, the synthetic material is remarkably fatigue-resistant, able to withstand repeated stretches and strains without tearing.

If the fabrication process could be significantly scaled up, materials made from nanofibrous hydrogels could be used to make stretchy and strong replacement tissues such as artificial tendons and ligaments.

Read about other researchand developments of hydrogels.

The team’s results are published in the journal Matter. The paper’s MIT co-authors include postdocs Jiahua Ni and Shaoting Lin; graduate students Xinyue Liu and Yuchen Sun; professor of aeronautics and astronautics Raul Radovitzky; professor of chemistry Keith Nelson; mechanical engineering professor Xuanhe Zhao; and former research scientist David Veysset PhD ’16, now at Stanford University; along with Zhao Qin, assistant professor at Syracuse University, and Alex Hsieh of the Army Research Laboratory.

Nature’s twist
In 2019, Lin and other members of Zhao’s group developed a new kind of fatigue-resistant material made from hydrogel – a gelatin-like class of materials made primarily of water and cross-linked polymers. They fabricated the material from ultrathin fibers of hydrogel, which aligned like many strands of gathered straw when the material was repeatedly stretched. This workout also happened to increase the hydrogel’s fatigue resistance.

“At that moment, we had a feeling nanofibers in hydrogels were important, and hoped to manipulate the fibril structures so that we could optimize fatigue resistance,” says Lin.

In their new study, the researchers combined a number of techniques to create stronger hydrogel nanofibers. The process starts with electrospinning, a fiber production technique that uses electric charges to draw ultrathin threads out of polymer solutions. The team used high-voltage charges to spin nanofibers from a polymer solution, to form a flat film of nanofibers, each measuring about 800 nanometers – a fraction of the diameter of a human hair.

They placed the film in a high-humidity chamber to weld the individual fibers into a sturdy, interconnected network, and then set the film in an incubator to crystallize the individual nanofibers at high temperatures, further strengthening the material.

They tested the film’s fatigue-resistance by placing it in a machine that stretched it repeatedly over tens of thousands of cycles. They also made notches in some films and observed how the cracks propagated as the films were stretched repeatedly. From these tests, they calculated that the nanofibrous films were 50x more fatigue-resistant than the conventional nanofibrous hydrogels.

Around this time, they read with interest a study by Ming Guo, associate professor of mechanical engineering at MIT, who characterized the mechanical properties of a lobster’s underbelly. This protective membrane is made from thin sheets of chitin, a natural, fibrous material that is similar in makeup to the group’s hydrogel nanofibers.

Guo found that a cross-section of the lobster membrane revealed sheets of chitin stacked at 36° angles, similar to twisted plywood, or a spiral staircase. This rotating, layered configuration, known as a bouligand structure, enhanced the membrane’s properties of stretch and strength.

“We learned that this bouligand structure in the lobster underbelly has high mechanical performance, which motivated us to see if we could reproduce such structures in synthetic materials,” Lin says.

© Courtesy of the researchers | mit.edu

Angled architecture
Ni, Lin, and members of Zhao’s group teamed up with Nelson’s lab and Radovitzky’s group in MIT’s Institute for Soldier Nanotechnologies, and Qin’s lab at Syracuse University, to see if they could reproduce the lobster’s bouligand membrane structure using their synthetic, fatigue-resistant films.

“We prepared aligned nanofibers by electrospinning to mimic the chinic fibers existed in the lobster underbelly,” Ni says.

After electrospinning nanofibrous films, the researchers stacked each of five films in successive, 36° angles to form a single bouligand structure, which they then welded and crystallized to fortify the material. The final product measured 9 square centimeters and about 30 microns to 40 microns thick – about the size of a small piece of Scotch tape.

Stretch tests showed that the lobster-inspired material performed similarly to its natural counterpart, able to stretch repeatedly while resisting tears and cracks – a fatigue-resistance Lin attributes to the structure’s angled architecture.

“Intuitively, once a crack in the material propagates through one layer, it’s impeded by adjacent layers, where fibers are aligned at different angles,” Lin explains.

The team also subjected the material to microballistic impact tests with an experiment designed by Nelson’s group. They imaged the material as they shot it with microparticles at high velocity, and measured the particles’ speed before and after tearing through the material. The difference in velocity gave them a direct measurement of the material’s impact resistance, or the amount of energy it can absorb, which turned out to be a surprisingly tough 40 kilojoules per kilogram. This number is measured in the hydrated state.

“That means that a 5mm steel ball launched at 200 meters per second would be arrested by 13mm of the material,” Veysset says. “It is not as resistant as Kevlar, which would require 1 millimeter, but the material beats Kevlar in many other categories.”

It’s no surprise that the new material isn’t as tough as commercial antiballistic materials. It is, however, significantly sturdier than most other nanofibrous hydrogels such as gelatin and synthetic polymers like PVA. The material is also much stretchier than Kevlar. This combination of stretch and strength suggests that, if their fabrication can be sped up, and more films stacked in bouligand structures, nanofibrous hydrogels may serve as flexible and tough artificial tissues.

“For a hydrogel material to be a load-bearing artificial tissue, both strength and deformability are required,” Lin says. “Our material design could achieve these two properties.”

This research was supported, in part, by MIT and the U. S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT.

3D printing is transforming everything from fashion and health care to transportation and toys. But this rapidly evolving technology, also known as additive manufacturing, can threaten national security and intellectual property rights.

To reduce illicit use of 3D printers, Zhanpeng Jin, PhD, associate professor in the Department of Computer Science and Engineering at the University at Buffalo, is developing a way to track the origin of 3D-printed items.

His concern was that, as long as people have the digital design for an item, which can be downloaded from the internet, sometimes as open-source material, people can print out anything they want, which can range from computer parts and toys to fully functional handguns and assault rifles.

"So, what would be the best way to protect our intellectual property from someone else printing the same design using their own printer?" Jin says. "We wanted to find something internal. What would be the inherent signatures printed by my own 3D printer instead of another 3D printer?"

3D printers build three-dimensional objects by adding successive layers of printing materials according to the digital design for a 3D model. Each 3D printer has an extruder, which pushes the building material along. The extruder's hot end then melts the material, and places it on the print bed to build the model.

In a paper, "ThermoTag: A Hidden ID of 3D Printers for Fingerprinting and Watermarking," published in the journal IEEE Transactions on Information Forensics and Security, a research team led by Jin describes how each extruder's hot end has its own unique heating properties, which impact the precise way that the 3D model is constructed.

Those thermodynamic properties can be used to identify the specific extruder and, thus, the model of 3D printer, as uniquely as a human fingerprint, or, as Jin calls it, a ThermoTag.

Jin compared the process to using a laptop to write a letter. Because software exists that can track keystrokes, an observer can see every step that went into the letter, including the writer's unique writing style. Similarly, because of the unique properties of each 3D printer's extruder, a researcher can examine the specific manner in which a 3D-printed object was made, and compare that to a database of various extruders until a match is made. From there, once the model printer is identified, the purchaser of said model can be tracked down if they had, say, used the printer to build an illegal assault rifle.

According to the research, Jin and his team discovered that, by examining and comparing the ThermoTag features of 45 different extruders of the same model, they were able to correctly identify the source printer with an accuracy rate of 92%.

"This ThermoTag will behave like the fingerprint of the 3D printer. When you print out a new product, you can use watermarking," Jin says, noting that watermarking can be used to invisibly embed such information as the printer's manufacturer, label and serial number in the product. "So that would make this watermark of this particular product unique."

It's possible, Jin says, that someone could replace their extruder to try to avoid detection. That's why it's important to create a database of these parts for comparison, he says.

Co-authors of the study are UB faculty members Chi Zhou, PhD, associate professor in the Department of Industrial and Systems Engineering, and Wenyao Xu, PhD, associate professor in the Department of Computer Science and Engineering. The lead student author is Yang Gao, and additional student co-authors include Wei Wang and Yincheng Jin, all graduate students in Jin's lab.