Category Archives: Research Features

The healing power of seaweed—Shedding new light on alginate microgels

Bull Kelp, a brown seaweed used to produce alginates, can grow as much as 2 feet per day. Photo credit: Jackie Hindering, www.themarinedetective.com
Bull Kelp, a brown seaweed used to produce alginates, can grow as much as 2 feet per day. Photo credit: Jackie Hindering, www.themarinedetective.com

Using seaweed to treat wounds dates back to Roman times. Alginate extracted from kelp and other brown seaweeds are still used in wound dressings today for skin grafts, burns and other difficult wounds. Biocompatible and biomimetic, alginate forms a gel when exposed to a wound, keeping tissue moist to speed healing, and reduce pain and trauma during dressing changes.

Microgels, a biodegradable biomaterial formed from microscopic polymer filaments, has broad and powerful applications in cell analysis, cell culture, drug delivery, and materials engineering.

Putting the two together to form alginate microgels could enable scientists to make important new inroads in the field of tissue engineering. But when it comes to forming microgels, the gelation process of alginate literally gets in the way.

Chang Kyoung Choi Mechanical Engineering-Engineering Mechanics
Chang Kyoung Choi
Mechanical Engineering-Engineering Mechanics

Michigan Tech researcher Chang Kyoung Choi has found a way around the problem. He creates alginate microgels by photocrosslinking the two in situ to form a bond. He uses ultraviolet (UV) light to easily cure microdroplets into microgels, a process known as photopolymerization. Curing the alginate microgels using UV light takes just tens of seconds. The result: alginate microgels that shrink or swell depending on their surrounding ion concentration, temperature, pH, and other external stimuli.

Perhaps more importantly, Choi is able to control the rate that alginate microgels break down. “A tissue scaffold should degrade at a rate proportional to the formation of new tissue, but until now, uncontrolled degradation of alginate has really limited its usefulness,” Choi says.

“Working in microfluidic devices, we can start applying UV light after the microfluids become steady, and turn off the light if necessary to stop the reaction,” he explains. “This solves the chief problem associated with previous ionic methods of making alginate microgels. Until now, the alginate phase of flow would cure before steady state was achieved, resulting in alginate microgels that clogged the microchannel.”

“Until now, uncontrolled degradation of alginate has really limited its usefulness.”

– CK Choi

Choi’s photocrosslinking technique also simplifies current methods of forming nonspherical alginate microgels that are better for observing objects, like cells, encapsulated inside. “Our preliminary results suggest that such high intensity UV does not reduce cell viability,” notes Choi.

Choi and graduate student Shuo Wang use oxidized methacrylated alginate (OMA) developed by their collaborator, Eben Alsberg at Case Western Reserve University. The team fabricated the microfluidic channels for this research at the Center for Nanophase Materials Sciences at Oak Ridge National Laboratory.


Verification and validation—Predicting uncertainties early on

Shabakhti Research

Mahdi Shabakhti
Mahdi Shahbakhti
Mechanical Engineering–Engineering Mechanics

The verification and validation (V&V) process for a typical automotive vehicle and powertrain electronic control unit takes approximately two years, and costs several million dollars. V&V are essential stages in the design cycle of an industrial controller, there to remove any gap between the designed and implemented controller. Computer modeling has brought about improvements over the years, but the gap remains.

Michigan Tech researcher Mahdi Shahbakhti has made significant progress to remove that gap, using system models to easily verify controller design. His solution features an adaptive sliding mode controller (SMC) that helps the controller deal with imprecisions in the implementation of the system.

The research is funded by the National Science Foundation GOALI program, or Grant Opportunities for Academic Liaison with Industry. Shahbakhti’s team and fellow researchers from the University of California, Berkeley, and Toyota USA in Ann Arbor, Michigan are nearing the end of their three-year collaborative GOALI project.

“Analog-to-digital conversion (ADC) is one of the main sources of controller implementation imprecisions, mostly due to sampling and quantization,” says Shahbakhti. “Our approach mitigates ADC imprecisions by first identifying them in the early stages of the controller design cycle. We first developed a mechanism for real-time prediction of uncertainties due to ADC and then determined how those uncertainties propagated through the controller. Finally we incorporated those predicted uncertainties into the discrete sliding mode controller (DSMC) design.”

“Analog-to-digital conversion (ADC) is one of the main sources of controller implementation imprecisions, mostly due to sampling and quantization.”

– Mahdi Shahbakhti

Shahbakhti and his team tested an actual electronic control unit at Michigan Tech in a real time processor-in-the-loop setup. Their approach significantly improved controller robustness to ADC imprecisions when compared to a baseline sliding controller. In a case study controlling the engine speed and air-fuel ratio of a spark ignition engine, the DSMC design with predicted uncertainty provided a 93 percent improvement compared to a baseline sliding controller.

Toyota works closely with the research team to integrate GOALI project results into the design cycle for its automotive controllers. The company provided team members with an initial week of training on its V&V method of industrial controllers, and also participates with Shabakhti’s team in online biweekly meetings. “The concept of this project is fundamental and generic—it can be applied to any control system, but complex systems, such as those in automotive applications, will benefit most,” notes Shahbakhti.


What’s in the air? Understanding long-range transport of atmospheric arsenic

Coal-fired power plant on the Navajo Nation near Page, Arizona
Coal-fired power plant on the Navajo Nation near Page, Arizona

Once emitted into the atmosphere, many air pollutants are transported long distances, going through a series of chemical reactions before falling back to the Earth’s surface. This makes air pollution not just a local problem, but a regional and a global one.

Shiliang Wu
Shilliang Wu, Geological & Mining Engineering & Sciences, Civil & Environmental Engineering

“If you’d been living in London in December 1952, you’d probably remember what air pollution can do—in just a couple of weeks, a smog event killed thousands of people,” says Michigan Tech researcher Shilling Wu.
“Today, photos of air pollution in China and India flood the Internet,” he adds. “Air pollution remains a significant challenge for the sustainability of our society, with detrimental effects on humans, animals, crops, and the ecosystem as a whole.”

An assistant professor with a dual appointment in Geological and Mining Engineering and Sciences, and Civil and Environmental Engineering, Wu examines the impacts of human activities on air quality, along with the complicated interactions between air quality, climate, land use, and land cover. Using well-established global models, he investigates a wide variety of pollutants including ozone, nitrogen oxides, volatile organic compounds, aerosols, mercury, and arsenic.

Wu’s research team recently developed the first global model to simulate the sources, transport, and deposition of atmospheric arsenic including source-receptor relationships between various regions. They were motivated by a 2012 Consumer Reports magazine study, which tested more than 200 samples of rice products in the US and found that many of them, including some organic products and infant rice cereals, contained highly toxic arsenic at worrisome levels.

“Our results indicate that reducing anthropogenic
arsenic emissions in Asia and South America can significantly reduce
arsenic pollution not only locally, but globally.”

– Shilliang Wu

“Our model simulates arsenic concentrations in ambient air over many sites around the world,” says Wu. “We have shown that arsenic emissions from Asia and South America are the dominant sources of atmospheric arsenic in the Northern and Southern Hemispheres, respectively. Asian emissions are found to contribute nearly 40 percent of the total arsenic deposition over the Arctic and North America. Our results indicate that reducing anthropogenic arsenic emissions in Asia and South America can significantly reduce arsenic pollution not only locally, but globally.”

Wu’s model simulation is not confined to any region or time period. “We can go back to the past or forward to the future; we can look at any place on Earth. As a matter of fact, some of my colleagues have applied the same models to Mars,” he says, adding: “In any case, the atmosphere is our lab, and we are interested in everything in the air.”

 


Tayloria Adams—Taking Dielectrophoresis to the Next Level

Tayloria Adams
“I am the first black woman to receive a PhD in chemical engineering at Michigan Tech. I hope this will encourage others!” —Tayloria Adams ‘11 ‘14

Last year the National Science Foundation awarded Michigan Tech alumna Tayloria Adams a prestigious Postdoctoral Research Fellowship in Biology. Adams earned her Master’s and PhD in Chemical Engineering here at Michigan Tech, graduating with nine scholarships, fellowships and awards, three peer-reviewed journal publications, a book chapter, and a patent—No. WO2015051372-A1, to be exact. Her doctoral research examined the dielectric behavior of human mesenchymal stem cells, for the purpose of cell sorting in microfluidic devices.

How did you come to Michigan Tech? 

While on the hunt for a graduate school I was drawn to Michigan for two reasons: my mother lived in Detroit for a while before I was born, and affirmative action was started in the state. I applied to Michigan Tech and scheduled a visit. The environment was very welcoming, which got me hooked! Meeting Dr. Adrienne Minerick during the last year of my master’s degree was icing on the cake. My first interactions with her were in the classroom as I took her Advanced Reactive Systems course. I enjoyed her teaching style. She put a lot of effort into giving meaningful lectures and keeping students engaged. I looked into her research and I was very interested in dielectrophoresis, especially its use in studying red blood cells. The rest is history!

“I am passionate about three things: healthcare-related research, minority student success in STEM, and social justice. These areas are my calling.”

– Tayloria Adams

What was the most challenging aspect of your studies?

Research. There is a huge learning curve when entering a new research field. Learning how to design experiments effectively and accepting that there is no such thing as a perfect experiment are both great challenges. Something will always go wrong, but working through it to still collect the necessary data is what builds character and improves research skills.

What have you done since graduation?

I worked in the Michigan Tech Center for Diversity and Inclusion (CDI) for one year after graduation, as the outreach coordinator. That year gave me the opportunity to grow as a mentor and advocate for underrepresented minority students. I am now conducting postdoctoral research in the Department of Neurology at the University of California, Irvine, in Lisa Flanagan’s lab, studying neural stem and progenitor cells (NSPCs) and their therapeutic potential. NSPCs are desirable because they form the three cell types of the central nervous system, astrocytes, neurons, and oligodendrocytes. However, one challenge is that NSPCs are grown as heterogeneous mixtures and we have little information regarding, which cells are best for neural repair. I’m using dielectrophoresis, an electrokinetic separation technique, as a method to target and enrich specific cells NSPCs. My goal is to effectively sort and characterize them.

You worked hard to educate and engage diverse people about the challenges facing underrepresented students at Michigan Tech. How would you describe the difference you made?

Working at Michigan Tech’s CDI provided me an outlet to engage in important conversations and be a part of the work. CDI was also very supportive of my research. I was able to practice research presentations in the center, use the space as a writing sanctuary when I was completing my dissertation, and almost all of the staff was present at my dissertation defense, which was immensely important to me. One of the best parts of my graduate education is that my daughter Aiyanna experienced college life at the undergraduate and graduate level before reaching college age. She’s learned about important campus resources such as CDI, and I am confident that this exposure has played a part in preparing her for college. As a parent this is something I am very proud of and would consider a success. My greatest frustration was the decline I saw in the number of African American students enrolled at Michigan Tech during my time there. A second frustration is the representation in faculty members. Michigan Tech is a great institution but these are areas where growth would make a huge impact on the community. I would say the difference I’ve made so far is showing what’s possible; but there is much more work to be done.

To learn more about Dr. Adams’s research, visit tayloriaadams.com.


Accelerated healing—Understanding physical and chemical cues in tissue repair

Rajachar Research

Rupak Rajachar
Rupak Rajachar
Biomedical Engineering

Made of fibrous connective tissue, tendons attach muscles to bones in the body, transferring force when muscles contract. But tendons are especially prone to tearing. Achilles tendinitis, one of the most common and painful sports injuries, can take months to heal, and injury often recurs.

Rupak Rajachar is developing a minimally-invasive, injectable hydrogel that can greatly reduce the time it takes for tendon fibers to heal, and heal well.

“To cells in the body, a wound must seem as if a bomb has gone off,” says Rajachar. His novel hydrogel formulation allows tendon tissue to recover organization by restoring the initial cues cells need in order to function. “No wound can go from injured to healed overnight,” he adds. “There is a process.”

Rajachar and his research team seek to better understand that process, looking at both normal and injured tissue to study cell behavior, both in vitro and in vivo with mouse models. The hydrogel they have created combines the synthetic—polyethylene glycol (PEG), and the natural—fibrinogen.

“Cells recognize and like to attach to fibrinogen,” Rajachar explains. “It’s part of the natural wound healing process. It breaks down into products known to calm inflammation in a wound, as well as products that are known to promote new vessel formation. When it comes to healing, routine is better; the familiar is better.”

“To cells in the body, a wound must seem as if a bomb has gone off.”

– Rupak Rajachar

The team’s base hydrogel has the capacity to be a therapeutic carrier, too. One formulation delivers low levels of nitric oxide (NO) to cells, a substance that improves wound healing, particularly in tendons. Rajachar combines NO and other active molecules and cells with the hydrogel, testing numerous formulations. “We add them, then image the gel to see if cells are thriving. The process takes place at room temperature, mixed on a lab bench.”

Hydrogel
SEM image of the fibrinogen-based hydrogel

Two commonly prescribed, simple therapies—range of motion exercises that provide mechanical stimulation, and local application of cold/heat—activate NO in the hydrogel, boosting its effectiveness.

“Even a single injection of the PEG-fibrinogen-NO hydrogel could accelerate healing in tendon fibers,” says Rajachar. “ Tendon tissues have a simple healing process that’s easier to access with biomaterials,” he adds. Healing skin, bone, heart, and neural tissue is far more complex. Next up: Rajachar plans to test variations of his hydrogel on skin wounds.