Novel Tools for the Treatment and Diagnosis of Epilepsy

by Nathi Magubane

A neurologist examines an encephalogram of a patient’s brain.
Throughout his career, Brian Litt has fabricated tools that support international collaboration, produced findings that have led to significant breakthroughs, and mentored the next generation of researchers tackling neurological disorders. (Image: iStock Photo/Alona Siniehina)

When Brian Litt of the Perelman School of Medicine and School of Engineering and Applied Science began treating patients as a neurologist, he found that the therapies and treatments for epilepsy were mostly reliant on traditional pharmacological interventions, which had limited success in changing the course of the disease.

People with epilepsy are often prescribed anti-seizure medications, and, while they are effective for many, about 30% of patients still continue to experience seizures. Litt sought new ways to offer patients better treatment options by investigating a class of devices that electronically stimulate cells in the brain to modulate activity known as neurostimulation devices.

Litt’s research on implantable neurostimulation devices has led to significant breakthroughs in the technology and has broadened scientists’ understanding of the brain. This work started not long after he came to Penn in 2002 with licensing algorithms to help drive a groundbreaking device by NeuroPace, the first closed-loop, responsive neurostimulator to treat epilepsy.

Building on this work, Litt noted in 2011 how the implantable neurostimulation devices being used at the time had rigid wires that didn’t conform to the brain’s surface, and he received support from CURE Epilepsy to accelerate the development of newer, flexible wires to monitor and stimulate the brain.

“CURE is one of the epilepsy community’s most influential funding organizations,” Litt says. “Their support for my lab has been incredibly helpful in enabling the cutting-edge research that we hope will change epilepsy care for our patients.”

Read the full story in Penn Today.

Brian Litt is a Professor in Bioengineering and Neurology.

Flavia Vitale is an Assistant Professor in Neurology with a secondary appointment in Bioengineering.

Jonathan Viventi is an Assistant Professor in Biomedical Engineering at Duke University.

The Penn Center for Precision Engineering for Health Announces First Round of Seed Funding

by Melissa Pappas

CPE4H is one of the focal points of Penn Engineering signature initiative on Engineering Health.

The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.

Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.

“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”

Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.

Evolving and Engineering Thermal Control of Mammalian Cells

Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies.  The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.

A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections

Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.

Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering

PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.

Towards an Artificial Muscle Replacement for Facial Reanimation

Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.

“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”

This article originally appeared in Penn Engineering Today.

Penn Health-Tech After Five Years: An Interview with Executive Director Katie Reuther

Penn Health-Tech director Katie Reuther (center) with Glory Durham, director of operations, Penn Health-Tech (at left), and Courtney Houtsma, program manager, Penn Health-Tech (at right), at a recent symposium.

A new interview in Penn Medicine News examines Penn Health-Tech (PHT) five years after its founding. PHT began as an experimental collaborative effort between the Perelman School of Medicine, the School of Engineering and Applied Science, and the Office of the Vice Provost for Research to provide funding, advising, and resources to empower innovators to develop transformative devices and technologies in the Penn community. Specifically, PHT specializes in connecting innovators from across Penn’s campus and schools to connect and to develop technology and medical devices to answer some of the most pressing needs in healthcare. Katherine (Katie) Reuther, Practice Associate Professor in Bioengineering, was appointed Executive Director of PHT in 2021 and is leading this venture into the next phase of its growth. Reuther, an alumna of Penn Bioengineering, followed up her doctoral studies with a M.B.A. from Columbia University and subsequently stayed at Columbia as Senior Lecturer in Design, Innovation, and Entrepreneurship in the Department of Biomedical Engineering. As such, her experience and expertise in the fields of both biomedical engineering and entrepreneurship position her well to shepherd PHT into its fullest potential:

“What appealed to me most about the position was a strong foundation, deep resources, and the potential and room to do more, including the opportunity to elevate Penn and Philadelphia as a national hub for health-technology innovation.”

Read the full interview with Reuther in “From ‘Experiment’ to $50 Million in Funding: After 5 Years, Where Penn Health-Tech is Going.”

Konrad Kording on the Future of Brain-Computer Interfaces

Konrad Kording (Photo by Eric Sucar)

Though the technology for brain-computer interfaces (or BCI’s) has existed for decades, recent strides have been made to create BCI devices which are safer, smaller, and more effective. Konrad Kording, Nathan Francis Mossell University Professor in Bioengineering, Neuroscience, and Computer and Information Science, helps to elucidate the potential future of this technology in a recent feature in Wired. In the article, he discusses the “invasive” aspects of previous BCI technology, in contrast to recent innovations, such as a new device by Synchron, which do not require surgery and are consequently much less risky:

“The device, called a Stentrode, has a mesh-like design and is about the length of a AAA battery. It is implanted endovascularly, meaning it’s placed into a blood vessel in the brain, in the region known as the motor cortex, which controls movement. Insertion involves cutting into the jugular vein in the neck, snaking a catheter in, and feeding the device through it all the way up into the brain, where, when the catheter is removed, it opens up like a flower and nestles itself into the blood vessel’s wall. Most neurosurgeons are already up to speed on the basic approach required to put it in, which reduces a high-risk surgery to a procedure that could send the patient home the very same day. ‘And that is the big innovation,” Kording says.

Read “The Age of Brain-Computer Interfaces Is on the Horizon” in Wired.

2022 Penn Bioengineering Senior Design Teams Win Multiple Accolades

After a year of hybrid learning, Penn Bioengineering (BE) seniors were excited to return to the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace for Senior Design (BE 495 & 496), a two-semester course in which students work in teams to conceive, design and pitch their capstone projects in bioengineering. This year’s projects include tools for monitoring health, software to improve communication for the healthcare and supply chain industries, and devices to improve patient care for women and underrepresented minorities.

The year culminated in the annual Senior Design Expo on April 13 in the Singh Center for Nanotechnology, in which the students presented their pitches to a panel of alumni judges, followed by demonstrations in the George H. Stephenson  Foundation Educational Laboratory & Bio-MakerSpace which were open to the entire Penn community. This year’s winners of the Bioengineering Senior Design Competition were teams Chrysalis, Modulo Prosthetics, and ReiniSpec.

Team 11 (ReiniSpec) From L to R: Ifeoluwa Popoola, Alexa Rybicki, JeongInn Park (TA), Caitlin Frazee, Michelle White, Caroline Kavanagh (on laptop).

The three winning teams went on to compete in the annual interdepartmental Senior Design Competition sponsored by the Penn Engineering Alumni Society. BE took home two of the four interdepartmental awards: Team Modulo Prosthetics won the “Technology and Innovation Prize,” recognizing the project which best represents the highest and best use of technology and innovation to leverage engineering principles; and Team ReiniSpec won the “Leadership Prize,” which recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project scope, advantages, and challenges, and addresses the commercialization and future potential of their research.

All BE teams were also required to submit their projects to local and national competitions, and were met with resounding success. “The creativity and accomplishment of this Senior Design class is really unparalleled,” said David Meaney, Solomon R. Pollack Professor in Bioengineering, Senior Associate Dean of Penn Engineering, and instructor for Senior Design. “The number of accolades received by these students, as well as the interest in transforming their ideas into real products for patients, reached a new level that makes us extremely proud.”

Keep reading for a full list of this year’s projects and awards.

Team 1 – MEViD

MEViD (Multichannel Electrochemical Viral Diagnostic) is a modular, low cost device that leverages electrochemistry to rapidly diagnose viral diseases from saliva samples.

Team members: Yuzheng (George) Feng, Daphne Kontogiorgos-Heintz, Carisa Shah, Pranshu Suri, & Rachel Zoneraich

Team 2 – MOD EZ-IO

MOD EZ-IO is a low-cost, novel intraosseous drill that uses force and RPM readings to alert the user via an LED when they have breached cortical bone and entered cancellous bone, guiding proper IO placement.

Team members: Gregory Glova, Kaiser Okyan, Patrick Paglia, Rohan Vemu, & Tshepo Yane

Team 3 – Harvest by Grapevine

Harvest by Grapevine is a user-centric software solution that merges social network communication and supply chain logistics to connect hospitals and suppliers under one unified platform.

Team members: Nicole Bedanova, Kerry Blatney, Blake Grimes, Brenner Maull, & Lukas Yancopoulos

Team 4 – CliniCall

CliniCall helps streamline and centralize communication channels, offering a real-time monitoring device that enables on-site/attending physicians to communicate with on-call physicians through a livestream of patients and data.

Team members: Neepa Gupta, Santoshi Kandula, Sue Yun Lee, & Ronil Synghal

Team 5 – PneuSonus

PneuSonus is a low-cost, user-friendly wearable strap that aids in detecting pediatric pneumonia by using frequency analysis of sound waves transmitted through the lungs to identify specific properties related to fluid presence, a valid indicator specific to pneumonia.

Team members: Iman Hossain, Kelly Lopez, Sophia Mark, Simi Serfati, & Nicole Wojnowski

Team 6 – Chrysalis

Chrysalis is a smart swaddle system comprising an electric swaddle and accompanying iOS application that comforts neonatal abstinence syndrome infants via stochastic resonance and maternal heartbeat vibrational patterns to reduce opioid withdrawal symptoms without pharmacological intervention or constant nurse oversight as well as streamlines the Eat, Sleep, Console documentation process for nurses.

Team members: Julia Dunn, Rachel Gu, Julia Lasater, & Carolyn Zhang

Team 7 – EquitOx

EquitOx is a revolutionized fingertip pulse oximeter designed for EMS that addresses racial inequality in medicine through the use of one-off tongue-calibrated SpO2 measurements.

Team members: Ronak Bhagia, Estelle Burkhardt, Juliette Hooper, Caroline Smith, & Kevin Zhao

Team 8 – Modulo Prosthetics

Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).

Team members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, & Zachary Spalding

Team 9 – Cor-Assist By Cygno Technologies

COR-ASSIST by Cygno Technologies is a low-cost intra-aortic balloon enhancement that directly supports heart function by increasing cardiac output to 2.8L/min, at a much lower cost and bleeding risk than the current Impella cardiac assist device.

Team members: Francesca Cimino, Allen Gan, Shawn Kang, Kristina Khaw, & William Zhang

Team 10 – Pedalytics

Pedalytics Footwear is a rechargeable sandal that continuously monitors foot health and prevents diabetic foot ulcer formation by novelly tracking three key metrics indicative of ulceration, temperature, oxygen saturation, and pressure, and sending alerts to patients via the Pedalytics app when metric abnormalities are detected.

Team members: Samantha Brosler, Constantine Constantinidis, Quincy Hendricks, Ananyaa Kumar, & María José Suárez

Team 11 – ReiniSpec

ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.

Team members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, & Michelle White

Learn more about the 2022 Senior Design projects, including full abstracts and photo gallery, on the Stephenson Bio-MakerSpace website.

Watch all the 2022 project pitches on the BE Labs Youtube channel 2022 Senior Design Playlist:

Ossum Technologies Wins 2022 Y-Prize with Tool for Stabilizing Fractures

by Ebonee Johnson

Cerclage wire is used to stabilize pieces of fractured bone; the OsPass aims to make it easier for surgeons to put that wire into place.

The Y-Prize, a student startup competition based on technologies developed at Penn Engineering, is hosted by the Wharton School’s Mack Institute for Innovation Management, Penn Wharton Entrepreneurship and the Penn Center for Innovation each year. The team with the best pitch takes home $10,000 in investment funding.

This year’s winning team was Ossum Technologies, composed of Ananya Dewan, Hoang Le, Shiva Teerdhala, all students in the Vagelos Life Sciences and Management Program, Bioengineering major Karan Shah and Savan Patel, a student in the Jerome Fisher Program for Management & Technology.

The team utilized the steerable needle technology developed by Mark Yim, Asa Whitney Professor of Mechanical Engineering and Applied Mechanics, and colleagues. Yim’s device is a flexible needle that can be guided through soft materials with simple handheld controls, enabling users to pinpoint hard-to-reach areas that might otherwise require more complicated tools or robotic assistance.

Read the full story in Penn Engineering Today.

Daniel A. Hammer Named Director of Center for Precision Engineering for Health

Daniel Hammer
Daniel Hammer, Ph.D.

by Evan Lerner

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.”

Read the full story in Penn Engineering Today.

BE Seminar: “Neural Engineering and the Primate Brain: Working at the Electrical and Optical Interface” (Bijan Pesaran)

Our final Penn Bioengineering seminar of the fall semester will take place this Thursday. Keep an eye on the BE events calendar for upcoming spring seminars.

Speaker: Bijan Pesaran, Ph.D.
Professor
Neural Science
New York University

Date: Thursday, December 16, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link
Room: Moore 216

Abstract: Neural engineering is enjoying an era of transformative growth. Classical methods that dominated the neurosciences for decades are being replaced by powerful new technologies. In this talk, I will discuss how to engineer electrical and optical interfaces to the primate brain. I will first present work on electrode interfaces that stimulate and record at the surface of and within the brain. I will show how simultaneously measuring and manipulating neurons immediately beneath electrode contacts during behavior delivers ground-truth data. The results have implications for electrode interface design and new generations of implantable biomedical devices. I will then turn to optical neural interfaces. Two-photon fluorescence microscopy images the activity of neurons expressing genetically-encoded calcium indicators and is most often performed in small animal models, such as the mouse, worm and fly. I will present a cellular-resolution robotic imaging platform to investigate the non-human primate brain at scale. I will finish by discussing potential applications of this technology to a range of scientific and clinical goals.

Bijan Pesaran Bio: Bijan Pesaran is interested in understanding large-scale circuits in the primate brain and how to engineer novel brain-based therapies. Bijan completed his undergraduate degree in Physics at the University of Cambridge, UK. After a year in the Theoretical Physics department at Bell Labs Murray Hill, he went on to earn his PhD in Physics at the California Institute of Technology. He then made the switch to neuroscience as a postdoctoral fellow in Biology at Caltech. Bijan has been on the faculty at New York University since 2006. He is currently a Professor of Neural Science in the Center for Neural Science. In 2013, he was a CV Starr Visiting Scholar at the Princeton Neuroscience Institute at Princeton University. Among other honors and awards, Bijan has received a Burroughs-Wellcome Career Award in the Biomedical Sciences, a Sloan Research Fellowship, a McKnight Scholar Award, the National Science Foundation CAREER Award and is a member of the Simons Collaboration for the Global Brain.

Penn Bioengineering Senior Raveen Kariyawasam Named 2022 Rhodes Scholar

2022 Rhodes Scholar, Raveen Kariyawasam

One of the two University of Pennsylvania seniors who were awarded Rhodes Scholarships for graduate study at the University of Oxford is Penn Engineering‘s own Raveen Kariyawasam, from Colombo, Sri Lanka.

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.

With an interest in health care innovation and accessibility, Kariyawasam is involved in several research projects, including his Wharton honors thesis that focuses on optimizing a low-cost electronic medical record system in Sri Lanka and the Philippines. He has received several research grants, including the Vagelos Undergraduate Research Grant, the Berkman Opportunity Fund grant, and the National Science Foundation’s Innovation Corps grant. At Penn, he is editor-in-chief of Synapse, a student-run health care magazine and is vice president of the Phi Sigma Biological Honor Society. He is a disc jockey for the student-run radio station, WQHS, and an executive board member of the Wharton Undergraduate Healthcare Club. He also is a former student ambassador at the Penn Health-Tech Center for Health Devices and Technology. At Oxford, Kariyawasam plans to pursue a D.Phil. degree.

Read more at Penn Today.

Developing New Technologies to Solve the Mysteries of the Brain

Flavia Vitale, assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founder of the multidisciplinary Vitale Lab. (Image: Penn Medicine News)

Neurology, bioengineering, and physical medicine and rehabilitation might not seem like three disciplines that fit together, but for Flavia Vitale, an assistant professor of all three, it makes perfect sense. As the director and principal investigator at the Vitale Lab, her research focuses on developing new technologies that help to study how the brain and neuromuscular systems function.

Years ago, while she was working at Rice University developing new materials and devices that work in the body in a safer, more effective way, former president Barack Obama launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, aimed at revolutionizing the understanding of the human brain. This emphasis on how little is known about brain structure and function inspired Vitale to refocus her research on developing technology and materials that will help researchers solve the mysteries of the brain.

In 2018, she joined the faculty at the Perelman School of Medicine as an assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founded the multidisciplinary Vitale Lab, where her team develops cutting edge materials and devices that will someday help clinicians diagnose and treat patients with complicated brain and neurological conditions. She is also one of the engineers looking forward to using new combined clinical/research facilities in neuroscience at Penn Medicine’s new Pavilion where new neurotechnoloigies will be developed and tested.

“My main goal is to create tools that can help solve mysteries of the brain, and address the needs of clinicians,” she says.

“My lab was recently awarded two grants totaling $4.5 million from the National Institute of Neurological Disorders and Stroke. In order to obtain more precise insights, noninvasively, into brain activity to improve gene therapy treatments for a range of diagnoses, from Parkinson’s disease to glioblastoma. The first grant is designated for the development of a novel surgical device for delivering gene-based therapeutics to the brain. The second is for optimization and pre-clinical validation of a novel EEG electrode technology, which uses a soft, flexible, conductive nanomaterial rather than metal and gels. We hope to confirm that these technologies work as well as, if not better than existing ones.”

Read the full story in Penn Medicine News.