Developing New Technologies to Solve the Mysteries of the Brain

Flavia Vitale, assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founder of the multidisciplinary Vitale Lab. (Image: Penn Medicine News)

Neurology, bioengineering, and physical medicine and rehabilitation might not seem like three disciplines that fit together, but for Flavia Vitale, an assistant professor of all three, it makes perfect sense. As the director and principal investigator at the Vitale Lab, her research focuses on developing new technologies that help to study how the brain and neuromuscular systems function.

Years ago, while she was working at Rice University developing new materials and devices that work in the body in a safer, more effective way, former president Barack Obama launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, aimed at revolutionizing the understanding of the human brain. This emphasis on how little is known about brain structure and function inspired Vitale to refocus her research on developing technology and materials that will help researchers solve the mysteries of the brain.

In 2018, she joined the faculty at the Perelman School of Medicine as an assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founded the multidisciplinary Vitale Lab, where her team develops cutting edge materials and devices that will someday help clinicians diagnose and treat patients with complicated brain and neurological conditions. She is also one of the engineers looking forward to using new combined clinical/research facilities in neuroscience at Penn Medicine’s new Pavilion where new neurotechnoloigies will be developed and tested.

“My main goal is to create tools that can help solve mysteries of the brain, and address the needs of clinicians,” she says.

“My lab was recently awarded two grants totaling $4.5 million from the National Institute of Neurological Disorders and Stroke. In order to obtain more precise insights, noninvasively, into brain activity to improve gene therapy treatments for a range of diagnoses, from Parkinson’s disease to glioblastoma. The first grant is designated for the development of a novel surgical device for delivering gene-based therapeutics to the brain. The second is for optimization and pre-clinical validation of a novel EEG electrode technology, which uses a soft, flexible, conductive nanomaterial rather than metal and gels. We hope to confirm that these technologies work as well as, if not better than existing ones.”

Read the full story in Penn Medicine News.

BE Seminar: “Dynamics of 3D Cell Migration and Organ Formation” (Kenneth Yamada)

Our next Penn Bioengineering seminar will be held on zoom next Thursday.

Kenneth Yamada, MD, PhD

Speaker: Kenneth Yamada, M.D., Ph.D.
NIH Distinguished Investigator
Cell Biology Section
National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH)

Date: Thursday, September 9, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: Real-time microscopy of the dynamics of cells and tissues in 3D environments is opening new windows to understanding the biophysical mechanisms of complex biological processes. Direct visualization is allowing us to explore fundamental questions in more depth that include: How do cells migrate in 3D? How do cancer cells invade? How is the extracellular matrix assembled? How are organs formed? Visualizing how cells move and organize into tissues is not only providing descriptive insights, but is also leading to the identification of novel, unexpected physical and mechanical mechanisms relevant to tissue engineering. Cells can use varying combinations of cell adhesion to adjacent cells and to the surrounding extracellular matrix with localized cellular contractility to migrate, invade, and produce the complex tissue architecture needed for organ formation.

Kenneth Yamada Bio: Kenneth Yamada has been an NIH Distinguished Investigator since 2011. He received MD and PhD degrees from Stanford. He was a Section Chief at the National Cancer Institute for 10 years and has been a Section Chief at NIDCR since 1990. He is an elected Fellow of the AAAS and American Society for Cell Biology. His research focuses on discovering novel mechanisms and regulators of cell interactions with the extracellular matrix and their roles in embryonic development and cancer. His research group focuses on the mechanisms by which three-dimensional (3D) extracellular matrix mediates key biological events, including cell migration, tissue morphogenesis, and cancer cell invasion. His research places particular emphasis on characterizing the dynamic movements of cells and their extracellular matrix as tissues are remodeled in 3D in real time. The biological systems they study include human primary cells migrating in 3D, human tumor cells and tissues, and mouse organ development. He places particularly high priority on developing future independent research leaders.

BE Seminar: “Synthetic Biochemistry: Engineering Molecules and Pathways for Precision Medicine” (Michael Lin)

Save the date for the first Penn Bioengineering seminar of the fall 2021 semester! This year’s seminars will be hybrids, held virtually on zoom and live on campus!

Michael Lin, Ph.D.

Speaker: Michael Lin, Ph.D.
Associate Professor
Neurobiology, Bioengineering, and by courtesy Chemical and Systems Biology
Stanford Medicine, Stanford University

Date: Thursday, September 2, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: The most effective medicines are those that target the earliest causes of disease, rather than later manifestations. Engineering of biomolecules is a promising but underexplored approach to precisely detecting or targeting disease causes. I will present our work to develop a novel approach to treating cancer by detecting the signaling abnormalities that give rise to cancer. Interestingly, this effort involves biomolecular engineering at multiple scales: proteins, pathways, and viruses. I will also discuss how our work has translated serenditously to developing treatments for SARSCoV2.

Michael Lin Bio: Michael Z. Lin received an A.B. summa cum laude in Biochemistry from Harvard, an M.D. from UCLA, and a Ph.D. from Harvard Medical School. After training in biochemistry and neurobiology as a PhD student with Michael Greenberg at Harvard Medical School, Dr. Lin performed postdoctoral research in fluorescent protein engineering with Chemistry Nobel Laureate Roger Y. Tsien at UCSD. Dr. Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, a Damon Runyon-Rachleff Innovation Award, and a NIH Pioneer Award.

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:

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.

Katherine Reuther Appointed Practice Associate Professor in Bioengineering

Katie Reuther, PhD, MBA

Katherine (Katie) Reuther, Ph.D., M.B.A. will return to Penn Engineering in July 2021 as the new Executive Director of Penn Health-Tech (PHT) and as Practice Associate Professor in Bioengineering. Reuther is an alumna of Penn Bioengineering, having obtained her Ph.D. at Penn in the laboratory of Louis Soslowsky, Fairhill Professor in Bioengineering and Orthopaedic Surgery.

“Dr. Reuther is a role model for biomedical innovation, linking formal training in engineering and entrepreneurship with deep practical experience in leading technologies through the commercialization pipeline. Dr. Reuther graduated with her Bachelor of Science in Biomedical Engineering, Magna cum Laude, from the College of New Jersey; she obtained her Ph.D. in Bioengineering at Penn in the laboratory of Dr. Louis Soslowsky and completed her MBA at Columbia, where she currently is a Senior Lecturer in Design, Innovation, and Entrepreneurship in the Department of Biomedical Engineering. During her tenure at Columbia, Dr. Reuther helped create and led Columbia’s Biomedical Engineering Technology Accelerator (BiomedX), overseeing more than 60 technologies leading to $80M in follow-on funding and 18 licenses to start-ups or start-ups industry.  Introducing both new courses and a new curriculum in biomedical innovation, Dr. Reuther was recently awarded Columbia’s highest teaching honor, the ‘2021 Presidential Award for Outstanding Teaching,’ this Spring as a recognition of her excellence in teaching and dedication to students.

Katie has extensive experience in developing and translating early-stage medical technologies and discoveries and providing formal educational training for aspiring medical entrepreneurs.  Dr. Reuther served as Director of Masters’ Studies for the Department of Biomedical Engineering and spearheaded the development of a graduate-level medical innovation program, including an interdisciplinary course available to scientists, engineers, and clinicians. Dr. Reuther provided advising and educational support to more than 100 student/faculty teams and start-ups, as they worked to develop and commercialize medical technologies. She will bring these extensive skills to PHT and Penn Bioengineering in two new, hands-on graduate courses in medical innovation centered around Penn Health-Tech ventures.”

Read the full announcement in OVPR news.

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

César de la Fuente Featured in “40 Under 40” List

César de la Fuente, Ph.D.

César de la Fuente, PhD, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Psychiatry, and Microbiology, was featured in the Philadelphia Business Journal’s Class of 2021 “40 Under 40” list. Currently focused on antibiotic discovery, creating tools for microbiome engineering, and low-cost diagnostics, de le Fuente pioneered the world’s first computer-designed antibiotic with efficacy in animal models.

De la Fuente was previously included in the AIChE’s “35 Under 35” list in 2020 and most recently published his work demonstrating a rapid COVID-19 diagnostic test which delivers highly accurate results within four minutes.

Read “40 Under 40: Philadelphia Business Journal’s complete Class of 2021” here.

Read other BE blog posts featuring Dr. de la Fuente here.