Week in BioE (July 12, 2019)

by Sophie Burkholder

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.

Read more on Weinstein’s research in a recent New York Times profile piece.

Penn Engineers Demonstrate Superstrong, Reversible Adhesive that Works like Snail Slime

A snail’s epiphragm. (Photo: Beocheck)

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.

This study is a collaboration between Penn Engineering, Lehigh University’s Department of Bioengineering, and the Korea Institute of Science and Technology.

Read the full story on Penn Engineering’s Medium blog. 

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.

People and Places

Daeyeon Lee, professor in the Department of Chemical and Biomolecular Engineering and member of the Bioengineering Graduate Group Faculty here at Penn, has been selected by the U.S. Chapter of the Korean Institute of Chemical Engineers (KIChE) as the recipient of the 2019 James M. Lee Memorial Award.

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.”

Read the full story on Penn Engineering’s Medium blog.

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.

Finally, we would like to congratulate Andre Churchwell, M.D., on being named Vanderbilt University’s Chief Diversity Officer and Interim Vice Chancellor for Equity, Diversity, and Inclusion. Churchwell is also a professor of medicine, biomedical engineering, and radiology and radiological sciences at Vanderbilt, with a long career focused in cardiology.

Penn Engineers’ ‘LADL’ Uses Light to Serve Up On-demand Genome Folding

Every cell in your body has a copy of your genome, tightly coiled and packed into its nucleus. Since every copy is effectively identical, the difference between cell types and their biological functions comes down to which, how and when the individual genes in the genome are expressed, or translated into proteins.

Scientists are increasingly understanding the role that genome folding plays in this process. The way in which that linear sequence of genes are packed into the nucleus determines which genes come into physical contact with each other, which in turn influences gene expression.

LADL combines CRISPR/Cas9 and optogenetics to bring two distant points in a linear gene sequence into physical contact, forming a folding pattern known as a “loop.” Looping interactions influence gene expression, so the researchers envision LADL as being a powerful tool for studying these dynamics.

Jennifer Phillips-Cremins, assistant professor in Penn Engineering’s Department of Bioengineering, is a pioneer in this field, known as “3-D Epigenetics.” She and her colleagues have now demonstrated a new technique for quickly creating specific folding patterns on demand, using light as a trigger.

The technique, known as LADL or light-activated dynamic looping, combines aspects of two other powerful biotechnological tools: CRISPR/Cas9 and optogenetics. By using the former to target the ends of a specific genome fold, or loop, and then using the latter to snap the ends together like a magnet, the researchers can temporarily create loops between exact genomic segments in a matter of hours.

The ability to make these genome folds, and undo them, on such a short timeframe makes LADL a promising tool for studying 3D-epigenetic mechanisms in more detail. With previous research from the Phillips-Cremins lab implicating these mechanisms in a variety of neurodevelopmental diseases, they hope LADL will eventually play a role in future studies, or even treatments.

Jennifer Phillips-Cremins, Ji Hun Kim and Mayuri Rege

Alongside Phillips-Cremins, lab members Ji Hun Kim and Mayuri Rege led the study, and Jacqueline Valeri, Aryeh Metzger, Katelyn R. Titus, Thomas G. Gilgenast, Wanfeng Gong and Jonathan A. Beagan contributed to it. They collaborated with associate professor of Bioengineering Arjun Raj and Margaret C. Dunagin, a member of his lab.

The study was published in the journal Nature Methods.

“In recent years,” Phillips-Cremins says, “scientists in our fields have overcome technical and experimental challenges in order to create ultra-high resolution maps of how the DNA folds into intricate 3D patterns within the nucleus. Although we are now capable of visualizing the topological structures, such as loops, there is a critical gap in knowledge in how genome structure configurations contribute to genome function.”

In order to conduct experiments on these relationships, researchers studying these 3D patterns were in need of tools that could manipulate specific loops on command. Beyond the intrinsic physical challenges — putting two distant parts of the linear genome in physical contact is quite literally like threading a needle with a thread that is only a few atoms thick — such a technique would need to be rapid, reversible and work on the target regions with a minimum of disturbance to neighboring sequences.

The advent of CRISPR/Cas9 solved the targeting problem. A modification of the gene editing tool allowed researchers to home in on the desired sequences of DNA on either end of the loop they wanted to form. If those sequences could be engineered to seek one another out and snap together under the other necessary conditions, the loop could be formed on demand.

Cremins Lab members then sought out biological mechanisms that could bind the ends of the loops together, and found an ideal one in the toolkit of optogenetics. The proteins CIB1 and CRY2, found in Arabidopsis, a flowering plant that’s a common model organism for geneticists, are known to bind together when exposed to blue light.

“Once we turn the light on, these mechanisms begin working in a matter of milliseconds and make loops within four hours,” says Rege. “And when we turn the light off, the proteins disassociate, meaning that we expect the loop to fall apart.”

“There are tens of thousands of DNA loops formed in a cell,” Kim says. “Some are formed slowly, but many are fast, occurring within the span of a second. If we want to study those faster looping mechanisms, we need tools that can act on a comparable time scales.”

As shown in a 2013 Nature Methods paper by fellow Penn bioengineer Lukasz Bugaj, the optical response of the CRY2 protein is a key component of LADL. When the blue light is turned on, CRY2 proteins in cell immediately find one another and bind together into clumps large enough to be seen under magnification. When the light is turned off, the clumps begin to dissolve away.”

Fast acting folding mechanisms also have an advantage in that they lead to fewer perturbations of the surrounding genome, reducing the potential for unintended effects that would add noise to an experiment’s results.

The researchers tested LADL’s ability to create the desired loops using their high-definition 3D genome mapping techniques. With the help of Arjun Raj, an expert in measuring the activity of transcriptional RNA sequences, they also were able to demonstrate that the newly created loops were impacting gene expression.

The promise of the field of 3D-epigenetics is in investigating the relationships between these long-range loops and mechanisms that determine the timing and quantity of the proteins they code for. Being able to engineer those loops means researchers will be able to mimic those mechanisms in experimental conditions, making LADL a critical tool for studying the role of genome folding on a variety of diseases and disorders.

“It is critical to understand the genome structure-function relationship on short timescales because the spatiotemporal regulation of gene expression is essential to faithful human development and because the mis-expression of genes often goes wrong in human disease,” Phillips-Cremins says. “The engineering of genome topology with light opens up new possibilities to understanding the cause-and-effect of this relationship. Moreover we anticipate that, over the long term, the use of light will allow us to target specific human tissues and even to control looping in specific neuron subtypes in the brain.”

The research was supported by the New York Stem Cell Foundation; Alfred P. Sloan Foundation; the National Institutes of Health through its Director’s New Innovator Award from the National Institute of Mental Health, grant no. 1DP2MH11024701, and a 4D Nucleome Common Fund, grant no. 1U01HL1299980; and the National Science Foundation through a joint NSF-National Institute of General Medical Sciences grant to support research at the interface of the biological and mathematical sciences, grant no. 1562665, and a Graduate Research Fellowship, grant no. DGE-1321851.

Originally published on the Penn Engineering Medium blog.

Week in BioE (June 28, 2019)

by Sophie Burkholder

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.

Read the rest of this story on Penn Today.

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.

 

Week in BioE (June 14, 2019)

by Sophie Burkholder

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

Though reduced contractions in certain regions of the heart can be an indicator of a certain condition, there is currently no way to directly measure contractile activity. This is why Cristian Linte, Ph.D., an Associate Professor of Biomedical Engineering in the Kate Gleason College of Engineering at the Rochester Institute of Technology (RIT), hopes to create a map of the heart that can quantify contraction power. In collaboration with Niels Otani, Ph.D., an Associate Professor in the School of Mathematics at RIT, Linte plans to use an $850,000 grant from the National Science Foundation to achieve a more comprehensive understanding of the heart through both medical imaging and mechanical modeling. The group hopes that their approach will lead to not only a better way to diagnose certain heart conditions and diseases, but also open up understanding of active contraction, passive motion, and the stresses within the heart walls that underlie each.

Celebrity Cat Lil Bub Helps Penn and German Researchers Draw Public Attention to Genetics

Lil Bub’s unique appearance has garnered millions of online fans, and now, an avenue for researchers to talk about genetics. (Photo Courtesy of Mike Bridavsky)

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.

Orsolya “Uschi” Symmons, a postdoctoral researcher at Penn in Associate Professor of Bioengineering Arjun Raj’s lab, led the research team along with Darío Lupiáñez at the Max-Delbrück Center for Molecular Medicine in Berlin, and Daniel Ibrahim at the Max Planck Institute for Molecular Geneticsin Berlin. Lil Bub’s owner, Mike Bridavsky, also contributed to the project.

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.

To read more of this story, visit Penn Engineering’s Medium Blog.

People and Places

The Alfred P. Sloan Foundation awarded a six-year grant to Barnard College and Columbia University’s School of Engineering and Applied Science to support graduate education for women in engineering. The funding will go towards a new five-year program that enables Barnard students to attain both a B.A. and M.S. in one year after their traditional four years of undergraduate education. The program will offer M.S. degrees in chemical engineering, biomedical engineering, and industrial engineering and operations research, and is one of the first of its kind for women’s colleges.

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.

Dan Huh’s Organs-on-Chips and Organoids: Best of Both Worlds

By Lauren Salig

Dan Huh, the Wilf Family Term Assistant Professor in the Department of Bioengineering, focuses his research on creating organs-on-chips: specially manufactured micro-devices with human cells that mimic the natural cellular processes of organs. Huh’s lab has engineered chips that approximate the functioning of placentas and lung disease, some of which were launched into space in May. Most recently, Huh published a review of organ-on-a-chip technology in the journal Science with graduate students Sunghee Estelle Park and Andrei Georgescu.

The June 2019 issue of Science is a special issue centered around the science of growing human organ models in the laboratory. Such in vitro organs are known as organoids; they grow and develop much like organs do in the body, as opposed to Huh’s organs-on-chips, in which cells from the relevant organs are grown within a fabricated device that imitates some of the organ’s functions and natural environment.

In a video accompanying the review article, Huh explains how organoid and organ-on-a-chip technologies differ and the advantages that accompany each approach:

Unlike Organ-on-a-Chip, which are heavily engineered man-made systems, organoids allow us to mimic the complex of the human body in a more natural way. So organoids represent a more realistic model, but they have problems because they develop in a highly variable fashion and it’s not very easy to control their environment. So we think that Organ-on-a-Chip Technology is a promising solution to many of these problems.

Read Huh, Park, and Georgescu’s review article at Science.

Originally posted on the Penn Engineering Medium blog.

BE Freshmen Present Their Final Projects

On May 8, 2019, first year Bioengineering students at the University of Pennsylvania gathered together for a marathon two-hour session in which no fewer than twenty-one groups presented the results of their final projects. These projects were the culmination of two semesters’ work in the courses BE 100 and 101, the department’s year-long introduction to Bioengineering. The topics were as diverse and creative as the students, ranging from medical devices and pediatric monitors to plant-care and diagnostic apps. They covered a variety of issues and needs, including tools to help the blind; lockboxes that incorporate breathalyzers (to stop you getting to your keys when intoxicated); mechanisms to sense epileptic seizures and monitor heart rate; and more. Each group had only four minutes to present the research, concept, and results of their project and give a brief demonstration.  In the end, the entire class voted and two clear winners emerged. In first place was Group R7 with Heart Guide, a heart-shaped ultrasonic collision device for the blind. Group R3 came in second place with Pulsar the Robot, an adorable pediatric heart rate monitor. The course’s instructor, Dr. Michael Rizk, ended by saying that all of the students should be very proud of their work and that these final projects and the skills learned in year one are the foundation on which the rest of their BE curriculum will be based.

Congratulations to all of our first years on their amazing work. Check out some photos of their impressive work below! For more information on the Penn Bioengineering Undergraduate Curriculum, visit the department website. Most BE student projects are created in the George H. Stephenson Foundation Education Laboratory and “Bio-MakerSpace”, the department’s primary teaching lab.

Week in BioE (May 31, 2019)

by Sophie Burkholder

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 is the Eduardo D. Glandt President’s Distinguished Professor with appointments in Materials Science and Engineering, Mechanical Engineering and Applied Mechanics, and Bioengineering. He is also the Director of the Center for Engineering MechanoBiology (CEMB), one of the NSF’s twelve Science and Technology Centers.

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.

Read the rest of this story on Penn Engineering’s Medium Blog.

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

TBx: Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng

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.

Week in BioE: April 19, 2019

by Sophie Burkholder

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.

Dr. Danielle Bassett, the Eduardo D. Glandt Faculty Fellow and associate professor of bioengineering and electrical and systems engineering in the School of Engineering and Applied Science, has two heroes: “Ingrid Daubechies for her work on wavelets, or “little waves,” which are beautiful mathematical objects that can be used to extract hidden structure in complex data. “Also, Maryam Mirzakhani for inspiring a child to believe that mathematics is simply painting. Would that we all could see the world just that bit differently.”

Read the full story on Penn Today.

Joel Boerckel, Ph.D, Assistant Professor of Orthopaedic Surgery and Bioengineering

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.

Week in BioE: April 5, 2019

by Sophie Burkholder

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 

Two groups of researchers from the University of California, Berkeley and the Keck Graduate Institute of the Claremont Colleges recently collaborated to design what they call a “CRISPR-Chip” –  a combination of the CRISPR-Cas9 System with a graphene transistor to sequence DNA for the purpose of genetic mutation diagnosis. While companies like 23andMe made genetic testing and analysis more common and accessible for the general public in recent years, the CRISPR-Chip looks to streamline the technology even more.

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

Depression is one of the most common mental health disorders in the United States, with nearly 3 million cases every year. For most patients suffering from depression, treatment involves prolonged psychotherapy, antidepressant medication, or even electroconvulsive therapy in extreme cases. Now, scientists at the University of North Carolina School of Medicine study the use of transcranial alternating current stimulation (tACS) to 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

Engineers at the University of Utah are part of team that recently received a $9.7 million grant from the National Institute of Health (NIH) to design new implantable hearing devices for deaf patients, with the hope to improve beyond the sound quality of existing devices. The work will build upon a previous project at the University of Utah called the Utah Electrode Array, a brain-computer interface originally developed by Richard Normann, Ph.D., that can send and receive neural impulses to and from the brain. This new device will differ from a typical cochlear implant because the Utah Electrode Array assembly will be attached directly to the auditory nerve instead of the cochlea, providing the patient with a much higher resolution of sound.

People & Places

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 overseer whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.

Read the rest of the story on Penn Engineering’s Medium blog.

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.

 

Week in BioE: March 29, 2019

by Sophie Burkholder

New Studies in Mechanobiology Could Open Doors for Cellular Disease Treatment

When we think of treatments at the cellular level, we most often think of biochemical applications. But what if we began to consider more biomechanical-oriented approaches in the regulation of cellular life and death? Under a grant from the National Science Foundation (NSF),Worcester Polytechnic Institute’s (WPI) Head of the Department of Biomedical Engineering Kristen Billiar, Ph.D., performs research that looks at the way mechanical stimuli can affect and trigger programmed cell death.

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.

Led by Paul Sajda, Ph.D., who received his doctoral degree from Penn, the researchers used a brain-computer interface to collect electroencephalography (EEG) signals from users immersed in virtual reality aerial navigation tasks of varying difficulty levels. In doing so, they were able to make connections between stressful situations and brain activity as transmitted through the EEG data, adding to the understanding of how the Yerkes-Dodson law actually operates in the human body and eventually demonstrating that the use of neurofeedback reduced the neural state of arousal in patients. The hope is that neurofeedback may be used in the future to help treat emotional conditions like post-traumatic stress disorder (PTSD).

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.

Read the full story on Penn Engineering’s Medium Blog. Media contact Evan Lerner.

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