UConn IMS

Yu Lei Invents Low-Abundance Biomarker Detection Platform for Early Diagnosis

from UConn Today

Dr. Yu Lei
Dr. Yu Lei

Yu Lei, professor of chemical and biomolecular engineering, has invented a new platform that can perform high-sensitivity readings for a variety of disease biomarkers.

In the 1970s, scientists invented the enzyme-linked immunosorbent assay (ELISA). Since then, ELISA has been the standard for detecting biomarkers.

Biomarkers are molecules present in the body that indicate the presence or severity of a disease. For example, autoantibodies can help detect autoimmune diseases, or a peptide known as amyloid-β can indicate Alzheimer’s disease.

One of the major limitations for ELISA is that if there is a low concentration of the molecule of interest, it cannot detect it. Lei’s invention addresses this problem by adding two amplification steps to ELISA’s process.

“We wanted to bridge the need for ultra-sensitivity, and also compatibility with the existing plate-based platform,” Lei says.

ELISA works using a “sandwich” of two antibodies specifically designed to capture/detect the biomarker of interest between them. One of these antibodies has an enzyme attached to it that will produce a readable signal when it encounters the substrate.

Lei introduced a two-step amplification to the ELISA reaction. Lei first added a tyramide signal amplification (TSA) process to amplify the signal of a low abundance biomarker. In Lei’s platform, the TSA step anchors numerous biotins onto the immunocomplexes. Lei then introduced the reporter enzyme alkaline phosphate (ALP) conjugated with streptavidin, which attaches to the biotins through the strong interaction between biotin and streptavidin.

Dr. Lei's Research
Lei’s technology advances traditional ELISA kits through the addition of two novel steps. (Yu Lei Provided image)

Lei added an ELFA-saturated ELFP substrate that ALP breaks down to produce a fluorescent signal. These molecules that precipitate through the system to form a readable layer consisting of fluorescent needles that a microscope captures as a series of images and counts. This fluorescent microneedle count corresponds to how much of the biomarker is in the sample.

“That’s the beauty of the system using ELFA-saturated ELFP substrate and counting-based method, we achieved rapid detection and at the same time no matter your initial number of target molecules their precipitating time is starting from the same point,” Lei says.

Lei successfully demonstrated that his process was able to achieve a resolution of 50 to 60 picograms per milliliter. This is about 20 times more sensitive than traditional ELISA using the same commercial ELISA kit.

Lei published his findings in the March issue of Analytica Chimica Acta.

This advancement could be extremely useful for early-stage detection of diseases and treatment.

“A lot of disease detection occurs when symptoms are already onset,” Lei says. “That biomarker concentration is already very high. So then, if we can detect at a very low concentration, we can capture the earliest stage and treatment may be more effective.”

Lei says the next step for this technology is to smoothly integrate it into conventional plate-based ELISA systems. This would allow the process, which currently takes about four hours for low-abundance biomarker detection, to be much faster by using advanced imaging systems.

Designing a Lighter, Denser Fuel Cell

from UConn Today

Fuel Cells
Fuel cells are a promising direction for cleaner energy, and a team of UConn researchers is working to improve their design (Adobe Stock).

Fuel cell technology is continuously evolving as renewable energy and alternate energy sources become an increasingly important means of reducing global dependence on fossil fuels. Planar fuel cells, a prevalent design, can be bulky, have compression issues, and uneven current distribution. Other drawbacks include problems with reactant gas transport, excess water removal, and fabrication challenges associated with their design.

A team of UConn researchers led by Jasna Jankovic, an assistant professor in the Department of Materials Science and Engineering in the School of Engineering, has devised a novel design for a tubular polymer electrolyte membrane (PEM) fuel cell that addresses those shortcomings and improves on existing tubular PEM fuel cell designs, most of which take a planar PEM fuel cell and curl it into a cylinder.

Jankovic and two grad students, Sara Pedram and Sean Small, took a more holistic approach that rethinks tubular fuel cell design from the ground up. Their disruptive, patent-pending concept could potentially have nearly twice the energy density of other tubular PEM fuel cells, be 50 percent lighter, have a replaceable inner electrode and electrolyte (if liquid), a leak-proof configuration, and require fewer precious metals.

That’s a big deal, says Michael Invernale, a senior licensing manager at UConn’s Technology Commercialization Services (TCS) working with Jankovic to bring the concept to market. Much of the effort to improve fuel cell design, he says, has focused on the end user instead of the greater good.

“A fuel cell with refillable components is a kind of solution that does that,” says Invernale.  “An airline relying on this technology would have more incentive to rebuild a component. Right now, it might be cheaper to replace the whole unit. That’s really where this design shines. The features of the design are green and sustainable and renewable.”

Fuel cells are essentially refuelable electrochemical power generation devices that combine hydrogen and oxygen to generate electricity, heat, and water. Each type is classified primarily by the kind of electrolyte it uses. Planar fuel cells are constructed using sandwich-like stacks of large, rectangular flow field plates made of graphite or metal, which account for about 80 percent of their weight and 40 percent of their cost. UConn’s design uses a single tube-shaped flow field that reduces its weight by half.

Jasna Jankovic
Dr. Jasna Jankovic

The concept is still in discovery and has I-Corps and Partnership for Innovation (PFI) funding from the National Science Foundation (NSF). The program was created to spur the translation of fundamental research to the marketplace, encourage collaboration between academia and industry, and train NSF-funded faculty, students, and other researchers in innovation and entrepreneurship skills.

Participating research teams have the opportunity to interview potential customers to learn more about their needs. Jankovic and her team conducted some 60 interviews during a UConn Accelerator program in early 2022 that helped them size up the market and answer important questions about whether or not to start a longer process, make the product themselves, or license the technology to another company.

“It was very useful to get feedback and guidance from people in industry” Jankovic says.

Jankovic led the team as PI, with Pedram and Small, acting as Entrepreneurial Lead and Co-Lead respectively. Lenard Bonville, the team’s industrial mentor, will support the team with his decades of industrial experience. The team will conduct another set of 100 interviews with industry to discover the market for their product and get guidance on its final design. NSF-Partnership for Innovation (PFI) funding will then be used to develop a prototype and pursue commercialization.

Fuel cells have a wide range of applications, from powering  homes and businesses, to keeping critical facilities like hospitals, grocery stores, and data centers up and running, and moving a variety of vehicles, including cars, buses, trucks, forklifts, trains, and more. Jankovic’s team is working toward obtaining a full patent on their design and thoroughly testing the concept. In the short term, they are focused on commercializing the technology and attracting potential partners.

Jankovic envisions creating a fuel cell roughly the size of a AA battery however, as a scalable and modular technology, it could be scaled-up to any practical size. The cylindrical shape would allow for more fuel cells to occupy the same amount of space as those in use now and be cheaper to manufacture, Invernale said. Jankovic views her fuel cell design as a replacement for Lithium-Ion batteries.

Jankovic said her seven years in industry before coming to UConn convinced her there was a need in the market for a new and better fuel cell design.

“From that experience, I knew that planar fuel cells had a few issues,” she says. “I kept asking around, and I said, ‘let’s do it and find out yes or no.”

IMS Welcomes Lisa Conant and Christina Tamburro

As research conducted by UConn IMS faculty members creates more funding opportunities, the need to expand administrative services to support the increased funding has led IMS to hire two new administrative team members.  Both Lisa Conant and Christina Tamburro come to UConn IMS from within the University.

Lisa Conant
Pre-Award Grants and Contracts Specialist Lisa Conant

Lisa Conant previously served as Pre-Award Grants and Contracts Specialist for the Sponsored Program Services (SPS) section of the Office of the Vice President of Research (OVPR). Lisa honed her financial skills in the non-profit social services and municipal sectors. She also provided her financial expertise to The Jackson Laboratory. An avid writer and editor in her personal time, Lisa also loves trying new international recipes. She served her community in Coventry, CT, as an elected town council member for four years and currently serves on the town’s Human Rights Commission. Lisa hopes her years of grants and research administration experience and skills will help support and grow IMS’ already incredibly impressive success in winning research grants and contracts. “My goal is to serve as a resource for IMS faculty and staff in all things pre-award,” Lisa says.

Christina Tamburro
Post-Award Grants and Contracts Specialist Christina Tamburro

Christina Tamburro comes to us from the College of Agriculture, Health and Natural Resources (CAHNR) where she served briefly as Business Operations Specialist before returning to her passion for finance here in IMS. Prior to her time in CAHNR, Christina served as a Post-Award Grants and Contracts Specialist for SPS.  Christina loves cooking and baking.  She won second prize in the Connecticut State Agricultural Fairs statewide apple pie contest in 2005. Additionally, Christina describes herself as a “history nut” with particular interest in the American Civil War and colonial New England. She hopes to contribute additional expertise, enthusiasm and understanding to the grant management process here at IMS.  “I am looking forward to working closely with grant holders, sponsors, and connections throughout the university to extend IMS’ outstanding reputation,” Christina says.

Please join all of us at IMS in welcoming Lisa and Christina.

Meet NDSEG Fellow Mason Freund

Mason Freund
Ph.D. student Mason Freund has aerospace science at the root of his research.

Since its inception in 1989, the National Defense Science and Engineering Graduate (NDSEG) Fellowship has been awarded to only 4400 students.  In that time, over 65,000 have applied.  The highly competitive fellowship, sponsored by the Air Force Office of Scientific Research (AFOSR), the Army Research Office (ARO), and the Office of Naval Research (ONR), was established by the U.S. Congress to increase the number of U.S. citizens receiving doctoral degrees in science and engineering disciplines of military importance.

Materials Science and Engineering Ph.D. candidate Mason Freund has been named a recipient of this prestigious fellowship.  IMS News spoke with Mason about his early interests in science and the catalysts and decisions leading to his being named a NDSEG Fellow.

You earned your Bachelor of Science degree in mechanical engineering with a concentration in aerospace engineering.  In your pursuit of your Ph.D. your focus remains on aerospace science.  When did you begin to be interested in aerospace science and what about aerospace science keeps you engaged? 

I think there’s always been some interest in aerospace science starting from playing with toys and enjoying sci fi movies as a kid. This steered me towards spaceships and planes and slowly evolved into interest in the sciences and engineering. Finally, being able to learn about aerospace engineering during my undergrad seemed to bring everything together. And now being a fellow under the Air Force Office of Scientific Research (AFOSR) I will be able to interact with the field on a deeper level. I am constantly learning new information and techniques that keeps the learning experience engaging but there are also always new discoveries and ideas that keep pushing the known boundaries to something that is better, faster, or stronger. I think those new discoveries and possibilities will keep me engaged for a long time.

How/when did you begin to tie materials science into your interest in aerospace science?

The mechanical engineering curriculum requires an introduction to materials science. I didn’t know what the field of materials science was or could lead to, but I quickly became interested in learning more about the field. I decided to go for a minor and take courses that could add another dimension to my curriculum and benefit my aerospace science interests.

Congratulations on being named a 2022 DoD NDSEG Fellow.  How did you come to apply for the NDSEG Fellowship and what was your reaction after learning you had been selected for the fellowship? 

My advisor (Volkan Ortalan) made me aware of some different fellowships early on in my graduate studies. After doing more research over the course of last fall, I applied to a few different fellowships. Then came a long 4-6 month wait to April when the results were expected to come out. I checked my email one night at the end of March and was surprised to see an email from NDSEG. I was then even more surprised and excited to realize it was an acceptance letter. It was the first one I got back, and I wasn’t even expecting a letter for at least another few days. I was very excited and slightly caught off guard, but it made my night and my week.

Tell us about your research and its short- and long-term implications for real-world applications. 

My group is primarily a microscopy group. We spend most time on transmission electron microscopes (TEM) in addition to other instruments and techniques. Our lab has a special ultrafast TEM which allows us to investigate reactions and dynamics at very short time scales. Specifically, my research will take advantage of these capabilities to investigate reaction dynamics of nano energetic materials to better understand behaviors from these materials as well as nanoparticle enhancement at the necessary timescales.

This work is useful for further insights into nano energetics and optimization for use in propellants and other related technologies as well as directly relating to programs within the AFOSR. The field of nano energetics plays a role in many propulsion applications as well as high power linear actuators. There are also possibilities for use in miniature applications such as micro or nano satellites. This research will provide a more fundamental understanding of the behaviors and can lead to better control, optimization, and performance of the technology.

After earning your bachelor’s degree, you chose to continue your graduate studies at UConn.  What was the catalyst for your decision?

As I mentioned, I started my minor and was taking MSE courses throughout my time in undergraduate studies. In one of the MSE courses the professor was Dr. Ortalan who is now my advisor. He asked me what I was planning on doing after graduation. I knew that I might want to go back to graduate school eventually, but I was also initially looking for jobs in industry. He mentioned about his open position for a graduate student and about the work that would be required but also the benefits and investment that it would be for my future. This really was the catalyst for my decision. I would have taken it either way but graduating in 2020 at the beginning of the pandemic and hearing about difficulties in job hiring made the decision even easier.

Cato T. Laurencin Named 2023 Priestley Medalist

from UConn Today

Dr. Cato Laurencin
Scientist and engineer, Dr. Cato T. Laurencin, has been honored for seminal and lasting research benefiting humankind.

Cato T. Laurencin, the University Professor and Albert and Wilda Van Dusen Distinguished Endowed Professor at the University of Connecticut will receive the 2023 Priestley Medal, the highest honor of the American Chemical Society.

He is recognized as the leading international figure in polymeric biomaterials chemistry and engineering who has made extraordinary scientific contributions, while at the same time he has had profound contributions to improving human health through the results of his work. While trained in polymeric chemistry, Laurencin’s overall training is broad and interdisciplinary. He received his B.S.E. in Chemical Engineering from Princeton University. He received his Ph.D. in Biochemical Engineering/Biotechnology from the Massachusetts Institute of Technology and simultaneously received his M.D., Magna Cum Laude from the Harvard Medical School. He then joined the faculty of the Massachusetts Institute of Technology and opened a polymer chemistry research laboratory. At the same time he trained and became a board certified orthopaedic surgeon.

Dr. Laurencin produced seminal work on polymeric nanofiber chemistry technology for biomedical purposes, heralding the new field. He pioneered the understanding and development of polymer-ceramic systems for bone regeneration for which the American Institute of Chemical Engineers named him one of the 100 engineers of the modern era at its Centennial celebration. In a three decade collaboration with Professor Harry Allcock at Penn State, Laurencin worked in the development of polyphosphazenes for biomedical purposes. Dr. Laurencin has had breakthrough achievements in the areas of materials chemistry and engineering of soft tissue implants for regeneration of tissue including the development of the Laurencin-Cooper (LC) Ligament for anterior cruciate ligament regeneration (knee). The development of the LC Ligament was highlighted by National Geographic Magazine in its “100 Discoveries that Changed the World” edition.

In his latest work, Dr. Laurencin has pioneered a new field, Regenerative Engineering, described as the Convergence of areas such as nanomaterials science and chemistry. His work has described the chemistry of signaling molecules for tissue regeneration and he published this work in Plos One (https://doi.org/10.1371/journal.pone.01016272014). He demonstrated the ability these molecules in combination with polymeric materials chemistry to induce tissue regeneration.  In his most recent work he has used principles of polymer chemistry to create cell-like structures. This has allowed the creation of what is being considered a new class of stem cells: synthetic artificial stem cells (SASC). The work was recently published in the Proceedings of the National Academy of Sciences.

The impact of the new field has become clear. The NIH Awarded him their highest and most prestigious award, the NIH Director’s Pioneer Award for his field of Regenerative Engineering. The NSF awarded him their most transformative grant, the Emerging Frontiers in Research and Innovation Grant (EFRI) for Regenerative Engineering. Dr. Laurencin is the Editor-in-Chief of Regenerative Engineering and Translational Medicine, a journal published by Springer Nature. He is the Founder of the Regenerative Engineering Society (now a community of the American Institute of Chemical Engineers). The American Institute of Chemical Engineers Foundation created and endowed the Cato T. Laurencin Regenerative Engineering Founder’s Award honoring Dr. Laurencin’s work and legacy in this new field. He is the first individual to receive highest distinctions across science, engineering, medicine and technology for this work. In science, he received the Philip Hauge Abelson Prize from the American Association for the Advancement of Science awarded “for signal contributions to the advancement of science in the United States”.  He was awarded both the highest/oldest honor of the National Academy of Engineering (the Simon Ramo Founders Award) and one of highest/oldest honors of the National Academy of Medicine (the Walsh McDermott Prize). And he received the National Medal of Technology and Innovation, our nation’s highest for technological achievement in ceremonies at the White House.  Most recently, he received the 2021 Spingarn Medal given for the “highest or noblest achievement by a living African American during the preceding year or years in any honorable field.”  The highest award of the NAACP, they stated “his exceptional career has made him the foremost engineer-physician-scientist in the world.”

Dr. Laurencin has also profoundly contributed to mentoring and fostering diversity. He has been responsible for the development of a generation of underrepresented engineers and scientists. In receiving the American Association for the Advancement of Science Mentor Award, it was noted that the majority of African-American faculty in bioengineering had been mentored by Laurencin. For his work in mentoring, he was honored by President Barack Obama with the Presidential Award for Excellence in Science, Math and Engineering Mentoring. Remarkably, he received the 2021 Hoover Medal given jointly by the American Institute of Chemical Engineers, the American Society of Mechanical Engineers (ASME), the American Society of Civil Engineers (ASCE), the American Institute of Mining, Metallurgical and Petroleum Engineers (AIME) and the Institute of Electrical and Electronics Engineers (IEEE), The purpose of the medal is “to recognize great, unselfish, non-technical services by engineers to humanity.” Dr. Laurencin’s extraordinary commitment to inclusion, equity and fairness along with his legendary work in mentoring lead to his selection.

Dr. Laurencin’s life, career and philosophy are contained in his recently published biography entitled “Success is What You Leave Behind,” published by Elsevier.