This Week in BioE (June 29, 2017)

Bioengineering Organ Systems

Two news stories this week detailed how bioengineering and biomedical engineering are transforming how human organ systems could be better manipulated for positive effects on health.

organ systemsOne of the critical organ transplant shortages  in medicine is the gap between patients needing a liver transplant (around 13,000 each year) and the those receiving a transplant (about 7,000). For many years, bioengineers tried to build liver tissue in sophisticated 2D and 3D structures. Yet we never really knew how nature ‘interpreted’ these structures. A research team at Cincinnati Children’s Hospital led by Takanori Takebe, MD, reported in Nature that mimicking the 3D shape of the liver was a critical part of making engineered organoids of liver show the same behavior as liver tissue in vivo. These findings show just how important form is for function in nature, bringing us a step closer to alleviating the pressure on organ transplants lists by providing engineering organs.

Not all organs need completely reconstructed replacements. Another critical target organ in the tissue engineering field is the pancreas, which is critical in regulating insulin release.  The nationwide increase in diabetes is only placing more emphasis on finding technologies to augment pancreatic function. Engineers at Duke report in Nature Biomedical Engineering that they could control glucose levels for over a week with a single injection of a new compound they synthesized in the lab.  Rather than many daily injections of insulin for controlling glucose levels in diabetics, this could lead to far less frequent injection.

Machine Diagnosis

We hear quite a bit about Big Data nowadays. This captures a very large field that includes methods to analyze bits of data reliably and quickly to establish patterns (i.e., machine learning) that can help us uncover very new and interesting relationships. Nearly all of this work focuses on narrow data streams, which means the data are largely linked to each other within a category. One example of a narrow data stream is the collection of different types of imaging scans (CT, MRI, PET) from the same patient, collated and compared to better establish how different areas of the brain function. Another example of a narrow data stream is the data contained in a patient’s electronic health record, where it includes facts from the patient’s visits with their physician and specialists.

One interesting thread that is emerging in Big Data is when one starts to cross narrow data streams and create ‘data fabric.’  This means that scientists and engineers are cross-correlating data that seem incompatible with each other, yet they are proving amazingly predictive.  One recent example is when we cross the analysis of speech — one of the earliest machine learning applications — with genetic screening data from patients. Remarkably, scientists at the University of Wisconsin-Madison developed an automated screening system that could analyze audio recordings and determine with 81% accuracy whether the speaker had Fragile X syndrome, a genetic disorder that can have a range of cognitive effects, indicated by genetic screening data. Creating these types of data fabrics could be very powerful in the future because it can use a relatively easy and accessible technology (speech recognition) as an early indicator for more through disease confirmation (genetic testing) and subsequent intervention.

Similarly, these data fabrics are allowing us to reduce our own variability in diagnosing diseases. Penn BE alum Anant Madabhushi developed an algorithm at Case Western Reserve University that was 100% accurate at identifying breast cancer by scanning mammograms, exceeding human performance. Technologies such as these that eliminate the possibility of human error could greatly decrease the rates of delayed or faulty diagnosis. Replacing physicians with computers ? I don’t think so. We all need the human touch, especially when it comes to finding out why we are sick. Capturing errors that humans make? I think so.

A Quick Note

Speaking of Penn alumni, Craig Simmons, Ph.D., who was a postdoctoral fellow in the lab of Penn BE secondary faculty member Peter F. Davies, has been named the interim director of the Institute of Biomaterials & Biomedical Engineering at the University of Toronto. His appointment begins next week. Congratulations to Dr. Simmons!

Ducheyne Edits New Biomaterials Text

Paul Ducheyne, Ph.D.

A Penn Bioengineering professor, Paul Ducheyne, Ph.D., is the editor-in-chief of the new second edition of Comprehensive Biomaterials II, released by Elsevier on June 1. The seven-volume collection, which Dr. Ducheyne edited along with faculty members from the University of California, Berkeley, Queensland University of Technology (Australia), University of Utah, and Johannes Gutenberg University Medical Center (Germany), collects articles written by experts in the field of biomaterials.

According to Elsevier, the articles “address the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, research and development, regulatory management, commercial aspects, and applications, including medical applications.”

In the preface to the collection, Dr. Ducheyne details how his team and Elsevier worked together to assure the continued high impact of the text by issuing it in both a print version and online via Elsevier’s Science Direct platform. He writes further, “It was the objective of the editorial team to compose the publication with chapters that would provide strategic insights for those working in diverse biomaterials applications, research and development, regulatory management, and industry.”

Bioengineering and BDM Go Together

by Joe Maggiore, Bioengineering ’19

BDM stage
Band Dance Music in performance

I’m a rising junior studying Bioengineering at Penn. I’m also the founder of a music group called Band Dance Music (BDM). The overall premise of the group is to take the same music that a DJ plays at a college party but to play it with an 11-piece live band. The idea for this group started before I got to Penn, but it was something that I was confident in pursuing despite all of the other time commitments during the school year.

Starting a band at Penn was definitely a challenge. There are already so many music groups on Penn’s campus that it’s very easy for a group that is just starting out to get drowned out by other more prominent groups. After really pushing marketing hard for auditions, it actually was pretty easy to find students who were interested in the idea behind the group. Interestingly, of the 11 members that are now in the group, nine of them are actually in the School of Engineering and Applied Science.

While bioengineering and band dance music seem like two totally disparate fields, I was actually able to bridge the gap between these areas while taking ENGR105 with Professor Rizk. At the end of this course, we are asked to create a graphical user interface (GUI) that combines the entire course’s material. This GUI is completely free form – it can be in any area of interest that you like.

Since for a while I’d been having trouble arranging music completely by ear, I thought this would be the perfect opportunity to create a GUI that would help me arrange music for the band. There is rarely free time to spare during the school year, so being able to work on a passionate project of mine while also being able to complete my course work was a win-win situation. The GUI definitely took me longer than expected to create since it involved having to process electronic music into parts that would be easier to arrange, but I eventually was able to finish the interface. It featured a tap metronome, a filtering system, and a visual music player so I could streamline the music writing process. Below is a pictures of the GUI I created.

BDM is always looking for more interesting people to join who have a passion for this unique concept for a band. If any bioengineers reading out there are interested, feel free to reach out to me – I’d love to talk more about it. Thanks for reading!

This Week in BioE (June 22, 2017)

Diversifying the Field

One of the ongoing issues in STEM (science, technology, engineering, and medicine) fields is a lack of diversity among students and faculty. Bioengineering stands out among other engineering fields because it enjoys terrific gender diversity. For example, about half of Penn Bioengineers are women, a feature of our class that goes back decades.

diversifyingHowever, diversity extends well beyond gender. For example, the National Research Mentoring Network (NRMN) has been working to increase diversity, including among students with disabilities. A consortium of people and groups providing mentors for science students, the MRMN recently highlighted the American Association for the Advancement of Science’s (AAAS) Entry Point! program, which focuses on helping students with physical disabilities. Mentoring, it turns out is a big part of helping these students succeed.

Another recent development that should help to increase diversity in the field is the awarding of a $1 million grant from the National Science Foundation’s Directorate of Engineering to the University of Wisconsin, Madison, and the College of Menominee Nation (CMN), a native American college in Wisconsin, to collaborate in engineering research and education. The new grant builds on a program begun in 2010 between the colleges to build labs and facilitate the transfer of pre-engineering students from CMN to UWM.

Brain Science Developments

Speaking of education, three recent news stories discuss how we might be able to expedite the learning process, increase intelligence, and reward ourselves when we create art. In one of the stories, a company called Kernel is investing $100 million in research at the University of Southern California to determine whether using brain implants, which have been helpful in some patients with epilepsy, can be used to increase or recover memory. If successful, this may bridge one critical treatment gap in neurology. About one out of every three people with epilepsy don’t respond to drug treatment.

In the second story, scientists at the University of Texas at Dallas were awarded a $5.8 million contract from DARPA to investigate the role of vagus nerve stimulation in accelerated learning of foreign languages. Stimulating the peripheral nervous system to activate and train areas of the brain is one more example that our nervous system is connected in ways that we do not yet understand completely. The Department of Defense hopes to use the technology to more quickly train intelligence operatives and code breakers.

Finally, in a third story involving the brain, a professor at Drexel University used functional near-infrared spectroscopy to determine which parts of the brain were activated while participants were making art. Dr. Girija Kaimal’s team found that creative endeavors activate the brain’s rewards pathway, as well as elevating the participants’ self-opinion. So making art always made people feel good about themselves; now we know more of the reasons why.

Ghana Trip to Study Tuberculosis: Day 29

Ghana 29.1
One of our favorite memories was visiting King Otumfuo Nana Osei Tutu II of the Asante region (left to right: Salim, Jason Grosz, David Pontoriero, Kaila Helm, Hope McMahon, Dr. David Issadore, Danielle Tsougarakis, Ethan Zhao, Kathleen Givan, Dr. Miriam Wattenbarger, Katharine Cocherl, Kate Panzer).

David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.

As we woke up early to prepare for the nine-hour flight ahead of us, we all acknowledged that time really does fly. Arriving at the Accra airport, we had to say goodbye to our Ghanaian friends Salim, Uncle Ebo, and Nana Yaa. The month has come and gone. It feels like the trip went quickly, but we have learned so much and gained many valuable experiences along the way. From our hospital and clinic visits, to our interactions with an herbalist and a fetish priestess, we were exposed to many healthcare settings found in Ghana. We had the opportunity to present our pediatric tuberculosis diagnostic ideas to a room filled with researchers and clinicians, getting invaluable feedback from multiple experts. Along with our academic pursuits, we also got to explore the Ghanaian culture and learn about customs, traditions, food, and much more. We met many friendly people along the way. These aspects are the memories that we will remember for years to come. As we move beyond this course, we are excited to continue pursuing our interests in biomedical diagnostics and problem solving that can be applied globally. We would like to thank everyone who helped make this unforgettable experience possible.

Foundational Engineering Theory in Design and Translation

What a nanoparticle remembers during its journey is pictorially represented in the above figure, and this “memory” is crucial in predicting its approach to the blood vessel wall and its subsequent capture by cell surface receptors, collectively determining the efficacy of therapeutic drug delivery. Reprinted from: Ramakrishnan et al, “Motion of a nano-spheroid in a cylindrical vessel flow: Brownian and hydrodynamic interactions,” J Fluid Mech. 2017;821:117-152, with permission of Cambridge UP, owner of copyright.

A recent article coauthored by Ramakrishnan Natesan, a postdoctoral fellow in the Department of Bioengineering who works in the lab of Dr. Ravi Radhakrishnan, and published in the Journal of Fluid Mechanics provides an elegant and rigorous approach to integrate the memory, errant motion, and adhesion effects in the dynamics of colloidal nanoparticles of different sizes and shapes. The method described in the article computationally analyzes how the hydrodynamic forces are influenced by size, shape, and nature of confining boundary amidst blood flow.

In traditional modes of therapeutic treatment, such as a direct intravenous (IV) injection, only a small fraction of injected drug accesses the diseased tissue. Suboptimal therapeutic delivery represents an acute challenge by limiting the efficacy of biotherapeutics. Strategies to address and overcome this challenge may be based on theoretical and computational approaches to in order to help design innovative, quantitative, experimental methods. Targeted therapeutic delivery using nanoparticles coated with specific targeting molecules is such an approach in therapeutic and diagnostic applications.

Targeted delivery is inherently a multiscale problem: a broad range of length and time scales govern the hydrodynamic, microscopic, and molecular interactions mediating nanoparticle motion in blood flow and capture due to cell binding. The events following upon the injection of a targeted therapeutic nanoparticle bearing a drug (nanocarrier) include flow through blood vessels and maneuvering around much larger entities in the blood, such as the red blood cells. Nanoparticles eventually break free to approach the wall of the blood vessel — a phenomenon collectively known as margination.

After margination, the nanoparticle is relatively free from the influences of the blood cells but starts to “feel” the approach to the wall. It needs to get excruciatingly close to the wall to stick — a phenomenon known as adhesion or capture. In the backdrop of this arduous journey is the inescapable randomness of its motion caused by Brownian forces, an erratic form of motion that only impacts nanoscale objects. The interplay among fluid forces, Brownian fluctuations, and wall interactions shape the detailed itinerary of the nanoparticle.  How it moves at a given location and given time is intricately coupled with the motion of the surrounding fluid, namely the blood plasma, which is mostly water. Together, they decide to pave the path forward in time described by a “memory function.”

“The optimization of future drug delivery agents, such as targeted therapeutic nanocarriers, could be based on our computations,” Dr. Ramakrishnan says. “This will, in effect, establish a rational computational platform for fast tracking the clinical translation from carrier design to clinical practice.”

Ghana Trip to Study Tuberculosis: Day 28

Ghana 28.2
Students enjoy their last dinner in Ghana at Buka, a Ghanaian and Nigerian restaurant in Accra (left to right: Jason Grosz, Ethan Zhao, Danielle Tsougarakis, Hope McMahon, Salim, Uncle Ebo, Kaila Helm, Kate Panzer, Katharine Cocherl, Kathleen Givan).

David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.

Today marked our last full day in Ghana. In the morning, we set off rather early to start our day in Accra. But first, we had to drop one of our students, Dave, at the airport so he could make his way to Rwanda to visit a college friend. As we traveled to the airport, we had the opportunity to get a better picture of what life is like in Ghana’s capital. It was nice to go back to Accra and see how different it was from Kumasi. It is a much larger city, with various government buildings, people walking about, and large advertising signs every few yards.

Ghana 28.1
Kwame Nkrumah stands with past Vice Provost Roy Nichols in front of the Benjamin Franklin statue on College Green.

Our first stop was the Kwame Nkrumah Memorial Park. Kwame Nkrumah was the first president of Ghana when the country gained independence in 1957. Interestingly, he went to Penn to earn a Master of Arts in philosophy and a Master of Science in education. The mausoleum in Accra contains his and his wife’s bodies. It is surrounded by various water fountains, which are a symbol of life to provide a sense of immortality for Nkrumah. Many Ghanaians want to continue the work that Nkrumah did not get to finish by helping Ghana to continue developing as an independent country. In addition, there is a museum that contains many of his clothes and pictures of him as he met with various world leaders. We even saw a picture of him on Penn’s campus, shaking the hand of then Vice Provost Roy Nichols.

After the tour, we met Dr. Ellis from KCCR for lunch at a nice open-air restaurant, called Buka. Many of us stuck to our favorites of chicken and fried plantains, but some ventured out to try guinea fowl and snails. After lunch, we walked around the area to some nearby vendors, where we were able to shop for last minute gifts. We soon realized how much more expensive Accra was, compared to Kumasi.

We headed back to the hotel to relax a bit before dinner. For our last night in Ghana, we went out to a restaurant that had a live jazz band. We had our last taste of Ghanaian cuisine and had fun dancing to highlife music. Highlife is a genre of music that we only recently learned is popular in both Ghana and Nigeria. To end our last night in Ghana, we headed back to the hotel. After spending some time to prepare, we huddled in the hotel’s lobby for our talent show, and as night turned into morning, we reluctantly headed to our rooms to finish packing for our early departure.

Ghana 28.3
The APOC program began and ended in Accra, the capital of Ghana.

Ghana Trip to Study Tuberculosis: Day 27

by Ethan Zhao, Bioengineering ’19; and Jason Grosz, Bioengineering ’19

Ghana 27.1
The APOC team poses in front of the rooms at Coconut Grove, resembling huts on the outside and furnished with beds and a bathroom on the inside (left to right: Salim, Ethan Zhao, Jason Grosz, Dr. Ocek Eke, Dr. Miriam Wattenbarger, Hope McMahon, David Pontoriero, Kaila Helm, Kathleen Givan, Kate Panzer, Danielle Tsougarakis, Katharine Cocherl, Nana Yaa).

David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.

Today was the second day that we spent in the coastal city of Cape Coast. Many of us woke up earlier than usual to walk along the beach and explore the resort. While walking along the beach, we noticed large rowboats in the distance that were anchored to the shore by ropes. We originally thought that they were fishing boats, but it turned out that they were digging up sand from the ocean floor to restore sand erosion on the beach.

Ghana 27.2
Students (left to right) Kate Panzer, Hope McMahon, Katharine Cocherl, and Danielle Tsougarakis stand along the beachfront of Coconut Grove in Cape Coast, with the Atlantic Ocean in the background.

After breakfast, we traveled outside of Cape Coast to Kakum National Park, which is a dense tropical rainforest on the coast that is home to many wildlife species, including monkeys, leopards, elephants, and antelope. It is also the home of one of Africa’s largest canopy walkways, consisting of rope suspension bridges more than one hundred feet above the forest floor. The views from the bridges were amazing, as we could see for miles across the tops of the rainforest trees. While we were on the bridges, it started drizzling, which was refreshing given the heat. After leaving Kakum National Park, we drove back to Accra, the capital of Ghana, where we will stay for the remainder of our trip.

Ghana 27.3
The APOC students stand on a platform among the treetops of Kakum National Park, 100 feet above the ground (left to right: Salim, David Pontoriero, Kathleen Givan, Kate Panzer, Ethan Zhao, Danielle Tsougarakis, Jason Grosz, Hope McMahon, Katharine Cocherl)

Chow Wins NIH Grant for Brain Study

Chow R01
Brian Chow, Ph.D.

The National Institutes of Health (NIH) has awarded a grant to Brian Chow, Ph.D., an assistant professor in the Department of Bioengineering, to study ultrafast genetically encoded voltage indicators (GEVIs). GEVIs are proteins that can detect changes in the electrical output of cells and report those changes by emitting different color light. His research seeks to create GEVIs that can report these changes much more rapidly – in fact, more than a million times more quickly than the velocity of the changes themselves – and apply these ultrafast GEVIs to the study of the brain.

The NIH-funded research will build on earlier research, employing de novo fluorescent proteins (dFPs) created in Dr. Chow’s lab. These dFPs, which are totally artificial and unrelated to natural proteins, report voltage changes in neurons by changing in brightness. Working with a team of investigators that includes faculty members from the Departments of Biochemistry & Biophysics and Neuroscience, Dr. Chow hopes to develop these ultrafast GEVIs.

“Monitoring thousands of neurons in parallel will shed new light on cognition, learning and memory, mood, and the physiological underpinnings of nervous system disorders,” he says.

Ghana Trip to Study Tuberculosis: Day 26

by Dave Pontoriero, Biotechnology MS ’18

Ghana 26.1
A Portuguese church found in the center of the Elmina Slave Castle.

David Issadore, a faculty member in the Department of Bioengineering at the University of Pennsylvania teaches an engineering course ENGR566 – Appropriate Point of Care Diagnostics. As part of this course, he and Miriam Wattenberger from CBE, have taken nine Penn students, most of them majoring in Bioengineering, to Kumasi, Ghana, to study the diagnosis of pediatric tuberculosis. While in Ghana, these students are blogging daily on their experiences.

Today, we said goodbye to our Kumasi friends and left the Ashanti region for the final leg of our trip. After our bonus night in the new student hostel (dormitory), we boarded the KNUST bus for a six-hour road trip to Cape Coast. The drive was pleasant, and the scenery became more coastal as we continued. Most people slept through it, but once the ocean became visible, everyone woke up in excitement because we knew we were getting close to Elmina, a beach town just west of Cape Coast.

As we drove through the town, we noticed that it resembled many of the beach towns back home. Our driver, Uncle Ebo, then parked in front of an enormous white castle. It was located on the edge of a peninsula, with a narrow beach to its left and crashing waves to its right. It had cannons situated all along its upper levels and a bustling group of locals hanging out in front of its entrance. It was the Elmina Slave Castle, also known as St. George’s Castle, and the team started to prepare for the tour.

Ghana 26.2
Cannons are found on the perimeter of the Elmina Slave Castle, which point out toward the Atlantic Ocean.

As we entered the castle, the mood became somber. A tour guide provided us with a background of the building, which was a Dutch fort used over the years to facilitate the sale and transport of people from Ghana and the surrounding countries during the slave trade. The first portion of the tour followed the path of a slave during their internment, beginning with the female quarters, then the courtyards used for public punishment, the male quarters, punishment cells, and lastly the final exit where people were loaded onto the ships for their journey across the Atlantic. It was a grim tour to take, and the guide shared some incredibly harrowing stories throughout. The second portion of the tour focused more on other aspects of the fort.

Once we loaded back onto the bus, the team reflected on the experience we had at Elmina Castle as we drove away. After a half-hour drive, we soon arrived to our new rooms at a local beachfront resort called Coconut Grove. Its beautiful facility included a private beach, an ocean-facing restaurant/bar, beachfront swings, a golf course, horse stables, and a crocodile pond (with ~10 real crocodiles!). We went out to a local restaurant with live music, danced a bit, then headed home to enjoy the amenities during one of our last nights together as a team.

Ghana 26.3
The breathtaking view of Elmina, a beach town on the coast of Ghana near Cape Coast.