We would like to congratulate Penn Bioengineering faculty members Arjun Raj, Ph.D., and Danielle Bassett, Ph.D., on their promotions from associate to full professors.
The Raj lab studies how biological processes work at the level of individual cells. Their work combines quantitative tools from genomics, imaging, biology, math, and computer science to develop models for how individual cells function, and in particular, how these individual cells can behave differently from each other. One major interest is in cancer, in which the lab is studying how individual cells can drive resistance to anti-cancer drugs. He and his lab also have a regularly updated blog discussing general topics related to scientific academia.
The Bassett lab takes an in-depth look at the use of network science and complex systems theory to study computational neuroscience in projects that involve the architecture of knowledge networks, the controllability of brain networks, and the dynamic networks in neuroscience. This fall, she will teach an elective course in network neuroscience open to graduate and undergraduate students that covers the use of network science in understanding overall brain circuitry. Bassett was recently profiled in Science Magazine.
The Drug Delivery Special Interest Group will deal with the science and technology of controlled release of active agents from delivery systems. Controlled drug release is achieved by the use of diffusion, chemical reactions, dissolutions or osmosis, used either singly or in combination. While the vast majority of such delivery devices are based on polymers, controlled release can also be achieved by the use of mechanical pumps. In a broader sense, controlled release also involves control over the site of action of the active agent, using the active agent using pro-drugs, targetable water soluble polymers or various microparticulate systems. Relevant aspects of toxicology, bioavailability, pharmacokinetics, and biocompatibility are also included.
The Society for Biomaterials is an interdisciplinary organization comprised of academic, industry, health care, and governmental professionals dedicated to promoting advancements in all aspects of biomaterial science and engineering, education, and professional standards to enhance human health and quality of life. The Society for Biomaterials was established in 1974, and is the oldest scientific organization in the field of biomaterials.
Mitchell joined the Department of Bioengineering at Penn in 2018 as Skirkanich Assistant Professor of Innovation. Previously, he was an NIH Ruth L. Kirschstein Postdoctoral Fellow with Institute Professor Robert Langer at the Koch Institute for Integrative Cancer Research at MIT. His research interests include biomaterials, drug delivery, and cellular and molecular bioengineering for applications in cancer research, immunotherapy, and gene therapy. Since joining Penn in 2018, Mitchell has received the NIH Director’s New Innovator Award, the Burroughs Wellcome Fund Career Award at the Scientific Interface, a Rising Star Award from the Biomedical Engineering Society, and the T. Nagai Award from the Controlled Release Society.
Mitchell’s new role as the Chair of the SFB’s Drug Delivery Special Interest Group will allow him to lead conversations across academia on the future of drug delivery as it relates to biomaterials. With his fellow officers, Mitchell will help spread knowledge about the field of controlled drug release by hosting research forums, helping to publish news and activities of the SFB in Biomaterials Forum, and foster connections and mentorship among members of his and other Special Interest Groups. We can’t wait to see where Mitchell’s leadership will help take the community of research on areas like toxicology, pharmacokinetics, and biocompatibility next!
DNA Microscopy Gives a Better Look at Cell and Tissue Organization
A new technique that researchers from the Broad Institute of MIT and Harvard University are calling DNA microscopy could help map cells for better understanding of genetic and molecular complexities. Joshua Weinstein, Ph.D., a postdoctoral associate at the Broad Institute, who is also an alumnus of Penn’s Physics and Biophysics department and former student in Penn Bioengineering Professor Ravi Radhakrishnan’s lab, is the first author of this paper on optics-free imaging published in Cell.
The primary goal of the study was to find a way of improving analysis of the spatial organization of cells and tissues in terms of their molecules like DNA and RNA. The DNA microscopy method that Weinstein and his team designed involves first tagging DNA, and allowing the DNA to replicate with those tags, which eventually creates a cloud of sorts that diffuses throughout the cell. The DNA tags subsequent interactions with molecules throughout the cell allowed Weinstein and his team to calculate the locations of those molecules within the cell using basic lab equipment. While the researchers on this project focused their application of DNA microscopy on tracking human cancer cells through RNA tags, this new method opens the door to future study of any condition in which the organization of cells is important.
Penn Engineers Demonstrate Superstrong, Reversible Adhesive that Works like Snail Slime
If you’ve ever pressed a picture-hanging strip onto the wall only to realize it’s slightly off-center, you know the disappointment behind adhesion as we typically experience it: it may be strong, but it’s mostly irreversible. While you can un-stick the used strip from the wall, you can’t turn its stickiness back on to adjust its placement; you have to start over with a new strip or tolerate your mistake. Beyond its relevance to interior decorating, durable, reversible adhesion could allow for reusable envelopes, gravity-defying boots, and more heavy-duty industrial applications like car assembly.
Such adhesion has eluded scientists for years but is naturally found in snail slime. A snail’s epiphragm — a slimy layer of moisture that can harden to protect its body from dryness — allows the snail to cement itself in place for long periods of time, making it the ultimate model in adhesion that can be switched on and off as needed. In a new study, Penn Engineers demonstrate a strong, reversible adhesive that uses the same mechanisms that snails do.
Low-Dose Radiation CT Scans Could Be Improved by Machine Learning
Machine learning is a type of artificial intelligence growing more and more popular for applications in bioengineering and therapeutics. Based on learning from patterns in a way similar to the way we do as humans, machine learning is the study of statistical models that can perform specific tasks without explicit instructions. Now, researchers at Rensselaer Polytechnic Institute (RPI) want to use these kinds of models in computerized tomography (CT) scanning by lowering radiation dosage and improving imaging techniques.
A recent paper published in Nature Machine Intelligence details the use of modularized neural networks in low-dose CT scans by RPI bioengineering faculty member Ge Wang, Ph.D., and his lab. Since decreasing the amount of radiation used in a scan will also decrease the quality of the final image, Wang and his team focused on a more optimized approach of image reconstruction with machine learning, so that as little data as possible would be altered or lost in the reconstruction. When tested on CT scans from Massachusetts General Hospital and compared to current image reconstruction methods for the scans, Wang and his team’s method performed just as well if not better than scans performed without the use of machine learning, giving promise to future improvements in low-dose CT scans.
A Mind-Controlled Robotic Arm That Requires No Implants
A new mind-controlled robotic arm designed by researchers at Carnegie Mellon University is the first successful noninvasive brain-computer interface (BCI) of its kind. While BCIs have been around for a while now, this new design from the lab of Bin He, Ph.D., a Trustee Professor and the Department Head of Biomedical Engineering at CMU, hopes to eliminate the brain implant that most interfaces currently use. The key to doing this isn’t in trying to replace the implants with noninvasive sensors, but in improving noisy EEG signals through machine learning, neural decoding, and neural imaging. Paired with increased user engagement and training for the new device, He and his team demonstrated that their design enhanced continuous tracking of a target on a computer screen by 500% when compared to typical noninvasive BCIs. He and his team hope that their innovation will help make BCIs more accessible to the patients that need them by reducing the cost and risk of a surgical implant while also improving interface performance.
KIChE is an organization that aims “to promote constructive and mutually beneficial interactions among Korean Chemical Engineers in the U.S. and facilitate international collaboration between engineers in U.S. and Korea.”
We would also like to congratulate Natalia Trayanova, Ph.D., of the Department of Biomedical Engineering at Johns Hopkins University on being inducted into the Women in Tech International (WITI) Hall of Fame. Beginning in 1996, the Hall of Fame recognizes significant contributions to science and technology from women. Trayanova’s research specializes in computational cardiology with a focus on virtual heart models for the study of individualized heart irregularities in patients. Her research helps to improve treatment plans for patients with cardiac problems by creating virtual simulations that help reduce uncertainty in either diagnosis or courses of therapy.
“It’s part of our ethos that technology can and should be a force for good. Our annual list of 35 innovators under 35 is a way of putting faces on that idea,” reads the 2019 award announcement. “This year’s list shows that even in our hard, cynical world, there are still lots of smart people willing to dedicate their lives to the idea that technology can make a safer, fairer world.”
De la Fuente was named in the list’s “Pioneers” category for his work researching antibiotics with a computational approach. Using algorithms, he creates artificial antibiotics to better understand how bacteria will evolve and how scientists can optimize treatments. De la Fuente, who was also recently featured in GEN’s Top 10 Under 40 list, further expands his search for medical solutions by extensively studying a variety of proteins, searching for molecules to develop into antimicrobials.
Included in the honor of being named on the 2019 Innovators List is an invitation for de la Fuente to speak at the EmTech MIT conference in September, an event that reflects on the potential impacts of the year’s biggest developments.
The NAE describes the Frontiers of Engineering program as one that “brings together outstanding early-career engineers from industry, academia, and government to discuss pioneering technical work and leading-edge research in various engineering fields and industry sectors. The goal is to facilitate interactions and exchange of techniques and approaches across fields and facilitate networking among the next generation of engineering leaders.”
Bassett and Tsourkas fit the grant’s description, as their proposed research requires them to combine their different areas of expertise to push the state of the art in engineering. The pair plans to engineer a new class of nanoparticles that can sense and differentially react to particular chemicals in their biochemical environment. This new class of nanoparticles could allow scientists to better study cellular processes and could eventually have important applications in medicine, potentially allowing for more personalized diagnoses and targeted treatment of disease.
To design and create this type of nanoparticle is no small task. The research demands Bassett’s background in engineering quantum-mechanical systems for use as environmental sensors, and Tsourkas’ ability to apply these properties to nanoscale “theranostic” agents, which are designed to target treatments based on a patient’s specific diagnostic test results.
By combining forces, Bassett and Tsourkas hope to introduce a new nanoparticle tool into their fields and to connect even more people in their different areas to promote future interdisciplinary work.
Innovations in Vascularization Could Lead to a New Future in Bioprinting
We may be one step closer to 3D-printing organs for transplants thanks to innovations in vascularization from researchers at Rice University and Washington University. Jordan Miller, Ph.D., a Penn Bioengineering alumnus, now an assistant professor of bioengineering at Rice, worked with his colleague Kelly Stevens, Ph.D., an assistant professor of the bioengineering department at Washington, to develop 3D-printed networks that mimicked the vascularized pathways for the transport of blood, lymph, and other fluids in the body. Their work appeared on a recent cover of Science, featuring a visual representation of the 3D-printed vessels in vasculature meant to mirror that of the human lung.
Relying heavily on open source 3D-printing, Miller and Stevens, along with collaborators from a handful of other institutions and start-ups, found ways to model dynamic vasculature systems similar to heart valves, airways systems, and bile ducts to keep 3D-printed tissue viable. The video below demonstrates the way the team successfully modeled vasculature in a small portion of the lung by designing a net-like structure around a sack of air. But Miller, a long-time supporter of open source printing and bioprinting, hopes that this is merely one step closer to what he sees as the ultimate goal of allowing for all organs to be bioprinted. Having that sort of power would reduce the complex issues that come with organ transplants, from organ availability to compatibility, and bring an end to a health issue that affects the over 100,000 people on the organ transplant waiting list.
A Combination of Protein Synthesis and Spectrometry Improve Cell Engineering
One goal of modern medicine is to create individualized therapeutics by figuring out a way to control cell function to perform specific tasks for the body without disrupting normal cell function. Balancing these two goals often proves to be one of the greatest difficulties of this endeavor in the lab, but researchers at Northwestern University found a way to combine the two functions at once in methods they’re calling cell-free protein synthesis and self-assembled monolayer desorption ionization (SAMDI) mass spectrometry. This innovation in the combination of the two methods accelerates the trial and error process that comes with engineering cells for a specific need, allowing researchers to cover a lot more ground in determining what works best in a smaller amount of time.
Leading the study are Milan Mrksich, Ph.D., a Henry Wade Rogers Professor of Biomedical Engineering at Northwestern, and Michael Jewett, Ph.D., a Charles Deering McCormick Professor of Teaching Excellence and co-director of the Center for Synthetic Biology at Northwestern. Together, they hope to continue to take advantage of the factory-like qualities of cell operations in order to use cells from any organisms to our advantage as needed. By helping to reduce the amount of time spent on trial and error, this study brings us one step closer to a world of efficient and individualized medicine.
Non-Invasive Sensory Stimulation as New Way of Treating Alzheimer’s
What if we could reduce the effects of Alzheimer’s disease with a non-invasive therapy comprised of only sensory inputs of light and sound? A recent study between Georgia Tech and MIT tries to make that possible. Alzheimer’s patients often have a larger than normal number of amyloid plaques in their brains, which is a naturally occurring protein that in excess can disrupt neurological function. The treatment — designed in part by Abigail Paulson, a graduate student in the lab of Annabelle Singer, Ph.D., assistant professor of Biomedical Engineering at Georgia Tech and Emory University — uses a combination of light and sound to induce gamma oscillations in brain waves of mice with high amounts of these amyloid plaques. Another lead author of the study is Anthony Martorell, a graduate student in the Tsai Lab at MIT, where Singer was a postdoctoral researcher.
This new approach is different from other non-invasive brain therapies for memory improvement, as tests demonstrated that it had the power to not only reach the visual cortex, but that it also had an effect on the memory centers in the hippocampus. An innovation like this could bring about a more widespread form of treatment for Alzheimer’s patients, as the lack of a need for surgery makes it far more accessible. Singer hopes to continue the project in the future by looking at how these sensory stimulations affect the brain throughout a variety of processes, and more importantly, if the therapy can be successfully applied to human patients.
NIH Grant Awarded to Marquette Biomedical Engineering Professor for Metal Artifact Reduction Techniques in CT Scans
Taly Gilat-Shmidt, Ph.D., an associate professor of biomedical engineering at Marquette University, recently received a $1.4 million grant from the National Institute of Health to improve methods for radiation treatment through metal artifact reduction techniques. When patients have some sort of metal that can’t be removed, such as an orthopaedic implant like a hip or knee replacement, it can interfere with the imaging process for CT scans and lead to inaccuracies by obscuring some tissue in the final images. These inaccuracies can lead to difficulty in devising treatment plans for patients who require radiation, as CT scans are often used to assess patients and determine which line of treatment is most appropriate. Gilat-Schmidt hopes to use the grant to implement tested algorithms to help reduce this variability in imaging that comes from metal implants.
People and Places
Activities for Community Education in Science (ACES), founded by Penn chemistry graduate students in 2014, aims to inspire interest and provide a positive outlook in STEM for kids and their families. The biannual event provides students grades 3–8 with an afternoon of demonstrations, experiments, and hands-on activities focused on physics and chemistry.
After an explosive opening demonstration, more than 70 students made their way between experiments in small groups, each participating in different experiments based on their age.
The Society of Women Engineers (SWE) is a non-profit organization serving as one of the world’s largest advocates for women in engineering and technology over the past six decades. With a mission to empower women to become the next leading engineers of the world, SWE is just one of many agents hoping to bring more diversity to the field. Our chapter of SWE at Penn focuses particularly on professional development, local educational outreach, and social activities across all general body members. In a new article from SWE Magazine, the organization collected social media responses from the public on the women engineers we should all know. With a diverse list of engineers from both the past and present, the article helps bring to light just how much even a handful of women contributed to the field of engineering already.
Chip Diagnostics is a Philadelphia-based device company founded in 2016 based on research from the lab of David Issadore, Assistant Professor of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science. The startup combines microelectronics, microfluidics, and nanomaterials with the aim to better diagnose cancer. The company is developing technologies and digital assays for minimally-invasive early cancer detection and screening that can be done using mobile devices.
There has been a long interest in diagnosing cancer using blood tests by looking for proteins, cells, or DNA molecules shed by tumors, but these tests have not worked well for many cancers since the molecules shed tend to be either nonspecific or very rare.
Issadore’s group aims to target different particles called exosomes: Tiny particles shed by cells that contain similar proteins and RNA as the parent cancer cell. The problem, explains Issadore, is that because of the small size of the exosomes, conventional methods such as microscopy and flow cytometry wouldn’t work. “As an engineering lab, we saw an opportunity to build devices on a nanoscale that could specifically sort the cancer exosomes versus the background exosomes of other cells,” he explains.
After Issadore was approached by the IP group at PCI Ventures in the early stages of their research, Chip Diagnostics has since made huge strides as a company. Now, as the awardee of the JPOD @ Philadelphia QuickFire Challenge, Chip Diagnostics will receive $30,000 in grant funding to further develop the first-in-class, ultra-high-definition exosomal-based cancer diagnostic. The award also includes one year of residency at Pennovation Works as well as access to educational programs and mentoring provided by Johnson & Johnson Family of Companies global network of experts.
Bio-inspiration Informs New Football Helmet Design from IUPUI Students
Art, design, biology, and engineering all interact with each other in a recent design for a football helmet from two students— one of media arts and the other of engineering — at the Indiana University – Purdue University Indianapolis. Directed by Lecturer in Media Arts and Science Zebulun Wood, M.S., and Associate Professor of Mechanical and Energy Engineering and Assistant Professor of Biomedical Engineering Andres Tovar, Ph.D., the students found inspiration in biological structures like a pomelo peel, nautilus shell, and woodpecker skull to create energy-absorbing helmet liners. The resulting design took these natural concussion-reducing structures and created compliant mechanism lattice-based liners the replace the foam traditionally placed in between two harder shells of a typical helmet. Their work not only exemplifies the benefits of bio-inspiration, but demonstrates the way that several different domains of study can overlap in the innovation of a new product.
Study of Mechanical Properties of Hyaluronic Acid Could Help Inform Current Debates Over Treatment Regulation for Osteoarthritis
Arthritis is an extremely common condition, especially in older patients, in which inflammation of the joints can cause high amounts of stiffness and pain. Osteoarthritis in particular is the result of the degradation of flexible tissue between the bones of a joint, which increases friction in joint motion. A common treatment of this form of arthritis is the injection of hyaluronic acid, which is meant to provide joint lubrication, and decreases this friction between bones. Recently, however, there has been a debate over hyaluronic acid’s classification by the FDA and whether it should remain based on the knowledge of the mechanical actions of the acid in treatment for osteoarthritis or if potential chemical action of the acid should be considered as well.
Because of limited ways of testing the mechanical properties of the acid, many researchers felt that there could be more to hyaluronic acid’s role in pain relief for arthritic patients. But Lawrence Bonassar, Ph.D., the Daljit S. and Elaine Sarkaria Professor in Biomedical Engineering at the Meinig School of Bioengineering of Cornell University, had another idea. With his lab, he created a custom-made tribometer to measure the coefficient of friction of a given lubricant by rubbing a piece of cartilage back and forth across a smooth glass plate. The research demonstrated that hyaluronic acid’s ability to reduce the coefficient of friction aligned with patients’ pain relief. Bonassar and his team hope that these results will demonstrate the heavy contribution of mechanical action that hyaluronic acid has in osteoarthritis treatment, and help bring an end to the debate over its FDA classification.
A New Way of Mapping the Heart Could Lead to Better Understanding of Contractile Activity
Celebrity Cat Lil Bub Helps Penn and German Researchers Draw Public Attention to Genetics
In 2015, a group of curious researchers set out to sequence the genome of a celebrity cat named Lil Bub. They were hoping to understand the genetics behind Lil Bub’s extra toes and unique skeletal structure, which contribute to her heart-warming, kitten-like appearance. However, an equally important goal of their “LilBUBome” project was to invite the general public into the world of genetics.
Because of Lil Bub’s online fame, the project garnered attention from her fans and the media, all hoping to discover the secret to Lil Bub’s charm. As early as 2015, Gizmodo’s Kiona Smith-Strickland reported on the team’s intentions to sequence Lil Bub’s genome, and, since then, many have been awaiting the results of the LilBUBome.
We would like to congratulate Jean Paul Allain, Ph.D., on being named the first head of the new Ken and Mary Alice Lindquist Department of Nuclear Engineering at Penn State. Allain, who is currently a Professor and head of graduate programs in the University of Illinois at Urbana-Champaign’s Department of Nuclear, Plasma, and Radiological Engineering, conducts research in models of particle-surface interactions. In addition to being head of the new department at Penn State, Allain will also hold a position as a Professor of Biomedical Engineering at the university.
We would also like to congratulate Andrew Douglas, Ph.D., on his appointment as the Vice Provost for Faculty Affairs at Johns Hopkins University. Douglas currently holds the position of Vice Dean for Faculty at the Whiting School of Engineering, and has joint appointments in Mechanical and Biomedical Engineering. Douglas’s research at Hopkins focuses on mechanical properties and responses of compliant biological tissue and on the nonlinear mechanics of solids, with a focus on soft tissues and organs like the heart and tongue.
De la Fuente, who started at Penn earlier this year, was recognized because he “is pioneering the computerization of biological systems for the development of transformative biotechnologies designed to solve societal grand challenges such as antibiotic resistance.”
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.