The instrument imaging team, from left: Philadelphia Orchestra bassist Duane Rosengard; Peter Noël, PhD, director of CT Research at the Perelman School of Medicine; luthier Zachary S. Martin; Leening Liu, a PhD student in Noël’s Laboratory of Advanced Computed Tomography Imaging; and Mark Kindig.
When you’re an expert in medical CT imaging, two things are bound to happen, says Peter Noël, PhD, associate professor of Radiology and director of CT Research at the Perelman School of Medicine. One: You develop an insatiable curiosity about the inner workings of all kinds of objects, including those unrelated to your research. And two: Both colleagues and complete strangers will ask for your help in imaging a wide variety of unexpected items.
Over the course of his career, in between managing his own research projects, Noël has imaged diverse objects ranging from animal skulls to tree samples from a German forest, all in the name of furthering scientific knowledge. But none has intrigued him as much as his current extracurricular project: the first known attempt to perform CT imaging of some of the world’s finest string basses.
The goal is to crack the code on what makes a world-class instrument. This knowledge could both increase the ability to better care for masterworks built between the 17th and 19th centuries, as well as providing insights into refining the building of new ones, including possibly shifting from older, scarcer European wood to the use of sustainably harvested U.S. wood.
That’s why Noël and Leening Liu, a PhD student in Noël’s Laboratory of Advanced Computed Tomography Imaging, have found themselves volunteering to run the basses through a Penn CT scanner occasionally, when they’re not developing next-generation CT technology.
“We always learn something out of projects like this … the more appealing part is that medical research can also be applied to non-medical things,” Noël said. “We have the opportunity to take what we learn in medicine and use it for something else—in this case, moving the arts forward.”
Leening Liu is a Ph.D. student in Bioengineering. She is a member of the Laboratory for Advanced Tomography Imaging (LACTI) with research interests including clinical applications of spectral CT and spectral CT thermometry.
Lasya Sreepada has always been fascinated by the brain and the underlying biology that shapes how people develop and age. “My curiosity traces back to observing differences between myself and my sister,” says Sreepada, a Ph.D. candidate in Bioengineering whose research unites efforts across Penn Medicine and Penn Engineering. “We grew up in the same environment but had remarkably different personalities, which led me to question what drove these differences and which brought me to the brain.”
Her academic journey began by applying medical imaging to understand how brain injuries sustained by professional athletes or military veterans impact their brain structure and chemistry over time. She became curious about how neurotrauma impacts aging and degeneration in the long term. Now, she leverages large, multimodal datasets to investigate neurodegenerative disease, with a particular focus on Alzheimer’s.
Congratulations to the 2024 Bioengineering student recipients of the annual Penn Engineering Graduate Student Awards! The awardees were honored in a ceremony on May 15, 2024, hosted by Dean Vijay Kumar and graduate program faculty leadership.
Master’s Student Awards: Elizabeth Brown – Outstanding Service Tianyu Cai – Outstanding Research Ekta Singh – Outstanding Service
PhD Student Awards: Dimitris Boufidis – Outstanding Service Katherine Mossburg – Outstanding Service Kelsey Swingle – Outstanding Teaching
Karen Xu, a 2024 doctoral graduate in Bioengineering at the University of Pennsylvania, is one of 100 doctoral students in the U. S. and Canada selected to receive a $25,000 Scholar Award from the P.E.O. Sisterhood.
The P.E.O. Scholar Awards were established in 1991 to provide substantial merit-based awards for women of the United States and Canada who are pursuing a doctoral-level degree at an accredited college or university. Scholar Awards recipients are a select group of women chosen for their high level of academic achievement and their potential for having a positive impact on society.
The P.E.O., founded January 21, 1869, at Iowa Wesleyan College, Mount Pleasant, Iowa, is a philanthropic educational organization dedicated to supporting higher education for women. There are approximately 6,000 local chapters in the United States and Canada with nearly a quarter of a million active members.
Xu graduated summa cum laude with a B.S.E. in Biomedical Engineering from Duke University in 2018, after which she joined the M.D.-Ph.D. program at the University of Pennsylvania. She completed her Ph.D. in Bioengineering in spring 2024, funded by an NIH NRSA F30 fellowship, and is set to earn her M.D. in 2026. Under the mentorship of Jason Burdick, Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado Boulder and Adjunct Professor in Bioengineering in Penn Engineering, and Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery in the Perelman School of Medicine and in Bioengineering in Penn Engineering, her doctoral research has focused on engineering disease models to facilitate therapeutic discoveries. Her doctoral thesis involved the fabrication of hydrogels as tissue mimics to investigate how extracellular environments affect cell behaviors, thereby informing repair of dense connective tissues.
Beyond her research, Xu has taught with the Educational Pipeline Program at the Netter Center and the Perelman School of Medicine, where she hopes to inspire and support the next generation of healthcare workers and scientists.
Wu is among 55second-year and third-year students selected from 406 candidates nominated by 192colleges and universities nationwide. Scholars are recognized for leadership, public service, and commitment to issues related to the environment or to Native American nations. Each scholar will be awarded as much as $7,000.
A Taiwanese-American undergraduate scientist from Woodbury, Minnesota, Wu is the founder and international director of Waterroots, a nonprofit environmental education project that uses climate storytelling to combat water insecurity in more than 20 countries. Wu is a researcher in Penn Engineering’s McBride Lab, where he works as a plant specialist for a project that promotes environmental stability and sustainable agriculture. He is the deputy director of research for the nonprofit Climate Cardinals, a member of Penn’s Student Advisory Group for the Environment, and the North America representative for the Tunza Eco-Generation Ambassador program. Wu is a Clinton Global Initiative Scholar, a Duke Interfaith Climate Fellow, an IEEE Bio-X Scholar, a 2023 Millennium Fellow, and a 2024 UN ECOSOC Youth Delegate. In addition, he is a resident advisor in Penn’s Stouffer College House, as well as a Penn Engineering and a VIPER student ambassador.
Wu is the 10th student from Penn to be named a Udall Scholar since Congress established the foundation in 1992 to honor Morris and Stewart Udall for their impact on the nation’s environment, public lands, and natural resources and for their support of the rights and self-governance of American Indians and Alaska Natives.
Left to right: Hong-Huy Tran, Chrissie Jaruchotiratanasakul, Manali Mahajan (Photo Courtesy of CiPD)
The Center for Innovation and Precision Dentistry (CiPD), a collaboration between Penn Engineering and Penn Dental Medicine, has partnered with Wharton’s Mack Institute for Innovation Management on a research project which brings robotics to healthcare. More specifically, this project will explore potential uses of nanorobot technology for oral health care. The interdisciplinary partnership brings together three students from different Penn programs to study the commercialization of a new technology that detects and removes harmful dental plaque.
“Our main goal is to bring together dental medicine and engineering for out-of-the-box solutions to address unresolved problems we face in oral health care,” says Hyun (Michel) Koo, Co-Founding Director of CiPD and Professor of Orthodontics. “We are focused on affordable solutions and truly disruptive technologies, which at the same time are feasible and translatable.”
Students test the GaitMate harness and structure as a tool to help recovering patients walk.
Penn students have been building their knowledge and hands-on experience in places all over the world through Penn Global Seminars. Last May, “Robotics and Rehabilitation” brought Penn students back to the tropical island of Jamaica to collaborate with local university students and make an impact on recovery and quality of life for patients in Kingston and beyond.
Course leaders Camillo Jose (CJ) Taylor, Raymond S. Markowitz President’s Distinguished Professor in Computer and Information Science (CIS), and Michelle J. Johnson, Associate Professor of Physical Medicine and Rehabilitation at the Perelman School of Medicine and Associate Professor in Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM) at Penn Engineering, brought the first cohort of students to the island in 2019.
“CJ and I are both Jamaicans by birth,” says Johnson. “We were both excited to introduce the next generation of engineers to robotics, rehabilitation and the process of culturally sensitive design in a location that we are personally connected to.”
As they built relationships with colleagues at the University of West Indies, Mona (UWI, Mona) and the University of Technology, Jamaica (UTECH), both Johnson and Taylor worked to tie the goals of the course to the location.
“In the initial iteration of the course, our goal was to focus on the applications of robotics to rehabilitation in a developing country where it is necessary to create solutions that are cost effective and will work in under-resourced settings,” says Taylor.
Taylor and Johnson wanted to make the course a regular offering, however, due to COVID-related travel restrictions, it wasn’t until last spring that they were able to bring it back. But when they did, they made up for lost time and expanded the scope of the course to include solving health problems for both people and the environment.
“While we started with a focus on people, we realized that the health and quality of life of a community is also impacted by the health of the environment,” says Taylor. “Jamaica has rich terrestrial and marine ecosystems, but those resources need to be monitored and regulated. We ventured into developing robotics tools to make environmental monitoring more effective and cost-friendly.”
One of those student-invented tools was a climate survey drone called “BioScout.”
“Our aim was to create a drone to monitor the ecosystem and wildlife in Jamaica,” says Rohan Mehta, junior in Systems Science and Engineering. “We wanted to help researchers and rangers who need to monitor wildlife and inspect forest sectors without entering and disturbing territories, but there were no available drones that met all of the following criteria necessary for the specific environment: affordable, modular, water-resistant and easy to repair. So we made our own.”
Another team of students created a smart buoy to reduce overfishing. The buoy was equipped with an alarm that goes off when fishermen get too close to a no-fishing zone.
Five other student teams dove into projects aligned to the original goals of the course. Their devices addressed patients’ decreased mobility due to diabetes, strokes and car accidents. These projects were sponsored by the Sir John Golding Rehabilitation Center.
One of which, the GaitMate, was engineered to help stroke patients who had lost partial muscle control regain their ability to walk.
“We developed a device that supports a patient’s weight and provides sensory feedback to help correct their form and gait as they walk on a treadmill, ultimately enhancing the recovery process and providing some autonomy to the patient,” says Taehwan Kim, senior in BE. “The device is also relatively cheap and simple, making it an option for a wide variety of physical therapy needs in Jamaica and other countries.”
A panel of expert and alumni judges chose 3 teams to advance to the School-wide, interdepartmental competition, to be held on May 3, 2024.
Team ADONA: Jude Barakat, Allison Elliott, Daniel Ghaderi, Aditi Ghalsasi, Taehwan Kim
ADONA (A Device for the Assisted Detection of Neonatal Asphyxia)
Hypoxic-ischemic encephalopathy (HIE) is a condition that arises from inadequate oxygen delivery or blood flow to the brain around the time of birth, resulting in long-term neurological damage. This birth complication is responsible for up to 23% of neonatal deaths worldwide. While effective treatments exist, current diagnostic methods require specialized neurologists to analyze an infant’s electroencephalography (EEG) signal, requiring significant time and labor. In areas where such resources and specialized training are even scarcer, the challenges are even more pronounced, leading to delayed or lack of treatment, and poorer patient outcomes. The Assisted Detection of Neonatal Asphyxia (ADONA) device is a non-invasive screening tool that streamlines the detection of HIE. ADONA is an EEG helmet that collects, wirelessly transmits, and automatically classifies EEG data using a proprietary machine learning algorithm in under two minutes. Our device is low-cost, automated, user-friendly, and maintains the accuracy and reliability of a trained neurologist. Our classification algorithm was trained using 1100 hours of annotated clinical data and achieved >85% specificity and >90% sensitivity on an independent 200 hour dataset. Our device is now produced in Agilus 30, a flexible and tear resistant material, that reduces form factor and ensures regulatory compliance. For our final prototype, we hope to improve electrode contact and integrate software with clinical requirements. Our hope is that ADONA will turn the promise of a safer birth into a reality, ensuring instant peace of mind and equitable access to healthcare, for every child and their families.
Team Epilog: Rohan Chhaya, Carly Flynn, Elena Grajales, Priya Shah, Dori Xu
Epilog
To address the critical need for effective, at-home seizure monitoring in pediatric neurology, particularly for Status Epilepticus (SE), our team developed Epilog: a rapid-application electroencephalography (EEG) headband. SE is a medical emergency characterized by prolonged or successive seizures and often presents with symptoms too subtle to notice or easily misinterpreted as post-convulsive fatigue. This leads to delayed treatment and increased risks of neurological damage and high mortality. Current seizure detection technologies are primarily based on motion or full-head EEG, rendering them ineffective at detecting SE and impractical for at-home use in emergency scenarios, respectively. Our device is designed to be applied rapidly during the comedown of a convulsive seizure, collect EEG data, and feed it into our custom machine learning algorithm. The algorithm processes this data in real-time and alerts caregivers if the child remains in SE, thereby facilitating immediate medical decision-making. Currently, Epilog maintains a specificity of 0.88 and sensitivity of 0.95, delivering decisions within 15 seconds post-seizure. We have demonstrated clean EEG signal acquisition from eight standard electrode placements and bluetooth data transmission from eight channels with minimal delay. Our headband incorporates all necessary electrodes and adjustable positioning of the electrodes for different head sizes. Our unique gel case facilitates rapid electrode gelation in less than 10 seconds. Our most immediate goals are validating our fully integrated device and improving features that allow for robust, long-term use of Epilog. Epilog promises not just data, but peace of mind, and empowering caregivers to make informed life-saving decisions.
Team NG-LOOP: Katherine Han, Jeffrey Huang, Dahin Song, Stephanie Yoon
NG-LOOP
Nasogastric (NG) tube dislodgement occurs when the feeding tube tip becomes significantly displaced from its intended position in the stomach, causing fatal consequences such as aspiration pneumonia. Compared to the 50% dislodgement rate in the general patient population, infant patients are particularly affected ( >60%) due to their miniature anatomy and tendency to unknowingly tug on uncomfortable tubes. Our solution, the Nasogastric Lightweight Observation and Oversight Product (NG-LOOP) provides comprehensive protection from NG tube dislodgement. Physical stabilization is combined with sensor feedback to detect and manage downstream complications of tube dislodgement. The lightweight external bridle, printed with biocompatible Accura 25 and coated with hydrocolloid dressing for comfort and grip, can prevent dislodgement 100% of the time given a tonic force of 200g. The sensor feedback system uses a DRV5055 linear hall effect sensor with a preset difference threshold, coupled with an SMS alert and smart plug inactivation of the feeding pump. A sensitivity of 90% and specificity of 100% in dislodgement detection was achieved under various conditions, with all feedback mechanisms being initiated in response to 100% of threshold triggers. Future steps involve integration with hospital-grade feeding pumps, improving the user interface, and incorporating more sizes for diverse age inclusivity.
Photos courtesy of Afraah Shamim, Coordinator of Educational Laboratories in the Penn BE Labs. View more photos on the Penn BE Labs Instagram.
Senior Design (BE 4950 & 4960) is a two-semester capstone course taught by David Meaney, Solomon R. Pollack Professor in Bioengineering and Senior Associate Dean of Penn Engineering, Erin Berlew, Research Scientist in the Department of Orthopaedic Surgery and Lecturer in Bioengineering, and Dayo Adewole, Postdoctoral Fellow of Otorhinolaryngology (Head and Neck Surgery) in the Perelman School of Medicine. Read more stories featuring Senior Design in the BE Blog.
Diagram of the optoPlateReader, a high-throughput, feedback-enabled optogenetics and spectroscopy device initially developed by Penn 2021 iGEM team.
For bioengineers today, light does more than illuminate microscopes. Stimulating cells with light waves, a field known as optogenetics, has opened new doors to understanding the molecular activity within cells, with potential applications in drug discovery and more.
Thanks to recent advances in optogenetic technology, much of which is cheap and open-source, more researchers than ever before can construct arrays capable of running multiple experiments at once, using different wavelengths of light. Computing languages like Python allow researchers to manipulate light sources and precisely control what happens in the many “wells” containing cells in a typical optogenetic experiment.
However, researchers have struggled to simultaneously gather data on all these experiments in real time. Collecting data manually comes with multiple disadvantages: transferring cells to a microscope may expose them to other, non-experimental sources of light. The time it takes to collect the data also makes it difficult to adjust metabolic conditions quickly and precisely in sample cells.
Now, a team of Penn Engineers has published a paper in Communications Biology, an open access journal in the Nature portfolio, outlining the first low-cost solution to this problem. The paper describes the development of optoPlateReader (or oPR), an open-source device that addresses the need for instrumentation to monitor optogenetic experiments in real time. The oPR could make possible features such as automated reading, writing and feedback in microwell plates for optogenetic experiments.
Left to right: Will Benman, Gloria Lee, Saachi Datta, Juliette Hooper, Grace Qian, David Gonzalez-Martinez, and Lukasz Bugaj (with Max).
The paper follows up on the award-winning work of six University of Pennsylvania alumni — Saachi Datta, M.D. Candidate at Stanford School of Medicine; Juliette Hooper, Programmer Analyst in Penn’s Perelman School of Medicine; Gabrielle Leavitt, M.D. Candidate at Temple University; Gloria Lee, graduate student at Oxford University; Grace Qian, Drug Excipient and Residual Analysis Research Co-op at GSK; and Lana Salloum, M.D. Candidate at Albert Einstein College of Medicine — who claimed multiple prizes at the 2021 International Genetically Engineered Machine Competition (iGEM) as Penn undergraduates.
The International Genetically Engineered Machine Competition (or iGEM) is the largest synthetic biology community and the premiere synthetic biology competition for both university and high school students from around the world. Hundreds of interdisciplinary teams of students compete annually, combining molecular biology techniques and engineering concepts to create novel biological systems and compete for prizes and awards through oral presentations and poster sessions.
The optoPlateReader was initially developed by Penn’s 2021 iGEM team, combining a light-stimulation device with a plate reader. At the iGEM competition, the invention took home Best Foundational Advance (best in track), Best Hardware (best from all undergraduate teams), and Best Presentation (best from all undergraduate teams), as well as a Gold Medal Distinction and inclusion in the Top 10 Overall and Top 10 Websites lists. (Read more about the 2021 iGEM team on the BE Blog.)
The original iGEM project focused on the design, construction, and testing of the hardware and software that make up the oPR, the focus of the new paper. After iGEM concluded, the team showed that the oPR could be used with real biological samples, such as cultures of bacteria. This work demonstrated that the oPR could be applied to real research questions, a necessary precursor to publication, and that the device could simultaneously monitor and manipulate living samples.
The main application for the oPR is in metabolic production (such as the creation of pharmaceuticals and bio-fuels). The oPR is able to issue commands to cells via light but can also take live readings about their current state. In the oPR, certain colors of light cause cells to carry out different tasks, and optical measurements give information on growth rates and protein production rates.
In this way, the new device is able to support production processes that can adapt in real time to what cells need, altering their behavior to maximize yield. For example, if an experiment produces a product that is toxic to cells, the oPR could instruct those cells to “turn on” only when the population of cells is dense and “turn off” when the concentration of that product becomes toxic and the cellular population needs to recover. This ability to pivot in real time could assist industries that rely on bioproduction.
The main challenges in developing this device were in incorporating the many light emitting diodes (LEDs) and sensors into a tiny space, as well as insulating the sensors from the nearby LEDs to ensure that the measured light came from the sample and not from the instrument itself. The team also had to create software that could coordinate the function of nearly 100 different sets of LEDs and sensors. Going forward, the team hopes to spread the word about the open-source oPR to other researchers studying metabolic production to enable more efficient research.
Lukasz Bugaj, Assistant Professor in Bioengineering and senior author of the paper, served as the team’s mentor along with Brian Chow, formerly an Associate Professor in Bioengineering and a founding member of the iGEM program at MIT, and Jose Avalos, Associate Professor of Chemical and Biological Engineering at Princeton University.
Key to the project’s development was the guidance of Bioengineering graduate students Will Benman, David Gonzalez Martinez, and Gabrielle Ho, as well as that of Saurabh Malani, a graduate student at Princeton University.
Visualization of a CAR T cell (in red) attacking a cancer cell (in blue) (Meletios Varras via Getty Images)
For patients with certain types of cancer, CAR T cell therapy has been nothing short of life changing. Developed in part by Carl June, Richard W. Vague Professor at Penn Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.
However, the process for manufacturing CAR T cells themselves is time-consuming and costly, requiring multiple steps across days. The state of the art involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.
Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step, thanks to the use of lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.
In a new paper in Advanced Materials, Michael J. Mitchell, Associate Professor in Bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student in Bioengineering and NSF Graduate Research Fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”
