Penn Bioengineering and COVID-19

A message from Penn Bioengineering Professor and Chair Ravi Radhakrishnan:

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.

RESEARCH

Novel Chest X-Ray Contrast

David Cormode, Associate Professor of Radiology and Bioengineering

Nanomedicine and Molecular Imaging Lab

Peter Noel, Assistant Professor of Radiology and BE Graduate Group Member

Laboratory for Advanced Computed Tomography Imaging

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).

Immunotherapy

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering

Mitchell Lab

Mike Mitchell is working with Saar Gill (Penn Medicine) on engineering drug delivery technologies for COVID-19 mRNA vaccination. He is also developing inhalable drug delivery technologies to block COVID-19 internalization into the lungs. These new technologies are adaptations of prior research published Volume 20 of Nano Letters (“Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering” January 2020) and discussed in Volume 18 of Nature Reviews Drug Discovery (“Delivery Technologies for Cancer Immunotherapy” January 2019).

Respiratory Distress Therapy Modeling

Ravi Radhakrishnan, Professor, and Chair of Bioengineering and Professor of Chemical and Biomolecular Engineering

Radhakrishnan Lab

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).

Diagnostics

Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine

Syd Shaffer Lab

Arjun Raj, Professor of Bioengineering

Raj Lab for Systems Biology

David Issadore, Associate Professor of Bioengineering and Electrical and Systems Engineering

Issadore Lab

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

Litt Lab

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.

BE Labs COVID-19 Efforts

BE Educational Labs Director Sevile Mannickarottu & Staff

BE Educational Labs staff members Dana Abulez (BE ’19, Master’s BE ’20) and Matthew Zwimpfer (MSE ’18, Master’s MSE ’19) take shifts to laser-cut face shields.

The George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace staff have donated their PPE to Penn Medicine. Two staff members (Dana Abulez, BE ’19, Master’s BE ’20 and Matthew Zwimpfer, MSE ’18, Master’s MSE ’19) took shifts to laser-cut face shields in collaboration with Penn Health-Tech. Dana and Matthew are also working with Dr. Matthew Maltese on his low-cost ventilator project (details below).

Low-Cost Ventilator

Matthew Maltese, Adjunct Professor of Medical Devices and BE Graduate Group Member

Children’s Hospital of Philadelphia Center for Injury Research and Prevention (CIRP)

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.

Face Shields

David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean

Molecular Neuroengineering Lab

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

Auditory Research Laboratory

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

The Hammer Lab

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.

Neuromatch Conference

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

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.

Neuromatch Academy

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

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

Spine Pain Research Lab

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 ksas@seas.upenn.edu.

 

 

Brain-machine interfaces: Villainous gadgets or tools for next-gen superheroes?

A Q&A with neuroscientist Konrad Kording on how connections between minds and machines are portrayed in popular culture, and what the future holds for this reality-defying technology.

Science fiction and superhero films portray brain-machine interfaces as malevolent robots that plug into human brains for fuel in The Matrix (top left) or as power-enhancing devices in X-Men (top right). In reality, they can help patients use artificial limbs or directly connect to computers. (Image credits, from top left to bottom right: Warner Brothers, 20th Century Fox, Intelligent Films, AFP Photo/Jean-Pierre Clatot)

For the many superheroes that use high-powered gadgets to save the day, there’s an equal number of villains who use technology nefariously. From robots that plug into human brains for fuel in “The Matrix” to the memory-warping devices seen in “Men in Black,” “Captain Marvel,” and “Total Recall,” technology that can control people’s minds is one of the most terrifying examples of technology gone wrong in science fiction and superhero films.

Now, progress made on brain-machine interfaces, technology that provides a direct communication link between a brain and an external device, is bringing us closer to a world that feels like science fiction. Elon Musk’s company NeuraLink is working on a device to let people control computers with their minds, while Facebook’s “mind-reading initiative” can decode speech from brain activity. Is this progress a glimpse into a dark future, or are there more empowering ways in which brain-machine interfaces could become a force for good?

Penn Today talked with Konrad Kording, a Penn Integrates Knowledge Professor of Neuroscience, Bioengineering, and Computer and Information Science whose group works at the interface of data science and neuroscience to better understand the human brain, to learn more about brain-machine interfaces and where real-world technologies and science fiction intersect.

Q: What are the main challenges in connecting brains to devices?

The key problem is that you need to get a lot of information out of brains. Today’s prosthetic devices are very slow, and if we want to go faster it’s a tradeoff: I can go slower and then I am more precise, or I can go faster and be more noisy. We need to get more data out of brains, and we want to do it electrically, meaning we need to get more electrodes into brains.

So what do you need? You need a way of getting electrodes into the brain without making your brain into a pulp, you want the electrodes to be flexible so they can stay in longer, and then you want the system to be wireless. You don’t want to have a big connector on the top of your head.

It’s primarily a hardware problem. We can get electrodes into brains, but they deteriorate quickly because they are too thick. We can have plugs on people’s heads, but it’s ruling out any real-world usage. All these factors hold us back at the moment.

That’s why the Neuralink announcement was very interesting. They get a rather large number of electrodes into brains using well-engineered approaches that make that possible. What makes the difference is that Neuralink takes the best ideas in all the different domains and puts them together.

Q: Most examples in pop culture of connecting brains to machines have villainous or nefarious ends. Does that match up with how brain-machine interfaces are currently being developed? 

Let’s say you’ve had a stroke, you can’t talk, but there’s a prosthetic device that allows you to talk again. Or if you lost your arm, and you get a new one that’s as good as the original—that’s absolutely a force for good.

It’s not a dark, ugly future thing, it’s a beautiful step forward for medicine. I want to make massive progress in these diseases. I want patients who had a stroke to talk again; I want vets to have prosthetic devices that are as good as the real thing. I think short-term this is what’s going to happen, but we are starting to worry about the dark sides.

Read the full interview at Penn Today.

Penn Engineers at the Forefront of Penn’s ‘Innovation Ecosystem’

By Lauren Salig

Andrei Georgescu, a member of Dan Huh’s bioengineering laboratory, prepares microfluidics for the lab’s work on organ-on-a-chip technology. Their innovative research was one of many Engineering projects featured in a recent video.

The University of Pennsylvania is highlighting its “ecosystem of innovation” in a new video, featuring some of the most cutting-edge work being done on campus and the infrastructure supporting that work. Alongside shots of the Singh Center for Nanotechnology, the Pennovation Center and the coming VentureLab are the familiar faces of Penn Engineers inventing the future.

The video includes the voices of Vijay Kumar, the Nemirovsky Family Dean of the School of Engineering and Applied Science; Dawn Bonnell, Penn’s Vice Provost of Research and the Henry Robinson Towne Professor of Materials Science and Engineering; and Konrad Kording, a Penn Integrates Knowledge Professor of Neurosciences and Bioengineering — each discussing the collaborative environment at the University.

A quick watch of the video reveals glimpses into Penn Engineering labs and projects where much of Penn’s innovation happens: PERCH’s flying robots that swarm together without using GPS, an investigation into 2-D room-temperature platforms for quantum technology, testing mechanical walking algorithms on robotic legs named Cassie, organs-on-a-chip that aid the study of diseases on Earth and in space, President’s Innovation Prize winners’ nanoscale implant company Visiplate aiming to treat blindness, blueprints for nanocrystals that self-assemble into materials with unique properties, Penn Electric Racing’s four-wheel drive competitive racecar, and PERCH lab spin-off Ghost Robotic’s Minitaur robot that senses the ground beneath its metal feet.

See if you can spot these Penn Engineering contributions in the video at Penn Today.

This article was originally posted on the Penn Engineering Medium blog.

Shoddy Science Uncovered in New Research

by Linda Tunesi

shoddy science
Konrad Kording, Ph.D.

Konrad Kording, professor in the Department of Bioengineering, and colleagues have a new technique for identifying fraudulent scientific papers by spotting reused images. Rather than scrap a failed study, for example, a researcher might attempt to pass off images from a different experiment to give the false impression that their own was a success.

Kording, a Penn Integrates Knowledge (PIK) Professor who also has an appointment in the Department of Neuroscience in Penn’s Perelman School of Medicine, and his collaborators developed an algorithm that can compare images across journal articles and detect such replicas, even if the image has been resized, rotated, or cropped.

They describe their technique in a paper recently published on the BioRxiv preprint server.

“Any fraudulent paper damages science,” Kording says. “In biology, many times fraud is detected when someone looks at a few papers and says ‘hey, these images look a little similar.’ We reckoned we could make an algorithm that does the same thing.”

“Science depends on building upon other people’s work,” adds Daniel Acuna, lead author on the paper, and a student in Kording’s lab at Northwestern University at the time the study was conducted. “If you cannot trust other people’s work, the scientific process collapses and, worse, the general public loses trust in us. Some websites were doing this, anonymously, but at a painstakingly slow rate.” Acuna is now an assistant professor in the School of Information Studies at Syracuse University.

While much of Kording’s work focuses on using data science to understand the brain, he is also curious about the process of research itself, or, as he puts it, “the science of science.” One of the Kording lab’s previous projects closely analyzed common methods of neuroscience research, and another turned a mirror on itself, describing how to structure a scientific paper.

Continued at the Penn Engineering Medium blog.

CIFAR Names Kording Associate Fellow

CIFAR
Konrad Kording, Ph.D.

Dr. Konrad Kording, a University of Pennsylvania PIK Professor in Bioengineering and Neuroscience, has been named an associate fellow by the Canadian Institute for Advanced Research (CIFAR), an advanced study institute headquartered in Toronto and partially funded by the government of Canada. Dr. Kording’s fellowship is in the institute’s Learning in Machines & Brains area, which has been one of CIFAR’s 14 interdisciplinary study fields since 2004. He joins 32 other fellows currently supported by the institute for their work in this area.

“The CIFAR program in Learning in Machines & Brains brings together many of the world’s leading deep learning scientists,” Dr. Kording says. “I look forward to collaborate with them to figure out how the brain learns.”

CIFAR was founded in 1982. Over the last 35 years, the institute has supported the work of scientists in 133 countries, including 18 Nobel Prize laureates.

New Faculty: Interview With Konrad Kording

Kording
Konrad Kording, PhD

This week, we present our interview with incoming faculty member Konrad Kording, who starts as a Penn Integrates Knowledge Professor in the Department of Bioengineering and the Department of Neuroscience in the Perelman School of Medicine. Konrad and Andrew Mathis discuss what neuroscience is and isn’t, the “C” word (consciousness), and what it’s like for a native of Germany to live in the United States.

 

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Uncertainty Investigated by Neuroscience

uncertainty

 

Uncertainty is part of life, but the underlying neuroscience of how we make decisions under conditions of uncertainty is only beginning to be understood. In a paper published Monday by Nature Human Behaviour, new Penn Bioengineering faculty member and Penn Integrates Knowledge Professor Konrad Kording, Ph.D., and his coauthor, Iris Vilares, Ph.D., of University College London, offer additional evidence that dopamine lies at the heart of how the brain operates when there is a lack of certainty.

Drs. Kording and Vilares devised a simple computerized test that examined the extent to which test takers relied on previous knowledge vs. what they saw at the present moment. They then administered the test to a cohort of patients with Parkinson’s disease, a condition associated with depleted dopamine levels. The patients were tested both while taking dopaminergic medication and while off it. They found that dopaminergic medication caused the patients to pay greater attention to sensory (i.e., visual) information — an effect that diminished as the patients learned. Ultimately, the study provided evidence that dopamine levels were related to the tendency to rely on new information, also called likelihood uncertainty.

“Scientists believe that understanding uncertainty is key to understanding how the brain computes,” Dr. Kording says. “There are many theories in this space. We provide fairly clean evidence for one of them, which is that dopamine encodes likelihood uncertainty. This information could change the way people think about the manner in which the brain deals with uncertainty.”

Konrad Kording: A Penn Integrates Knowledge Professor Coming to Penn BE

konrad kording
Konrad Kording, PhD

The Department of Bioengineering at the University of Pennsylvania is proud to announce that Konrad Kording, PhD, currently professor of physical medicine and rehabilitation, physiology, and applied mathematics at Northwestern University, will join the BE faculty in the fall.

Dr. Kording, a neuroscientist with advanced degrees in experimental physics and computational neuroscience, is a native of Germany. After earning his PhD in 2001 at the Swiss Federal Institute of Technology in Zurich, he held fellowships at University College, London, and MIT before arriving at Northwestern in 2006.

Kording’s groundbreaking interdisciplinary research uses data science to understand brain function, improve personalized medicine, collaborate with clinicians to diagnose diseases based on mobile phone data, and even understand the careers of professors.  Across many areas of biomedical research, his group analyzes large datasets to test new models and thus get closer to an understanding of complex problems in bioengineering, neuroscience, and beyond.

Dr. Kording’s appointment will be shared between the BE Department and the Department of Neuroscience in the Perelman School of Medicine.