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.

Sonura Named Among 2023 PHL Inno Under 25 Honorees

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce

A team of recent Penn Bioengineering graduates have been included in list of prominent young Philadelphia innovators as chosen by The Philadelphia Business Journal and PHL Inno.

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce founded Sonura as their Senior Design Project in Bioengineering. The team, who all graduated in 2023, picked up a competitive President’s Innovation Prize for their beanie that promotes the cognitive and socioemotional development of newborns in the NICU by protecting them from the auditory hazards of their environments while fostering parental connection. Now, they have been included in the list of fourteen Inno Under 25 honorees for 2023.

“To determine this year’s list, the Philadelphia Business Journal and PHL Inno sought nominations from the public and considered candidates put forth by our editorial team. To be considered, nominees must be 25 years of age or younger and work for a company based in Greater Philadelphia and/or reside in the region.

Honorees span a wide range of industries, including consumer goods, biotechnology and environmental solutions. Many are products of the region’s colleges and universities, though some studied farther afield before setting up shop locally.”

Read “Announcing the 2023 PHL Inno Under 25 honorees” and “Inno Under 25” in PHL Inno. Penn affiliates can subscribe through Penn’s library services.

Safe and Sound: Sonura Supports Newborn Development by Sequestering Disruptive Noise

by Nathi Magubane

Recipients of the 2023 President’s Innovation Prize, team Sonura, five bioengineering graduates from the School of Engineering and Applied Science, have created a device that filters out disruptive environmental noises for infants in neonatal intensive care units. Their beanie offers protection and fosters parental connection to newborns while also supporting their development.

Machines beeping and whirring in a rhythmic chorus, the droning hum of medical equipment, and the bustles of busy health care providers are the familiar sounds of an extended stay at a hospital. This cacophony can create a sense of urgency for medical professionals as they move about with focused determination, closely monitoring their patients, but for infants in neonatal intensive care units (NICU) this constant noise can be overwhelming and developmentally detrimental.

Enter Tifara Boyce, from New York City; Gabriela Cano, from Lawrenceville, New Jersey; Gabriella Daltoso, from Boise, Idaho; Sophie Ishiwari, from Chicago, and Caroline Magro, from Alexandria, Virginia, bioengineering graduates from the School of Engineering and Applied Science, who have created the Sonura Beanie. Their device filters out harmful noises for NICU infants while supporting cognitive and socioemotional development by allowing parents to send voice messages to their newborns.

The Sonura team members are recipients of the 2023 President’s Innovation Prize, which includes an award of $100,000 and an additional $50,000 living stipend per team member. The recent graduates will spend the year developing their product.

“The Penn engineers behind Sonura are determined to make a difference in the world,” says President Liz Magill. “They identified a substantial medical challenge that affects many parents and their newborn children. With the guidance of their mentors, they are taking key steps to address it and in doing so are improving the developmental prospects for children in the NICU. I am proud the University is able to support their important work.”

The Sonura Beanie’s creation began in the Stephenson Foundation Educational Laboratory and Bio-MakerSpace as a part of the Bioengineering Senior Design class project.

Prototype of the Sonura Beanie. (Image: Courtesy of the Sonura team)

She was particularly struck by the noisiness of the environment and considered the neurodevelopmental outcomes that may arise following long-term exposure to the harsh sounds at a critical developmental stage for infants. This concern prompted Magro to consult her team about potential solutions.

“I was really eager to tackle this problem because it bears some personal significance to me,” says Cano, who works on the device’s mobile application. “My sister was a NICU baby who was two months premature, so, when Caroline and I started talking about the issues a disruptive environment could cause, it seemed like the pieces of a puzzle started to come together.”

Read the full story in Penn Today.

Penn Bioengineering Senior Design Team “Sonura” Wins 2023 President’s Innovation Prize

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce pose on College Green.
Sonura

University of Pennsylvania President Liz Magill announced on April 21, the recipients of the 2023 President’s Engagement and Innovation Prizes.

Awarded annually, the Prizes empower Penn students to design and undertake post-graduation projects that make a positive, lasting difference in the world. Each Prize-winning project will receive $100,000, as well as a $50,000 living stipend per team member. The Prizes are the largest of their kind in higher education. All Prize recipients collaborate with a Penn faculty mentor.

A team of fourth-year Bioengineering majors, Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce, have received the President’s Innovation Prize for their project, Sonura.

“This year’s President’s Engagement and Innovation Prize recipients are fueled by a desire to make a difference—in their community, across the country, and around the world,” Magill said. “Communities for Childbirth, Act First, and Sonura embody an inspiring blend of passion and purpose. They are addressing consequential challenges with compelling solutions, and their dedication and smarts are exemplary. I congratulate them and wish them success as they launch and grow their ventures.”

The 2023 Prize recipients—selected from an applicant pool of 76—will spend the next year implementing the projects:

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce for Sonura: Daltoso, from Boise, Idaho; Ishiwari, from Chicago; Cano, from Lawrenceville, New Jersey; Magro, from Alexandria, Virginia; and Boyce, from Jamaica, Queens, New York, are bioengineering majors in the School of Engineering and Applied Science. Their startup, Sonura, is developing a beanie that promotes the cognitive and socioemotional development of newborns in the NICU by protecting them from the auditory hazards of their environments while fostering parental connection. The Sonura Beanie is composed of a frequency-dependent filter and a mobile application. The Sonura team is mentored by Brian Halak, a lecturer in the Engineering Entrepreneurship program. Sonura was developed in Penn’s Stephenson Foundation Bio-MakerSpace and was part of their Bioengineering Senior Design class.

To learn more about the 2023 President’s Engagement and Innovation Prizes, visit Penn Today.

Engineering Entrepreneurship with Professor Thomas Cassel

Thomas A.V. Cassel, Practice Professor in Mechanical Engineering and Applied Mechanics in the School of Engineering and Applied Science, recently sat down with Dayo Adetu (BSE 2019, MSE 2021), President of the Penn Graduate Association of Bioengineers (GABE), to give his insight into engineering entrepreneurship. Cassel is the Director of Penn’s Engineering Entrepreneurship Program, which he founded twenty one years ago. He joined Penn’s faculty in 1999 following a 20-year career of entrepreneurial business leadership.

Watch the video to hear about Cassel’s favorite Penn memories, the day-to-day experience of working at a startup, advice for venturing into entrepreneurship, and more.

Alumni Spotlight: Lamis Elsawah

Lamis Elsawah (BSE 2019)

Lamis Elsawah graduated with a B.S.E. in Bioengineering with a concentration in Medical Devices in 2019. She is currently a Design Engineer at Johnson & Johnson’s DePuy Synthes. We caught up with Lamis to hear about why she chose Penn Bioengineering and what she enjoyed about the curriculum.

“Penn had been my dream school for years prior to even applying to college, so their having a top notch bioengineering program was icing on the cake when it was time for me to apply. Prior to applying, I actually had the opportunity to meet with Dr. Meaney (who was the Bioengineering Department Chair up until I graduated) the summer before my senior year in high school and he was always a constant support throughout my bioengineering education up until graduation. Since Bioengineering had less than 100 students per class, it really allowed us to develop that familial feel with our core Bioengineering professors and lab staff. I honestly don’t think I would have survived junior and senior year without the help of Sevile and the entire lab staff, so I will be forever grateful.

I always like to say that junior year labs are really what made me an engineer. Those were some of the most challenging classes I took, but it was really rewarding once I reached the end. Between those lab courses and Biomechatronics taught by Professor Dourte, it prepared me to become a design engineer and apply all that I had learned. I also had the opportunity to get my minor in Engineering Entrepreneurship and be taught by Professor Cassel, which increased my interest in the business side of developing medical devices. The combination of my studies ultimately led me to Imperial College, London where I received my Master’s in Medical Device Design and Entrepreneurship.

The bioengineering curriculum at Penn allowed me to have a vast knowledge of the field that I will always be grateful for. It not only provided me with the mechanical experience, but also the electrical and biological background. I plan on staying an active alumna in both the Engineering Alumni Society and the Penn Alumni Board as a result of my wonderful experience at Penn Engineering and Penn as a whole.”

This post is part of BE’s Alumni Spotlight series. Read more testimonies from BE Alumni on the BE website.