UCI Biomedical Engineering Discovery Magazine Fall 2018 by UC Irvine Samueli School of Engineering

BME DISCOVERY DEPARTMENT OF BIOMEDICAL ENGINEERING

FALL 2018

Inspiring Engineering Minds to Advance Human Health

FROM THE CHAIR

We are fortunate to be located in Orange County, the world’s medical device capital. Here, the life sciences industry employs more than 164,000 people and accounts for more than $35.3 billion in annual economic activity over the biotech, pharmaceuticals and medical device manufacturing sectors. By nature, this industry is risk averse, and innovation generally is not a high priority. Here at UCI, we are eager to change this, as advancing health care is a serious calling and an urgent business that deserves our utmost talent and dedication. Working with our industry and medical partners, we seek to inspire the minds of our young biomedical engineers to make health care more accessible and more personal, not just for the wealthy few but for all of the world’s citizens. In this newsletter, you will read two stories focused on how our faculty and students are establishing partnerships with companies to develop biomedical technologies and more quickly accelerate the move from lab to product. We are building a department with people who will take on this responsibility and tackle the hard problems head on. In the last year, we have added two stellar faculty members: Christine King and Daryl Preece. King, our very own Ph.D. graduate, completed a postdoc in neurology and was research manager at the PRISMS (Pediatric Research Integrating Sensor Monitoring Systems) at UCLA. She is our first assistant professor of teaching, and has already made an impact on the quality of our curriculum by introducing innovative pedagogical methods of learning. Preece earned a Ph.D. at the University of Glasgow, Scotland. His research utilizes focused light sources to study subcellular movements and forces. Preece was named a Spark Fellow by the BLI Foundation and worked

at UCSD before joining us. Congratulations to professors Anna Grosberg, who was promoted to associate professor with tenure; and Bernard Choi and Elliot Botvinick, both of whom were promoted to full professors! Our faculty members continue to rack up accolades in recognition of their contributions to the field. Kyriacos Athanasiou won the Savio L-Y. Woo Translational Biomechanics Medal, Enrico Gratton won the prestigious Avanti Award in Lipids for his contribution to biophysics, and Bruce Tromberg was named the 2018 Mentor of the Year by UCI’s Institute for Clinical and Translational Science. Our faculty also ensures that our research remains at the forefront, earning robust government funding (NIH, NSF, etc.) to fight debilitating diseases such as Alzheimer’s, cardiovascular diseases, cancer and diabetes. Eight of our graduate students received competitive fellowships, including four who won the coveted NSF Graduate Research Fellowship. Finally, with mixed emotions, we bid farewell to our dear colleague Bruce Tromberg, a member of UCI for 30 years, who was named the next director of the NIH’s National Institute of Biomedical Imaging and Bioengineering. Bruce is a dear friend, a giant in the field of biophotonics, a founding faculty member of the Department of Biomedical Engineering and a leader at UCI, in Orange County and beyond. We will miss him greatly, but we are proud to send him off to lead the nation’s preeminent research and funding agency for biomedical engineering research. This newsletter is about the people we cherish at UCI BME: their stories, their aspirations, their visions and their accomplishments. Please read on for all the details. Sincerely, Abe Lee William J. Link Professor and Chair Department of Biomedical Engineering, University of California, Irvine

PAGE 12 “For some students, this was the first time they’ve ever had to use tools and build something that moves. Much of what they learned is directly applicable to skills needed during their senior year design course as well as in industry, graduate school and as an entrepreneur.”

1 PAGE 14 “So we believe this represents an important first in all joint healing studies.”

CONTENTS

PAGE 4 “It is a priority to develop new crop varieties faster, cheaper and with higher quality results.”

BME DISCOVERY is published annually by the UCI Samueli School’s communications staff for the Department of Biomedical Engineering. Chair: Abe Lee BME Dept. Administrator: Cathy Ta Editor-in-Chief: Shelly Nazarenus Art Direction: Michael Marcheschi, m2dg.com Publisher: Mike Delaney, Meridian Graphics

By The Numbers

Research and Funding

Experiential Learning

Wheelchair Wizards

Joint Venture

Tissue Therapy

Accolades

Wound Warriors

Directory

ON THE COVER: UCI biomedical engineering researchers are creating an implantable device that could eliminate difficult treatments for millions of Type 1 diabetic patients. The device serves as a bioartificial pancreas. See story page 18.

BY THE NUMBERS STUDENT POPULATION UC IRVINE DEPARTMENT OF BIOMEDICAL ENGINEERING Founded in 2002, the biomedical engineering department’s growth in the Samueli School has been rapid. The department merges UCI’s strengths in medicine, biological sciences and engineering. BME faculty are competitive in garnering extramural grants, with expenditures topping $30M on an annual basis. Strong ties with many of Orange County’s more than 300 biomedical device and biotech companies provide students and faculty with distinct opportunities to solve contemporary medical challenges.

134

GRADUATE STUDENTS (FALL 2017) M.S., PH.D. DEGREES Biomedical Engineering

481

UNDERGRADUATE STUDENTS (FALL 2017) 2

B.S. DEGREES Biomedical Engineering Biomedical Engineering: Premedical

UCI Department of Biomedical Engineering

FACULTY & RECOGNITION

RESEARCH & EXPENDITURES

$38.8M

FULL-TIME FACULTY

AFFILIATED FACULTY

NIH NEW INNOVATOR AWARDS

NSF CAREER AWARDS

DARPA YOUNG FACULTY AWARD

ENDOWED CHAIRS

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RESEARCH EXPENDITURES (2016-17)

WORLD-CLASS CENTERS, including 1 NSF I/UCRC and 2 NIH P41

RESEARCH THRUSTS Biomedical Computational Technologies Biomedical Nanoscale Systems Biomolecular/Genetic Engineering Biophotonics Cardiovascular Neuroengineering Tissue Engineering

RESEARCH & FUNDING

CREATING INNOVATION THROUGH STRONG RELATIONSHIPS

Academia has long relied on corporate collaborators to advance research and discovery, while corporations have benefited from the resulting innovation. Nowhere is this more evident than in the U.S.’s 76 National Science Foundation Industry/ University Cooperative Research Centers, one of them co-directed from UCI. Abe Lee, Samueli School biomedical engineering professor and chair, co-directs the Center for Advanced Design and Manufacturing of Integrated Microfluidics – known as CADMIM – along with Ian Papautsky at the University of Illinois at Chicago. CADMIM collaborates with a host of corporate partners and government labs to develop next-generation lab-on-a-chip devices and diagnostic tools for agriculture, health care and pharmaceuticals. In one of CADMIM’s longeststanding partnerships, DuPont Pioneer, a global agricultural company that applies biotechnology in its research and development programs, is hoping for help with its bottom line. Changing weather patterns and other environmental factors have necessitated the development of new crop varieties that can adapt and thrive in varying conditions, while rapid changes in products and services have created a need for the company to shorten its product-

development cycle. DuPont Pioneer conducts genotypic selection to find suitable traits to produce more robust crops, and it has started exploring the potential of microfluidics to accomplish this goal at less expense than conventional industrial assays. DuPont scientist Yue Yun says genotyping with microfluidics can provide much higher throughput and higher quality outcomes. “We are a [crop] breeding company and are processing millions of samples each year,” Yun says. “It is a priority to develop new crop varieties faster, cheaper and with higher quality results.” The collaboration has also yielded trained students and postdocs – at least 10 in the case of DuPont – who can advance the company’s goals. “This collaboration has been very fruitful,” Yun says. “It provided a working prototype for a potential microfluidic instrument. The students are amazing and the PIs are writing fantastic grant proposals.” Stewardship is important, too. “The bigger picture is building a community between collaborators.” Adds UCI’s Lee: “This is a continuous pipeline. We are always coming up with new ideas and concepts, and having the CADMIM ecosystem as a resource has been a major advantage.”

UCI Department of Biomedical Engineering

THREE BME PROFESSORS EARN FUNDING FOR INNOVATIVE PROJECTS Biomedical engineering professors won three out of eight 2018 Pilot Grants awarded by the UC Irvine Institute for Clinical and Translational Science. The professors – Wendy Liu, Christopher Hughes and Michelle Khine – each will receive $25,000 for their research. The ICTS Pilot Grants support exceptionally innovative and/or unconventional research projects that have the potential to create or overturn fundamental paradigms. Liu, associate professor of biomedical engineering and chemical engineering & materials science, is conducting research on immunomodulatory biomaterials for use in wound care. Her approach targets the immune response through biomaterials that would decrease inflammation and promote tissue repair, with the goal of promoting more complete skin regeneration. The long-term goal is to develop improved strategies for treatment of acute and chronic skin wounds. “We know that the immune system is a key regulator of wound healing, but biomaterials-based therapies that target immune cells for tissue regeneration have been largely unexplored,” says Liu. “We are extremely grateful to the ICTS for this award, which will enable us to carry out this work.” Hughes, director of the Edwards Lifesciences Center for Advanced Cardiovascular Technology and professor of molecular biology & biochemistry and biomedical engineering, earned funding for his project to validate a microfluidic device that allows researchers to grow a perfused, vascularized micro tumor. The idea is to see how an individual patient’s tumor cells respond to combinations of FDAapproved anti-cancer drugs, resulting in a truly personal drugscreening methodology. Khine, professor of biomedical engineering and chemical engineering & materials science, is working on conformable wearable electronics to monitor congestive heart failure (CHF). Her team has developed low-cost, disposable, adhesive bandage-type ultrasensitive sensors that adhere to the skin. These sensors would continuously monitor hemodynamic and respiratory parameters to detect and alert users of early CHF signs.

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PROFESSORS WIN NIH GRANT TO ADVANCE UNDERSTANDING OF ALZHEIMER’S Biomedical engineering professor Gregory Brewer and his collaborator, Charles Glabe, UC Irvine professor of molecular biology & biochemistry, have won a five-year $2.9 million grant from the National Institutes of Health’s National Institute on Aging. Brewer and Glabe will seek to address gaps in knowledge about how age impacts the origins of Alzheimer’s Disease. The hypothesis put forward by Brewer and Glabe could flip conventional ideas about how the debilitating disease begins. Scientists have long believed that Alzheimer’s begins when the brain’s neurons secrete sticky clumps of protein called beta amyloid. This amyloid accumulates in extracellular spaces in the brain and is thought to be the cause of neurodegeneration. But failed drug trials over 11 years have led some researchers to reconsider this idea. By contrast, the two UCI scientists think that age-related metabolic changes could be what drives the change of production and accumulation of the beta amyloid aggregates, and that this happens inside the brain’s neurons, not outside in extracellular spaces. Results of their early experiments indicate that they could be on to something. “Recent clinical trials of drugs that inhibit secretion of beta amyloids and decrease their concentration in interstitial fluid worsen memory in humans and have no effect on plaque accumulation,” says Brewer. He and Glabe will test the hypothesis that age-related oxidative shifts direct amyloid processing toward a more pathogenic, aggregationprone state that hastens neurodegeneration. “An accurate understanding of the disease mechanisms will provide a better focus for development of drugs that prevent or reverse cognitive decline,” Brewer adds.

FOUR GARNER NSF GRADUATE RESEARCH FELLOWSHIPS Four biomedical engineering graduate students – the largest number ever, says department chair Abe Lee – won coveted fellowships this year from the National Science Foundation. The NSF Graduate Research Fellowship includes a yearly stipend of $46,000 for three years to help finance graduate studies. Among the 2,000 national winners selected from a field of 12,000 applicants is Jason Chen, advised by Professor Zhongping Chen (no relation). Chen works to develop ex vivo and in vivo optical coherence tomography systems to study the structural and functional relationship of the body’s mucociliary apparatus - the self-clearing mechanism of the bronchi and an essential piece of the upper respiratory tract’s defense mechanism. These tomography systems could measure all of the parameters of the mucociliary apparatus simultaneously without disturbing mucociliary transport, leading to advances in understanding a broad spectrum of respiratory diseases. 6

Austin Lefebvre seeks to understand why certain tumors are more invasive than others. With adviser Michelle Digman, biomedical engineering assistant professor, Lefebvre uses advanced imaging techniques to investigate the metabolic and physical characteristics of 3D breast cancer tumor clusters in aggressive and non-aggressive cell types. He hopes to model how this invasiveness functions and why some cells in the clusters lead the process, potentially developing therapeutics to stop tumor invasion. Tam Vu works on the development of a rapid and ultrasensitive diagnostic test that can identify antibiotic-resistant pathogens from a small blood sample. Under the guidance of adviser Weian Zhao, associate professor of pharmaceutical sciences, Vu is developing a cheaper, faster and more sensitive test for earlier treatment and prevention of sepsis by partitioning a blood sample into millions of droplets and then screening the droplets for the presence of specific bacterial genes.

CHAN ZUCKERBERG INITIATIVE FUNDS ASSISTANT PROFESSOR’S PILOT PROJECT UC Irvine biomedical engineer Jered Haun has received a grant from the Silicon Valley Community Foundation, a donor-advised fund of the Chan Zuckerberg Initiative. An assistant professor, Haun is developing an integrated microfluidic device that increases the speed and efficiency at which tissue is broken down into single cells. Researchers need to isolate individual cells from tissue to conduct analysis and sequencing, thereby identifying disease. However, evaluating individual cells within tissue is a major challenge, particularly for rare cell types such as stem cells. “The need to first dissociate tissue remains a significant barrier, as current methods are labor intensive, slow and inefficient,” says Haun. “We have developed microfluidic technologies that will dramatically improve this process.” He uses three different devices that were designed to work in concert, each operating at a different size scale, from the full tissue specimen down through aggregates and finally single cells. The multifaceted approach enables Haun to appropriately tailor flow properties, resulting in a gradual and complete breakdown in a fast, efficient and gentle manner. The one-year pilot project will optimize design and operating procedures for five different tissues: liver, skin, pancreas, kidney and heart. The Chan Zuckerberg Initiative was launched in December 2015 by Mark Zuckerberg, founder and CEO of Facebook, and his wife, Priscilla Chan, a pediatrician and founder and CEO of The Primary School in East Palo Alto. The Chan Zuckerberg Initiative is a new kind of philanthropic organization dedicated to advancing human potential and promoting equal opportunity through world-class engineering, grantmaking, impact investing, policy and advocacy work.

Erik Alexander Gonzalez-Leon uses self-assembling methods to tissue engineer the meniscus, the thin fibrous cartilage between the surfaces of joints. Under the direction of his research adviser, Distinguished Professor Kyriacos Athanasiou, he adds biochemical and mechanical stimuli during tissue culturing to enhance the mechanical properties of the meniscus, bringing it closer to native tissue. Ultimately, he hopes to tissue engineer meniscus constructs that can be used in translational in-vivo studies. Gonzalez-Leon also was named a 2018 Howard Hughes Medical Institute Gilliam Fellow. Forty-five graduate students from across the country and their advisers won the Gilliam fellowships this year (out of 231 applicants). The doctoral candidates selected by the committee all demonstrated the potential to become leaders in their fields. Gonzalez-Leon and Athanasiou will receive $50,000 a year – including a stipend, a training allowance and an institutional allowance – for up to three years while Gonzalez-Leon completes his doctorate. UCI Department of Biomedical Engineering

GRADUATE STUDENT RECEIVES AMERICAN HEART ASSOCIATION PREDOCTORAL FELLOWSHIP Biomedical engineering graduate student Yan Li has won a two-year American Heart Association Predoctoral Fellowship. The $53,688 award will help her advance her research into the development of a high-speed intravascular imaging system that can detect and characterize atherosclerosis, the narrowing of the arteries due to the buildup of plaque on artery walls. Li is designing and building a trimodal OCT/US/NIRF system, which can simultaneously analyze the arteries using optical coherence tomography, ultrasound and near infrared fluorescence. Each of the three approaches plays a specific and complementary role in characterizing the structure and composition of the arteries and the extent of any atherosclerosis occurring there. The AHA awards the predoctoral fellowships to promising graduate students whose research relates to cardiovascular function, disease and stroke or to related problems, and who intend to pursue careers aimed at improving global cardiovascular health. “I am so excited and proud to receive this predoctoral fellowship as an international student,” says Li, a third-year doctoral student whose graduate adviser is biomedical engineering Professor Zhongping Chen. “It encourages me a lot to go further in my future research.”

FELLOWSHIPS RECOGNIZE POTENTIAL PUBLIC IMPACT Biomedical engineering graduate student Rachel Gurlin (pictured) was named a Public Impact Distinguished Fellow this year by the UC Irvine Department of Graduate Studies. The Public Impact Distinguished Fellowships support doctoral or MFA students whose current research has the potential to significantly improve or enrich the local, national or global community. Gurlin, who expects to receive her doctorate next year, works in the lab of Professor Elliot Botvinick, where she uses tissue engineering and microfabrication techniques to develop a skinintegrated bioartificial pancreas device for the treatment of Type 1 diabetes. Gurlin, who will receive a $12,000 Public Impact Fellowship stipend, also has won several other awards to support her research. The recipient of a T32 CARE (Cardiovascular Applied Research and Entrepreneurship) Fellowship, an ARCS Scholar Award, a Mazda Foundation Scholarship and the 2015 Business Plan School of Medicine Award, she also serves as president of the Graduate Association of Biomedical Engineering Students.

BME Discovery

In addition to the Distinguished Fellowship, the Department of Graduate Studies awards 10 Public Impact Fellowships, carrying a $1,000 stipend each year. This year, biomedical engineering graduate students won three of those awards. Recipients include Michael Chu, who researches mobile health monitoring, specifically developing and applying wearable health systems for disease detection. His current work focuses on creating sensors to measure the respiratory health of asthmatic patients. His graduate adviser is Professor Michelle Khine. Lancy Lin, who also works in Khine’s lab, is developing point-of-care (POC) and wearable health-monitoring methods to detect and manage congestive heart failure and other chronic or infectious conditions. Currently she researches low-cost platforms that can continuously monitor symptoms and severity of heart failure. Jie Zheng works in the lab of neurology Professor Jack Lin. Using intracranial electrode recordings, she studies the neural dynamics underlying emotional memory processing. She also attempts to improve memory and neuropsychiatric therapies using brain stimulation. She frequently presents her work at international neuroscience conferences and was named one of 10 Graduate Student Award winners at a recent Cognitive Neuroscience Society meeting.

NIH FELLOWSHIP FURTHERS ENGINEERED CARTILAGE RESEARCH Graduate student Evelia Y. Salinas received a three-year NIH diversity supplement fellowship ($183,000) in support of her work in the lab of Distinguished Professor Kyriacos Athanasiou. The fellowship is connected to an NIH R01 grant to Athanasiou for his research on the self-assembling process in tissue engineering of articular cartilage. The self-assembled constructs made in Athanasiou’s laboratory require no scaffolds or organization techniques, and are mechanically robust and biochemically similar to native articular cartilage. Salinas aims to evaluate the synergistic effects of combined mechanical stimuli, such as shear and tensile loading, on the neocartilage constructs.

BIOMEDICAL STARTUP RECEIVES VENTURE CAPITAL SUPPORT TO FURTHER ITS EFFORTS 8

Until recently, doctors did not have an effective tool for monitoring patients’ blood flow during surgery or in patients with peripheral artery disease, a leading cause of lower-limb amputation. Laser Associated Sciences, founded by a trio of UC Irvine alumni that includes two biomedical engineers, is helping to solve that dilemma. The company has developed a user-friendly, biophotonic instrument that can measure blood flow and oxygenation inside the veins, heart and arteries. Biomedical engineers Sean White and Bruce Yang, who serve as the company’s CEO and chief engineer, respectively, are working with physicist Tyler Rice. Their patented technology uses a postage-stamp-sized camera and a small laser diode; it clips onto a patient’s toe to measure blood flow in the arteries, veins and capillaries.

“Successful completion of this supplement will yield engineered cartilage that can be further examined with in vivo studies, allowing for the examination of whether improved tensile and compressive stiffness will translate to greater durability in vivo,” says Salinas. Salinas also won the 2018 Career Development Award from the Biomedical Engineering Society, which supports travel to the society’s annual meeting for underrepresented graduate students, postdoctoral fellows, early career faculty and early career professionals from underrepresented populations in biomedical engineering. Salinas received complimentary registration and a travel stipend to the October meeting in Atlanta, Georgia.

LAS, originally funded through business plan competitions, now has venture capital backing. The company recently completed a 100-patient clinical investigation and is preparing a larger trial. Initial results are promising. Vascular and interventional radiologist Dr. Mahmood Razavi, who practices at St. Joseph Hospital in Orange, California, provided welcome feedback. “There is no good way to monitor blood flow intra-procedurally in real time,” Razavi says. “We don’t always understand the impact of angiographic changes on the patient’s outcome, so this is a great way to monitor flow during and after the procedure. It provides critical information during re-vascularization... it tells us when we have done enough and when we haven’t.” Next steps include an outpatient home-monitoring product. White thinks LAS can help fill an important medical gap. “We are measuring something that no other technology is measuring right now and it’s really simple to use,” he says. UCI Department of Biomedical Engineering

APPLYING ENGINEERING TO HEART DISEASE THERAPEUTICS Dr. Arash Kheradvar is attacking heart disease, one innovative technology at a time. The medical doctor, who also has a doctorate in bioengineering, has amassed 15 U.S. and international patents on heart valves and other medical devices and methods. “I was always intrigued by research and the advanced technologies you could work on to elevate the standard of care and affect a larger group of patients,” the Samueli School biomedical engineering professor says. His first startup, FoldaValve, is commercializing a transcatheter aortic valve. Now in preclinical testing, the device protects the heart’s leaflets during catheterization procedures and transcatheter implants. Kheradvar’s lab, part of UC Irvine’s Edwards Lifesciences Center for Advanced Cardiovascular Technology, also is developing patient-specific hybrid tissue-engineered heart valves, using the patient’s own cells and tissues. This approach reduces the chance of valve failure due to calcification as well as immune system rejection. “It would work like a native organ because we are using the patient’s own cells,” Kheradvar says. He is developing prototypes of transcatheter mitral and tricuspid valves using permanent scaffolds instead of those that are absorbed by the body. Work on several other technologies is ongoing in Kheradvar’s lab as well. They include a 3D echocardiographic particle velocimetry imaging technique, which enables cardiologists to see and measure the heart’s blood pathways and velocity in real time; and a method for measuring energy dissipation, fluid dynamics and other parameters in pediatric heart disease patients. And in a collaboration with electrical engineering and computer science Professor Hamid Jafarkhani, Kheradvar is investigating the use of artificial intelligence and deep learning to develop improved techniques for characterizing the unique anatomies of patients with congenital heart defects. “We are trying to advance technologies that are eventually going to help patient diagnosis and treatment,” he says.

BME Discovery

STUDENTS

LORI BRANDT

EXPERIENTAL LEARNING Undergraduates get hands-on opportunity working with heart valves

UCI Department of Biomedical Engineering

“WE’RE SURGEONS!” SAID DARWIN SALGADO, A SECONDYEAR BIOMEDICAL ENGINEERING STUDENT, WHO HAD JUST FINISHED SUTURING HIS 3D PRINTED HEART VALVE INTO A PIG HEART. SALGADO WAS ONE OF 30 UNDERGRADUATES PARTICIPATING IN THE HANDS-ON PROJECT PROVIDED BY THE BIOMEDICAL ENGINEERING SOCIETY (BMES) AT UC IRVINE.

complete safety training prior to entering the lab, used a surgical scalpel and scissors to cut out the aortic valve and replace it with the plastic valve they had modeled. They also further dissected the heart to see the atrium and ventricular regions.

In teams of two, the undergraduates suited up with lab jackets, goggles and gloves, and spent two hours completing the task designed to give them an understanding of heart anatomy and current cardiovascular diseases. UCI BMES board members designed the two-quarter program.

The project was the brainchild of Cynthia Hernandez, activities coordinator for BMES. Her brother, a chemical engineering and materials science major, had participated in the Chem-E Car project, and Hernandez thought there should be a similar hands-on experience for BME students. Heart valves are a big industry, especially in Orange County, home to two large medical device companies – Medtronic and Edwards Life Sciences – that most students hope to work for one day.

“We were really excited to be able to offer this experience to students. It’s something they can put on their resumes to help them get internships and jobs,” says Andrew Chang, UCI BMES president. The student society used the project to recruit members this year, more than doubling last year’s 49 members to 112. During fall quarter, the students researched the appropriate dimensions of a heart valve, learned to model their valves in SolidWorks, a computer-aided design and modeling program, and used a 3D printer to create and refine prototype heart valves. Then in winter quarter, they learned about the structure and flow of blood through the heart, the current state of prominent heart diseases as well as methods of treatments. The project’s culmination was the opportunity to work with a mammalian heart in a lab in Engineering Tower. The students, who all had been required to

BME Discovery

Two biomedical engineering graduate student researchers – David Li and Ziwei Zhong – were on hand to assist. “They did pretty well,” says Zhong of the undergraduates. “They were all able to suture a valve in.”

“I thought it would be cool to give students the experience to do something with the resources on campus and have an opportunity to work with heart valves,” says Hernandez, a second-year student. She joined the BMES board last spring so she could propose the project. It was funded with grants from the Samueli School Engineering Student Council. Salgado, who is interested in working with medical devices, said he learned a lot about the heart’s four chambers, adding that the night’s most difficult part was trying not to break the plastic valve while sewing it in. “It was hard to maneuver,” he says, “but I enjoyed myself; it was a fun project.”

WHEELCHAIR WIZARDS Biomedical engineering students design, build and test their prototypes

12 12

LORI BRANDT

DEBBIE MORALES

UCI Department of Biomedical Engineering

MORE THAN 120 BIOMEDICAL ENGINEERING STUDENTS TOOK ON A CHALLENGE FROM THE FREE WHEELCHAIR MISSION (FWM), A NONPROFIT ORGANIZATION THAT PROVIDES FREE WHEELCHAIRS TO IMPOVERISHED PEOPLE WITH DISABILITIES IN DEVELOPING NATIONS. The FWM has been collaborating for several years with David Reinkensmeyer, professor of mechanical and aerospace engineering, and his graduate students. FWM founder and CEO Don Schoenderfer was excited to extend the challenge to undergraduates. He is interested in a design for a wheelchair lever driver to allow users to travel farther and more easily by reducing strain on upper extremity muscles. His company provided CAD designs and wheelchairs for students to use in developing their prototypes. Christine King, BME assistant professor of teaching, taught the class, Engineering Analysis/Design: Computer Aided Design, which gave students 10 weeks to formulate teams, come up with a design and build a prototype. Each team had a $220 budget, with $71 designated for materials. A lever driver would assist those who have upper extremity weakness and trouble using the traditional push rim. Students were instructed to design a lever arm that would enable wheelchair users to propel themselves forward and backward, stop and turn around without having to use the push rim. Schoenderfer was on hand for the final demonstration day. Twenty-one teams of five or six students tested their chairs by traveling 10 meters, up and back, and then spinning in place. “It was cool,” says Schoenderfer. “Lots of creative ideas. And what a great experience for these students; I can imagine them using these skills in their first job.” Two teams stood out. The Wheelchair Masters team traveled 10 meters in only 25 seconds. The Wheel Wizards team was able to do it in 40 seconds. Both had the best designs and prototypes, according to King.

BME Discovery

“We used a gimbal ratchet, which allowed two-way rotation,” says Micah Lim, team leader for Wheelchair Masters. “One unintended benefit of our design was that it braked.” On competition day, each team had 15 minutes to assemble their prototype before they took turns racing. Some never made it past the starting line. The class taught the future engineers how to design in CAD software and how to translate those designs into a real-world prototype. “For some students, this was the first time they’ve ever had to use tools and build something that moves,” explains King. “Much of what they learned is directly applicable to skills needed during their senior year design course as well as in industry, graduate school and as an entrepreneur.”

JOINT VENTURE Researchers create breakthrough treatment for crippling jaw disease

LORI BRANDT WITH CONTRIBUTORS BRIAN BELL AND JANET WILSON STEVE ZYLIUS

UCI Department of Biomedical Engineering

BME Discovery

IT’S LIKELY THAT KYRIACOS ATHANASIOU COULD HAVE MADE MULTIPLE MILLIONS BY NOW IF HE HAD CONTINUED THE PATH OF BIOMEDICAL TECHNOLOGY ENTREPRENEUR. The senior academic has spent his career inventing medical products, including biomimetic tissue for treating damaged knees, jaws, hips, shoulders and other joints. Companies that he co-founded in the 1990s produced 15 FDA-approved products before being acquired by large medical companies for over $300 million. He sat in the corner office and became an authority on translating engineering innovations into commercially available medical instruments and devices.

“But my heart was and always will be in academics,” says the UC Irvine Distinguished Professor of biomedical engineering. “I’ve never been interested in creating products solely for making money. To me it’s about the excitement and passion of coming up with solutions to some of the most difficult problems that afflict humans.” To the benefit of people with joint problems everywhere, that’s what Athanasiou has proceeded to do. Of Greek ancestry, the Cyprus native earned a Ph.D. at Columbia University in 1989. He was on the faculty at the University of Texas, then Rice University in Houston, each for a decade, before moving to UC Davis as chair of the biomedical engineering department in 2009. He finally arrived at UCI in 2017. It was at the University of Texas in the 90s, where he began inventing biomaterials to make cartilage heal and repair itself. “There weren’t a lot of remedies for people suffering with joint ailments in those days,” says Athanasiou. “The doctor would give the patient painkillers until the time came for a knee or hip replacement with implants made out of metal or plastic. We viewed the problem of a small defect in cartilage as a purely mechanical issue involving stress concentrations, which intensify in areas in and around tiny defects in joints. That’s how we came up with biodegradable implants that we would use to fill in the cracks, allowing for the return of smooth joint movement.”

He also co-invented an intraosseous infusion device to deliver drugs and other vital substances through bones, instead of veins. The device is a drill that helps health care personnel insert IV lines directly into the bones of people whose veins are inaccessible due to severe dehydration or shock. It saved countless lives in the cholera epidemic that swept Haiti after the devastating 2010 earthquake. Emergency response and ambulance teams all over the world carry variations on the technology, and it’s been featured on popular television shows such as “ER,” “Grey’s Anatomy” and “Inside Combat Rescue.” Athanasiou’s most recent invention draws on more than 20 years of research with teams at multiple universities. It tackles the problem of temporomandibular joint (TMJ) dysfunction, a common jaw defect. About 25 percent of adults worldwide – 90 percent of them premenopausal women – have difficulty eating and talking, chronic mouth pain, arthritis and other issues due to degeneration in the cartilage disc that hinges together two key jawbones. Athanasiou’s research group has successfully tested a first-ever tissue implant to safely treat TMJ dysfunction. Using animal models, scientists at UCI, UC Davis and the University of Texas School of Dentistry in Houston removed a tiny bit of existing rib tissue, isolated its cartilage cells and utilized them to tissueengineer jaw disc cartilage via a “self-assembling” process they created. They then surgically inserted the new cartilage into the faulty hinge point of the jaw joint. The approach was allogeneic, meaning that the rib cells were taken from one individual and the new cartilage was implanted into another. Two months later, the defects were completely gone. “We were able to show that we could achieve exceptional healing of the TMJ area after eight weeks of treatment,” says Athanasiou, senior author on the study, published in Science Translational Medicine. The next steps will be to ensure long-term effectiveness and safety of the implant in the animals, followed by clinical trials. Athanasiou says the results might also apply to the treatment of hip, knee and other joint problems. “This is the first time that cogent

UCI Department of Biomedical Engineering

healing has been shown in the TMJ area and, I dare say, the first time anyone has shown successful biomechanical healing in any joint. It’s key that we can achieve regeneration of an ailing tissue with our engineered implant, one that’s mechanically suited to withstand stresses,” he says. “So we believe this represents an important first in all joint healing studies.” Lori Setton, the Lucy and Stanley Lopata Distinguished Professor and Chair of Biomedical Engineering at Washington University in St. Louis, says that Athanasiou has made an enormous impact on cellular approaches to musculoskeletal tissue regeneration and repair. “He advanced an understanding of single cell mechanics and mechano-biology at a time when tools were barely emerging, and he developed novel approaches to promote tissue formation from cellular self-assembly. “He also has seeded the academic field with trainees who’ve emerged as strategic leaders in the field,” continues Setton, who serves as president of the Biomedical Engineering Society. “Professor Athanasiou will be seen as a father of musculoskeletal tissue engineering, and his legacy will be long-lived.” BME Discovery

“THIS IS THE FIRST TIME THAT COGENT HEALING HAS BEEN SHOWN IN THE TMJ AREA AND, I DARE SAY, THE FIRST TIME ANYONE HAS SHOWN SUCCESSFUL BIOMECHANICAL HEALING IN ANY JOINT.”

UCI Department of Biomedical Engineering

TISSUE THERAPY An implantable device could one day provide a welcome remedy for a demanding disease ANNA LYNN SPITZER

BME Discovery

STEVE ZYLIUS

WHEN SAMUELI SCHOOL DOCTORAL CANDIDATE RACHEL GURLIN WAS 11 YEARS OLD, HER YOUNGER SISTER WAS DIAGNOSED WITH TYPE 1 DIABETES, AND GURLIN WATCHED AS SHE INJECTED HERSELF SEVERAL TIMES EACH DAY WITH INSULIN TO REGULATE HER BLOOD SUGAR. Now Gurlin, who works in the lab of biomedical engineering Professor Elliot Botvinick, is helping create an implantable device that could enable her sister – and 2040 million other Type 1 patients worldwide – to permanently eliminate difficult treatments.

Type 1 diabetes is an autoimmune disease. The body attacks beta cells in the pancreas, preventing the organ from producing the insulin needed to

move glucose from the bloodstream into other cells. In addition to insulin shots, treatments include insulin pumps, which continuously deliver the medication through a catheter; or pancreas or islet transplantation, which can unleash a host of complications. Gurlin and Botvinick’s small device functions as a bioartificial pancreas, using a two-step process to deliver insulin naturally. First, the device is implanted subcutaneously, possibly in the lower back. After implantation, blood vessels from the host tissue grow into slits within the device, providing oxygenation to the local area. In the second step, islets (clusters of hormoneproducing cells) are inserted into the implanted device. Those islets could comprise donor cells or stem cells cultivated to become islets, but they will interact with the tissue around them while producing insulin – just like the pancreas does. Gurlin and Botvinick call their two-step procedure a “civil engineering” approach. “We build the house first, put in the plumbing (blood vessel growth and tissue interaction), inspect it, and then populate it (with the islets),” says Gurlin. Measuring 13 millimeters square in its current iteration for testing in mice, the device will scale up for humans to about the size of a business card. It is made of medical grade silicone, which allows oxygen to pass though, and its onemillimeter depth means multiple layers can be stacked on top of one another to increase the number of islets housed and the amount of insulin produced. Gurlin makes plastic molds in a 3D printer, fills them with liquid silicone and bakes them before removing the devices, each of which has multiple tiny channels within for holding the islets. After the patient’s tissue grows successfully into the implanted device, islets are injected using long microtubing connected to a syringe. Researchers hope the islets and the patient’s tissue will mutually support each other.

UCI Department of Biomedical Engineering

There are two major hurdles: keeping tissue oxygenated and protecting the implanted device from immune system rejection. The slits built into the flexible silicone seem to be meeting the first challenge by allowing the recipient’s own tissue to grow and thrive in the device. The second challenge is more difficult. An implanted device triggers two immune responses: inflammation, as the body surrounds the invader with scar tissue; and an adaptive reaction that creates antibodies to destroy transplanted cells. Gurlin and Botvinick are working closely with Eugenia Kharlampieva, associate professor of polymer chemistry at the University of Alabama at Birmingham, whose lab is developing an ultrathin antiinflammatory coating to prevent scar tissue from forming. Made from natural compounds, the coating can be deposited directly on the device surface to prevent the recipient’s immune system from rejecting the implant. “I am very excited about this collaboration as this is a wonderful opportunity to apply our material to these devices,” Kharlampieva says. “We hope our coating will be able to suppress undesirable immune responses to ensure successful implantation.” The adaptive immune system is more difficult. A number of approaches are under investigation, and Gurlin and Botvinick intend to be ready. “Rachel is staying ahead of the game. As the biologists develop [these], she’s making sure there is a device ready for

them,” says her mentor, who credits Gurlin with overcoming multiple obstacles. “There are so many difficult elements to this, and in every challenge, she has created breakthroughs.” Testing in mice is underway but researchers are wary of predicting the onset of human testing. “Type 1 patients have been promised time and time again that a cure is around the corner,” Gurlin says. “Out of respect for them, we want to work as hard as possible … but will not promise any timelines until we are sure.” Regardless, Botvinick is optimistic about long-term success. “This project is a huge challenge in any context, and we don’t shy away from that,” he says. “I feel that tissue therapy will be the ultimate cure for diabetes. And by cure,” he adds, “I mean a complete biological reversal of the disease. You don’t have to do anything to manage it; you don’t have to take pills or poke yourself or monitor your sugar. It’s complete autonomous control by cells.”

Measuring 13 millimeters square in its current iteration for testing in mice, the device will scale up for humans to about the size of a business card.

“TYPE 1 PATIENTS HAVE BEEN PROMISED TIME AND TIME AGAIN THAT A CURE IS AROUND THE CORNER. OUT OF RESPECT FOR THEM, WE WANT TO WORK AS HARD AS POSSIBLE . . . BUT WILL NOT PROMISE ANY TIMELINES UNTIL WE ARE SURE.”

BME Discovery

ACCOLADES

DOCTORAL CANDIDATE RECOGNIZED FOR TEACHING The UC Irvine Division of Teaching Excellence and Innovation recognized biomedical engineering doctoral candidate Rachel June Smith for excellence in undergraduate teaching at the 25th annual Celebration of Teaching, held last spring. 22

Smith (pictured top right) was one of two doctoral students campuswide selected for the 2018 Most Promising Future Faculty Award by UCI’s Senate Council on Teaching, Learning and Student Experience; Graduate Division; Division of Teaching Excellence and Innovation; and Division of Teaching and Learning. She received a dissertation fellowship and fee waiver, as well as an engraved award. “I was incredibly shocked and deeply humbled when I learned I had received this award,” says Smith, whose graduate adviser is Assistant Professor Beth Lopour. “I am so grateful to the Graduate Division for their financial support, and I am extremely motivated through this experience to keep pursuing excellence in teaching, research and service to prepare myself to educate the next generation of scholars.” When she is not teaching, Smith researches biomedical signal processing, specifically in a form of pediatric epilepsy called infantile spasms. She develops computational tools to analyze the brain signals of infants diagnosed with this condition, and hopes that comparing their brain signals to those of healthy infants can help doctors predict which babies will respond to treatments that could give them the best chance at a normal life.

TROMBERG, 2018 MENTOR OF THE YEAR, TO HEAD NIH INSTITUTE It has been a big year for biomedical engineer Bruce Tromberg. In May, UC Irvine’s Institute for Clinical and Translational Science recognized him with its 2018 Mentor of the Year award, given to an exceptional faculty member who shows an outstanding commitment to mentoring, advising and support of clinical and translational science research. Then, in September, the National Institutes of Health selected him to lead the National Institute of Biomedical Imaging and Bioengineering, headquartered in Bethesda, Maryland. He will assume that role early next year as the institute’s second director. Tromberg, a professor with joint appointments in biomedical engineering and surgery, is director of the Beckman Laser Institute and Medical Clinic. A UCI faculty member since 1990, he has pioneered the development, clinical translation and commercialization of biophotonics technologies for medical imaging, sensing and image-guided therapy. He has more than 400 publications and 18 patents, and is co-founder or adviser for six startup companies in the field of biophotonics and biomedical optics. The principal investigator of the Laser Microbeam and Medical Program, a NIH Biomedical Technology Center, he also is a member of an NIH Advisory Council. Tromberg has received several awards, including the Michael S. Feld Biophotonics Award from The Optical Society (OSA) and the Directors’ Award from the International Society for Optical Engineering (SPIE). He is a fellow of OSA, SPIE and the American Institute for Medical and Biological Engineers. UCI Department of Biomedical Engineering

ASSISTANT PROFESSOR ELECTED TO BIOPHYSICAL SOCIETY COUNCIL Michelle Digman, Samueli School biomedical engineering assistant professor, was elected by her peers to serve a three-year term on the Biophysical Society (BPS) Council, the group’s governing body. BPS, founded in 1958, has more than 9,000 members. A 15-year society veteran, Digman was one of four new council members elected. The organization has played an integral role in her career development, she says, and she plans to use her new position to continue serving its members. “This society provides a supportive environment that promotes diversity and inclusion in STEM, enhances the visibility of our research efforts to the community, and provides grants and awards to those highly innovative individuals who have made huge impacts in biophysics and continue to do so. I hope to work together with the organization to encourage young diverse researchers to push the envelope in these areas and to strengthen the society’s programs in diversity and inclusion, education and outreach to our communities,” says Digman, who will begin her term on March 5, 2019. While her lab focuses on spectroscopy, protein dynamics, metabolic alterations in cells and tissues, and fluorescence imaging technologies, Digman also serves as the Samueli School’s co-equity adviser, and she wants to bring this perspective to her new role. “I understand the importance of having a climate of respect and inclusivity, and would like to contribute my experiences to help foster this environment within BPS,” she says. 23

DEAN REWARDS FACULTY FOR EXCELLENCE Each spring, Samueli School of Engineering Dean Gregory Washington recognizes faculty for their excellence in research and teaching. This year, two biomedical engineering professors earned praise. Anna Grosberg, biomedical engineering associate professor, won the Early Career Excellence in Research award. Since joining the faculty in 2012, Grosberg, who researches cardiac tissue engineering and modeling, has published 15 peer-reviewed journal articles, which have been cited more than 1,400 times. She also has raised $2.5 million in grants, including a prestigious five-year NIH R01 award in collaboration with the UC Irvine School of Medicine. Zoran Nenadic, biomedical engineering professor, is the recipient of this year’s Senior Career Excellence in Research award. Nenadic has worked on the development of a biomimetic brain-computer

BME Discovery

interface system that is helping paralyzed patients regain walking function. The system reconnects the brain and muscles of those with paralysis in a fully implantable device. Nenadic’s work has been featured in more than 1,000 media outlets worldwide, including Time Magazine, Reuters, ABC News, CBS News, Newsweek and more. His published research paper ranks second on the all-time list of most accessed articles by the Journal of NeuroEngineering and Rehabilitation.

ATHANASIOU AWARDED WOO MEDAL Kyriacos Athanasiou was awarded the 2018 Savio L-Y. Woo Translational Biomechanics Medal by the American Society of Mechanical Engineers in recognition of his exceptional contributions to bioengineering. Athanasiou, Distinguished Professor of biomedical engineering, researches musculoskeletal and cartilaginous tissues, and develops clinical instruments and devices. He focuses primarily on regeneration of cartilage, specifically tissue found in knee, hip and shoulder joints, and in the temporomandibular joint. ASME honored him for “inventing intraosseous infusion (injection directly into the marrow of a bone), developing corresponding patented technologies, and translating those technologies to clinical use worldwide.” Athanasiou received a bronze medal and a $1,000 honorarium at the World Congress of Biomechanics conference in Dublin, Ireland, this summer. He said he was “delighted” to receive the award, adding: “It is humbling to be recognized with a medal that carries the name of one of the fathers of biomechanics. Indeed, Professor Woo is a world-class leader and one of my inspirations as a graduate student and throughout my career.” The Woo medal, first awarded in 2016, is named for the Distinguished Professor Emeritus of bioengineering at the University of Pittsburgh. Woo is considered a pioneer of bioengineering and is renowned for his 45 years of tissue repair and translational research.

Athanasiou, who directs UCI’s DELTAi (Driving Engineering and Life-science Translational Advances @Irvine) lab, joined the faculty last year, after serving as chair of the biomedical engineering department at UC Davis. “I continue to be dazzled and delighted by the scientific and engineering excellence that permeates [UCI],” he says. “This is the perfect environment for people like me and my group to perform high-quality work that can be peer-accepted and recognized with great awards like the Woo Medal.”

GRATTON WINS 2019 BPS AVANTI AWARD IN LIPIDS The Biophysical Society has named biomedical engineering professor Enrico Gratton its 2019 Avanti Award in Lipids winner. BPS will honor Gratton at its 63rd annual meeting next spring in Baltimore, Maryland. Biophysics is a field that applies the theories and methods of physics to the understanding of biological systems. Gratton was honored for his more than 30 years of pioneering work in the development and application of spectroscopy techniques for the study of biological membranes. His work has led to the determination of membrane heterogeneity and membrane nanodomains. “It is a real pleasure and a great honor to be the recipient of the 2019 Avanti Award in Lipids. I have dedicated many of my efforts to the study of lipids using fluorescence techniques,” says Gratton, who is the principal investigator for UC Irvine’s Laboratory for Fluorescence Dynamics, the country’s only national research center dedicated to fluorescence. He adds: “Clearly, I could not have written the papers and developed the ideas without the contributions of incredible collaborators who have inspired me in this research for many years.” BPS President Angela Gronenborn, from the University of Pittsburg, praises Gratton’s impact on the field. “The Avanti Award provides the society the opportunity to highlight and reflect on a researcher’s career and his or her lifetime contributions to biophysics,” she says. “Enrico has been furthering our understanding of biophysics for over 30 years and we look forward to honoring his lifetime’s work.”

UCI Department of Biomedical Engineering

BIOMEDICAL ENGINEERING RESEARCHERS WIN SYMPOSIUM AWARDS The Samueli School’s biomedical engineering department was well represented last June at the University of California 19th Annual Systemwide Bioengineering Symposium. Two department members – a graduate student and a postdoctoral researcher – won awards at the event, held June 21-23 at UC Riverside. The symposium, “Meeting Biomedical Needs with Cutting Edge Science and Technology,” brought together all 10 UC campuses with industry leaders to share bioengineering’s latest developments. Prizes were awarded for oral presentations, poster presentations, rapid-fire competition and undergraduate capstone designs. Maha Rahim, a postdoc in the lab of Assistant Professor Jered Haun, won an award of excellence for her oral presentation on bioimaging. Her presentation focused on the lab’s development of a high-content imaging platform for tumors that utilizes fluorescence lifetime-imaging microscopy. Graduate student Julien Morival won an outstanding achievement award in the poster presentation category of the conference’s molecular and cellular engineering track. Morival, whose adviser is Assistant Professor Tim Downing, researches cardiomyocyte maturation – the process of creating cardiac muscle cells from stem cells.

UNIVERSITY-INDUSTRY COLLABORATION EFFORT RECOGNIZED Last spring, UC Irvine’s Institute for Clinical and Translational Science honored biomedical engineering professor and department chair Abe Lee, along with his longtime industry partner Fiona Adair from Beckman Coulter, for their exemplary commitment to collaborative research. The two received the 2018 Industry-University Partnership Award for their years-long joint effort to develop innovative and affordable microscale technologies. Lee, the William J. Link Professor and Chair of Biomedical Engineering, and Adair, vice president of strategy and innovation at Beckman Coulter Diagnostics, were honored May 4 at the 10th annual ICTS “People Who Make a Difference in Human Health” awards dinner, held at UCI Applied Innovation. The collaboration with Beckman Coulter began in 2006, when Lee began directing an NSF-sponsored public-private consortium called the Micro/Nano Fluidics Fundamentals Focus (MF3) Center, headquartered at UCI. The Industry-University Cooperative Research Center, now called CADMIM, seeks to develop simpler, faster, and less expensive microscale tools and technologies to address problems in human health, agriculture and the environment. Beckman Coulter was an early industry partner. Despite their sometimes conflicting goals and aspirations, the two very different entities have worked side by side since then, creating a durable partnership. “We had established personal relationships, and both sides wanted and visualized the value of working together,” Lee says. “We enjoy this relationship very much, and it has resulted in a broader UCI-BEC partnership. We continue to push the forefront of microfluidics for clinical diagnostics, and we hope to change the field in the next five years.”

BME Discovery

ALUMNI

WOUND WARRIORS UCI alumni partner with doctor to engineer potential stem cell treatment for diabetic foot ulcers

JANET WILSON

STEVE ZYLIUS

FOR AHMED ZOBI, IT’S HIS MOTHER. FOR HUGO SALAS, A BELOVED GRANDMOTHER. FOR JUSTIN STOVNER, A MALE RELATIVE WHO HAS ENDURED 10 SURGERIES. FOR DR. DEREK BANYARD, IT’S HIS FATHER AND THE LARGELY AFRICAN AMERICAN PATIENTS WHOSE LIMBS HE’S HAD TO AMPUTATE OR WHO HAVE DIED TOO YOUNG.

All have seen people they care for suffer from Type 2 diabetes. Together, the three recent UC Irvine biomedical engineering graduates and the young physician with the UCI plastic surgery department’s Center for Tissue Engineering have co-founded a startup called Syntr Health Technologies. Their first goal? Perfecting a device to quickly and inexpensively process one’s own fat tissue into a potent tool to help heal dangerous foot ulcers. UCI Department of Biomedical Engineering

Syntr founders Justin Stovner, Hugo Salas, Dr. Derek Banyard and Ahmed Zobi (from left) assemble before a vastly magnified, highresolution image of the type of stem cells their startup utilizes.

Syntr’s partners are aiming for a highquality, effective solution at an affordable price. With their “Syntrfuge” technology, cells from a person’s own fat could be extracted, activated and re-injected near the damaged area in under an hour, spurring the growth of healthy new tissue. “Did you know that diabetic foot ulcers can spread like wildfire from a single cut in a few weeks?” Zobi says. “Our hope is that we can catch the ulcer in time.” The entrepreneurs already have patents pending worldwide for their Syntrfugebased system, conceived during a senior-year class in 2015. As part of the BioENGINE program, the students had access to Applied Innovation and other UCI technology transfer centers and awards. They received a key National Institutes of Health grant last fall and are about to seek Food & Drug Administration clearance for testing. The project is emblematic of stepped-up efforts to turn stellar campus research into real-world products. It’s not easy. After graduating in 2016, Zobi, 24, Salas, 36, and Stovner, 24, faced an important decision: Should they take $80,000-a-year engineering jobs or pass up steady employment to pursue their dream? They chose the latter. Together with Banyard, 37, they formed the company. Each has different survival strategies: living off credit cards, moving back in with parents, selling blood for cash, driving for Lyft and moonlighting at urgent-care clinics.

Nearly 30 million diabetic Americans risk death because they can’t feel their feet. Nerve dysfunction and lack of circulation mean that an ingrown toenail or small cut can go undetected, leading to deeply infected wounds that linger for months. Skin substitutes can cost up to $9,000, and many patients are simply told to keep the area clean and stay off their feet – with often disastrous outcomes such as amputation. Half of those who lose a limb die within five years. BME Discovery

“We all could have gotten good jobs with industry straight out of college, but I decided to stay with this because I believe in it,” Stovner says. “I’ve wanted to invent something since high school, and I just want to contribute something to the world.” Adds Salas: “We all wanted to make a medical contribution to society, not just go on to working for someone else.” The undergraduates first came together because they knew they had compatible skill sets from earlier classes together. They identified promising intellectual property from Banyard’s research lab and bioengineering faculty, ultimately helping them solve a dilemma. Banyard and his

colleagues had built on Belgian research showing that stem cells can be activated to function three to five times better than they normally would. This “stressing” of fat stem cells is critical to jump-start them for regenerative healing purposes. To accomplish this, the biomedical and tissue engineers were trying to develop a pump system to aid cancer and diabetes treatments, but it was slow and prone to leaks. The students took over the project and instead created a leak-free spinning device on a CD to activate the cells. They had a prototype in about a month. The team hasn’t slowed down since, winning numerous competitions and keeping up an eye-popping schedule of business pitching, online fundraising, product testing, grant writing and other tasks. They’ve refused to be knocked down by rejection, applying to the NIH three times before 27 receiving a $300,000 award in October. That was a huge milestone – not only do they have gas money now, but they’re in the door for possible larger federal or state stem cell funding in coming years. That would let them work with high-level experts and preserve equity in the company rather than giving it to private investors. “I entered medicine to make a positive impact on society,” Banyard says. “To also start a profitable business would be icing on the cake.” Besides cash, there are other challenges: Procuring fat cells from diabetics seeking cosmetic surgery – which are precisely the cells needed – is tough, even in imageconscious Orange County. The young executives are negotiating with an area veterans hospital and others. They’re starting in vivo testing and improving the aesthetics of their device, which was originally crafted with less than $100 worth of plastic and metal. The team members are confident they’ll have a market-ready product to be used in hospitals and doctors’ offices within three years. “Sure, everyone wants to be profitable, but we want to save lives,” Zobi says. “Diabetes is a horrible disease.”

DIRECTORY Abraham P. Lee, Ph.D.

Gregory J. Brewer, Ph.D.

William J. Link Chair in Biomedical Engineering and Department Chair and Professor of Biomedical Engineering; Mechanical and Aerospace Engineering

Email: jpbrody@uci.edu

Zhongping Chen, Ph.D.

NEWLY PROMOTED

Email: elliot.botvinick@uci.edu

Email: adurkin@uci.edu

Professor of Biomedical Engineering; Surgery

Enrico Gratton, Ph.D.

Research Interests: biomedical optics, optical coherence tomography, bioMEMS, biomedical devices

Professor of Biomedical Engineering; Developmental and Cell Biology; Physics and Astronomy

Email: z2chen@uci.edu

Research Interests: design of new fluorescence instruments, protein dynamics, single molecule, fluorescence microscopy, photon migration in tissues

Bernard Choi, Ph.D.

Michael Berns, Ph.D.

Research Interests: laser microbeams, cellular mechanotransduction, mechanobiology

Research Interests: spatial frequency domain imaging, wide-field functional imaging, quantitative near-infrared spectroscopy of superficial tissues, chemometrics, fluorescence spectroscopy, quantitative spectral imaging

Research Interests: bioinformatics, micro-nanoscale systems

Email: athens@uci.edu

Professor of Surgery; Biomedical Engineering; Chemical Engineering and Materials Science

Associate Professor of Biomedical Engineering

Associate Professor of Biomedical Engineering;

Research Interests: understanding and enhancing the healing processes of musculoskeletal tissues as well as the bodyâ&#x20AC;&#x2122;s cartilaginous tissues; applying the translation of engineering innovations to clinical use, especially in terms of instruments and devices

Elliot Botvinick, Ph.D.

Anthony Durkin, Ph.D.

James Brody, Ph.D.

Distinguished Professor of Biomedical Engineering

Email: mwberns@uci.edu

Email: tim.downing@uci.edu

Email: gjbrewer@uci.edu

Kyriacos Athanasiou, Ph.D.

Research Interests: photomedicine, laser microscopy, biomedical devices

Research Interests: stem cell and tissue engineering, regenerative biology, cell reprogramming, epigenomics, mechanobiology

Research Interests: neuronal networks, decoding brain learning and memory, brain-inspired computing, Alzheimerâ&#x20AC;&#x2122;s disease, brain aging, neuron cell culture

Email: aplee@uci.edu

Arnold and Mabel Beckman Chair in Laser Biomedicine and Professor of Surgery; Biomedical Engineering; Developmental and Cell Biology

Assistant Professor of Biomedical Engineering

Adjunct Professor of Biomedical Engineering

Research Interests: lab-ona-chip health monitoring instruments, drug delivery micro/nanoparticles, integrated cell-sorting microdevices, lipid vesicles as carriers for cells and biomolecules, high-throughput droplet bioassays, microfluidic tactile sensors

Tim Downing, Ph.D.

Professor of Surgery; Biomedical Engineering

NEWLY PROMOTED

Email: egratton@uci.edu

Research Interests: biomedical optics, in vivo optical imaging, microvasculature, light-based therapeutics

Anna Grosberg, Ph.D. Associate Professor of Biomedical Engineering; Chemical Engineering and Materials Science

Email: choib@uci.edu

Michelle Digman, Ph.D. Assistant Professor of Biomedical Engineering; Developmental and Cell Biology

Research Interests: biophotonics, fluorescence spectroscopy and microscopy, nanoscale imaging, mechanotransduction, cancer cell migration, fluorescence lifetime and metabolic mapping Email: mdigman@uci.edu

NEWLY PROMOTED

Research Interests: computational modeling of biological systems, biomechanics, cardiac tissue engineering Email: grosberg@uci.edu

Jered Haun, Ph.D. Assistant Professor of Biomedical Engineering; Chemical Engineering and Materials Science Research Interests: nanotechnology, molecular engineering, computational simulations, targeted drug delivery, clinical cancer detection Email: jered.haun@uci.edu

UCI Department of Biomedical Engineering

Elliot E. Hui, Ph.D.

Frithjof Kruggel, M.D.

Daryl Preece, Ph.D.

Associate Professor of Biomedical Engineering

Professor of Biomedical Engineering

Assistant Professor of Biomedical Engineering

Research Interests: microscale tissue engineering, bioMEMS, cell-cell interactions, global health diagnostics Email: eehui@uci.edu

Tibor Juhasz, Ph.D. Professor of Ophthalmology; Biomedical Engineering

Research Interests: laser-tissue interactions, high-precision microsurgery with lasers, laser applications in ophthalmology, corneal biomechanics Email: tjuhasz@uci.edu

Arash Kheradvar, M.D. Professor of Biomedical Engineering; Mechanical and Aerospace Engineering Research Interests: cardiac mechanics, cardiovascular devices, cardiac imaging Email: arashkh@uci.edu

Michelle Khine, Ph.D. Professor of Biomedical Engineering; Chemical Engineering and Materials Science

Research Interests: development of novel nano- and microfabrication technologies and systems for single cell analysis, stem cell research, in vitro diagnostics Email: mkhine@uci.edu

Research Interests: biomedical signal and image processing, anatomical and functional neuroimaging in humans, structure-function relationship in the human brain Email: fkruggel@uci.edu

Chang C. Liu, Ph.D. Assistant Professor of Biomedical Engineering; Chemistry; Developmental and Cell Biology

Research Interests: genetic engineering, directed evolution, synthetic biology, chemical biology Email: ccl@uci.edu

Wendy F. Liu, Ph.D. Associate Professor of Biomedical Engineering; Chemical Engineering and Materials Science

Research Interests: biomaterials, microdevices in cardiovascular engineering, cell-cell and cellmicro-environment interactions, cell functions and controls Email: wendy.liu@uci.edu

Beth A. Lopour, Ph.D. Assistant Professor of Biomedical Engineering; Mechanical and Aerospace Engineering

Research Interests: computational neuroscience, signal processing, mathematical modeling, epilepsy, translational research

Christine King, Ph.D.

Email: beth.lopour@uci.edu

Assistant Professor of Teaching Biomedical Engineering

Zoran Nenadic, Ph.D.

Research Interests: engineering and STEM education, active learning, wireless health systems, rehabilitation, brain-computer NEW FACULTY interfaces, robotics MEMBER Email: kingce@uci.edu

Professor of Biomedical Engineering; Electrical Engineering and Computer Science

Research Interests: adaptive biomedical signal processing, control algorithms for biomedical devices, brain-machine interfaces, modeling and analysis of biological neural networks Email: znenadic@uci.edu

BME Discovery

Research Interests: nano-optics, neuro-photonics, optical forces and mechanotransduction, singular optics and biophotonics

NEW FACULTY Email: dpreece@uci.edu MEMBER

William C. Tang, Ph.D. Professor of Biomedical Engineering; Electrical Engineering and Computer Science

Research Interests: micro-electro-mechanical systems (MEMS) nanoscale engineering for biomedical applications, microsystems integration, microimplants, microbiomechanics, microfluidics Email: wctang@uci.edu

Bruce Tromberg, Ph.D. Director of Surgery; Biomedical Engineering; Physiology and Biophysics Research Interests: photon migration, diffuse optical imaging, nonlinear optical microscopy, photodynamic therapy Email: bjtrombe@uci.edu

AFFILIATED FACULTY Alpesh N. Amin, M.D. Thomas & Mary Cesario Chair and Professor of Medicine; Biomedical Engineering; Paul Merage School of Business; Program in Nursing Science Email: anamin@uci.edu

Pierre F. Baldi, Ph.D. UCI Chancellor’s Professor of Computer Science; Biological Chemistry; Biomedical Engineering; Developmental and Cell Biology Email: pfbaldi@ics.uci.edu

Bruce Blumberg, Ph.D. Professor of Developmental and Cell Biology; Biomedical Engineering; Environmental Health Sciences; Pharmaceutical Sciences Email: blumberg@uci.edu

Andrew Browne, M.D. Assistant Clinical Professor of Ophthalmology; Biomedical Engineering Email: abrowne1@uci.edu

Peter J. Burke, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical Engineering and Materials Science Email: pburke@uci.edu

Dan M. Cooper, M.D. Professor of Pediatrics; Biomedical Engineering Email: dcooper@uci.edu

Robert Corn, Ph.D. Professor of Chemistry; Biomedical Engineering Email: rcorn@uci.edu

Nancy A. Da Silva, Ph.D. Professor of Chemical Engineering and Materials Science; Biomedical Engineering Email: ndasilva@uci.edu

Hamid Djalilian, M.D. Professor of Otolaryngology; Biomedical Engineering Email: hdjalili@uci.edu

James Earthman, Ph.D. Professor of Chemical Engineering and Materials Science; Biomedical Engineering Email: earthman@uci.edu

Gregory R. Evans, M.D. Professor of Surgery; Biomedical Engineering Email: gevans@uci.edu

Lisa Flanagan-Monuki, Ph.D. Associate Professor of Neurology; Biomedical Engineering Email: lflanaga@uci.edu

Ron Frostig, Ph.D. Professor of Neurobiology and Behavior; Biomedical Engineering Email: rfrostig@uci.edu

Zhibin Guan, Ph.D. Professor of Chemistry; Biomedical Engineering Email: zguan@uci.edu

Gultekin Gulsen, Ph.D. Associate Professor of Radiological Sciences; Biomedical Engineering; Electrical Engineering and Computer Science; Physics and Astronomy Email: ggulsen@uci.edu

Ranjan Gupta, Ph.D. Professor of Orthopaedic Surgery; Anatomy and Neurobiology; Biomedical Engineering Email: ranjang@uci.edu

Frank P. Hsu, M.D. Department Chair and Professor of Neurosurgey; Biomedical Engineering; Otolaryngology Email: fpkhsu@uci.edu

Lan Huang, Ph.D. Professor of Physiology & Biophysics; Biomedical Engineering Email: lanhuang@uci.edu

Christopher Hughes, Ph.D. Director of Edwards Lifesciences Cardiovascular Technology Center and Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: cchughes@uci.edu

James V. Jester, Ph.D. Professor in Residence, Ophthalmology; Biomedical Engineering Email: jjester@uci.edu

Joyce H. Keyak, Ph.D. Professor in Residence of Radiological Sciences; Biomedical Engineering; Mechanical and Aerospace Engineering Email: jhkeyak@uci.edu

Young Jik Kwon, Ph.D. Professor of Pharmaceutical Sciences; Biomedical Engineering; Chemical Engineering and Materials Science; Molecular Biology and Biochemistry Email: kwonyj@uci.edu

Jonathan Lakey, Ph.D. Professor of Surgery; Biomedical Engineering Email: jlakey@uci.edu

Arthur D. Lander, Ph.D. Donald Bren Professor and Professor of Developmental and Cell Biology; Biomedical Engineering; Logic and Philosophy of Science; Pharmacology Email: adlander@uci.edu

Thay Q. Lee, Ph.D. Professor in Residence of Orthopaedic Surgery; Biomedical Engineering; Physical Medicine and Rehabilitation Email: tqlee@uci.edu

Guann-Pyng Li, Ph.D. Director of the UCI Division of the California Institute for Telecommunications and Information Technology; Director of the Integrated Nanosystems Research Facility and Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical Engineering and Materials Science Email: gpli@uci.edu

Jack Lin, M.D. Professor of Clinical Neurology; Biomedical Engineering Email: linjj@uci.edu

John Lowengrub, Ph.D. UCI Chancellor’s Professor of Mathematics; Biomedical Engineering; Chemical Engineering and Materials Science Email: jlowengr@uci.edu

Ray Luo, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: rluo@uci.edu

Marc J. Madou, Ph.D. UCI Chancellor’s Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Chemical Engineering and Materials Science Email: mmadou@uci.edu

Baruch D. Kuppermann, M.D. Professor of Ophthalmology; Biomedical Engineering Email: bdkupper@uci.edu

UCI Department of Biomedical Engineering

John Middlebrooks, Ph.D.

Professor of Otolaryngology; Biomedical Engineering; Cognitive Sciences; Neurobiology and Behavior Email: j.midd@uci.edu

Sabee Molloi, Ph.D. Professor of Radiological Sciences; Biomedical Engineering Email: symolloi@uci.edu

Jogeshwar Mukherjee, Ph.D. Professor and Director, Preclinical Imaging; Radiological Sciences, School of Medicine; Biomedical Engineering Email: j.mukherjee@uci.edu

J. Stuart Nelson, Ph.D. Professor of Surgery; Biomedical Engineering Email: jsnelson@uci.edu

Qing Nie, Ph.D. Professor of Mathematics; Biomedical Engineering Email: qnie@math.uci.edu

Pranav Patel, M.D. Chief, Division of Cardiology; Director of Cardiac Catheterization Laboratory and Cardiac Care Unit (CCU) and Health Sciences Associate Clinical Professor of Medicine; Biomedical Engineering Email: pranavp@uci.edu

David J. Reinkensmeyer, Ph.D. Professor of Anatomy and Neurobiology; Biomedical Engineering; Mechanical and Aerospace Engineering; Physical Medicine and Rehabilitation Email: dreinken@uci.edu

Phillip C-Y Sheu, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Computer Science Email: psheu@uci.edu

Andrei M. Shkel, Ph.D. Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Electrical Engineering and Computer Science Email: ashkel@uci.edu

Zuzanna S. Siwy, Ph.D. Professor of Physics and Astronomy; Biomedical Engineering; Chemistry Email: zsiwy@uci.edu

Ramesh Srinivasan, Ph.D. Professor of Cognitive Sciences; Biomedical Engineering Email: r.srinivasan@uci.edu

Peter Tseng, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: tsengpc@uci.edu Vasan Venugopalan, Sc.D. Department Chair and Professor of Chemical Engineering and Materials Science; Biomedical Engineering; Mechanical and Aerospace Engineering; Surgery Email: vvenugop@uci.edu

Szu-Wen Wang, Ph.D. Professor of Chemical Engineering and Materials Science; Biomedical Engineering Email: wangsw@uci.edu

H. Kumar Wickramasinghe, Ph.D. Henry Samueli Endowed Chair in Engineering and Department Chair and Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical Engineering and Materials Science Email: hkwick@uci.edu

Brian Wong, M.D. Professor of Otolaryngology; Biomedical Engineering Email: bjwong@uci.edu

Xiangmin Xu, Ph.D. Associate Professor of Anatomy and Neurobiology; Biomedical Engineering; Electrical Engineering and Computer Science; Microbiology and Molecular Genetics Email: xiangmin.xu@uci.edu

Albert Fan Yee, Ph.D. Professor of Chemical Engineering and Materials Science; Biomedical Engineering; Chemistry Email: afyee@uci.edu

Fan-Gang Zeng, Ph.D. Director of Hearing Research and Professor of Otolaryngology; Anatomy and Neurobiology; Biomedical Engineering; Cognitive Sciences Email: fzeng@uci.edu

Weian Zhao, Ph.D. Associate Professor of Pharmaceutical Sciences; Biomedical Engineering Email: weianz@uci.edu

BME Discovery

EXECUTIVE ADVISORY BOARD Abe Lee UC Irvine Bill Link Versant Ventures David Bardin University Medical Pharmaceuticals David Cuccia Modulated Imaging Bruce Feuchter Stradling Yocca Carlson & Rauth Stanton Rowe Edwards Lifesciences Corp. Thomas Yuen PrimeGen Biotech Nicholas Alexopolous Broadcom Foundation Vasudev Bailey Quid Thomas Frinzi Johnson & Johnson Vision Thomas Burns Glaukos Corp.

EMPLOYMENT OPPORTUNITY

RECRUITMENT FOR TENURE-TRACK POSITION IN DEVICES FOR PRECISION MEDICINE

The Department of Biomedical Engineering in the Samueli School of Engineering at UC Irvine invites applications for a tenure-track faculty position at the assistant professor level with a target start date of July 1, 2019. We seek a Ph.D.-level scientist or engineer who will establish a strong and dynamic research program in personalized and precision medicine, broadly defined. Areas of interest span from diagnostic devices and wearables to targeted therapeutics, genomics and genome engineering. The candidate should also be committed to teach biomedical engineering at the undergraduate and graduate levels. Candidates must have a doctorate in biomedical engineering or related field; postdoctoral experience is desirable. This position falls under the Samueli School of Engineering’s grand challenge theme of health and wellness, with the ultimate goal of increased life expectancy and quality of life. Over the next few years, the school intends to grow our existing strengths toward this grand challenge through hiring, infrastructure and capital investment. In addition, the biomedical engineering department has strong collaborative relationships with the School of Medicine in UCI’s Henry and Susan Samueli College of Health Sciences. The selected candidate’s research program should fit within this interdisciplinary and collaborative culture. Applications should include a cover letter, a curriculum vitae including a publication list, a concise statement of proposed research and a teaching statement. A separate statement that addresses past and/or potential contributions to diversity, equity and inclusion must also be included in the application materials. Applicants should arrange for a minimum of two letters of recommendation to be submitted on their behalf. Applications will be accepted until the position is filled. To ensure full consideration, applications and supporting materials should be received by Nov. 25, 2018. Apply online at https://recruit.ap.uci.edu/apply/JPF04958

UC Irvine, established in 1965, is ranked among the nation’s best research institutes, and is part of the NIH Clinical and Translational Science Award Program. Research facilities most relevant to this position include the Integrated Nanosystems Research Facility, the California Institute of Telecommunications & Information Technology, the Edwards Lifesciences Center for Advanced Cardiovacscular Technologies, the Center for Advanced Design & Manufacturing of Integrated Microfluidics, the Beckman Laser Institute, the Laboratory for Fluorescence Dynamics, the Chao Family Comprehensive Cancer Center, and the Sue and Bill Gross Stem Cell Center - the first California Institute of Regenerative Medicine Center in the state of California. The list of the top 50 NIH Funded Universities in the United States includes UCI with over $400M in yearly funding. Exceptional programs in faculty housing within walking distance from campus are offered to all incoming faculty members. In addition, Irvine is one of the safest communities in the U.S. and offers a very pleasant year-round climate, numerous recreational and cultural opportunities, and one of the highest-ranked public-school systems in the nation. UCI is an Equal Opportunity/Affirmative Action Employer advancing inclusive excellence. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, protected veteran status, or other protected categories covered by the UC nondiscrimination policy. A recipient of an NSF ADVANCE award for gender equity, UCI is responsive to the needs of dual career couples, supports work-life balance through an array of family-friendly policies, and is dedicated to broadening participation in higher education. For more information about the department, visit http://engineering.uci.edu/dept/bme

UCI Department of Biomedical Engineering

LAST LOOK Imagine living with spinal cord paralysis and learning that you could walk again. An implantable brain-computer interface device in development at UC Irvine is working to accomplish this by circumventing the damaged portion of the spinal cord and sending the brain’s signals directly to a patient’s legs. The two-part device, funded by an $8 million NSF grant, consists of a surgically implanted electrode grid/ brain-signal circuit (demonstrated here by BME’s Zoran Nenadic) and a lowpower transmitter/receiver implanted in the chest cavity. Progress is promising. Researchers have fabricated ultra-low-power components, conducted measurements, recorded brain signals and completed a prototype chest unit. “Since these systems are fully implantable, they will be inconspicuous, work around the clock and access much stronger brain signals, facilitating highly accurate control of movement,” Nenadic says.

BME Discovery

NONPROFIT ORG. U.S. POSTAGE

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University of California, Irvine Samueli School of Engineering Department of Biomedical Engineering 3120 Natural Sciences II Irvine, CA 92697-2715

Invest in a brilliant future.

BE A BME SUPPORTER. We believe in meeting tomorrow’s technological challenges by providing the highest-quality engineering education and research rigor today. We invite you to invest in the future of UC Irvine’s biomedical engineering program. It is through private donations like yours that we can continue to provide outstanding opportunities for our students and researchers. Your contribution, regardless of amount, makes a difference toward what BME can accomplish.

To find out more about supporting the advancement of the biomedical engineering department, please visit https://ua-web.uadv.uci.edu/egiving. From the “area of support” drop-down menu, select Engineering School and from the “gift designation” drop-down menu, you may either select Biomedical Engineering or Biomedical Graduate Fellowship Fund. This will ensure that your support will go directly to the department. For more information, please contact Ed Hand, assistant dean for development, at elhand@uci.edu or (949) 824-5094.

To learn more about the BME Department, please visit http://engineering.uci.edu/dept/bme