Developing Endotracheal Tubes that Release Antimicrobial Peptides

by Evan Lerner

Scanning electron microscope images of endotracheal tubes at three levels of magnification. After 24 hours of Staphylococcus epidermidis exposure, tubes coated with the researchers’ AMPs (right) showed decreased biofilm production, as compared with tubes coated with just polymer (center) and uncoated tubes (left).

Endotracheal tubes are a mainstay of hospital care, as they ensure a patient’s airway is clear when they can’t breathe on their own. However, keeping a foreign object inserted in this highly sensitive part of the anatomy comes is not without risk, such as the possibility of infection, inflammation and a condition known as subglottic stenosis, in which scar tissue narrows the airway.

Broad-spectrum antibiotics are one way to mitigate these risks, but come with risks of their own, including harming beneficial bacteria and contributing to antibiotic resistance.

With this conundrum in mind, Riccardo Gottardi, Assistant Professor of Pediatrics at the Children’s Hospital of Philadelphia (CHOP) and of Bioengineering at Penn Engineering, along with Bioengineering graduate students and lab members Matthew Aronson and Paul Gehret, are developing endotracheal tubes that can provide a more targeted antimicrobial defense.

In a proof-of-concept study published in the journal The Laryngoscope, the team showed how a different type of antimicrobial agent could be incorporated into the tubes’ polymer coating, as well as preliminary results suggesting these devices would better preserve a patient’s microbiome.

Instead, the investigators explored the use of antimicrobial peptides (AMPs), which are small proteins that destabilize bacterial membranes, causing bacterial cells to fall apart and die. This mechanism of action allows them to target specific bacteria and makes them unlikely to promote antimicrobial resistance. Prior studies have shown that it is possible to coat endotracheal tubes with conventional antibiotics, so the research team investigated the possibility of incorporating AMPs into polymer-coated tubes to inhibit bacterial growth and modulate the upper-airway microbiome.

The researchers, led by Matthew Aronson, a graduate student in Penn Engineering’s Department of Bioengineering, tested their theory by creating a polymer coating that would release Lasioglossin-III, an AMP with broad-spectrum antibacterial activity. They found that Lasio released from coated endotracheal tubes, reached the expected effective concentration rapidly and continued to release at the same concentration for a week, which is the typical timeframe that an endotracheal is used before being changed. The investigators also tested their drug-eluting tube against airway microbes, including S. epidermidis, S. pneumoniae, and human microbiome samples and observed significant antibacterial activity, as well as prevention of bacterial adherence to the tube.

Read “CHOP Researchers Develop Coating for Endotracheal Tubes that Releases Antimicrobial Peptides” at CHOP News.

This post originally appeared in Penn Engineering Today.

Penn Bioengineering Senior Design Team Wins Hamlyn Symposium Prize

The winners of the Medical Robots for Contagious Disease Challenge Award for Best Application (L to R): Yasmina Al Ghadban, Phuong Vu, and Rob Paslaski.

Three recent Penn Bioengineering graduates took home the Best Application Award from the Medical Robotics for Contagious Disease Challenge, part of the three-month Hamlyn Symposium on Medical Robotics. Organized by the Hamlyn Centre at Imperial College, London, UK, in collaboration with the UK-RAS Network, the challenge involved “creating a 2-minute video of robotic or AI technology that could be used to tackle contagious diseases” in response to the current and potential future pandemics. Yasmina Al Ghadban, Rob Paslaski, and Phuong Vu were members of the Penn Bioengineering senior design team rUmVa who designed and built a cost-effective, autonomous robot that can quickly disinfect rooms by intelligently sanitizing high-touch surfaces and the air. The Best Application Award comes with a prize of £5,000.

The full Team rUmVa (L to R): Yasmina Al Ghadban, Rachel Madhogarhia, Phuong Vu, Jeong Inn Park, and Rob Paslaski.

Team rUmVa, which also included Bioengineering seniors Rachel Madhogarhia and Jeong Inn Park, also received a Berkman Opportunity fund grant from Penn Engineering and was one of three teams to win Penn Bioengineering’s Senior Design competition. Senior Design work is conducted every year on-site in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (which successfully reopened for in-person activities this Spring semester). Read the full list of Spring 2021 Senior Design Award Winners here.

rUmVa and the other challenge winners were honored during the Hamlyn Symposium’s virtual closing ceremony on July 29, 2021.

Read rUmVa’s abstract and final papers, along with those of all of the Penn Bioengineering Teams’, on the BE Labs Senior Design 2021 website. rUmVa’s presentation can be viewed on Youtube:

Student Research Highlight: Colin Huber

Colin Huber, Ph.D. student

Colin Huber, a Ph.D. candidate in Bioengineering studying head impact biomechanics and concussion in sports at the Center for Injury Research and Prevention (CIRP) at the Children’s Hospital of Philadelphia (CHOP), recently published “Variations in Head Impact Rates in Male and Female High School Soccer” in Medicine & Science in Sports & Exercise with colleagues from CHOP’s Minds Matter Concussion Frontier Program and the CIRP.

Colin’s paper, the goal of which was to compare “to compare head impact exposure rates (head impacts/exposure period) in male and female high school soccer by using multiple methodological approaches,” was recently profiled in the Penn Engineering Research & Innovation Newsletter.

Read the full story in the ADRO Newsletter.

Penn Bioengineering Graduate Shreya Parchure Receives Rose Award

Shreya Parchure (BSE/MSE 2021)

Shreya Parchure, a recent graduate of Penn Bioengineering, was selected by a committee of faculty for a 2021 Rose Award from the Center for Undergraduate Research and Fellowships (CURF). The Rose Award recognizes outstanding undergraduate research projects completed by graduating seniors under the supervision of a Penn faculty member and carries with it a $1,000 award. Parchure’s project, titled “BDNF Gene Polymorphism Predicts Response to Continuous Theta Burst Stimulation (cTBS) in Chronic Stroke Patients,” was done under the supervision of Roy H. Hamilton, Associate Professor in Neurology and Physical Medicine and Rehabilitation and director of the Laboratory for Cognition and Neural Stimulation in the Perelman School of Medicine. Parchure’s work in Hamilton’s lab previously resulted in a 2020 Goldwater Scholarship.

Parchure graduated in Spring 2021 with a B.S.E. in Bioengineering, with concentrations in Neuroengineering and Medical Devices and a minor in Chemistry, as well as a M.S.E. in Bioengineering. During her time as an undergraduate, she was a Rachleff Scholar, a recipient of a Vagelos Undergraduate Research Grant, and the Wolf-Hallac Award. She was active in many groups across the university and beyond, serving as a United Nations Millennium Fellow, a volunteer with Service Link and the Hospital of the University of Pennsylvania (HUP), a CURF Research Peer Advisor, and co-editor-in-chief of the Penn Bioethics Journal. She is now pursuing a M.D./Ph.D. through the Medical Scientist Training Program at Penn Bioengineering and the Perelman School of Medicine.

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.

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