With a ‘Liquid Assembly Line,’ Penn Researchers Produce mRNA-Delivering-Nanoparticles a Hundred Times Faster than Standard Microfluidic Technologies

by Evan Lerner

Michael Mitchell, Sarah Shepherd and David Issadore pose with their new device.

The COVID vaccines currently being deployed were developed with unprecedented speed, but the mRNA technology at work in some of them is an equally impressive success story. Because any desired mRNA sequence can be synthesized in massive quantities, one of the biggest hurdles in a variety of mRNA therapies is the ability to package those sequences into the lipid nanoparticles that deliver them into cells.

Now, thanks to manufacturing technology developed by bioengineers and medical researchers at the University of Pennsylvania, a hundred-fold increase in current microfluidic production rates may soon be possible.

The researchers’ advance stems from their design of a proof-of-concept microfluidic device containing 128 mixing channels working in parallel. The channels mix a precise amount of lipid and mRNA, essentially crafting individual lipid nanoparticles on a miniaturized assembly line.

This increased speed may not be the only benefit; more precisely controlling the nanoparticles’ size could make treatments more effective. The researchers tested the lipid nanoparticles produced by their device in a mouse study, showing they could deliver therapeutic RNA sequences with four-to-five times greater activity than those made by conventional methods.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, and David Issadore, Associate Professor in Penn Engineering’s Department of Bioengineering, along with Sarah Shepherd, a doctoral student in both of their labs. Rakan El-Mayta, a research engineer in Mitchell’s lab, and Sagar Yadavali, a postdoctoral researcher in Issadore’s lab, also contributed to the study.

They collaborated with several researchers at Penn’s Perelman School of Medicine: postdoctoral researcher Mohamad-Gabriel Alameh, Lili Wang, Research Associate Professor of Medicine, James M. Wilson, Rose H. Weiss Orphan Disease Center Director’s Professor in the Department of Medicine, Claude Warzecha, a senior research investigator in Wilson’s lab, and Drew Weissman, Professor of Medicine and one of the original developers of the technology behind mRNA vaccines.

It was published in the journal Nano Letters.

“We believe that this microfluidic technology has the potential to not only play a key role in the formulation of current COVID vaccines,” says Mitchell, “but also to potentially address the immense need ahead of us as mRNA technology expands into additional classes of therapeutics.”

Read the full story in Penn Engineering Today.

Penn Engineering’s Latest ‘Organ-On-a-Chip’ is a New Way to Study Cancer-related Muscle Wasting

by Melissa Pappas

Bioengineering’s Dan Huh and colleagues have developed a number of organ-on-a-chip devices to simulate how human cells grow and perform in their natural environments. Their latest is a muscle-on-a-chip, which carefully captures the directionality of muscle cells as they anchor themselves within the body. See the full infographic at the bottom of this story. (Illustration by Melissa Pappas).

Studying drug effects on human muscles just got easier thanks to a new “muscle-on-a-chip,” developed by a team of researchers from Penn’s School of Engineering and Applied Science and Inha University in Incheon, Korea.

Muscle tissue is essential to almost all of the body’s organs, however, diseases such as cancer and diabetes can cause muscle tissue degradation or “wasting,” severely decreasing organ function and quality of life. Traditional drug testing for treatment and prevention of muscle wasting is limited through animal studies, which do not capture the complexity of the human physiology, and human clinical trials, which are too time consuming to help current patients.

An “organ-on-a-chip” approach can solve these problems. By growing real human cells within microfabricated devices, an organ-on-a-chip provides a way for scientists to study replicas of human organs outside of the body.

Using their new muscle-on-a-chip, the researchers can safely run muscle injury experiments on human tissue, test targeted cancer drugs and supplements, and determine the best preventative treatment for muscle wasting.

organ-on-a-chip
Dan Huh, Ph.D.

This research was published in Science Advances and was led by Dan Huh, Associate Professor in the Department of Bioengineering, and Mark Mondrinos, then a postdoctoral researcher in Huh’s lab and currently an Assistant Professor of Biomedical Engineering at Tulane University. Their co-authors included Cassidy Blundell and Jeongyun Seo, former Ph.D. students in the Huh lab, Alex Yi and Matthew Osborn, then research technicians in the Huh lab, and Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in the Department of Materials Science and Engineering. Lab members Farid Alisafaei and Hossein Ahmadzadeh also contributed to the research. The team collaborated with Insu Lee and professors Sun Min Kim and Tae-Joon Jeon of Inha University.

In order to conduct meaningful drug testing with their devices, the research team needed to ensure that cultured structures within the muscle-on-a-chip were as close to the real human tissue as possible. Critically, they needed to capture muscle’s “anisotropic,” or directionally aligned, shape.

“In the human body, muscle cells adhere to specific anchor points due to their location next to ligament tissue, bones or other muscle tissue,” Huh says. “What’s interesting is that this physical constraint at the boundary of the tissue is what sculpts the shape of muscle. During embryonic development, muscle cells pull at these anchors and stretch in the spaces in between, similar to a tent being held up by its poles and anchored down by the stakes. As a result, the muscle tissue extends linearly and aligns between the anchoring points, acquiring its characteristic shape.”

The team mimicked this design using a microfabricated chip that enabled similar anchoring of human muscle cells, sculpting three-dimensional tissue constructs that resembled real human skeletal muscle.

The the full story in Penn Engineering Today.

Watch the Winners of the 2021 Senior Design Competition

by Priyanka Pardasani

Team OtoAI

Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market. While the pandemic made this year’s competition logistically challenging, students and organizers were able to come together virtually to continue the tradition.

This year’s virtual format provided an opportunity for judges from around the country to participate in evaluating projects. Brad Richards, Director of Alumni Relations at Penn Engineering who helped plan the competition, was able to help recruit more than 60 volunteers to serve on the panel.

“The broad number of judges from varying industries made this competition incredibly meaningful, we will absolutely be integrating a virtual component to allow for more judges in the future.”

Eighteen teams total, three from each department, virtually presented to the panel of judges, who awarded $2,000 prizes in four categories.

Technology & Innovation Prize

This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.

Winner: Team OtoAI
Department: Bioengineering
Team Members: Krishna Suresh, Nikhil Maheshwari, Yash Lahoti, Jonathan Mairena, Uday Tripathi
Advisor: Steven Eliades, Assistant Professor of Otorhinolaryngology in Penn’s Perelman School of Medicine
Abstract: OtoAI is a novel digital otoscope that enables primary care physicians to take images of the inner ear and leverages machine learning to diagnose abnormal ear pathologies.

Read the full list of winners and watch their videos in Penn Engineering Today.

Bioengineering Graduate Sofia Gonzalez Honored with Leadership Awards

Sofia Gonzalez (BSE & MSE 2021)

Sofia Gonzalez, who graduated with both bachelor’s and master’s degrees in Bioengineering this spring, was one of a select number of Penn students to receive 2021 Student Leadership Awards. Gonzalez was awarded a Penn Alumni Student Award of Merit as well as the William A. Levi Kite & Key Society Award for Service and Scholarship. Awardees were celebrated during the university’s annual Ivy Day, “a tradition recognizing students’ leadership, service, and scholarship for nearly 150 years.”

Gonzalez discussed the importance of diverse representation in the Student Leadership Awards Book:

“Sofia reflected that on countless college tours, she noticed a striking pattern: only one of the ambassadors she encountered was a female engineer, and none of them were Latinx. While the nation was reckoning with racism, Sofia was leading critical discussions about how Kite & Key could improve in areas of diversity, equity, and inclusion to mirror the Penn student body. Sofia is now graduating, confident that she took measurable strides toward breaking the cycle of underrepresentation at America’s first University. Sofia’s work leaves a lasting legacy at Penn and beyond.”

Gonzalez also served as a Senior Advisor to the Biomedical Engineering Society (BMES) and as President of the Kite and Key Society, a society which welcomes all visitors to campus, acquaints prospective students and families with the undergraduate experience, and fosters a community of students dedicated to serving the University of Pennsylvania. Having completed her degrees, Gonzalez is headed for the first year of a rotational program as a member of the Merck Manufacturing Leadership Development Program in Durham, NC.

Following her time at Merck, Gonzalez will continue her education at the MIT Sloan School of Management. Gaining admission to the M.B.A. program via the Early Admission offering, she will matriculate within the following five years.

Read the full list of 2021 award winners and learn more about the awards on the Ivy Day website.

Guest Post: Learning About Regulatory Affairs Through a Virtual Internship

by Casey Colleran (BSE 2021, MSE 2022)

In this guest post, recent Penn Bioengineering graduate and master’s student Casey Colleran writes about her experience in virtual internship at Janssen Pharmaceuticals.

Casey Colleran

During the summer of 2020, I was privileged enough to join the Global Regulatory Affairs team at Janssen Pharmaceutical Companies of Johnson & Johnson. Despite the uncertainties brought on by COVID-19, Janssen was able to bring together a group of five interns to participate in this virtual internship. This remote opportunity provided me with a valuable understanding of Regulatory Affairs, and the pharmaceutical industry. Throughout the 11 weeks, I was able to work alongside Regulatory Scientists in several functional areas of the organization. I learned about the regulations that govern the pharmaceutical industry, and the strategy that goes into communicating with the FDA and other health authorities.

As we rotated through each of these functional areas, myself and the other interns were also able to observe how the pandemic impacted the organization. We were asked to develop our own solutions on how to address these new challenges. Through this task, I learned how to present information in a meaningful way, analyze anecdotal data, improve processes, and communicate across different networks. As a team, myself and four other interns developed probing questions to help us understand how the COVID-19 pandemic has impacted the regulatory landscape, and the different strengths and opportunities employees observed in Janssen’s response to the pandemic. As we rotated through the different functional areas of Janssen’s Global Regulatory Affairs group, we used that time to ask our questions, and make note of anecdotal data that would provide us more insight as to how to address the new challenges brought on by the pandemic, and the virtual work environment. We then created a “COVID-19 Playbook” which broke down the main themes we had heard in our responses, such as the need for a more flexible organization, more efficient and effective communication, improved connectivity in the virtual workplace, and more. We developed suggestions on programming and guidelines that would help strengthen each of these areas, and presented these suggestions to the Senior Leadership Team.

Summer 2020 Janssen interns

Leadership development opportunities were also focal to the internship. I was paired with several amazing mentors who provided me with personalized feedback on how to become a more effective leader. The culture of the organization was extremely welcoming, and I cherish the relationships that I was able to build with my colleagues, so much so that I joined Janssen as a part time contractor this past year. Through this role as a contractor, I have been able to learn more about the day-to-day activities of a Regulatory Scientist through hands-on activities. As a contractor, I have been an integral part of a new “FLEx” Program. As a part of this program, I offer support to Regulatory Scientists by taking on their more routine submissions, giving them the opportunity to work on more strategic based activities, and focus on their personal growth and learning. It has been such a wonderful experience to work closely with these Regulatory Scientists who are still early in their career, as we have been able to learn from each other as well. It has also given me a greater understanding of the regulatory landscape, and by taking part in this new program I again get to see much of my feedback be considered and implemented.

I am so grateful that I had the opportunity to work in such an amazing environment, developed so many skills, and built a network that led me to additional opportunities in Regulatory Affairs at Janssen.

‘I Look Like an Engineer’

Penn Engineering students (clockwise) Nyasha Zimunhu, Fahmida Lubna, Celestina Saven, Sanjana Hemdev, Sabrina Green and Sydney Kariuki all participated in the “I Look Like an Engineer” campaign, locally organized by AWE.

Penn Engineering’s Advancing Women in Engineering (AWE) program, dedicated to recruiting, retaining and promoting all female-identified students in the School, participated in the “I Look Like an Engineer” social media movement for the third year in a row. The movement, aimed at promoting diversity around underrepresented groups like women and people of color, was started by software developer Isis Anchalee in 2015.

Francesca Cimino

Francesca Cimino, member of AWE and a rising senior in the Department of Bioengineering, has always been passionate about changing the stereotypes and breaking down the barriers that prevent engineers of diverse backgrounds from thriving. She wanted to continue AWE’s tradition of participating in the movement to showcase the diversity already present within the field and prove that there is no single characteristic that defines an engineer.

At the conclusion of the campaign, Cimino responded to questions about the importance of diversity and what a more equal world in engineering looks like.

Why did you decide to get involved with AWE?

I applied to be a part of AWE’s Student Advisory Board during the spring semester of my freshman year. Being on the board was very enticing to me because I was looking to make connections with more women engineers at the time. I wanted to create my own community of women engineers while also wanting to help foster a community for all. AWE’s message and goals really resonated with me as well, so I knew it would be a perfect fit.

How important has mentorship from other female engineers been for you?

Being able to interact and learn from women who have experience in the industries I am most interested in has been very valuable to me. It has been inspiring to learn about their stories and the fact that I can relate to many of them has definitely allowed me to become more confident as I get closer to starting my career. Mentorship is something AWE really values and the board has worked to develop a mentoring network for women engineers, which I really admire.

Read the full Q&A in Penn Engineering Today.

Bioengineering Senior Design 2021

Each Penn Bioengineering (BE) student’s undergraduate experience culminates in Senior Design, a two-semester capstone project in which student teams conceive, design, and develop a bioengineering project, whether a medical device, molecular biological therapeutic, or research tool. Projects are inherently interdisciplinary, and can involve biomaterials, electronics, mechanics, molecular biology, nanotechnology, and microfluidics. Research and development is supervised by BE faculty, lab staff, and graduate student TA’s and project managers, and work is conducted in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (which successfully reopened for in-person activities this Spring semester).

This year’s 11 teams included the variety and innovation we’ve come to expect from our outstanding students, ranging from devices which track medical conditions, such afib and POTS, to technology responding to our post-COVID world, such as a disinfecting robot and a kit to make telemedicine more effective. The year finished with presentations to alumni judges, and BE’s annual Demo Day (the only in-person demo day on the engineering campus this year) on April 15, 2021, in which students showcased their designs to faculty.

Several teams were highlighted for awards recognition.

  • Tula won the Grand Prize Award at the Weiss Tech House Senior Design Pitch competition, sponsored by Penn’s Weiss Tech House, as well as a Berkman Opportunity Fund grant from Penn Engineering. Tula’s members are Bioengineering student Shreya Parchure (BSE 2021 & MSE 2021), Mechanical Engineering student Miriam Glickman (BSE 2021 & MSE 2022), and Computer Science students Ebtihal Jasim (BSE 2021) and Tiffany Tsang (BSE 2021).
  • TelemedTree (David Alanis Garza, Aurora Cenaj & Raveen Kariyawasam) and rUmVA (Yasmina Al Ghadban, Rachel Madhogarhia, Jeong Inn Park, Robert Paslaski & Phuong Vu) also received Berkman Opportunity Fund grants.
  • RHO Therapeutics was named a finalist in the Rice 360 Design Competition for 2021 (David Bartolome, Ethan Boyer, Patrisia de Anda, Kelly Feng & Jenny Nguyen).
  • OtoAI (Yash Lahoti, Nikhil Maheshwari, Jonathan Mairena, Krishna Suresh & Uday Tripathi) took home a Wharton Venture Lab’s Innovation Fund Validation Phase Award for 2021 and won the Technology and Innovation Prize for Penn Engineering’s interdepartmental Senior Design Competition.
  • In addition, three teams won BE’s internal Senior Design competition: IdentiFly (MEAM student Armando Cabrera, ESE student Ethan Chaffee, MEAM student Zachary Lane, ESE student Nicoleta Manu & BE student Abum Okemgbo), OtoAI, and rUmVa.

Short descriptions of each project are below. See each project’s full abstract, final paper, and video presentation here. The full 2021 presentation Youtube playlist is linked below.

reActive is a low-cost wearable device that measures ground reaction force as well as knee angle to aid physical therapists in quantifying an athlete’s recovery from an ACL injury.

EndoMagno is a novel magnetic endoscopy probe that effectively grips metallic objects by interfacing with an endoscope.

NoFib is an at-home wearable for athletes with histories of atrial fibrillation or those recovering from ablation surgeries who wish to continue their workout regimen and track their cardiac recovery without needing to leave their residence.

Tula is a smart compression stocking platform to improve quality of life for people with Postural Orthostatic Tachycardia Syndrome (POTS), a disease which causes fainting upon standing due to blood pooling in legs. Tula can predict a POTS attack through real-time heart rate monitoring and then prevent fainting using dynamic compression.

RHO Therapeutics is a low-cost, wearable glove device that trains fine motor movements using a rehabilitative game that causes motor-mediated flexion and extension of the patient’s hand to aid in chronic stroke rehabilitation. 

EarForce aims to monitor fighter pilots’ health during training and in-flight missions via a low-cost headphone system. The device collects physiological data through the ear and is compatible with existing pilot headphone systems.

IdentiFly is a low-cost device which will provide labs with an easy to integrate way to automatically sort fruit flies by sex. 

TeleMedTree introduces a new level of telemedicine. It is an affordable precision-focused, at-home diagnostic kit to help immunocompromised individuals with respiratory conditions receive a high quality monitoring of their health that is on par or better than what is possible during an in-person visit.

OtoAI is a novel digital otoscope that enables primary care physicians to take images of the inner ear and leverages machine learning to diagnose abnormal ear pathologies.

Synchro-Sense is a device which detects when patients on ventilators are at maximum inhalation and triggers an X-ray image capture for accuracy. 

rUmVa is a cost-effective, autonomous robot that can quickly disinfect rooms by intelligently sanitizing high-touch surfaces and the air. 

Senior Design 2021 Presentation Playlist

Bioengineering Graduate Dayo Adetu Wins Graduate Leadership Award

Dayo Adetu (BSE 2019, MSE 2021)

Congratulations to recent Penn Bioengineering graduate Dayo Adetu, who was awarded a 2021 Graduate Leadership Award, one of only sixteen recipients across the university. Adetu is a recipient of the Dr. Andy Binns Award for Outstanding Service to Graduate and Professional Student Life. This award is presented to “graduate or professional students, upon their graduation from Penn, who have significantly impacted graduate and professional student life through service involvement in student life initiatives or organizations.” Adetu wins this award for her “service and leadership in advancing wellness and diversity initiatives across departments in the School of Engineering.”

Adetu graduated with a BSE in Bioengineering (BE) in 2019, concentrating in Biomedical Devices and minoring in Engineering Entrepreneurship, Math, and African Studies. She went on to pursue two Master’s degrees in BE and Mechanical Engineering and Applied Mechanics (MEAM) (concentration: Design and Manufacturing), graduating with both in 2021. She also received a certificate in Integrated Product Design. For the 2020-2021 academic year, she served as President of the Penn chapters of both the Graduate Association of Bioengineers (GABE) and the Mechanical Engineering Graduate Association (MEGA). She was the 2021 MEAM MSE Graduation student speaker and also received the Penn Engineering Graduate Award for Outstanding Service for both BE and MEAM Departments.

Learn more about the Penn Graduate Leadership Awards and read the full list of recipients on the Grad Center at Penn website.

Bioengineering Graduate Gabriel DeSantis Awarded Fulbright Grant

Gabriel DeSantis (BSE 2020, MSE 2021)

Congratulations to recent Penn Bioengineering graduate Gabriel DeSantis on being awarded a Fulbright grant for the 2021-22 academic year:

“The Fulbright Program is the United States government’s flagship international educational exchange program, awarding grants to fund as long as 12 months of international experience.

‘As an avenue for building cross-cultural understanding, the U.S. Student Fulbright Program is an unparalleled opportunity for American students to represent our country and our University across the world,’ says Jane Morris, executive director of Penn’s Center for Undergraduate Research and Fellowships, which supports applicants. ‘We are so proud of all our Penn Fulbright students who will be contributing to this important mission through their study, research, and English teaching as Fulbrighters.’

Gabriel DeSantis, from Wellesley, Massachusetts, received his bachelor’s degree from Penn Bioengineering in 2020 and will graduate in May with a master’s degree in bioengineering from the School of Engineering and Applied Science. He was awarded a Fulbright to conduct research in Portugal at the International Iberian Nanotechnology Laboratory. There he will be creating a 3D bio-printed model to optimize the texture and nutritional profiles of cultivated meat. At Penn his academic interests included biology, food science, and sustainability, which he hopes to use to develop new systems of food production. On campus, DeSantis was a Penn Abroad Leader and board member of the Graduate Association of Bioengineers. He is a past chair of the Mask and Wig Club. He currently works as a research assistant for Allevi, a Philadelphia-based bioprinting company at Pennovation Works.”

Read the full list of Fulbright awardees in Penn Today.

Bioengineering Graduate Students Take the Annual BETA Day Online

By GABE Outreach Chairs and Ph.D. students David Gonzalez-Martinez and David Mai

BETA Day Biomaterials workshop

Every spring, the Graduate Association of Bioengineers (GABE) at Penn partners up with iPraxis, an educational non-profit organization based in Philadelphia, to organize BETA Day, an event that brings together Bioengineering graduate students and local Philadelphia grade school students to introduce them to the field of bioengineering, the life of graduate students, and hands-on scientific demonstrations. Due to COVID-19 restrictions, we adapted the traditional in-person BETA Day into a virtual event on Zoom. This year, we assembled kits containing the necessary materials for our chosen demonstrations and worked with iPraxis to coordinate their delivery to partner schools and their students. This enabled students to perform their demonstrations in a hands-on manner from their own homes; over 40 students were able to participate in extracting their own DNA and making biomaterials with safe household materials.

Michelle Johnson presents on her work in robotics

The day began with a fantastic lecture by Michelle Johnson, Associate Professor in Bioengineering and Physical Medicine and Rehabilitation, who introduced students to the field of rehabilitation robotics and shared her experience as a scientist. Students then learned about DNA and biomaterials through lectures mediated by the graduate students Dayo Adetu and Puneeth Guruprasad. After each lecture, students broke into breakout rooms with graduate student facilitators where they were able to get some hands-on scientific experience as they extracted DNA from their cheek cells and fabricated alginate hydrogels. Michael Sobrepera, a graduate student in Dr. Johnson’s lab, concluded the event by giving a lecture on the process of robotics development and discussed where the field is heading and some important considerations for the field.

Dayo Adetu, Bioengineering Master’s student and GABE President, teaches the students about Genetic Engineering

While yet another online event may seem unexciting, throughout the lectures students remained exceptionally engaged and raised fantastic questions ranging from the accessibility of low income communities to novel robotic therapeutic technologies to the bioethical questions robotic engineers will face as technologies advance. The impact of BETA day was evident as the high school students began to discuss the possible majors they would like to pursue for their bachelor’s degrees. Events like BETA Day give a glimpse into possible STEM fields and careers students can pursue.