Tag: coronavirus

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Rapid COVID-19 Diagnostic Test Delivers Results Within 4 Minutes With 90 Percent Accuracy

RAPID, a low-cost COVID-19 diagnostic test, can detect SARS-CoV-2 within four minutes with 90 percent accuracy

Even as COVID-19 vaccinations are being rolled out, testing for active infections remains a critical tool in fighting the pandemic. Existing rapid tests that can directly detect the virus rely on reverse transcription polymerase chain reaction (RT-PCR), a common genetic assay that nevertheless requires trained technicians and lab space to conduct.

Alternative testing methods that can be scaled up and deployed in places where those are in short supply are therefore in high demand.

Penn researchers have now demonstrated such a method, which senses the virus by measuring the change in an electrical signal when a piece of the SARS-CoV-2 virus binds to a biosensor in their device, which they call RAPID 1.0.

The work, published in the journal Matter, was led by César de la Fuente, a Presidential Assistant Professor who has appointments in Engineering’s departments of Chemical and Biomolecular Engineering, and Bioengineering, as well as in Psychiatry and Microbiology in the Perelman School of Medicine.

“Prior to the pandemic, our lab was working on diagnostics for bacterial infections. But then, COVID-19 hit. We felt a responsibility to use our expertise to help—and the diagnostic space was ripe for improvements,” de la Fuente said. “We feel strongly about the health inequities witnessed during the pandemic, with testing access and the vaccine rollout, for example. We believe inexpensive diagnostic tests like RAPID could help bridge some of those gaps.”

The RAPID technology uses electrochemical impedance spectroscopy (EIS), which transforms the binding event between the SARS-CoV-2 viral spike protein and its receptor in the human body, the protein ACE2 (which provides the entry point for the coronavirus to hook into and infect human cells), into an electrical signal that clinicians and technicians can detect. That signal allows the test to discriminate between infected and healthy human samples. The signal can be read through a desktop instrument or a smartphone.

Read more about RAPID at Penn Medicine News.

Originally posted on Penn Engineering Today.

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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.

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Becoming a Bioengineer, Both at Home and On Campus

by Erica K. Brockmeier

The junior year BE-MAD lab series includes modules on dialysis, drug delivery, insect limb control, microfluidics, cell-cell communication, ECG analysis (pictured here), and spectroscopy. (Image: Bioengineering Educational Lab)

While the majority of courses remained online this spring, a small number of lab-based undergraduate courses were able to resume limited in-person instruction. One course was BE 310, the second semester of the Bioengineering Modeling, Analysis, and Design lab sequence. Better known as BE-MAD, this junior-year bioengineering course was able to bring students back to the teaching lab safely this spring while adapting its curriculum to keep remote learners engaged with hands-on lab modules at home.

An Essential Step Towards Becoming a Bioengineer

After learning the basics of chemistry, physics, biology, and math during freshman year and studying bioengineering fundamentals throughout sophomore year, BE-MAD is designed to provide essential hands-on experience to bioengineering majors during their junior years. In BE-MAD, students integrate what they’ve learned so far in the classroom to addressing complex, real-world problems by breaking down the silos that exist across different STEM fields.

“Usually what we hear from students is that this BE 309/310 sequence is when they really feel like they are engineers,” says Brian Chow, one of the BE 310 instructors. “They can put what they learn in classes to work in some practical setting and applied context.”

BE-MAD is also an important course to prepare students for senior design and is designed to be a “safe space to fail,” allowing students to build confidence through trial and error within a supportive environment, explains Sevile G. Mannickarottu, director of the educational laboratories. “We’re trying to build skills needed for senior year as well as teaching students how to think critically about problems by pulling together the materials they’ve learned all in one place,” he says. “By senior year, we want them to, when presented with a problem, not be afraid.”

Adapting BE-MAD for Both Remote and Hybrid Instruction

Traditionally, the BE-MAD lab is taught in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary bioengineering teaching lab, and includes modules on dialysis, drug delivery, insect limb control, microfluidics, cell-cell communication, ECG analysis, and spectroscopy. In the fall, the first lab in the series (BE-309) pivoted to remote learning using video tutorials of lab experiments and providing real data to students for analysis.

This spring, with more aspects of on-campus life able to reopen, the Educational Laboratory staff and BE-MAD instructors developed protocols in collaboration with David Meaney, Penn Engineering senior associate dean and an instructor for BE 309, and Penn’s Environmental Health and Radiation Safety office to safely reopen the teaching lab and Bio-MakerSpace for both BE-310 and for bioengineering senior design students.

The BE-MAD lab was also recreated on Gather.Town, an online video chat platform where students can speak with group members or instructors. Student groups also had their own tables where they could meet virtually to work on data analysis and lab report writing.

To continue to meet the needs of remote students, BE 310 instructor Lukasz Bugaj says that the curriculum was adapted to be two parallel courses—one that could be done entirely at home and the other in-person. The challenge was to adjust the content so that it could be completed either in-person or virtually, and could be switched from in-person to virtual at a moment’s notice because of COVID precautions, all while maximizing the hands-on experience, says Bugaj. “That’s a real credit to the lab staff of Sevile and Michael Patterson, who put a lot of work into revamping this entire class.”

Read the full story in Penn Today.

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Michael Mitchell on Keeping mRNA Vaccines Viable

A National Institute of Allergy and Infectious Diseases lab freezer used for COVID-19 vaccine research. Both of the current mRNA-based COVID vaccines require ultra-cold freezers to prevent their mRNA from degrading, spurring research into other ways to stabilize the molecule.

As the technology behind two of the COVID-19 vaccines, Messenger RNA (mRNA) is having a moment. A single-stranded counterpart to DNA, mRNA translates its genetic code into proteins; by injecting mRNA engineered to produce proteins found on the exterior of the virus, the vaccine can train a person’s immune system to recognize the real thing without making them sick.

However, because mRNA is a relatively unstable molecule, distributing these vaccines involves extra logistical challenges. Doses must be transported and stored at ultra-cold temperatures to make sure the mRNA inside doesn’t degrade and lose the genetic information it carries.

Michael Mitchell
Michael Mitchell

As mRNA vaccines and other therapies take off, researchers are looking for other ways to forestall this degradation. One of them is Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, who is studying the use of lipid nanoparticles to encapsulate and protect mRNA on its way into the cell. That sort of packaging would be particularly beneficial in proposed mRNA therapies for certain genetic disorders, which aim to deliver the correct protein-making instructions to specific organs, or even a fetus in utero.

But for stabilizing mRNA for vaccine distribution, many other strategies are being explored. In “Keeping covid vaccines cold isn’t easy. These ideas could help,” Wudan Yan of MIT Technology Review reached out to Mitchell for insight on LIONs, or lipid inorganic nanoparticles. These nanoparticles work the opposite way of Mitchell’s organic ones, with the mRNA stabilized by binding to their exteriors.

Continue reading at MIT Technology Review.

Originally posted in Penn Engineering Today.

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BE Seminar: “Understanding Spatiotemporal Cell Reprogramming for Precision Medicine” (Xiling Shen)

Xiling Shen, Ph.D.

Speaker: Xiling Shen, Ph.D.
Hawkins Family Associate Professor
Biomedical Engineering
Duke University

Date: Thursday, April 15, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Abstract:

Bodily cells undergo transformations in space and time during development, disease progression, and therapeutic treatment. A holistic approach that combines engineering tools, patient-derived models, and analytical methods is needed to map cellular reprogramming and expose new therapeutic opportunities. The talk will cover our effort across the entire spectrum from bench to bedside, including organogenesis during embryonic development, epigenetic and metabolic reprogramming of cancer metastasis and COVID-19 patients, and organoid technology to guide precision- and immune-oncology.

Xiling Shen Bio:

Dr. Shen is the Hawkins Family Associate Professor in the Department of Biomedical Engineering at Duke University. He is also the director of the Woo Center for Big Data and Precision Health. He received his BS, MS, and PhD degrees from Stanford University and the NSF career award at Cornell University. He is the steering committee chair of the NCI Patient-Derived Model of Cancer Consortium. His lab studies precision medicine from a systems biology perspective. Areas of interests include cancer, stem cells, the but-brain axis, and infectious diseases.

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Bioengineering Contributes to “New COVID-19 Testing Technology at Penn”

César de la Fuente, Ph.D., a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, is leading a team to develop an electrode that can be easily printed at low cost to provide COVID-19 test results from your smart phone.

A recent Penn Medicine blog post surveys the efforts across Penn and the Perelman School of Medicine to develop novel says to detect SARS-CoV-2 and features several Department of Bioengineering faculty and Graduate Group members, including César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering; Arupa Ganguly, Professor in Genetics; A.T. Charlie Johnson, Rebecca W. Bushnell Professor in Physics and Astronomy; Lyle Ungar, Professor in Computer and Information Science; and Ping Wang, Associate Professor in Pathology and Laboratory Medicine.

Read “We’ll Need More than Vaccines to Vanquish the Virus: New COVID-19 Testing Technology at Penn” by Melissa Moody in Penn Medicine News.

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“The Bio-MakerSpace — Fostering Learning and Innovation Across Many Disciplines”

Penn Bioengineering’s BioMakerSpace in action (photo taken pre-pandemic)

Writing for the Penn Health-Tech blog, Hannah Spector profiled the George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace, the primary teaching lab for the Department of Bioengineering at Penn Engineering. This interdisciplinary Bio-MakerSpace (aka BioMakerSpace) is open to the entire Penn community for independent research and has become a hub for student startups in recent years:

One example is Strella Biotechnology, founded in 2019 by Katherine Sizov (Biology 2019 & President’s Innovation Prize winner). Strella is developing sensors with the ability to reduce the amount of food waste due to going bad in storage. “Having a Bio-MakerSpace that gives you the functionalities of both a wet lab and a traditional electronics lab is extremely helpful in developing novel technologies” says Sizov on the BE Labs Youtube channel.

The Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities, including highly knowledgeable lab staff. Seth Fein (BSE ’20, MSE ’21) has worked at the lab since Fall 2020. “Because bioengineering spans many fields, we encourage interdisciplinary work. Students from Mechanical, Electrical, and Chemical Engineering have all found valuable resources in the lab,” says Fein.

The article also discusses the many resources the BioMakerSpace provides to Penn students and their efforts to keep the lab functional, safe, and open for research and education during the current semester.

Penn Health-Tech is an interdisciplinary center launched in 2017 to advance medical device innovation across the Perelman School of Medicine and the School of Engineering and Applied Sciences by forging collaborative connections among Penn researchers and providing seed funding to incubate novel ideas to advance health care.

Continue reading “The Bio-MakerSpace — Fostering Learning and Innovation Across Many Disciplines” at the Penn Health-Tech blog.

Read more BE blog posts featuring the BioMakerSpace.

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Seminar: “The Coming of Age of De Novo Protein Design” (David Baker)

David Baker, Ph.D.

Speaker: David Baker, Ph.D.
Professor
Biochemistry
University of Washington

Date: Thursday, March 18, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “The Coming of Age of De Novo Protein Design”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Biochemistry & Biophysics.

Abstract:

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen’s principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. I will describe the de novo design of fluorescent proteins, membrane penetrating macrocycles, transmembrane protein channels, allosteric proteins that carry out logic operations, and self-assembling nanomaterials and polyhedra. I will also discuss the application of these methods to COVID-19 challenges.

Bio:

David Baker is the director of the Institute for Protein Design, a Howard Hughes Medical Institute Investigator, a professor of biochemistry and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. His research group is a world leader in protein design and protein structure prediction. He received his Ph.D. in biochemistry with Randy Schekman at the University of California, Berkeley, and did postdoctoral work in biophysics with David Agard at UCSF. Dr. Baker is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Dr. Baker is a recipient of the Breakthrough Prize in Life Sciences, Irving Sigal and Hans Neurath awards from the Protein Society, the Overton Prize from the ISCB, the Feynman Prize from the Foresight Institute, the AAAS Newcomb Cleveland Prize, the Sackler prize in biophysics, and the Centenary Award from the Biochemical society. He has also received awards from the National Science Foundation, the Beckman Foundation, and the Packard Foundation. Dr. Baker has published over 500 research papers, been granted over 100 patents, and co-founded 11 companies. Seventy-five of his mentees have gone on to independent faculty positions.

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‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’

William H. Peranteau, Michael J. Mitchell, Margaret Billingsley, Meghana Kashyap, and Rachel Riley (Clockwise from top left)

As COVID-19 vaccines roll out, the concept of using mRNA to fend off viruses has become a part of the public dialogue. However, scientists have been researching how mRNA can be used to in life-saving medical treatments well before the pandemic.

The “m” in “mRNA” is for “messenger.” A single-stranded counterpart to DNA, it translates the genetic code into the production of proteins, the building blocks of life. The Moderna and Pfizer COVID-19 vaccines work by introducing mRNA sequences that act as a set of instructions for the body to produce proteins that mimic parts of the virus itself. This prepares the body’s immune response to recognize the real virus and fight it off.

Because it can spur the production of proteins that the body can’t make on its own, mRNA therapies also have the potential to slow or prevent genetic diseases that develop before birth, such as cystic fibrosis and sickle-cell anemia.

However, because mRNA is a relatively unstable molecule that degrades quickly, it needs to be packaged in a way that maintains its integrity as its delivered to the cells of a developing fetus.

To solve this challenge, Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is researching the use of lipid nanoparticles as packages that transport mRNA into the cell. He and William H. Peranteau, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at Children’s Hospital of Philadelphia, recently co-authored a “proof-of-concept” paper investigating this technique.

In this study, published in Science Advances, Mitchel examined which nanoparticles were optimal in the transport of mRNA to fetal mice. Although no disease or organ was targeted in this study, the ability to administer mRNA to a mouse while still in the womb was demonstrated, and the results are promising for the next stages of targeted disease prevention in humans.

Mitchel spoke with Tom Avril at The Philadelphia Inquirer about the mouse study and its implications for treatment of rare infant diseases through the use of mRNA, ‘the messenger of life.’

Penn bioengineering professor Michael J. Mitchell, the other senior author of the mouse study, tested various combinations of lipids to see which would work best.

The appeal of the fatty substances is that they are biocompatible. In the vaccines, for example, two of the four lipids used to make the delivery spheres are identical to lipids found in the membranes of human cells — including plain old cholesterol.

When injected, the spheres, called nanoparticles, are engulfed by the person’s cells and then deposit their cargo, the RNA molecules, inside. The cells respond by making the proteins, just as they make proteins by following the instructions in the person’s own RNA. (Important reminder: The RNA in the vaccines cannot become part of your DNA.)

Among the different lipid combinations that Mitchell and his lab members tested, some were better at delivering their cargo to specific organs, such as the liver and lungs, meaning they could be a good vehicle for treating disease in those tissues.

Continue reading Tom Avril’s ‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’ at The Philadelphia Inquirer.

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An ‘Electronic Nose’ to Sniff Out COVID-19

by Erica K. Brockmeier

Postdoc Scott Zhang at work in the Johnson lab. (Photo: Eric Sucar, University Communications)

Even as COVID-19 vaccines are being rolled out across the country, the numerous challenges posed by the pandemic won’t all be solved immediately. Because herd immunity will take some time to reach and the vaccine has not yet been approved for some groups, such as children under 16 years of age, the coming months will see a continued need for tools to rapidly track the disease using real-time community monitoring.

A team of Penn researchers is working on a new “electronic nose” that could help track the spread of COVID-19. Led by physicist Charlie Johnson, the project, which was recently awarded a $2 million grant from the NIH, aims to develop rapid and scalable handheld devices that could spot people with COVID-19 based on the disease’s unique odor profile.

Dogs and devices that can detect diseases

Long before “coronavirus” entered into the vernacular, Johnson was collaborating with Cynthia Otto, director of the Penn Vet Working Dog Center, and Monell Chemical Senses Center’s George Preti to diagnose diseases using odor. Diseases are known to alter a number of physical processes, including body odors, and the goal of the collaboration was to develop new ways to detect the volatile organic compounds (VOCs) that were unique to ovarian cancer.

The next step is to scale down the current device, and the researchers are aiming to develop a prototype for testing on patients within the next year.

Since 2012, the researchers have been developing new ways to diagnose early-stage ovarian cancer. Otto trained dogs to recognize blood plasma samples from patients with ovarian cancer using their acute sense of smell. Preti, who passed away last March, was looking for the specific VOCs that gave ovarian cancer a unique odor. Johnson developed a sensor array, an electronic version of the dog’s nose, made of carbon nanotubes interwoven with single-stranded DNA. This device binds to VOCs and can determine samples that came from patients with ovarian cancer.

Last spring, as the pandemic’s threat became increasingly apparent, Johnson and Otto shifted their efforts to see if they could train their disease-detecting devices and dogs to spot patients with COVID-19.

Continue reading at Penn Today.

N.B.: A.T. Charlie Johnson, Rebecca W. Bushnell Professor of Physics and Astronomy at the Penn School of Arts & Sciences, and Lyle Ungar, Professor in Computer and Information Science at Penn Engineering and Psychology at the School of Arts & Sciences, are both members of the Penn Bioengineering Graduate Group.