Illuminating the Unseen: Former Penn iGEM Team Publishes Award-Winning Optogenetic Device

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.

Much of the original work was conducted in Penn Bioengineering’s Stephenson Foundation Educational Laboratory & Bio-MakerSpace, with important contributions made by Michael Patterson, Director of Educational Laboratories in Bioengineering, and Sevile Mannickarottu, Director of Technological Innovation and Entrepreneurship in Penn Engineering’s Entrepreneurship Program.

Read “High-throughput feedback-enabled optogenetic stimulation and spectroscopy in microwell plates” in Communications Biology.

This project was supported by the Department of Bioengineering, the School of Engineering and Applied Science, and the Office of the Vice Provost for Research (OVPR), and by funding from the National Institute of Health (NIH), the National Science Foundation (NSF), and the Department of Energy (DOE).

The iGEM program was created at the Massachusetts Institute of Technology in 2003. Read stories in the BE Blog featuring recent Penn iGEM teams here.

2023 PIP-Winning Team Sonura: Where Are They Now?

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.

Estelle Sunghee Park Appointed Assistant Professor at Purdue University

Estelle Park, Ph.D.

Penn Bioengineering is proud to congratulate Sunghee Estelle Park, Ph.D. on her appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Park earned her Ph.D. at Penn Bioengineering, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her appointment at Purdue will begin January 2024.

During her Ph.D. research, Park forged a unique path that combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Using a microengineered model of the human retina, she discovered previously unknown roles of the MAPK, IL-17, PI3K-AKT, and TGF-β signaling pathways in the pathogenesis of age-related macular degeneration (AMD), presenting novel therapeutic targets that could be further investigated for the development of AMD treatments. More recently, she tackled a significant challenge in the organoid field, the limited tissue growth and maturity in conventional organoid cultures, by designing microengineered systems that enabled organoids to grow with unprecedented levels of maturity and human-relevance. By integrating these platforms with bioinformatics and computational analyses, she identified novel disease-specific biomarkers of inflammatory bowel disease (IBD) and intestinal fibrosis, including previously unknown link between the presence of lncRNA and the development of IBD.

“The unique interdisciplinary expertise I gained from these projects has shaped me into a scholar with a strong collaborative ethos, a quality I hold in high esteem as we work towards advancing our knowledge and management of health and disease,” says Park.

Her vision as an independent researcher is to become a leading faculty who makes impactful contributions to our fundamental understanding of the factors influencing the structural and functional changes of human organs in health and disease. To achieve this, she plans to lead a stem cell bioengineering laboratory with a primary focus on tissue engineering and regenerative medicine. This will involve developing human organoids-on-a-chip systems and establishing next-generation biomedical devices and therapies tailored for regenerative and personalized medicine.

“I am grateful to all my Ph.D. mentors and lab mates at the BIOLines lab and especially my advisor Dr. Dan Huh, for his exceptional guidance, unwavering support, and invaluable mentorship throughout my Ph.D. journey,” says Park. “Dan’s expertise, dedication, and commitment to excellence have been instrumental in shaping both my research and professional development, while also training me to become an independent scientist and mentor.”

Congratulations to Dr. Park from everyone at Penn Bioengineering!

Engheta, Margulies Elected to the American Academy of Arts & Sciences

Two faculty affiliated with the Department of Bioengineering at the University of Pennsylvania have been elected to the American Academy of Arts & Sciences. They join nearly 270 new members honored in 2023, recognized for their excellence, innovation, leadership, and broad array of accomplishments.

Nader Engheta
Nader Engheta, the H. Nedwill Ramsey Professor.

Nader Engheta is the H. Nedwill Ramsey Professor, with affiliations in the departments of Electrical and Systems Engineering (primary appointment), Bioengineering (secondary appointment) and Materials Science and Engineering (secondary appointment) in the School of Engineering and Applied Science; and Physics and Astronomy (secondary appointment) in the School of Arts & Sciences. His current research activities span a broad range of areas including optics, photonics, metamaterials, electrodynamics, microwaves, nano-optics, graphene photonics, imaging and sensing inspired by eyes of animal species, microwave and optical antennas, and physics and engineering of fields and waves. He has received numerous awards for his research, including the 2023 Benjamin Franklin Medal in Electrical Engineering, the 2020 Isaac Newton Medal and Prize from the Institute of Physics (U.K.), the 2020 Max Born Award from OPTICA (formerly OSA), induction to the Canadian Academy of Engineering as an International Fellow (2019), U.S. National Academy of Inventors (2015), and the Ellis Island Medal of Honor from the Ellis Island Honors Society (2019). He joins four other Penn faculty elected to the Academy this year.

Read the announcement and the full list of Penn electees in Penn Today.

Susan Margulies, Ph.D. (Photo: Jack Kearse)

Susan Margulies, Professor in the Wallace H. Coulter Department of Biomedical Engineering in the College of Engineering at Georgia Tech, was also elected. Margulies is both Professor Emeritus in Penn Bioengineering and an alumna of the program, having earned her Ph.D. with the department in 1987. Margulies is an expert in pediatric traumatic brain injury and lung injury. She previously served as Chair of Biomedical Engineering at Georgia Tech/Emory University and in 2021 became the first biomedical engineer selected to lead the National Science Foundation’s (NSF) Directorate of Engineering.

Read the announcement of Margulies’ elected to the Academy at Georgia Tech.

Penn Bioengineering Alumnus Michael Magaraci Featured with New Haven Recycling Startup

Recycling bin full of plastic water bottles.
Credit: sdominick/Getty Images.

Michael Magaraci, Research Scientist at Protein Evolution and alumnus of Penn Bioengineering, featured in CT Insider for the New Haven, CT startup’s quest to replace the global recycling system. The company, founded in 2021, is working on methods to eventually recycle polyester fabrics, rugs, and other materials that end up in landfills. Magaraci, who serves as director of platform engineering, earned a bachelor’s degree in Bioengineering and Economics in the Jerome Fisher Program in Management & Technology from Penn Engineering and the Wharton School of Business in 2013. He stayed with Penn Bioengineering for his doctoral research, completed in 2021. During his time at Penn, he worked as a Teaching Assistant and Laboratory Technician, advised Penn iGEM Teams, and served with Engineers Without Borders.

Read “Meet the New Haven startup that wants to digest your plastic” in CT Insider.

Penn Bioengineering Alumnus Joshua Doloff Seeks a Pain-free Treatment for Diabetes

Person taking a finger stick blood test.
Credit: Darryl Leja, NHGRI Flickr

Joshua C. Doloff, Assistant Professor of Biomedical Engineering and Materials Science & Engineering at Johns Hopkins University, featured in The Jewish News Syndicate for his work on “Hope,” a new technology which offers pain- and injection-free treatment to people with Type 1 or “juvenile” diabetes. Doloff is an alumnus of Penn Bioengineering, Class of 2004:

“Doloff received his bachelor’s degree from the University of Pennsylvania and his graduate degrees from Boston University. In addition to his post in Johns Hopkins’ Department of Biomedical Engineering, he is a member of the Translational Tissue Engineering Center at Johns Hopkins University School of Medicine. His lab is interested in systems biology with an emphasis on engineering improved therapies in the fields of cancer, autoimmunity, transplantation medicine, including Type 1 diabetes and ophthalmology.”

Read “Technion researchers offer ‘Hope’ for treating diabetes, minus the painful jabs” in the Jewish News Syndicate.

2022 PIP/PEP Prize Winners: Where are they now?

by Brandon Baker

William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize. (Photo: Eric Sucar)

In April 2022, three President’s Prize-winning teams were selected from an applicant pool of 71 people to develop projects that promote engagement and innovation. Each project received $100,000, as well as a $50,000 living stipend per team member.

The President’s Innovation Prize and President’s Engagement Prize winners included Grapevine, which aims to better connect buyers and suppliers to stabilize the medical supply chain market; IF Ventures, with its mission to scale impact by supporting college students with early-stage startup ideas that have measurable social and environmental impact; and Cosmic Writers, which organizes writing workshops to cultivate K-12 students to be better writers and communicators — and, therefore, better citizens.

“In less than a year, these three PIP and PEP prize-winning teams have already proven their commitment to making a difference in the world,” says President Liz Magill. “Their projects are ambitious and inspiring, and I am proud the University has been able to provide financial and networking support for these determined changemakers.”

Grapevine, 2022 President’s Innovation Prize Winners

After graduating in May 2022, Luka Yancopoulos, an Environmental Studies major and a Bioengineering major in the School of Engineering and Applied Science and William Danon, a History major, relocated to an office space in Westchester, New York, and got to work on a research and validation process — first, by spending a day at a Penn Medicine facility, Lancaster General Health, then by committing hundreds of hours to interviewing distributor and procurement teams alike, along with potential client companies. The mission, as any researcher knows, was to understand key pain points. They also onboarded veterans in logistics, technology, and payment security and processing while devising an organizational structure in which Yancopoulous leads on technology and design solutions while Danon interfaces with customers to know what needs remain unmet.

Grapevine soft launched in fall 2022 and, they say, has interfaced with 30 companies through its digital platform to facilitate sales among 40 suppliers, amounting to more than $20,000 in transactions. The appeal of the platform, they say, remains the concept of the “digital supply chain network,” which Yancopoulos says partners can use to connect with resellers, hospitals, distributors, and others to reduce the risk of supply chain disruption that is not just a product of the pandemic, he adds, but “forever ongoing.”

“It’s driven by the principle that together we’re stronger, and I mean that in every aspect of my life,” he says. “That people are stronger, and with Grapevine we work to [bolster] supply chains and increase the accessibility of health care products — together.”

Since winning the President’s Innovation Prize, they’ve focused on working with small- to medium-sized businesses — whether local clinics or high-quality, specialized resellers — that struggle to compete with or pay for traditional, large-scale distributors that are better-resourced or too expensive. It’s allowed them to also find new users, like health care-adjacent businesses including funeral homes and tattoo parlors.

Their current tagline: “Grow with us,” Danon says.

Watch a video overview of Grapevine’s progress since receiving the PIP prize and read more about the other PIP/PEP prize winners at Penn Today.

Read more stories featuring Grapevine.

Penn Bioengineering Alumna Cynthia Reinhart-King Invited to White House Summit

Cynthia Reinhart-King

Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was one of a handful of experts invited to take part in the White House Summit in Biotechnology and Biomanufacturing on September 14, 2022 in Washington, D.C. Reinhart-King and her colleagues gathered to discuss “bio-based solutions to global challenges ranging from food security and climate change to health security and supply chain disruptions.”

Reinhart-King is an alumna of Penn Bioengineering, graduating with her doctorate in 2006.  She delivered the Grace Hopper Lecture for Penn Engineering in 2019, and was named President-Elect of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers, in 2021.

Read “Preeminent engineering researcher takes part in national summit on biotechnology and biomanufacturing” in Vanderbilt University Research News.

Alumni Spotlight: Penelope Georges

Penelope earned her Ph.D.  in Bioengineering in 2006. She is now Associate Director of STEM Initiatives at Princeton University.

Penelope Georges, Ph.D.

“My time at Penn spoiled me for many job experiences that followed.  The Institute for Medicine and Engineering (IME) was collaborative, familial, and stimulating. During my Ph.D. work, I felt simultaneously nurtured and challenged.  Most credit for this prolific phase of my career is due to the members of Dr. Paul Janmey’s laboratory during my tenure at Penn – starting with the big man himself.  My research mentor promoted a research experience that centered on respect for others, not only within our field of study but also outside the academy.   Respect meant the expectation of forming strong relationships and collaborations and having reverence for scientific experts and practitioners alike.  The foundation of the lab’s ethos was collaboration for the greater good. 

Dr. Janmey set the tone for lab members to hold each other in high regard and to be team players.   I would not have been as successful without this support.  Beyond the lab, the IME at the time had a remarkable staff assistant in Marvin Jackson who was central to promoting camaraderie across the Institute.  Marvin was a critical presence in the IME and I believe that many scientific collaborations were made possible due to the environment he cajoled.

Outside the IME, some the most meaningful moments of my Ph.D. studies came from traveling outside the U.S. to collaborate internationally.  I was fortunate to travel as close as Mechanicsville, PA and as far as the Czech Republic to attend meetings, perform experiments, and make connections with colleagues.   Through travel and meeting many different types of people, I learned the culture of being in academia and developed a broader view of scientific research. 

As of recently, my career has focused on pedagogy in higher education.  At Princeton, I serve within an entity that has a central mission of improving science and engineering literacy for all its constituents: the Council on Science and Technology.  I develop new science and engineering courses and introduce interactive research-based teaching methods into these courses. I am involved in policy issues on STEM education at Princeton and beyond.  The skills I learned at Penn that are critical to my current position are to recognize problems and design innovative solutions and the ability to communicate and collaborate with researchers across many disciplines.  I am very grateful to be an alumna of a remarkable program.”

Learn more about Georges’s work and research.

Taimoor Qazi Appointed Assistant Professor at Purdue University

Taimoor H. Qazi, Ph.D.

The Department of Bioengineering is proud to congratulate Taimoor H. Qazi, Ph.D. on his appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Qazi’s appointment will begin in Fall 2022.

Qazi obtained his Ph.D. at the Technical University of Berlin and the Charité Hospital in Berlin, Germany working on translational approaches for musculoskeletal tissue repair using biomaterials and stem cells under the co-advisement of Georg Duda, Director of the Berlin Institute of Health and David Mooney, Mercator Fellow at Charité – Universitätsmedizin Berlin. After arriving at Penn in 2019, Qazi performed research on microscale granular hydrogels in the Polymeric Biomaterials Laboratory of Jason Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. While conducting postdoctoral research, Qazi also collaborated with the groups of David Issadore, Associate Professor in Bioengineering and in Electrical and Systems Engineering, and Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. Qazi’s postdoctoral research was supported through a fellowship from the German Research Foundation, and resulted in several publications in high-profile journals, including Advanced Materials, Cell Stem Cell, Small, and ACS Biomaterials Science and Engineering.

“Taimoor has done really fantastic research as a postdoctoral fellow in the group,” says Burdick. “Purdue has a long history of excellence in biomaterials research and will be a great place for him to build a strong research program.”

Qazi’s future research program will engineer biomaterials to make fundamental and translational advances in musculoskeletal tissue engineering, including the study of how rare tissue-resident cells respond to spatiotemporal signals and participate in tissue repair, and developing modular hydrogels that permit minimally invasive delivery for tissue regeneration. The ultimate goal is to create scalable, translational, and biologically inspired healthcare solutions that benefit a patient population that is expected to grow manifold in the coming years.

Qazi is looking to build a strong and inclusive team of scientists and engineers with diverse backgrounds interested in tackling problems at the interface of translational medicine, materials science, bioengineering, and cell biology, and will be recruiting graduate students immediately. Interested students can contact him directly at thqazi@seas.upenn.edu.

“I am excited to launch my independent research career at a prestigious institution like Purdue,” says Qazi. “Being at Penn and particularly in the Department of Bioengineering greatly helped me prepare for the journey ahead. I am grateful for Jason’s mentorship over the years and the access to resources provided by Jason, Dave Issadore, Ravi, Dave Meany and other faculty which support the training and professional development of postdoctoral fellows in Penn Bioengineering.”

Congratulations to Dr. Qazi from everyone at Penn Bioengineering!