Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)
The lab of Penn’s César de la Fuente sits at the interface of machines and biology, with much of its work focused on innovative treatments for infectious disease. When COVID-19 appeared, de la Fuente and his colleagues turned their attention to building a paper-based biosensor that could quickly determine the presence of SARS-CoV-2 particles from saliva and from samples from the nose and back of the throat. The initial iteration, called DETECT 1.0, provides results in four minutes with nearly 100% accuracy.
Clinical trials for the diagnostic began Jan. 5, with the goal of collecting 400 samples—200 positive for COVID-19, 200 negative—from volunteers who also receive a RT-PCR or “reverse transcription polymerase chain reaction” test. This will provide a comparison set against which to measure the biosensor to determine whether the results the researchers secured at the bench hold true for samples tested in real time. De la Fuente expects the trial will take about a month.
If all goes accordingly, he hopes these portable rapid breath tests could play a part in monitoring the COVID status of faculty, students, and staff around Penn.
César de la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab, the Machine Biology Group, does today. (Photo: Eric Sucar)
Taking on COVID-19 research in this fashion made sense for this lab. “We’re the Machine Biology Group, and we’re interested in existing and emerging pathogens,” says de la Fuente, who has appointments in the Perelman School of Medicine and School of Engineering and Applied Science. “In this case, we’re using a machine to rapidly detect SARS-CoV-2.”
To this point in the pandemic, most SARS-CoV-2 diagnostics have used RT-PCR. Though effective, the technique requires significant space and trained workers to employ, and it is costly and takes hours or days to provide results. De la Fuente felt there was potential to create something inexpensive, quicker, and, perhaps most importantly, scalable.
Penn Medicine researchers have developed a unifying definition of ‘cytokine storm’ to provide a framework to assess and treat patients whose immune systems have gone rogue.
Penn Medicine’s David Fajgenbaum (left) and Carl June (right). (Image: Penn Medicine News)
One of the most elusive aspects for clinicians treating COVID-19 is the body’s immune response to the virus. In the most severe cases of COVID-19, the immune system goes into overdrive, resulting in a fever, multiorgan system damage, and often death—a cytokine storm. But how to detect and treat a cytokine storm requires that clinicians can identify it as such.
Two Penn Medicine researchers have developed a unifying definition of “cytokine storm” to provide physicians with a framework to assess and treat severely-ill patients whose immune systems have gone rogue. Cytokine storms can be triggered by different pathogens, disorders, or treatments, from COVID-19 to Castleman disease to CAR T cell therapy.
In a paper published in the New England Journal of Medicine, David Fajgenbaum,an assistant professor of translational medicine & human genetics and director of the Center for Cytokine Storm Treatment & Laboratory (CSTL), and Carl June,a professor of pathology and laboratory medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center, and the Parker Institute for Cancer Immunotherapies define a cytokine storm as requiring elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond what could be attributed to a normal response to a pathogen, if a pathogen is present.
“There has never been a defining central review of what a cytokine storm is and how to treat one, and now with COVID-19, that is a major issue,” says Fajgenbaum, a Castleman disease patient who has previously experienced five cytokine storms himself. “I’ve spent the last 10 years of my life as a cytokine storm patient and researcher, so I know the importance of having a comprehensive unified definition to find therapies that work across the various types of cytokine storms.”
There is widespread recognition that the immune response to a pathogen, but not the pathogen itself, can contribute to multiorgan dysfunction and other symptoms. Additionally, similar cytokine storm syndromes can occur with no obvious infection.
Since the country began shutting down in March, I have joined the majority of the world in calling the times “unprecedented”: The word, which I rarely used before the pandemic, is now a staple of my lockdown lexicon. In March, we all got the email that changed the trajectory of the rest of our semester and the school year. Since then, COVID-19 has been impacting lives here at Penn, around the nation, and the world. Hanging out with friends and family on Zoom, managing work and school from home, social distancing, wearing masks everywhere, and constantly washing hands have been the reality of our new normal for months.
It has been almost ten months since the World Health Organization declared COVID-19 a pandemic and this has posed a global crisis like nothing most of us have experienced in our lifetime. At Penn, the campus community including students and staff have rallied to keep each other safe, all while doing what is possible to ensure that lectures, teaching, and research are possible in ways that uphold the university’s mission of “strengthening the quality of education and producing innovative research and models of healthcare delivery by fostering a vibrant inclusive environment and fully embracing diversity.”
BE students Alexa Rybicki, Ifeoluwa Popoola, and Caitlin Frazee meet for BE 309 in the Gather.Town virtual lab space.
In Penn Engineering’s Bioengineering Department, the Stephenson Foundation Educational Laboratory & Bio-MakerSpace has been at the heart of ensuring that lab-based classes run as smoothly as possible given the circumstances. First off, during the summer, the lab launched a Slack site that not only kept students engaged and connected through fun, daily “Questions of the Day” but also gave them the opportunity to reach out to our staff and obtain their expertise for coursework and personal projects. The staff at the Stephenson Lab also supported and continue to support Senior Design students (BE 495) with their projects by ordering, receiving, packaging, arranging pickups, or mailing supplies needed to complete their Senior Design projects. In addition, class time takes place using Gather.Town to recreate our Bio-MakerSpace virtually. In other classes, video tutorials of some of the experiments students were missing out on were produced over the summer and made available to students so they could learn by seeing what the lab staff were doing in the videos. For the Bioengineering Modeling, Analysis, and Design (BE MAD) class (BE 309), in addition to videos, our lab Engineer, Michael Patterson, developed software through which students can enter design criteria and have experimental data emailed to them.
Picking up lab supplies outside in the Engineering complex
The staff at the lab also supported a Rehabilitation Engineering course (BE 514) taught by Michelle Johnson, Associate Professor in Physical Medicine and Rehabilitation and Bioengineering, by putting together supplies that enabled students in the class to reengineer toy bunny rabbits to be more accessible to children with disabilities. Optical Microscopy (BE 518), another Bioengineering course, taught by Christopher Fang-Yen, Associate Professor in Bioengineering and Neuroscience, offers students an introduction to the fundamental concepts of optics and microscopy. The staff at the lab put together kits and made them available for pickup by the students in the class.
In a time when the shape of education looks vastly different from what we anticipated this year, the Bio-MakerSpace has been instrumental in ensuring that students still have access to resources that make their learning experience an enriching one. In these unprecedented times, the lab has been able to encourage students to keep up and be engaged with their coursework while also fostering creativity in students, virtually and remotely. While we may not know what life after the pandemic will look like, one thing to be sure of is that the Stephenson Lab will always be a reliable place for Penn students to get support for personal projects and coursework when needed.
Solumtochukwu (Somto) Egbogais a Master’s Student in Bioengineering, graduating December 2020. She also is a student employee for the Stephenson Foundation Bioengineering Laboratory & Bio-MakerSpace.
The Penn Bioengineering student spotlight series continues with David Alanis Garza. David is a senior from Monterrey, Mexico finishing his dual degree in Bioengineering in the School of Engineering and Applied Sciences and Health Care Management at the Wharton School, with minors in Chemistry and Math. He currently serves as the Captain of the Medical Emergency Response Team (MERT), managing clinical operations and the organization’s response to COVID-19. He is also a Penn tour guide and a member of the Sigma Phi Epsilon fraternity. In his free time, he enjoys mountain climbing, camping, and playing guitar.
What drew you to the field of Bioengineering?
I first became interested in BE during my high school physics class, in which my teacher motivated our lesson in electromagnetism by explaining the basics behind an MRI machine and how defibrillators are basically glorified capacitors. I realized that my lifelong dream to be a surgeon would best be served if I armed myself with a scalpel and screwdriver alike. With the fast paced advances in the medical field, the best physicians must not only understand the underlying pathophysiology of disease, but also how to interact with and keep up with innovations in the biomedical engineering field. At Penn, I have enjoyed discovering that BE is much more wide than what I initially appreciated.
Have you ever done research with a professor on campus? What did you like, and what didn’t you like about it?
I have had the opportunity to work in the Center for Resuscitation Science on a research project investigating diagnostic patterns in the electrocardiogram of Pulseless Electrical Activity (PEA). I truly enjoyed the opportunity to take on more responsibility as the first author of the manuscript we are currently working on, and learned so much about communication in science when presenting the research during American Heart Association’s Resuscitation Science Symposium this last weekend. What I learned in Bioengineering, especially in BE 309/310 (Lab) and BE 301 (Signals and Systems), has been incredibly useful for my research. I am also currently completing a Wharton senior thesis exploring how financial derivative securities could be used to hedge risk in emergency departments. Penn is incredibly supportive of students seeking to gain more research experience, offering an abundance of opportunities for guided and independent projects. I truly enjoyed the opportunity of finding answers to very specific questions in my fields, as well as the valuable relationships with my mentors I formed along the way.
What have been some of your favorite courses and/or projects in Bioengineering so far?
BE 305 (Engineering Principles of Human Physiology) has been my favorite course at Penn. In this class, we were able to understand, quantify, and hack the body’s physiology through an engineering lens. From building a pulseoximeter with our phone cameras, to determining the blood volume of the left ventricle over time with MRI images, this class was very much hands on. A close second is BE 301 (Bioengineering Signals and Systems). I hadn’t previously grasped how this discipline was relevant to medicine until this class, but now I find myself applying what I learned in my research. Lastly, as many other BE students will tell you, the human-cockroach machine interface project in BE lab has been one of my most challenging and rewarding undertakings at Penn. Our team linked a wearable device that measured the forearms position and muscle contractions, so that when the wearer painted a picture, a cockroach leg would be moved and stimulated to paint an imitation of the image. Overcoming my phobia of cockroaches and the countless hours of trial and error were all worth it, for I can now brag about how my team made an artist out of a cockroach leg.
What advice would you give to your freshman self?
It is a great idea to identify which area of BE research you are interested in, and plan your academics so that you can take the closely related courses early on. This will empower you to conduct research with greater responsibilities or give you marketable skills that employers may look for when hiring for internships of your interest. BE upperclassmen are always willing to help, so feel free to reach out to us for any advice.
What do you hope to pursue after obtaining your undergraduate degree?
I will be taking a gap year in which I will be working in the area of hospital administration and clinical engineering before I begin my medical school journey. As of right now, I am interested in specializing in emergency medicine or surgery, but I know my interests may change as my understanding of medicine grows throughout the next years.
Have you done or learned anything new or interesting during quarantine?
The COVID pandemic gave me a unique opportunity to manage the clinical operations of MERT’s emergency medical services during an unprecedented challenge. As a result, I learned a lot about how different hospitals and health care systems are managing their response, not to mention the standard protocols to ensure the safety and wellness of our patients and providers. On a less professional note, I have been able to get a bit better at chess and guitar.
Jamie Moni, a freshman in Penn’s Department of Bioengineering, spent his summer before starting Penn participating in the 2020 Africana Studies Summer Institute, a pre-freshman program hosted by the Center for Africana Studies. A recent piece by Penn Today’s KristineGarcía profiling the thirty-four-year-old program and its transition to a virtual format featured Moni’s thoughts on the program:
“Jamie Moni is a bioengineering major who participated from his home in Hillsborough, New Jersey. The Institute was one of the first programs he sought out after enrolling at Penn, Moni says. ‘My parents were really happy that there’s a program like this at Penn, especially because there’s not a lot of Black people in my town. Most of the African Americans that I interact with on a daily basis are my family,’ Moni says, whose ancestry is from Cameroon. ‘It’s been interesting, to say the least.’
Moni has a close relationship with his peer mentor, Niko Simpkins, who ‘has been really one of the best things that I took out of the Africana Institute.’ A fellow engineering major, Simpkins gives Moni study tips and introduced him to the National Society of Black Engineers as well as STEM-specific workshops.”
GRASP lab researchers (from left) Bernd Pfrommer, Kenneth Chaney, and Caio Mucchiani assembling telemedicine cart prototypes in Levine hall earlier this spring. (Image courtesy of Kenneth Chaney and Bernd Pfrommer)
And while innovation in health care usually brings to mind new treatments and medicines, the efforts of clinicians, engineers, and IT specialists demonstrate the importance technological infrastructure for rapidly deployable, tech-based solutions so clinicians can provide the best care to patients amid social distancing and coronavirus restrictions.
The telemedicine revolution
In late March, telemedicine was key for allowing Penn Medicine clinicians to deliver care while avoiding potentially risky in-person interactions. Chief Medical Information Officer C. William Hanson III and his team helped set up the IT infrastructure for scaling up telemedicine capabilities and provided guidance to clinicians. Thanks to the quick pivot, Penn Medicine went from 300 telemedicine visits in February to more than 7,500 visits per day in a matter of weeks.
But far from seeing telemedicine as a temporary solution during the pandemic, Hanson has been a long-time advocate for this approach to health care. In his role as liaison between clinicians and the IT community in the past 10 years Hanson, helped establish remote ICU monitoring protocols and broadened opportunities for televisits with specialists. Now, with the pandemic removing many of the previous barriers to entry, be they technical, insurance-based, or simply a lack of familiarity, Hanson believes that telemedicine is here to stay.
“As the pandemic evolved, people were aware that telemedicine could help the health care system, as well as doctors and patients, during this crisis,” he says. “Now, there are definitely places where telemedicine makes good sense, and we will continue to use that as part of our way of handling a problem.” Other benefits include removing geographic barriers to entry for new patients, reduced appointment times, increased patient satisfaction, and reduced health care provider burnout.
Simple solutions for COVID-19 challenges
As the director of Penn’s Telestroke Program, neurologist Michael Mullen has experience diagnosing from a distance. This spring, telemedicine carts his group uses were repurposed in COVID ICUs. At the same time, Mullen and group wanted to expand their ability to assess stroke patients remotely, so he reached out to Brian Litt, faculty director of Penn Health-Tech, to see how he could collaborate to create an analogous telemedicine station using readily available, cost-effective components.
Rapid and simple solutions are at the heart of Penn’s ModLab, a subgroup of the GRASP lab focused on robots made of configurable individual components. As part of a COVID-19 rapid response initiative, engineers worked with Mullen to figure out a viable solution in record time. “The idea was to make it as simple and as fast as possible,” says graduate student Caio Mucchiani. “With robotics, usually you want to make things more sophisticated, however, given the situation, we needed to know how we could use off-the-shelf components to make something.”
Fellow graduate student Ken Chaney, postdoc Bernd Pfrommer, and Mucchiani came up with a plan that replicated the required specs of the existing telemedicine carts, including state-of-the-art cameras for detailed imaging as well as a reliable, easily rechargeable battery. The team then put together 10 telemedicine carts, assembling the prototypes with social distancing and masks at the GRASP lab in early April.
While changes to treatment approaches mean that these carts still require additional field testing, Mullen is still eager to expand the program, be it for diagnosing patients safely or educating medical students in an era of social distancing. “In the setting of COVID, when everything was getting crazy, it was remarkable to see the energy that GRASP brought to help,” adds Mullen. “Everyone was really busy, and it was amazing to see this group of people who wanted to use their expertise to help.”
Ravi Radhakrishnan, Professor and Chair of the Department of Bioengineering and Professor in Chemical and Biomolecular Engineering, is among the many faculty who quickly adapted their courses to an online format in the wake of the COVID-19 pandemic. Now, a recent publication in the American Institute of Chemical Engineers (AIChE) Journal reflects one of these revamped courses. The course BE 559: “Multiscale Modeling of Chemical and Biological Systems” provides theoretical, conceptual, and hands-on modeling experience on three different length and time scales: (1) electronic structure (A, ps); (2) molecular mechanics (100A, ns); and (3) deterministic and stochastic approaches for microscale systems (um, sec). During the course, students gained hands-on experience in running codes on real applications together with the following theoretical formalisms: molecular dynamics, Monte Carlo, free energy methods, deterministic and stochastic modeling. The transition to the online format was greatly facilitated by a grant from the Extreme Science and Engineering Discovery Environment (XSEDE) which provided cloud and supercomputing resources to the students facilitating the computational laboratory experience. Radhakrishnan’s article, “A survey of multiscale modeling: Foundations, historical milestones, current status, and future prospects,” reviews the foundations, historical developments, and current paradigms in multiscale modeling (MSM).
Radhakrishnan aspires to modernize computational science, integrating Multiscale Modeling and Data Science for Biological and Biomedical Science & Engineering. His team does so by integrating multiphysics modeling, computing, data science to tackle applications. The integrative approach is pictorially depicted here in terms of modeling different length and timescales using techniques such as molecular dynamics of atomistic systems, Brownian dynamics of coarse-grained systems, and field equations governing continuum scales of macroscopic systems.
“The AIChE 35 Under 35 Award was founded to recognize young chemical engineers who have achieved greatness in their fields,” reads the 2020 award announcement. “The winners are a group of driven, engaged, and socially active professionals, representing the breadth and diversity that chemical engineering exemplifies.”
De la Fuente was named in the list’s “Bioengineering” category for his his lab’s work in machine biology. Their goal is to develop computer-made tools and medicines that will combat antibiotic resistance. De la Fuente has already been featured on several other young innovators lists, including MIT Technology Review’s 35 under 35 and GEN’s Top 10 under 40, both in 2019. His research in antibiotic resistance has been profiled in Penn Today and Penn Engineering Today, and he was recently awarded Penn Health-Tech’s inaugural NEMO Prize for his proposal to develop paper-based COVID diagnostic system that could capture viral particles on a person’s breath.
In addition to being named on the 2020 list, the honorees will receive a $500 prize and will be celebrated at the 2020 AIChE Annual Meeting this November.
Learn more about de la Fuente’s pioneering research on his lab website.
When the COVID-19 pandemic began taking hold in the United States, one of the first “superspreader” events was an academic conference. Such conferences have long been a primary way for researchers to share new findings and launch collaborations, but with thousands of people from around the world, indoors and in close proximity, it quickly became clear that the traditional format for these events would need to radically change.
Konrad Kording
Konrad Kording, a Penn Integrates Knowledge Professor with appointments in the departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine, was ahead of the curve on this shift. With the issues of prohibitive costs and environmental impact of travel in mind, Kording had already started brainstorming ways of reinventing the traditional conference format when the pandemic made it a necessity.
The resulting event, Neuromatch, involved algorithmically analyzing participants’ work in order to connect researchers who might not otherwise meet. Building on the success of that “unconference,” Kording and his colleagues launched the Neuromatch Academy, a free-ranging online summer school organized around the same principles.
Ashley Juavinett writing for The Simons Collaboration on the Global Brain, recently dug into how Neuromatch was able to pull together 1,750 students from 70 countries in a matter of months:
Kording already had experience quickly pulling together online events. Early in the pandemic, together with Dan Goodman, Titipat Achakulvisut and Brad Wyble, he developed an online ‘unconference,’ which featured both lectures and a virtual networking component designed to mimic the in-person interactions that make conferences so valuable. (For more, see “Designing a Virtual Neuroscience Conference.”) Soon after, they decided to spin that success into a full-fledged summer school offering live lectures with top computational neuroscientists, guided coding exercises to teach mathematical approaches to neural modeling and analysis, and community support from mentors and teaching assistants (TAs).
The result was a summer school with well-designed content, a diverse student body, including participants from U.S.-sanctioned Iran, and a determined group of organizers who managed to pull off the most inclusive computational neuroscience school yet. NMA now has its eye on a future with even broader representation across countries, languages and skill levels. This year has been incredibly difficult for many, but NMA has provided an important precedent for how to collaborate across, and even dismantle, all sorts of barriers.
When the coronavirus pandemic began in March, María Suarez, junior in bioengineering, left Penn’s campus and returned home to Costa Rica. What should have been the final weeks of club activities, social events and end-of-year celebrations shifted to months spent at home, far away from Philadelphia. But Suarez, like many others, wanted to do something productive with her time in quarantine. Drawing on her bucolic roots, she decided to start a garden.
“I was born and raised in a very rural area,” Suarez says. “There is a huge river in my backyard where I learned how to count by throwing pebbles in the river with my mother and sister. Nature is a big part of my life, and it’s really shaped my personality. As a child, I planted herbs, like basil, mint and oregano, with my parents. When you are close to the land like this, gardening was something that grew naturally out of our lifestyle.”
As the spring semester shifted into summer, Suarez returned to her love of planting and embarked on an ambitious project to grow a vegetable garden in her backyard. Unlike the smaller herb gardens she had grown as a child, this vegetable garden required deeper horticultural knowledge as well as intense work under the hot sun.
“To begin the garden, I had to clear the land I wanted to use and remove all the grass and stones from the soil,” Suarez shares. “It was the dry season in Costa Rica and the ground was very difficult to work with.”
After clearing the land, Suarez had to bring nutrients back into the soil of her garden plot. Luckily, her family has been maintaining a natural compost pile for many years.
“Basically, the compost pile is a hole in the ground where we put our natural food waste. There are worms and animals there that help us naturally decompose the waste and they produce a very nutrient rich soil.” Suarez explains. “The compost is a five-minute walk from my garden, and I had to take at least ten trips with a wheelbarrow to bring enough back. It was a great arm workout.”
Once the soil was placed and watered, Suarez was finally able to plant her seeds. After a few days, she saw celery and zucchini plants beginning to sprout. Throughout the summer, Suarez’s crops grew well, and she was able to harvest the vegetables and share them with her family.
“It was very fulfilling to see the products of my efforts,” Suarez says.
