“The proposed studies lay the foundation to make a major scientific impact in the childhood leukemia field and ultimately improve outcomes for children,” says Vining.
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?”
Georgia Georgostathi accepts the Wolf-Hallac Award from Dean Vijay Kumar.
Each spring, awards are given to undergraduate students in the School of Engineering and Applied Science in recognition of outstanding scholarly achievements and service to the School and University community. The 2024 award recipients were recognized in a ceremony held on Wednesday, March 27, 2024 at the Penn Museum.
Read the full list of Bioengineering undergraduate award winners below.
The Wolf-Hallac Award: Georgia Georgostathi. This award was established in October 2000 to recognize the graduating female senior from across Penn Engineering’s departments who is seen as a role model, has achieved a high GPA (in the top 10% of their class), and who has demonstrated a commitment to school and/or community.
Alexandra Dumas accepts the Maddie Magee Award for Undergraduate Excellence.
The Maddie Magee Award for Undergraduate Excellence: Alexandra Dumas. This award is given to a Penn Engineering senior who best exemplifies the energy, enthusiasm, and excellence of Penn Engineering alumna Madison “Maddie” N. Magee (MEAM BS ’21, BE MS ’21).
The Hugo Otto Wolf Memorial Prize: Jude Barakat & Dori Xu. This prize is awarded to one or more members of each department’s senior class, distinguishing students who meet with great approval of the professors at large through “thoroughness and originality” in their work.
The Herman P. Schwan Award: Angela Song. This department award honors a graduating senior who demonstrates the “highest standards of scholarship and academic achievement.”
Penn Engineering Exceptional Service Awards recognize students for their outstanding service to the University and their larger communities: Srish Chenna, Daniel Ghaderi, Taehwan Kim and Daphne Nie.
Chaitanya Karimanasseri accepts the Bioengineering Student Leadership Award.
The Bioengineering Student Leadership Award: Chaitanya Karimanasseri. This award is given annually to a student in Bioengineering who has demonstrated, through a combination of academic performance, service, leadership, and personal qualities, that they will be a credit to the Department, the School, and the University.
Additionally, the Bioengineering Department also presents a single lab group with the Albert Giandomenico Award which reflects their “teamwork, leadership, creativity, and knowledge applied to discovery-based learning in the laboratory.” This year’s group consists of Alexandra Dumas, Georgia Georgostathi, Daphne Nie and Angela Song.
A full list of Penn Engineering award descriptions and recipients can be found here.
BE award winners enjoy the ceremony reception in the Penn Museum.
LeAnn Dourte, Practice Associate Professor in Bioengineering, has been one of the most active members of the Penn Engineering faculty in pioneering the Structured, Active, In-Class Learning (SAIL) model of education. In a recent issue of the Penn Almanac, Dourte boils down her practical advice for faculty looking to make their courses more interactive and dynamic into one simple philosophy: “Just change 10 minutes.”
“The effectiveness of these 10-minute activities hinges on their alignment with learning objectives. Students are always on the lookout for anything that they see as busy-work, so articulating the purpose of such activities is paramount to their success. These are some of the goals I think about when I design activities with my learning objectives in mind. While some of these approaches are specific to subjects with quantitative problem solving, many have applications across disciplines.”
Dourte’s article articulates her active learning approach, along with a list of specific learning objectives, including encouraging diverse perspectives, promoting error recognition and correction, and more.
Members of Team Sonura: Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, & Caroline Magro (credit: Penn BE Labs)
In April 2023, three President’s Prize-winning teams were selected from an application pool of 76 to develop post-graduation projects that make a positive, lasting difference in the world. Each project received $100,000 and a $50,000 living stipend per team member.
The winning projects include Sonura, the winner of the President’s Innovation Prize (PIP), who are working to improve infant development by reducing harsh noise exposure in neonatal intensive care units. To accomplish this, they’ve developed a noise-shielding beanie that can also relay audio messages from parents.
Sonura, a bioengineering quintet, developed a beanie that shields newborns from the harsh noise environments present in neonatal intensive care units (NICUs)—a known threat to infant wellbeing—and also supports cognitive development by relaying audio messages from their parents.
Since graduating from the School of Engineering and Applied Science, the team of Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, and Caroline Magro, has collaborated with more than 50 NICU teams nationwide. They have been helped by the Intensive Care Nursery (ICN) at the Hospital of the University of Pennsylvania (HUP), which shares Sonura’s goal of reducing NICU noise. “Infant development is at the center of all activities within the HUP ICN,” note Daltoso and Ishiwari. “Even at the most granular level, like how each trash can has a sign urging you to shut it quietly, commitment to care is evident, a core tenet we strive to embody as we continue to grow.”
An initial challenge for the team was the inability to access the NICU, crucial for understanding how the beanie integrates with existing workflows. Collaboration with the HUP clinical team was key, as feedback from a range of NICU professionals has helped them refine their prototype.
In the past year, the team has participated in the University of Toronto’s Creative Destruction Lab and the Venture Initiation Program at Penn’s Venture Lab, and received funding from the Pennsylvania Pediatric Device Consortium. “These experiences have greatly expanded our perspective,” Cano says.
With regular communication with mentors from Penn Engineering and physicians from HUP, Children’s Hospital of Philadelphia, and other institutes, Sonura is looking ahead as they approach the milestone of completing the FDA’s regulatory clearance process within the year. They will begin piloting their beanie with the backing of NICU teams, further contributing to neonatal care.
Read the full story and watch a video about Sonura’s progress in Penn Today.
Read more stories featuring Sonura in the BE Blog.
Penn Engineers have developed a way to target lung diseases, including lung cancer, with lipid nanoparticles (LNPs). (wildpixel via Getty Images)
Penn Engineers have developed a new means of targeting the lungs with lipid nanoparticles (LNPs), the miniscule capsules used by the Moderna and Pfizer-BioNTech COVID-19 vaccines to deliver mRNA, opening the door to novel treatments for pulmonary diseases like cystic fibrosis.
In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, demonstrates a new method for efficiently determining which LNPs are likely to bind to the lungs, rather than the liver. “The way the liver is designed,” says Mitchell, “LNPs tend to filter into hepatic cells, and struggle to arrive anywhere else. Being able to target the lungs is potentially life-changing for someone with lung cancer or cystic fibrosis.”
Previous studies have shown that cationic lipids — lipids that are positively charged — are more likely to successfully deliver their contents to lung tissue. “However, the commercial cationic lipids are usually highly positively charged and toxic,” says Lulu Xue, a postdoctoral fellow in the Mitchell Lab and the paper’s first author. Since cell membranes are negatively charged, lipids with too strong a positive charge can literally rip apart target cells.
Typically, it would require hundreds of mice to individually test the members of a “library” of LNPs — chemical variants with different structures and properties — to find one with a low charge that has a higher likelihood of delivering a medicinal payload to the lungs.
Instead, Xue, Mitchell and their collaborators used what is known as “barcoded DNA” (b-DNA) to tag each LNP with a unique strand of genetic material, so that they could inject a pool of LNPs into just a handful of animal models. Then, once the LNPs had propagated to different organs, the b-DNA could be scanned, like an item at the supermarket, to determine which LNPs wound up in the lungs.
Four University of Pennsylvania undergraduates have received 2024 Goldwater Scholarships, awarded to second- or third-year students planning research careers in mathematics, the natural sciences, or engineering.
They are among the 438 students named 2024 Goldwater Scholars from 1,353 undergraduates students nominated by 446 academic institutions in the United States, according to the Barry Goldwater Scholarship & Excellence in Education Foundation. Each scholarship provides as much as $7,500 each year for as many as two years of undergraduate study.
Mrksich, from Hinsdale, Illinois, is majoring in bioengineering. She is interested in developing drug delivery systems that can serve as novel therapeutics for a variety of diseases. Mrksich works in the lab of Michael J. Mitchell where she investigates the ionizable lipid component of lipid nanoparticles for mRNA delivery. At Penn, Mrksich is the president of the Biomedical Engineering Society, where she plans community building and professional development events for bioengineering majors. She is a member of the Kite and Key Society, where she organizes virtual programming to introduce prospective students to Penn. She is a member of Tau Beta Pi engineering honor society, and the Sigma Kappa sorority. She also teaches chemistry to high schoolers as a volunteer in the West Philadelphia Tutoring Project through the Civic House. After graduating, Mrksich plans to pursue an M.D./Ph.D. in bioengineering.
Mrksich was awarded a Student Award for Outstanding Research (Undergraduate) by the Society for Biomaterials earlier this year. Read the story in the BE Blog.
Like space shuttles using booster rockets to breach the atmosphere, lipid nanoparticles (LNPs) equipped with the new molecule more successfully deliver medicinal payloads. (Love Employee via Getty Images)
Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.
In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. For this paper, Mitchell and his co-authors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease.
Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA to cells, but the methods for creating these molecules are time- and cost-intensive. “We offer a novel construction strategy for rapid and cost-efficient synthesis of these lipidoids,” says Xuexiang Han, a postdoctoral student in the Mitchell Lab and the paper’s co-first author.
