Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 million commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.
Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.
“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”
Penn Health-Tech’s Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize awards $80,000 to support early-stage ideas joining engineering and medicine. The goal of the prize is to encourage collaboration between the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science by supporting innovative ideas that might not receive funding from traditional sources.
This year, the NEMO Prize has been awarded to a team of researchers from Penn Engineering’s Department of Bioengineering. Their project aims to develop a technology that can detect multiple cancer biomarkers in single cells from tumor biopsy samples.
As cancer cells grow in the body, one of the characteristics that influences tumor growth and response to treatment is cancer cell state heterogeneity, or differences in cell states. Methods that rapidly catalogue cell heterogeneity may be able to detect rare cells responsible for tumor growth and drug resistance.
Single-cell transcriptomics (scRNA-seq) is the standard method for studying cell states; by amplifying and analyzing the cell’s complement of RNA sequences at a given time, researchers can get a snapshot of what proteins the cell is in the process of making. However, this method does not fully capture the function of the cell. The field of proteomics, which captures the actual protein content of cells along with post-translational modifications, provides a better picture of the cell’s function, but single-cell proteomic methods with the same sensitivity as scRNA-seq do not currently exist.
This collaborative project, which joins Assistant Professors Alex Hughes and Lukasz Bugaj, as well as Professor Andrew Tsourkas, aims to change that by developing multiplexed, sensitive and highly specific single-cell proteomics technologies to advance our understanding of cancer, its detection and its treatment.
This new technology, called scProteome-seq, builds from Hughes’s previous work.
“My specific expertise here is as an inventor of single-cell western blotting, which is the core technology that our team is building on,” says Hughes. “Single-cell proteomics technologies of this type have a track-record of commercial translation for applications in basic science and clinical automation, so our approach has a high potential for real-world impact.”
The current technology from Hughes’ lab separates proteins in cells by their molecular weight and “blots” them on a piece of paper. Improvements to this technology included in this project will remove the limitation of using light-emitting dyes to detect different proteins and instead use DNA barcodes to differentiate them.
Kariyawasam is a double major in Engineering’s Department of Bioengineering, with concentrations in computational medicine and medical devices, and in the Wharton School, with concentrations in finance and entrepreneurship and innovation.
“We are so proud of our newest Penn Rhodes Scholars who have been chosen for this tremendous honor and opportunity,” said President Amy Gutmann. “The work Raveen has done in health care innovation and accessibility and Nicholas has done to support student well-being while at Penn is impressive, and pursuing a graduate degree at Oxford will build upon that foundation. We look forward to seeing how they make an impact in the future.”
The Rhodes is highly competitive and one of the most prestigious scholarships in the world. The scholarships provide all expenses for as long as four years of study at Oxford University in England.
According to the Rhodes Trust, about 100 Rhodes Scholars will be selected worldwide this year, chosen from more than 60 countries. Several have attended American colleges and universities but are not U.S. citizens and have applied through their home country, including Kariyawasam in Sri Lanka.
Katherine (Katie) Reuther, Ph.D., M.B.A. will return to Penn Engineering in July 2021 as the new Executive Director of Penn Health-Tech (PHT) and as Practice Associate Professor in Bioengineering. Reuther is an alumna of Penn Bioengineering, having obtained her Ph.D. at Penn in the laboratory of Louis Soslowsky, Fairhill Professor in Bioengineering and Orthopaedic Surgery.
“Dr. Reuther is a role model for biomedical innovation, linking formal training in engineering and entrepreneurship with deep practical experience in leading technologies through the commercialization pipeline. Dr. Reuther graduated with her Bachelor of Science in Biomedical Engineering, Magna cum Laude, from the College of New Jersey; she obtained her Ph.D. in Bioengineering at Penn in the laboratory of Dr. Louis Soslowsky and completed her MBA at Columbia, where she currently is a Senior Lecturer in Design, Innovation, and Entrepreneurship in the Department of Biomedical Engineering. During her tenure at Columbia, Dr. Reuther helped create and led Columbia’s Biomedical Engineering Technology Accelerator (BiomedX), overseeing more than 60 technologies leading to $80M in follow-on funding and 18 licenses to start-ups or start-ups industry. Introducing both new courses and a new curriculum in biomedical innovation, Dr. Reuther was recently awarded Columbia’s highest teaching honor, the ‘2021 Presidential Award for Outstanding Teaching,’ this Spring as a recognition of her excellence in teaching and dedication to students.
Katie has extensive experience in developing and translating early-stage medical technologies and discoveries and providing formal educational training for aspiring medical entrepreneurs. Dr. Reuther served as Director of Masters’ Studies for the Department of Biomedical Engineering and spearheaded the development of a graduate-level medical innovation program, including an interdisciplinary course available to scientists, engineers, and clinicians. Dr. Reuther provided advising and educational support to more than 100 student/faculty teams and start-ups, as they worked to develop and commercialize medical technologies. She will bring these extensive skills to PHT and Penn Bioengineering in two new, hands-on graduate courses in medical innovation centered around Penn Health-Tech ventures.”
César de la Fuente, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Microbiology, and Psychiatry, was the inaugural recipient of the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize from Penn Health-Tech in 2020 for his low-cost, rapid COVID test. Now with promising results recently published in the journal Matter (showing 90 percent accuracy in as little as four minutes), Penn Health-Tech caught up with de la Fuente to discuss his experience over the past year:
“How did [your project] evolve in the past year?
‘We started with one prototype and now have three entirely different prototypes for the test. Two use electrochemistry, and we are now working on a new technology that uses calorimetry. With calorimetry, when the cotton swabs are exposed to the virus, they change color. This means users are able to see if they’re affected by a virus through a simple color change, making it more of a visual detection method.'”
New research from Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering and Director of Penn Medicine’s McKay Orthopaedic Research Laboratory, announces a “new biosealant therapy may help to stabilize injuries that cause cartilage to break down, paving the way for a future fix or – even better – begin working right away with new cells to enhance healing.” Their research was published in Advanced Healthcare Materials. The study’s lead author was Jay Patel, a former postdoctoral fellow in the McKay Lab and now Assistant Professor at Emory University and was contributed to by Claudia Loebel, a postdoctoral research in the Burdick lab and who will begin an appointment as Assistant Professor at the University of Michigan in Fall 2021. In addition, the technology detailed in this publication is at the heart of a new company (Forsagen LLC) spun out of Penn with support from the Penn Center for Innovation (PCI) Ventures Program, which will attempt to spearhead the system’s entry into the clinic. It is co-founded by both Mauck and Patel, along with study co-author Jason Burdick, Professor in Bioengineering, and Ana Peredo, a PhD student in Bioengineering.
One example is Strella Biotechnology, founded in 2019 by Katherine Sizov (Biology 2019 & President’s Innovation Prize winner). Strella is developing sensors with the ability to reduce the amount of food waste due to going bad in storage. “Having a Bio-MakerSpace that gives you the functionalities of both a wet lab and a traditional electronics lab is extremely helpful in developing novel technologies” says Sizov on the BE Labs Youtube channel.
The Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities, including highly knowledgeable lab staff. Seth Fein (BSE ’20, MSE ’21) has worked at the lab since Fall 2020. “Because bioengineering spans many fields, we encourage interdisciplinary work. Students from Mechanical, Electrical, and Chemical Engineering have all found valuable resources in the lab,” says Fein.
The article also discusses the many resources the BioMakerSpace provides to Penn students and their efforts to keep the lab functional, safe, and open for research and education during the current semester.
Penn Health-Tech is an interdisciplinary center launched in 2017 to advance medical device innovation across the Perelman School of Medicine and the School of Engineering and Applied Sciences by forging collaborative connections among Penn researchers and providing seed funding to incubate novel ideas to advance health care.
Continue reading “The Bio-MakerSpace — Fostering Learning and Innovation Across Many Disciplines” at the Penn Health-Tech blog.
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.”
The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.
When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.
Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.
Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.
“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”
De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.
The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.
In response to the unprecedented challenges presented by the global outbreak of the novel coronavirus SARS-CoV-2, Penn Bioengineering’s faculty, students, and staff are finding innovative ways of pivoting their research and academic projects to contribute to the fight against COVID-19. Though these projects are all works in progress, I think it is vitally important to keep those in our broader communities informed of the critical contributions our people are making. Whether adapting current research to focus on COVID-19, investing time, technology, and equipment to help health care infrastructure, or creating new outreach and educational programs for students, I am incredibly proud of the way Penn Bioengineering is making a difference. I invite you to read more about our ongoing projects below.
Novel Chest X-Ray Contrast
David Cormode, Associate Professor of Radiology and Bioengineering
The Cormode and Noel labs are working to develop dark-field X-ray imaging, which may prove very helpful for COVID patients. It involves fabricating diffusers that incorporate gold nanoparticles to modify the X-ray beam. This method gives excellent images of lung structure. Chest X-ray is being used on the front lines for COVID patients, and this could potentially be an easy to implement modification of existing X-ray systems. The additional data give insight into the health state of the microstructures (alveoli) in the lung. This new contrast mechanics could be an early insight into the disease status of COVID-19 patients. For more on this research, see Cormode and Noel’s chapter in the forthcoming volume Spectral, Photon Counting Computed Tomography: Technology and Applications, edited by Katsuyuki Taguchi, Ira Blevis, and Krzysztof Iniewski (Routledge 2020).
Computational Models for Targeting Acute Respiratory Distress Syndrome (ARDS). The severe forms of COVID-19 infections resulting in death proceeds by the propagation of the acute respiratory distress syndrome or ARDS. In ARDS, the lungs fill up with fluid preventing oxygenation and effective delivery of therapeutics through the inhalation route. To overcome this major limitation, delivery of antiinflammatory drugs through the vasculature (IV injection) is a better approach; however, the high injected dose required can lead to toxicity. A group of undergraduate and postdoctoral researchers in the Radhakrishnan Lab (Emma Glass, Christina Eng, Samaneh Farokhirad, and Sreeja Kandy) are developing a computational model that can design drug-filled nanoparticles and target them to the inflamed lung regions. The model combines different length-scales, (namely, pharmacodynamic factors at the organ scale, hydrodynamic and transport factors in the tissue scale, and nanoparticle-cell interaction at the subcellular scale), into one integrated framework. This targeted approach can significantly decrease the required dose for combating ARDS. This project is done in collaboration with Clinical Scientist Dr. Jacob Brenner, who is an attending ER Physician in Penn Medicine. This research is adapted from prior findings published in Volume 13, Issue 4 of Nanomedicine: Nanotechnology, Biology and Medicine: “Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions” (May 2017).
Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine
Arjun Raj, David Issadore, and Sydney Shaffer are working on developing an integrated, rapid point-of-care diagnostic for SARS-CoV-2 using single molecule RNA FISH. The platform currently in development uses sequence specific fluorescent probes that bind to the viral RNA when it is present. The fluorescent probes are detected using a iPhone compatible point-of-care reader device that determines whether the specimen is infected or uninfected. As the entire assay takes less than 10 minutes and can be performed with minimal equipment, we envision that this platform could ultimately be used for screening for active COVID19 at doctors’ offices and testing sites. Support for this project will come from a recently-announced IRM Collaborative Research Grant from the Institute of Regenerative Medicine with matching funding provided by the Departments of Bioengineering and Pathology and Laboratory Medicine in the Perelman School of Medicine (PSOM) (PI’s: Sydney Shaffer, Sara Cherry, Ophir Shalem, Arjun Raj). This research is adapted from findings published in the journal Lab on a Chip: “Multiplexed detection of viral infections using rapid in situ RNA analysis on a chip” (Issue 15, 2015). See also United States Provisional Patent Application Serial No. 14/900,494 (2014): “Methods for rapid ribonucleic acid fluorescence in situ hybridization” (Inventors: Raj A., Shaffer S.M., Issadore D.).
HEALTH CARE INFRASTRUCTURE
Penn Health-Tech Coronavirus COVID-19 Collaborations
Brian Litt, Professor of Bioengineering, Neurology, and Neurosurgery
In his role as one of the faculty directors for Penn Health-Tech, Professor Brian Litt is working closely with me to facilitate all the rapid response team initiatives, and in helping to garner support the center and remove obstacles. These projects include ramping up ventilator capacity and fabrication of ventilator parts, the creation of point-of-care ultrasounds and diagnostic testing, evaluating processes of PPE decontamination, and more. Visit the Penn Health-Tech coronavirus website to learn more, get involved with an existing team, or submit a new idea.
Dr. Maltese is rapidly developing a low-cost ventilator that could be deployed in Penn Medicine for the expected surge, and any surge in subsequent waves. This design is currently under consideration by the FDA for Emergency Use Authorization (EUA). This example is one of several designs considered by Penn Medicine in dealing with the patient surge.
David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean
Led by David Meaney, Kevin Turner, Peter Bruno and Mark Yim, the face shield team at Penn Health-Tech is working on developing thousands of rapidly producible shields to protect and prolong the usage of Personal Protective Equipment (PPE). Learn more about Penn Health-Tech’s initiatives and apply to get involved here.
Update 4/29/20: The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Dr. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold. Read the full post on the Penn Engineering blog.
OUTREACH & EDUCATION
Student Community Building
Yale Cohen, Professor of Otorhinolaryngology, Department of Psychology, BE Graduate Group Member, and BE Graduate Chair
Yale Cohen, and Penn Bioengineering’s Graduate Chair, is working with Penn faculty and peer institutions across the country to identify intellectually engaging and/or community-building activities for Bioengineering students. While those ideas are in progress, he has also worked with BE Department Chair Ravi Radhakrishnan and Undergraduate Chair Andrew Tsourkas to set up a dedicated Penn Bioengineering slack channel open to all Penn Bioengineering Undergrads, Master’s and Doctoral Students, and Postdocs as well as faculty and staff. It has already become an enjoyable place for the Penn BE community to connect and share ideas, articles, and funny memes.
Undergraduate Course: Biotechnology, Immunology, Vaccines and COVID-19 (ENGR 35)
Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering and Chemical and Biomolecular Engineering
This Summer Session II, Professor Dan Hammer and CBE Senior Lecturer Miriam R. Wattenbarger will teach a brand-new course introducing Penn undergraduates to a basic understanding of biological systems, immunology, viruses, and vaccines. This course will start with the fundamentals of biotechnology, and no prior knowledge of biotechnology is necessary. Some chemistry is needed to understand how biological systems work. The course will cover basic concepts in biotechnology, including DNA, RNA, the Central Dogma, proteins, recombinant DNA technology, polymerase chain reaction, DNA sequencing, the functioning of the immune system, acquired vs. innate immunity, viruses (including HIV, influenza, adenovirus, and coronavirus), gene therapy, CRISPR-Cas9 editing, drug discovery, types of pharmaceuticals (including small molecule inhibitors and monoclonal antibodies), vaccines, clinical trials. Some quantitative principles will be used to quantifying the strength of binding, calculate the dynamics of enzymes, writing and solving simple epidemiological models, methods for making and purifying drugs and vaccines. The course will end with specific case study of coronavirus pandemic, types of drugs proposed and their mechanism of action, and vaccine development.
Update 4/29/20: Read the Penn Engineering blog post on this course published April 27, 2020.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording facilitated Neuromatch 2020, a large virtual neurosciences conferences consisting of over 3,000 registrants. All of the conference talk videos are archived on the conference website and Dr. Kording has blogged about what he learned in the course of running a large conference entirely online. Based on the success of Neuromatch 1.0, the team are now working on planning Neuromatch 2.0, which will take place in May 2020. Dr. Kording is also working on facilitating the transition of neuroscience communication into the online space, including a weekly social (#neurodrinking) with both US and EU versions.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording is working to launch the Neuromatch Academy, an open, online, 3-week intensive tutorial-based computational neuroscience training event (July 13-31, 2020). Participants from undergraduate to professors as well as industry are welcome. The Neuromatch Academy will introduce traditional and emerging computational neuroscience tools, their complementarity, and what they can tell us about the brain. A main focus is not just on using the techniques, but on understanding how they relate to biological questions. The school will be Python-based making use of Google Colab. The Academy will also include professional development / meta-science, model interpretation, and networking sessions. The goal is to give participants the computational background needed to do research in neuroscience. Interested participants can learn more and apply here.
Journal of Biomedical Engineering Call for Review Articles
Beth Winkelstein, Vice Provost for Education and Eduardo D. Glandt President’s Distinguished Professor of Bioengineering
The American Society of Medical Engineers’ (ASME) Journal of Biomechanical Engineering (JBME), of which Dr. Winkelstein is an Editor, has put out a call for review articles by trainees for a special issue of the journal. The call was made in March 2020 when many labs were ramping down, and trainees began refocusing on review articles and remote work. This call continues the JBME’s long history of supporting junior faculty and trainees and promoting their intellectual contributions during challenging times.
Update 4/29/20: CFP for the special 2021 issue here.
Are you a Penn Bioengineering community member involved in a coronavirus-related project? Let us know! Please reach out to firstname.lastname@example.org.