Vector Flow Imaging Helps Visualize Blood Flow in Pediatric Hearts
A group of biomedical engineers at the University of Arkansas used a new ultrasound-based imaging technique called vector flow imaging to help improve the diagnosis of congenital heart disease in pediatric patients. The study, led by associate professor of biomedical engineering Morten Jensen, Ph.D., collaborated with cardiologists at the local Children’s Hospital in Little Rock to produce images of the heart in infants to help potentially diagnose congenital heart defects. Though the use of vector flow imaging has yet to be developed for adult patients, this type of imaging could possibly provide more detail about the direction of blood flow through the heart than traditional techniques like echocardiography do. In the future, the use of both techniques could provide information about both the causes and larger effects of heart defects in patients.
Using Stem Cells to Improve Fertility in Leukemia Survivors
One of the more common side effects of leukemia treatment in female patients is infertility, but researchers at the University of Michigan want to change that. Led by associate professor of biomedical engineering Ariella Shikanov, Ph.D., researchers in her lab found ways of increasing ovarian follicle productivity in mice, which directly relates to the development of mature eggs. The project involves the use of adipose-derived stem cells, that can be found in human fat tissue, to surround the follicles in an ovary-like, three-dimensional scaffold. Because the radiation treatments for leukemia and some other cancers are harmful to follicles, increasing their survival rate with this stem cell method could reduce the rate of infertility in patients undergoing these treatments. Furthermore, this new approach is innovative in its use of a three-dimensional scaffold as opposed to a two-dimensional one, as it stimulates follicle growth in all directions and thus helps to increase the follicle survival rate.
Penn Engineers Look at How Stretching & Alignment of Collagen Fibers Help Cancer Cells Spread
Cancer has such a massive impact on people’s lives that it might be easy to forget that the disease originates at the cellular level. To spread and cause significant damage, individual cancer cells must navigate the fibrous extracellular environment that cells live in, an environment that Penn Engineer Vivek Shenoy has been investigating for years.
Shenoy’s most recent study on cancer’s mechanical environment was led by a postdoctoral researcher in his lab, Ehsan Ban. Paul Janmey, professor in Physiology and Bioengineering, and colleagues at Stanford University also contributed to the study. Shenoy also received the Heilmeier Award this March and delivered the Heilmeier Award Lecture in April.
Controlled Electrical Stimulation Can Prevent Joint Replacement Infections
Joint replacements are one of the most common kinds of surgery today, but they still require intense post-operative therapy and have a risk of infection from the replacement implant. These infections are usually due to the inflammatory response that the body has to any foreign object, and can become serious and life-threatening if left untreated. Researchers at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences hope to offer a solution to preventing infections through the use of controlled electrical stimulation. Led by Mark Ehrensberger, Ph.D., Kenneth A. Krackow, M.D., and Anthony A. Campagnari, Ph.D., the treatment system uses the electrical signal to create an antibacterial environment at the interface of the body and the implant. While the signal does not prevent infections completely, these antibacterial properties will prevent infections from worsening to a more serious level. Patented as the Biofilm Disruption Device TM, the final product uses two electrode skin patches and a minimally invasive probe that delivers the electrical signal directly to the joint-body interface. The researchers behind the design hope that it can help create a more standard way of effectively treating joint replacement infections.
People and Places
For their senior design project, four bioengineering seniors — Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng — created a low-cost tuberculosis diagnostic that they called TBx. Using their knowledge of the photoacoustic effect of certain dyes, the platform the group created can detect the presence of lipoarabinomannan in patient urine. The four seniors presented TBx at the Rice360 Design Competition in Houston, Texas this spring, which annually features student-designed low-cost global health technologies.
New Vascularized Patches Could Help Patient Recovery from Heart Attacks
Heart attacks are the result of a stoppage of blood flow to the heart – an interruption to normal function that can result in severe tissue damage, or even tissue death. This loss of healthy tissue function is one of the biggest challenges in treating patients that undergo heart attacks, as the damaged tissue increases their risk of having future attacks. One of the main solutions to this issue right now is the creation of cardiac tissue scaffolds using stem cells to create a platform for new and healthy tissue to grow in vivo. A group of biomedical engineers at Michigan Technological University hopes to expand on this basis by focusing not just on cellular alignment in the scaffold but on that of microvessels too. Led by Feng Zhao, Ph.D., Associate Professor of Biomedical Engineering, the team hopes that this new attention on microvessel organization will improve the vasculature of the scaffolds, and thus improve the success of the scaffolds in vivo, allowing for a better recovery from heart attacks.
Some Stem Cells May Be More Fit Than Others
Stem cells are one of the hottest research areas in the field of bioengineering today. Widely known as the cells in the human embryo that have the ability to eventually transform into specific cells for the brain, lung, and every other organ, stem cells are also of recent interest because researchers found ways to reverse this process, transforming organ-specific cells back to the pluripotent stem cell level. This achievement however, is mostly applicable to individual stem cells, and doesn’t fully encapsulate the way this process might work on a larger population level. So Peter Zandstra, Ph. D., a bioengineering faculty member at the University of British Columbia, decided to research just that.
Using mouse embryonic fibroblasts (MEFs), Zandstra and his lab attempted to track the cells throughout their reprogramming, to more clearly trace each back to its respective parent population. Surprisingly, they found that after only one week of reprogramming, nearly 80% of the original cell population had been removed, meaning that most of the parent generation was not “fit” enough to undergo the process of reprogramming, indicating that perhaps some stem cells will have a better chance of survival in this process than others. This research may suggest that not all cells have the capacity to undergo reprogramming, as many researchers originally thought.
A New Microdevice Will Help Model Bronchial Spasms
The difficulty in breathing associated with asthma is the result of bronchial spasms, which are a kind of muscle contraction in the airways. But little was known about just how these spasms occurred in patients, so Andre Levchenko, Ph.D., Professor of Biomedical Engineering at Johns Hopkins, and his lab created a microdevice to model them. Calling the device a “bronchi on a chip,” Levchenko and his team used a microphysiological model to look at some of the biochemical and mechanical signals associated with these kinds of muscle contractions. They found that the contractions operate in a positive feedback system, so that those caused by disturbance from allergens will subsequently cause even more contractions to occur. But surprisingly, they also found that a second contraction, if triggered at the right time during the initial contraction, could actually stop the process and allow the muscles to relax. Because asthma is a notoriously difficult disease to translate from animal to human models, this new device opens the door to understanding different mechanisms of asthma before taking research to clinical trials.
New CHOP Research Center to Focus Research on Pediatric Airway Disorders
A new bioengineering lab at the Children’s Hospital of Philadelphia called the Center for Pediatric Airway Disorders will specialize in a variety of airway procedures for pediatric patients such as tracheal reconstruction and recurrent laryngeal nerve reinnervation. This new lab will be one of the first to give a unique focus to the application of bioengineering to pediatric laryngology. The interdisciplinary center brings together students and researchers from all different fields, including materials science and microbiology, to find new ways of repairing tissue and regenerating organs related to respiratory disorders. Specific areas of research will involve the modeling of children’s vocal cords, understanding the mechanisms of fibrosis, and improving surgical procedures.
Deeper Understanding of Sickle Cell Anemia Could Lead to New Treatments
Though sickle cell anemia is a common and well-known disease, a new study of its causes at the nanoscale level might reveal previously unknown information about the assembly of hemoglobin fibers. Using microscopes with the ability to visualize these molecules at such a small level, researchers at the University of Minnesota found that the beginning organizations that lead to sickle cell anemia are much less ordered than originally thought. Led by Associate Professor of Biomedical Engineering David Wood, Ph.D., the team of researchers used this higher level of microscopy to find that hemoglobin self-assembly process, which was originally thought to be 96% efficient, is actually only 4% efficient. Wood hopes that this new knowledge will help allow for the development of new and better treatments for patients with sickle cell anemia, as there are currently only two FDA-approved ones on the market.
People & Places
Penn Today asked five Penn researchers about the women in STEM who have been a source of inspiration and encouragement throughout their own careers. Their responses include active researchers who have paved the way for better inclusion in STEM and famous female scientists from the past who broke boundaries as they made strides with their research.
This week, we want to congratulate Joel Boerckel, Ph.D., Assistant Professor of Orthopaedic Surgery and Bioengineering, and his lab on receiving a second R01 Grant from the National Institute of Arthritis and and Musculoskeletal Skin Diseases for their work on defining the roles of YAP and TAZ in embryonic bone morphogenesis and mechanoregulation of fracture repair. Dr. Boerckel is a member of the McKay Orthopaedic Research Laboratory.
We would also like to congratulate Christopher Yip, Ph. D., on being appointed as the new dean of the University of Toronto’s Faculty of Applied Science and Engineering. A professor in both the Department of Chemical Engineering and Applied Chemistry the Institute of Biomaterials and Biomedical Engineering, Dr. Yip’s research involves the use of molecular imaging to understand the self-assembly of proteins.
Tulane Researchers Use Cancer Imaging Technique to Help Detect Preeclampsia
Preeclampsia is potentially life-threatening pregnancy disorder that typically occurs in about 200,000 expectant mothers every year. With symptoms of high blood pressure, swelling of the hands and feet, and protein presence in urine, preeclampsia is usually treatable if diagnosed early enough. However, current methods for diagnosis involve invasive procedures like cordocentesis, a procedure which takes a sample of fetal blood.
Researchers at Tulane School of Medicine led by assistant professor of bioengineering Carolyn Bayer, Ph.D., hope to improve diagnostics for preeclampsia with the use of spectral photoacoustic imaging. Using this technique, Bayer’s team noticed a nearly 12 percent decrease in placental oxygenation in rats with induced preeclampsia when compared to normal pregnant rats after only two days. If success in using this imaging technology continues at the clinical level, Bayer plans to find more applications of it in the detection and diagnosis of breast and ovarian cancers as well.
New CRISPR-powered device detects genetic mutations in minutes
This new chip eliminates the long and expensive amplification process involved in the typical polymerase chain reaction (PCR) used to read DNA sequences. In doing so, the CRISPR-Chip is much more of a point-of-care diagnostic, having the ability to quickly detect a given mutation or sequence when given a pure DNA sample. Led by Kiana Aran, Ph.D., the research team behind the CRISPR-Chip hopes that this new combination of nanoelectronics and modern biology will allow for a new world of possibilities in personalized medicine.
New Method of Brain Stimulation Might Alleviate Symptoms of Depression
Led by Flavio Frohlich, Ph.D., who has an adjunct appointment in biomedical engineering, this team of researchers based this new solution on information from each patient’s specific alpha oscillations, which are a kind of wave that can be detected by an electroencephalogram (EEG). Those who suffer from depression tend to have imbalanced alpha oscillations, so Frohlich and his team sought to use tACS to restore this balance in those patients. After seeing positive results from data collected two weeks after patients in a clinical trial receives the tACS treatment, Frohlich hopes that future applications will include treatment for even more mental health disorders and psychiatric illnesses.
University of Utah Researchers Receive Grant to Improve Hearing Devices for Deaf Patients
Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Scholar in the Department of Materials Science and Engineering and Secondary Faculty in Bioengineering, has been named the recipient of the 2018–19 George H. Heilmeier Faculty Award for Excellence in Research for “for pioneering multi-scale models of nanomaterials and biological systems.”
The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for George H. Heilmeier, a Penn Engineering alumnus and advisor whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.
We would also like to congratulate Jay Goldberg, Ph.D., from Marquette University on his election as a fellow to the National Academy of Inventors. Nominated largely for his six patents involving medical devices, Goldberg also brings this innovation to his courses. One in particular called Clinical Issues in Biomedical Engineering Design allows junior and senior undergraduates to observe the use of technology in clinical settings like the operating room, in an effort to get students thinking about how to improve the use of medical devices in these areas.
Billiar, who received his M.S.E. and Ph.D. from Penn, began his research by first noticing the way that cells typically respond to the mechanical stimuli in their everyday environment, such as pressure or stretching, with behaviors like migration, proliferation, or contraction. He and his research team hope to find a way to eventually predict and control cellular responses to their environment, which they hope could open doors to more forms of treatment for disorders like heart disease or cancer, where cellular behavior is directly linked to the cause of the disease.
Self-Learning Algorithm Could Help Improve Robotic Leg Functionality
Obviously, one of the biggest challenges in the field of prosthetics is the extreme difficulty in creating a device that perfectly mimics whatever the device replaces for its user. Particularly with more complex designs that involve user-controlled motion for joints in the limbs or hands, the electrical circuits implemented are by no means a perfect replacement of the neural connections in the human body from brain to muscle. But recently at the University of Southern California Viterbi School of Engineering, a team of researchers led by Francisco J. Valero-Cuevas, Ph. D., developed an algorithm with the ability to learn new walking tasks and adapt to others without any additional programming.
The algorithm will hopefully help to speed the progress of robotic interactions with the world, and thus allow for more adaptive technology in prosthetics, that responds to and learns with their users. The algorithm Valero-Cuevas and his team created takes inspiration from the cognition involved with babies and toddlers as they slowly learn how to walk, first through random free play and then from pulling on relevant prior experience. In a prosthetic leg, the algorithm could help the device adjust to its user’s habits and gait preferences, more closely mimicking the behavior of an actual human leg.
Neurofeedback Can Improve Behavioral Performance in High-Stress Situations
We’re all familiar with the concept of being “in the zone,” or the feeling of extraordinary focus that we can sometimes have in situations of high-stress. But how can we understand this shift in mindset on a neuroengineering level? Using the principal of the Yerkes-Dodson law, which says that there is a state of brain arousal that is optimal for behavioral performance, a team of biomedical engineering researchers at Columbia University hope to find ways of applying neurofeedback to improving this performance in demanding high-stress tasks.
Ultrasound Stimulation Could Lead to New Treatments for Inflammatory Arthritis
Arthritis, an autoimmune disease that causes painful inflammation in the joints, is one of the more common diseases among older patients, with more than 3 million diagnosed cases in the United States every year. Though extreme measures like joint replacement surgery are one solution, most patients simply treat the pain with nonsteroidal anti-inflammatory drugs or the adoption of gentle exercise routines like yoga. Recently however, researchers at the University of Minnesota led by Daniel Zachs, M.S.E., in the Sensory Optimization and Neural Implant Coding Lab used ultrasound stimulation treatment as a way to reduce arthritic pain in mice. In collaboration with Medtronic, Zachs and his team found that this noninvasive ultrasound stimulation greatly decreased joint swelling in mice who received the treatment as opposed to those that did not. They hope that in the future, similar methods of noninvasive treatment will be able to be used for arthritic patients, who otherwise have to rely on surgical remedies for serious pain.
People and Places
Leadership and Inspiration: EDAB’s Blueprint for Engineering Student Life
To undergraduates at a large university, the administration can seem like a mysterious, all-powerful entity, creating policy that affects their lives but doesn’t always take into account the reality of their day-to-day experience. The Engineering Deans’ Advisory Board (EDAB) was designed to bridge that gap and give students a platform to communicate with key decision makers.
The 13-member board meets once per week for 60 to 90 minutes. The executive board, comprised of four members, also meets weekly to plan out action items and brainstorm. Throughout his interactions with the group, board president Jonathan Chen, (ENG ‘19, W ‘19), has found a real kinship with his fellow board members, who he says work hard and enjoy one another’s company in equal measure.
Bioengineering major Daphne Cheung (ENG’19) joined the board as a first-year student because she saw an opportunity to develop professional skills outside of the classroom. “For me, it was about trying to build a different kind of aptitude in areas such as project management, and learning how to work with different kinds of people, including students and faculty, and of course, the deans,” she says.
Purdue University College of Engineering and Indiana University School of Medicine Team Up in New Engineering-Medicine Partnership
The Purdue University College of Engineering and the Indiana University School of Medicine recently announced a new Engineering-Medicine partnership, that seeks to formalize ongoing and future collaborations in research between the two schools. One highlight of the partnership is the establishment of a new M.D./M.S. degree program in biomedical engineering that will allow medical students at Indiana University to receive M.S.-level training in engineering technologies as they apply to clinical practice. The goal of this new level of collaboration is to further involve Purdue’s engineering program in the medical field, and to exhibit the benefits that developing an engineering mindset can have for medical students. The leadership of this new partnership includes
A New Microscopy Technique Could Reduce the Risk of LASIK Surgery
Though over ten million Americans have undergone LASIK vision corrective surgery since the option became available about 20 years ago, the procedure still poses some risk to patients. In addition to the usual risks of any surgery however, LASIK has even more due to the lack of a precise way to measure the refractive properties of the eye, which forces surgeons to make approximations in their measurements during the procedure. In an effort to eliminate this risk, a University of Maryland team of researchers in the Optics Biotech Laboratory led by Giuliano Scarcelli, Ph. D., designed a microscopy technique that would allow for precise measurements of these properties.
Using a form of light-scattering technology called Brillouin spectroscopy, Scarcelli and his lab found a way to directly determine a patient’s refractive index – the quantity surgeons need to know to be able to measure and adjust the way light travels through the eye. Often used as a way to sense mechanical properties of tissues and cells, this technology holds promise for taking three-dimensional spatial observations of these structures around the eye. Scarcelli hopes to keep improving the resolution of the new technique, to further understanding of the eye, and reduce even more of the risks involved with LASIK surgery.
Taking Tissue Models to the Final Frontier
Space flight is likely to cause deleterious changes to the composition of bacterial flora, leading to an increased risk of infection. The environment may also affect the susceptibility of microorganisms within the spacecraft to antibiotics, key components of flown medical kits, and may modify the virulence of bacteria and other microorganisms that contaminate the fabric of the International Space Station and other flight platforms.
“It has been known since the early days of human space flight that astronauts are more prone to infection,” says Dongeun (Dan) Huh, Wilf Family Term Assistant Professor in Bioengineering at Penn Engineering. “Infections can potentially be a serious threat to astronauts, but we don’t have a good fundamental understanding of how the microgravity environment changes the way our immune system reacts to pathogens.”
In collaboration with G. Scott Worthen, a physician-scientist in neonatology at the Children’s Hospital of Philadelphia, Huh will attempt to answer this question by sending tissues-on-chips to space. Last June, the Center for the Advancement of Science in Space (CASIS) and the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), announced that the duo had received funding to study lung host defense in microgravity at the International Space Station.
Huh and Worthen aim to model respiratory infection, which accounts for more than 30 percent of all infections reported in astronauts. The project’s goals are to test engineered systems that model the airway and bone marrow, a critical organ in the immune system responsible for generating white blood cells, and to combine the models to emulate and understand the integrated immune responses of the human respiratory system in microgravity.
Sappi Limited Teams Up with the University of Maine to Develop Paper Microfluidics
At the Westbrook Technology Center of Sappi, a global pulp and paper company, researchers found ways to apply innovations in paper texture for medical use. So far, these include endeavors in medical test devices and patches for patient diagnostics. In collaboration with the Caitlin Howell, Ph.D., Assistant Professor of Chemical and Biomedical Engineering at the University of Maine, Sappi hopes to continue advances in these unconventional uses of their paper, especially as the business in paper for publishing purposes declines.
Sappi’s projects with the university focus on the development of paper microfluidics devices as what’s now becoming a widespread solution for obstacles in point-of-care diagnostics. One project in particular, called Sharklet, uses a paper that mimics shark skin as a way to impede unwanted microbial growth on the device – a key characteristic needed for its transition into commercial use. Beyond this example, Sappi’s work in developing paper microfluidics underscores the benefits of these devices in their mass producibility and adaptability.
New Observations of the WNT Pathway Deepen the Understanding of Protein Signaling in Cellular Development
Scientists at Rice University recently found that a protein signaling pathway called WNT, typically associated with its role in early organism development, can both listen for signals from a large amount of triggers and influence cell types throughout embryonic development. These new findings, published in PNAS, add to the already known functions of WNT, deepening our understanding of it and opening the doors to new potential applications of it in stem cell research.
Led by Aryeh Warmflash, Ph. D., researchers discovered that the WNT pathway is different between stem cells and differentiated cells, contrary to prior belief that it was the same for both. Using CRISPR-Cas9 gene editing technology, the Warmflash lab observed that the WNT signaling pathway is actually context-dependent throughout the process of cellular development. This research brings a whole new understanding to the way the WNT pathway operates, and could open the doors to new forms of gene therapy and treatments for diseases like cancers that involve genetic pathway mutations.
People and Places
In a recent article from Technical.ly Philly, named Group K Diagnostics on a list of ten promising startups in Philadelphia. Group K Diagnostics founder Brianna Wronko graduated with a B.S.E. from Penn’s Department of Bioengineering in 2017, and her point-of-care diagnostics company raised over $2 million in funding last year. Congratulations Brianna!
We would also like to congratulate Pamela K. Woodward, M.D., on her being named as the inaugural Hugh Monroe Wilson Professor of Radiology at the Washington University School of Medicine in St. Louis. Also a Professor of Biomedical Engineering at the university, Dr. Woodward leads a research lab with a focus on cardiovascular imaging, including work on new standards for diagnosis of pulmonary blood clots and on an atherosclerosis imaging agent.
Lastly, we would like to congratulate all of the following researchers on their election to the National Academy of Engineering:
David Bishop, Ph. D., a professor at the College of Engineering at Boston University whose current research involves the development of personalized heart tissue as an all-encompassing treatment for patients with heart disease.
Joanna Aizenberg, Ph. D., a professor of chemistry and chemical biology at Harvard University who leads research in the synthesis of biomimetic inorganic materials
Gilda Barabino, Ph. D., the dean of the City College of New York’s Grove School for Engineering whose lab focuses on cartilage tissue engineering and treatments for sickle cell disease.
Karl Deisseroth, M.D., Ph. D., a professor of bioengineering at Stanford University whose research involves the re-engineering of brain circuits through novel electromagnetic brain stimulation techniques.
Rosalind Picard, Ph.D., the founder and director of the Affective Computing Research Group at the Massachusetts Institute of Technology’s Media Lab whose research focuses on the development of technology that can measure and understand human emotion.
And finally, Molly Stevens, Ph. D., the Research Director for Biomedical Material Sciences at the Imperial College of London with research in understanding biomaterial interfaces for biosensing and regenerative medicine.
Synthetic Spinal Discs from a Penn Research Team Might Be the Solution to Chronic Back Pain
Spinal discs, the concentric circles of collagen fiber found between each vertebra of the spine, can be the source of immense back pain when ruptured. Especially for truck and bus drivers, veterans, and cigarette smokers, there is an increased risk in spinal disc rupture due to overuse or deterioration over time. But these patients aren’t alone. In fact, spinal discs erode over time for almost everyone, and are one of the sources of back pain in older patients, especially when the discs erode so much that they allow direct bone-to-bone contact between two or more vertebrae.
Robert Mauck, Ph.D., who is the director of the McKay Orthopaedic Research Laboratory here at Penn and a member of the Bioengineering Graduate Group Faculty, led a research team in creating artificial spinal discs, with an outer layer made from biodegradable polymer and an inner layer made with a sugar-like gel. Their findings appear in Science Translational Medicine. These synthetic discs are also seeded with stem cells that produce collagen over time, meant to replace the polymer as it degrades in vivo over time. Though Mauck and his time are still far from human clinical trials for the discs, they’ve shown some success in goat models so far. If successful, these biodegradable discs could lead to a solution for back pain that integrates itself into the human body over time, potentially eliminating the need of multiple invasive procedures that current solutions require. Mauck’s work was recently featured in Philly.com.
An Untethered, Light-Activated Electrode for Innovations in Neurostimulation
Neurostimulation, a process by which nervous system activity can be purposefully modulated, is a common treatment for patients with some form of paralysis or neurological disorders like Parkinson’s disease. This procedure is typically invasive, and because of the brain’s extreme sensitivity, even the slightest involuntary movement of the cables, electrodes, and other components involved can lead to further brain damage through inflammation and scarring. In an effort to solve this common problem, researchers from the B.I.O.N.I.C. Lab run by Takashi D.Y. Kozai, Ph. D., at the University of Pittsburgh replaced long cables with long wavelength light and a formerly tethered electrode with a smaller, untethered one.
The research team, which includes Pitt senior bioengineering and computer engineering student Kaylene Stocking, centered the device on the principle of the photoelectric effect – a concept first described in a publication by Einstein as the local change in electric potential for an object when hit with a photon. Their design, which includes a 7-8 micron diameter carbon fiber implant, is now patent pending, and Kozai hopes that it will lead to safer and more precise advancements in neurostimulation for patients in the future.
A New Microfluidic Chip Can Detect Cancer in a Drop of Blood
Many forms of cancer cannot be detected until the disease has progressed past the point of optimum treatment time, increasing the risk for patients who receive late diagnoses of these kinds of cancer. But what if the diagnostic process could be simplified and made more efficient so that even a single drop of blood could be enough input to detect the presence of cancer in a patient? Yong Zeng, Ph.D., and his team of researchers at the University of Kansas in Lawrence sought to answer that question.
They designed a self-assembled 3D-nanopatterned microfluidic chip to increase typical microfluidic chip sensitivity so that it can now detect lower levels of tumor-associated exosomes in patient blood plasma. This is in large part due to the nanopatterns in the structure of the chip, which promote mass transfer and increase surface area, which in turn promotes surface-particle interactions in the device. The team applied the device to their studies of ovarian cancer, one of the notoriously more difficult kinds of cancer to detect early on in patients.
A Wearable Respiration Monitor Made from Shrinky Dinks
Michelle Khine, Ph. D., a professor of biomedical engineering at the University of California, Irvine incorporates Shrinky Dinks into her research. After using them once before in a medical device involving microfluidics, her lab recently worked to incorporate them into a wearable respiration monitor – a device that would be useful for patients with asthma, cystic fibrosis, and other chronic pulmonary diseases. The device has the capability to track the rate and volume of its user’s respiration based on measurements of the strain at the locations where the device makes contact with the user’s abdomen.
Paired with Bluetooth technology, this sensor can feed live readings to a smartphone app, giving constant updates to users and doctors, as opposed to the typical pulmonary function test, which only provides information from the time at which the test takes a reading. Though Khine and her team have only tested the device on healthy patients so far, they look forward to testing with patients who have pulmonary disorders, in hopes that the device will provide more comprehensive and accessible data on their respiration.
People and Places
Ashley Kimbel, a high school senior from Grissom High School in Huntsville, Alabama, designed a lightweight prosthetic leg for local Marine, Kendall Bane, after an attack in Afghanistan led him to amputate one of his legs below the knee. Bane, who likes to keep as active as possible, said the new lighter design is more ideal for activities like hiking and mountain biking, especially as any added weight makes balance during these activities more difficult. Kimbel used a CAD-modeling software produced by Siemens called Solid Edge, which the company hopes to continue improving in accessibility so that more students can start projects like Kimbel’s.
We would also like to congratulate Eva Dyer, Ph.D., and Chethan Pandarinath, Ph.D., both of whom are faculty members at the Walter H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, on receiving research fellowships from the Alfred P. Sloan Foundation. Dr. Dyer, who formerly worked with Penn bioengineering faculty member Dr. Konrad Kording while he was at Northwestern University, leads research in the field of using data analysis methods to quantify neuroanatomy. Dr. Pandarinth leads the Emory and Georgia Tech Systems Neural Engineering Lab, where he works with a team of researchers to use properties of artificial intelligence and machine learning to better understand large neural networks in the brain.
Louisiana Tech Sends First All-Female Team to RockOn
A team of faculty and students from Louisiana Tech University will participate in RockOn, a NASA-sponsored workshop on rocketry and engineering. Mechanical Engineering Lecturer Krystal Corbett, Ph.D., and Assistant Professor of bioengineering Mary Caldorera-Moore, Ph.D., will work together to lead the university’s first team of three all-female students at the event. At the program, they will have the chance to work on projects involving components of spacecraft systems, increasing students’ experience in hands-on activities and real-world engineering.
Refining Autism Treatments Using Big Data
Though treatments like therapy and medication exist for patients with autism, one of the biggest challenges that those caring for these patients face is in measuring their effects over time. Many of the markers of progress are qualitative, and based on a given professional’s opinion on a case-by-case basis. But now, a team of researchers from Rensselaer Polytechnic Institute (RPI) hopes to change that with the use of big data.
Juergen Hahn, Ph. D., and his lab recently published a paper in Frontiers in Cellular Neuroscience discussing their findings in connecting metabolic changes with behavioral improvements in autistic patients. Their analysis looks for multiple chemical and medical markers simultaneously in data from three distinct clinical trials involving metabolic treatment for patients. Being able to quantitatively describe the effects of current autism treatments would revolutionize clinical trials in the field, and lead to overall better patient care.
Penn Engineers Can Detect Ultra Rare Proteins in Blood Using a Cellphone Camera
One of the frontiers of medical diagnostics is the race for more sensitive blood tests. The ability to detect extremely rare proteins could make a life-saving difference for many conditions, such as the early detection of certain cancers or the diagnosis of traumatic brain injury, where the relevant biomarkers only appear in vanishingly small quantities. Commercial approaches to ultrasensitive protein detection are starting to become available, but they are based on expensive optics and fluid handlers, which make them relatively bulky and expensive and constrain their use to laboratory settings.
Knowing that having this sort of diagnostic system available as a point-of-care device would be critical for many conditions — especially traumatic brain injury — a team of engineers led by Assistant Professor in the Department of Bioengineering, David Issadore, Ph.D., at the University of Pennsylvania have developed a test that uses off-the-shelf components and can detect single proteins with results in a matter of minutes, compared to the traditional workflow, which can take days.
Treating Cerebral Palsy with Battery-Powered Exoskeletons
Cerebral palsy is one of the most common movement disorders in the United States. The disorder affects a patient’s control over even basic movements like walking, so treatments for cerebral palsy often involve the use of assistive devices in an effort to give patients better command over their muscles. Zach Lerner, Ph.D., is an Assistant Professor of Mechanical Engineering and faculty in Northern Arizona University’s Center for Bioengineering Innovation whose research looks to improve these kinds of assistive devices through the use of battery-powered exoskeletons.
Lerner and his lab recently received three grants, one each from the National Institute of Health (NIH), the National Science Foundation (NSF), and the Arabidopsis Biological Resource Center, to continue their research in developing these exoskeletons. Their goal is to create devices with powered assistance at joints like the ankle or knee to help improve patient gait patterns in rehabilitating the neuromuscular systems associated with walking. The team hopes that their work under these new grants will help further advance treatment for children with cerebral palsy, and improve overall patient care.
People & Places
David Aguilar, a 19-year-old bioengineering student at Universitat Internacional de Catalunya made headlines recently for a robotic prosthetic arm that he built for himself using Lego pieces. Due to a rare genetic condition, Aguilar was born without a right forearm, a disability that inspired him to play with the idea of creating his own prosthetic arm from age nine. His design includes a working elbow joint and grabber that functions like a hand. In the future, Aguilar hopes to continue improving his own prosthetic designs, and to help create similar versions of affordable devices for other patients who need them.
This week, we would like to congratulate two recipients of the National Science Foundation’s Career Awards, given to junior faculty that exemplify the role of teacher-scholars in their research. The first recipient we’d like to acknowledge is the University of Arkansas’ Kyle Quinn, Ph.D., who received the award for his work in developing new image analysis methods and models using the fluorescence of two metabolic cofactors. Dr. Quinn completed his Ph.D. here at Penn in Dr. Beth Winkelstein’s lab, and received the Solomon R. Pollack Award for Excellence in Graduate Bioengineering Dissertation Research for his work.
The second recipient of the award we wish to congratulate is Reuben Kraft, Ph.D., who is an Assistant Professor in Mechanical and Biomedical Engineering at Penn State. Dr. Kraft’s research centers around developing computational models of the brain through linking neuroimaging and biomechanical assessments. Dr. Kraft also collaborates with Kacy Cullen, Ph.D., who is a secondary faculty member in Penn’s bioengineering department and a member of the BE Graduate Group faculty.
Finally, we’d like to congratulate Dawn Elliott, Ph.D., on being awarded the Orthopaedic Research Society’s Adele L. Boskey, PhD Award, awarded annually to a member of the Society with a commitment to both mentorship and innovative research. Dr. Elliott’s spent 12 years here at Penn as a member of the orthopaedic surgery and bioengineering faculty before joining the University of Delaware in 2011 to become the founding director of the bioengineering department there. Her research focuses primarily on the biomechanics of fibrous tissue in tendons and the spine.
Detecting Infectious Diseases with Paper-Based Devices
Despite great advancements in diagnostics technology over the past few decades, patient accessibility to these technologies remains one of the biggest challenges of the field today. Particularly in low-resource areas, even simple processes can end up taking weeks or months to return results from tests that are normally completed in days. But what if these tests could be simplified to smaller, at-home tests based on properties of microfluidics – something like a pregnancy test but for infectious diseases like HIV?
Jacqueline Linnes, Ph.D., and her team of researchers at Purdue University are working towards finding a way to do just that by creating paper-based devices that use microfluidics to help carry out the necessary diagnostic tests. Specifically, her lab designed such a paper-based system that can detect HIV nucleic acids within 90 minutes of receiving a drop of patient blood. The success of this design shows promise for producing devices for diseases whose diagnostics process involve similar pathways of pathogen detection, opening the door to more applications of at-home tests based in the properties of paper microfluidics.
Here at Penn, undergraduate bioengineering students enrolled in the two-semester laboratory course Bioengineering Modeling, Analysis, and Design (BE 309 & BE 310) have the chance to create their own models of paper microfluidics delivery systems based on given time constraints in a multi-step process. Though the students’ challenge only involves water as a substrate, Linnes’ research demonstrates the later implications of studying fluid flow through a medium as cheap and accessible as paper.
Watch the video below demonstrating Dr. Linnes’ device:
Funding for Cancer Research in Tumor Mimicry and Imaging
Two of the deadliest forms of cancer today are breast cancer and pancreatic cancer, with the latter having a five-year survival rate of only about 8%. Because cancer treatments are often adjusted according to a unique patient-to-patient basis, learning how to improve predictions of tumor behavior could help determine proper therapies sooner.
Chien-Chi Lin, Ph.D., an associate professor of biomedical engineering at Indiana University – Purdue University Indianapolis, recently received a grant from the National Institute of Health to advance his research in pancreatic cancer treatment. His project under the grant involves the development of bio-inspired, responsive, and viscoelastic (BRAVE) cell-laden hydrogels to help understand cell interactions in pancreatic ductal adenocarcinoma, which is the most common form of malignancy in the pancreas. These hydrogels mimic tumor tissue, as well as model tumor development over time, helping to eventually find better ways of treating pancreatic cancer.
Penn’s Women in Computer Science (WiCS) Hosts FemmeHacks
Penn President Amy Gutmann and Penn Engineering Dean Vijay Kumar stopped by FemmeHacks at the Pennovation Center Feb. 9. The annual event is a beginner-friendly collegiate hackathon for women-identifying people with an interest in computer programming, and featured a day of all-levels workshops Feb. 8. The event is sponsored by Penn’s Women in Computer Science student organization.
Though the event is not specifically tailored towards applications in bioengineering, skills relating to coding and software development are increasingly important for those interested in pursuing a career in medical device design. In fact, in the evaluation of new medical devices, the FDA often focuses more on software over hardware, as the former is associated with more security liabilities, due to its relative novelty.
Case Western Reserve University and Cleveland Clinic announced the launch of an alliance last year with the goal of creating better synergy across the two renowned institutions, hoping to provide more opportunities for students with interest in medicine at all levels, from high school to postdoctoral education. Though researchers from both institutions frequently partner on projects, this new alliance will create a more structured platform for future collaborations.
We would like to commend Steven George, M.D./Ph.D., on his new position as the chair of the Department of Biomedical Engineering at the University of California at Davis. His research involves the development of “organ-on-a-chip” technologies using stem cells and microfluidics to mimic human organ functions of vascularized cardiac, tumor, and pancreatic tissues.
Finally, we want to congratulate Paul Yock, M.D., on his being chosen to receive the National Academy of Engineering’s 2019 Fritz J. and Dolores H. Russ Prize. The prize honors two of Dr. Yock’s inventions from his research in interventional cardiology, one of which is Rapid Exchange, which is a kind of stenting and balloon angioplasty system. Dr. Yock is the Martha Meier Weiland Professor in the School of Medicine and Professor of Bioengineering.
Drugs are commonly injected directly into an injury site to speed healing. For chronic pain, clinicians can inject drugs to reduce inflammation in painful joints, or can inject nerve blockers to block the nerve signals that cause pain. In a recent study, a group from UCLA developed a technique to deform a material surrounding nerve fibers to trigger a response in the fibers that would relieve pain. The combination of mechanics and treatment – i.e., ‘mechanoceuticals’ – is a clever way to trick fibers and reverse painful symptoms. Done without any injections and simply controlling magnetic fields outside the body, this approach can be reused as necessary.
The design of this mechanoceutical was completed by Dino Di Carlo, PhD, Professor of Bioengineering, and his team at UCLA’s Sameuli School of Engineering. By encasing tiny, magnetic nanoparticles within a biocompatible hydrogel, the group used magnetic force to stimulate nerve fibers and cause a corresponding decrease in pain signals. This promising development opens up a new approach to pain management, one which can be created with different biomaterials to suit different conditions, and delivered “on demand” without worrying about injections or, for that matter, any prescription drugs.
Understanding the Adolescent Brain
It’s no surprise that adults and adolescents often struggle to understand one another, but the work of neurologists and other researchers provides a possible physical reason for why that might be. Magnetic resonance elastrography (MRE) is a tool used in biomedical imaging to estimate the mechanical properties, or stiffness, of tissue throughout the body. Unexpectedly, a recent study suggests that brain stiffness correlates with cognitive ability, suggesting MRE may provide insight into patients’ behavior, psychology, and psychiatric state.
A new paper in Developmental Cognitive Neuroscience published the results of a study using MRE to track the relative “stiffness” vs. “softness” of adult and adolescent brains. The University of Delaware team, led by Biomedical Engineering Assistant Professor Curtis Johnson, PhD, and his doctoral student Grace McIlvain, sampled 40 living subjects (aged 12-14) and compared the properties to healthy adult brains.
The study found that children and adolescent brains are softer than those of adults, correlating to the overall malleability of childhood development. The team hopes to continue their studies with younger and older children, looking to demonstrate exactly when and how the change from softness to stiffness takes place, and how these properties correspond to individual qualities such as risk-taking or the onset of puberty. Eventually, establishing a larger database of measurements in the pediatric brain will help further studies into neurological and cognitive disorders in children, helping to understand conditions such as multiple sclerosis, autism, and cerebral palsy.
Can Nanoparticles Replace Stents?
Researchers and clinicians have made amazing advances in heart surgery. Stents, in particular, have become quite sophisticated: they are used to both prop open clogged arteries as well as deliver blood-thinning medication slowly over days to weeks in the area of the stent. However, the risk of blood clotting increases with stents and the blood vessels can constrict over time after the stent is placed in the vessel.
A recent NIH grant will support the design of a stent-free solution to unclog blood vessels. Led by Shaoqin Gong, PhD, Vilas Distinguished Professor of Biomedical Engineering at UW-Madison, the team used nanoparticles (or nanoclusters) to directly target the affected blood vessels and prevent regrowth of the cells post-surgery, eliminating the need for a stent to keep the pathways open. These nanoclusters are injected through an intravenous line, further reducing the risks introduced by the presence of the stent. As heart disease affects millions of people worldwide, this new material has far-reaching consequences. Their study is published in the September edition of Biomaterials.
NIST Grant Supports
The National Institute of Standards and Technology (NIST) awarded a $30 million grant to Johns Hopkins University, Binghamton University, and Morgan State University as part of their Professional Research Experience Program (PREP). Over five years, this award will support the collaboration of academics from all levels (faculty, postdoc, graduate, and undergraduate) across the three universities, enabling them to conduct research and attend NIST conferences.
The principal investigator for Binghamton U. is Professor and Chair of the Biomedical Engineering Department, Kaiming Ye, PhD. Dr. Ye is also the Director of the Center of Biomanufacturing for Regenerative Medicine (CBRM), which will participate in this collaborative new enterprise. Dr. Ye hopes that this grant will create opportunities for academics and researchers to network with each other as well as to more precisely define the standards for the fields of regenerative medicine and biomaterial manufacturing.
The gift honors the late A. James Clark, former CEO of Clark Enterprises and Clark Construction Group LLC, one of the country’s largest privately-held general building contractors. It is designed to prepare future engineering and business leaders, with an emphasis on low income families and first-generation college students. Clark never forgot that his business successes began with an engineering scholarship. This has guided the Clark family’s longstanding investments in engineering education and reflects its commitment to ensure college remains accessible and affordable to high-potential students with financial need.
We are proud to say that three incoming Clark Scholars from the Freshman Class of 2022 will be part of the Bioengineering Department here at Penn.
And finally, our congratulations to the new Dean of the School of Engineering at the University of Mississippi: David A. Puleo, PhD. Dr. Puleo earned his bachelor’s degree and doctorate in Biomedical Engineering from Rensselaer Polytechnic Institute. Most recently he served as Professor of Biomedical Engineering and Associate Dean for Research and Graduate Studies at the University of Kentucky’s College of Engineering. Building on his research in regenerative biomaterials, he also founded Regenera Materials, LLC in 2014. Over the course of his career so far, Dr. Puleo received multiple teaching awards and oversaw much departmental growth within his previous institution, and looks poised to do the same for “Ole Miss.”
There are two types of fat in the human body: brown and white. Brown fat, the “good” fat, is rich in mitochondria, which gives it its brown appearance. Whereas white fat stores calories and acts as an insulator, mitochondria-rich brown fat burns energy to produce heat throughout the body and maintains body temperature. White fat, conversely, uses its stored energy to insulate the body and keep its temperature level. While all fat serves a purpose in the body, an excess of white fat cells causes obesity, a condition affecting one in three adults in the U.S. and the root cause of many potential health problems. Finding ways to convert white fat to brown opens a possibility of treating this problem naturally.
A new study in Scientific Reports proposes a clever way to convert fat types. Professor of Biomedical Engineering Samuel Sia, PhD, of the Columbia University School of Engineering and Applied Science, led a team which developed a method of converting white fat into brown using a tissue-grafting technique. After extracting and converting the fat, it can then be transplanted back into the patient. White fat is hard-wired to convert to brown under certain conditions, such as exposure to cold temperatures, so the trick for Dr. Sia’s team was finding a way to make the conversion last for long periods. The studies conducted with mice suggested that using these methods, newly-converted fat stayed brown for a period of two months.
Dr. Sia’s team will proceed to conduct further tests, especially on the subjects’ metabolism and overall weight after undergoing the procedure, and they hope that eventual clinical trials will result in new methods to treat or even prevent obesity in humans.
Cremins Lab Student Appointed Blavatnik Fellow
The Perelman School of Medicine named Linda Zhou, a student in BE’s Cremins Laboratory, a Blavatnik Fellow for the 2018-2019 academic year. The selection process for this award is highly competitive, and Linda’s selection speaks to the excellent quality of her scholarship and academic performance. The fellows will be honored in a special ceremony at the Museum of Natural History in New York City.
Linda received her B.S. in Biophysics and Biochemistry from Yale University and is currently pursuing her M.D./Ph.D. in the Genomics and Computational Biology Program at Penn. “I am honored to be named a Blavatnik Fellow and am extremely excited to continue my graduate studies investigating neurological disorders and the 3D genome,” she said. “This support will be integral to achieving my long term goal of driving scientific discovery that will help treat human disease.”
Linda’s research is overseen by Penn Bioengineering Assistant Professor Jennifer Phillips-Cremins, PhD. “Linda is an outstanding graduate student,” said Dr. Cremins. “It is a true delight to work with her. She is hard working, intelligent, kind, and has extraordinary leadership ability. Her unrelenting search for ground-state truth makes her a shining star.”
The Blavatnik Family Fellowship in Biomedical Research is a new award announced by the Perelman School of Medicine in May of this year. This generous gift from the Blavatnik Family Foundation awards $2 million to six recipients in the Biomedical Graduate Studies Program at Penn for each of the next four years.
Growing Lungs in a Lab
As the demand for lung transplants continues to rise, so does the need for safe and effective transplanted lungs. Bioengineered lungs grown or created in labs are one way of meeting this demand. The problem – as is ever the case with transplants – is the high rate of rejection. The results of success are always better when cells from the patient herself (or autologous cells) are used in the transplanted organ.
Recently Joan Nichols, PhD, Professor of Internal Medicine, and Microbiology and Immunology, at the University of Texas Medical Branch at Galveston, successfully bioengineered the first human lung. Her latest study published in Science Translational Medicine describes the next milestone for Dr. Nichols’ lab: successfully transplanting a bioengineered lung into a pig.
These advances are possible due to Dr. Nichols’ work with autologous cells, continuing the trend of “on demand” medicine (i.e. medicine tailor for a specific patient) which we track on this blog. Dr. Nichols’ particular method is to build the structure of a lung (using the harvested organs of dead pigs in this case), de-cellularize the tissue, and then repopulate it with autologous cells from the intended recipient. This way, the host body recognizes the cells as friendly and the likelihood of acceptance increases. While further study is needed before clinical trials can begin, Dr. Nichols and her team see the results as extremely promising and believe that we are on the way to bioengineered human lungs.
Nanoparticles Combat Dental Plaque
Combine a diet high in sugar with poor oral hygiene habits and dental cavities likely result. The sugar triggers the formation of an acidic biofilm (plaque) on the teeth, eroding the surface. Early childhood dental cavities affect one in every four children in the United States and hundreds of millions more globally. It’s a particularly severe problem in underprivileged populations.
The flu virus is notoriously contagious, but there may be a way to stop it before it starts. In order for the influenza virus to successfully transport itself into the cells of a human host, it needs a certain protein called hemagglutinin which mediates its entry. By interfering with this vital ingredient, researchers can effectively kill the virus.
A new study in the Proceedings of the National Academy of Sciences discusses a method of disrupting the process by which this protein causes the virus to infect its host cells. This discovery could lead to more effective flu vaccines that target the flu virus at its root, rather than current ones which have to keep up with the ongoing changes and mutations of the virus itself. Indeed, the need for different vaccines to address various “strains” of the flu is moot if a vaccine can stop the virus from infecting people in the first place.
This breakthrough results from grants provided by the NSF, the Welch Foundation, and the NIH to Rice University and Baylor College of Medicine. Lead researchers José Onuchic, PhD, Harry C. and Olga K. Wiess Chair of Physics and Professor of Chemistry and BioSciences at Rice University; Jianpeng Ma, PhD, Professor of Bioengineering at Rice University and Lodwick T. Bolin Professor of Biochemistry at Baylor College of Medicine; and Qinghua Wang, PhD, Assistant Professor of Biochemistry at Baylor College of Medicine. Their team will continue to study the important role proteins play in how the flu virus operates.
People and Places
This week, we congratulate a few new leadership appointments in bioengineering. First, the Georgia Institute of Technology appointed Penn BE alumnus Andréas García, PhD, the new Executive Director of the Parker H. Petit Institute for Bioengineering and Bioscience. In addition to his new role, Dr. García is also the George W. Woodruff School of Mechanical Engineering Regents Professor. He conducts research in biomolecular, cellular, and tissue engineering and collaborates with a number of research centers across Georgia Tech. Dr. García graduated with both his M.S.E. and Ph.D. from the University of Pennsylvania’s Department of Bioengineering.
Secondly, the University of Minnesota Institute for Engineering in Medicine (IEM) named the Distinguished McKnight University Professor John Bischof, PhD, their new director. This follows Dr. Bischof’s recent position as interim director for the IEM. Dr. Bischof earned his Ph.D. in Mechanical Engineering at the University of California at Berkeley, and is currently a faculty member in both the Mechanical Engineering and Biomedical Engineering Departments at the University of Minnesota. Dr. Bischof holds the Carl and Janet Kuhrmeyer Chair in Mechanical Engineering.
At an earlier, but no less impressive, point in his academic career, Tanishq Abraham became the youngest person to graduate with a degree in biomedical engineering. The fifteen year old recently graduated summa cum laude from the University of California, Davis. As part of his graduating research, Abraham – a first-generation Indian-American – designed a device to measure the heart rates of burn victims. Abraham has already been accepted by U.C. Davis for his Ph.D. and plans to continue on to his M.D.
Finally, the work continues to create affordable and well-fitted prosthetics, especially for remote, rural, and underfunded areas both in the U.S. and abroad. Unfortunately, recent studies published by the Centre for Biomedical Engineering at the India Institute of Technology Delhi (IIT) demonstrate the uphill nature of this battle; stating that India alone contains over half a million upper limb amputees. To address this explosive population, researchers and entrepreneurs are using new bioengineering technologies such as digital manufacturing, 3D scanning and printing, and more. The best innovations are those that save time, resources, and money, without sacrificing quality in the prosthetic or patient comfort. Penn Engineering’s Global Biomedical Service (GBS) program similarly responds to this need, as each year students follow an academically rigorous course with a two-week immersive trip to China, where they learn how to create and fit prosthetic limbs for local children in conjunction with Hong Kong Polytechnic University.