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November 8, 2017November 8, 2017

Penn Bioengineering at BMES 2017

BMES 2017

The annual meeting of the Biomedical Engineering Society (BMES) was held in Phoenix on October 11-14. The professional society for bioengineers and biomedical engineers this year played host not only to faculty from Penn’s Bioengineering Department but also to several undergraduate and graduate students, as well as staff

As previously mentioned here, three of the undergraduate students from the Center for Engineering MechanoBiology (CEMB) presented their work at the BMES meeting. The three students – Kimberly DeLuca from New Jersey Institute of Technology; John Durel from the University of Virginia; and Olivia Leavitt from Worcester Polytechnic Institute – spent 10 weeks over the summer at Penn working on individual research projects in the labs of Penn faculty.

Olivia worked in the laboratory of Beth Winkelstein, Ph.D., Professor of Bioengineering and Vice Provost for Education at Penn. Olivia’s project studied how matrix proteases influence the nerve impulses, but not the structure, of connective tissue. Jacob’s project, developed with Professor Jason Burdick, Ph.D., generated new insights into how single stem cells sense the mechanical environment and ‘make decisions’ about which type of cell they will become. Kimberly’s work was done in the lab of Robert Mauck, Ph.D., Professor of Orthopaedic Surgery at Penn’s Perelman School of Medicine, and it studies how to make materials with unique mechanical properties that could eventually find use in tissue engineering applications.

“I am very pleased to have been a part of the CEMB’s first round of undergraduate summer interns, and while there are certainly some small kinks to be worked out around the edges, the CEMB offered an invaluable experience. If I had to go back and decide again whether or not to chose this internship versus others, I would do it again in a heart-beat,” John Durel said.

BMES 2017 — (left to right) Bioengineering Department Chair David Meaney, BMES Co-president Olivia Teter, and GABE board members Meagan Ita and Varsha Viswanath.

Also attending BMES were officers of the undergraduate chapter of BMES at Penn. As we previously reported, the chapter won the Student Outreach Achievement Award for the year, repeating its win from 2015. Penn’s contingent from the BMES chapter, as well as from the Graduate Association of Bioengineers (GABE), were on hand to receive awards and recognition (see photo above).

Finally, Sevile Mannickarottu, instructional laboratories director for the Bioengineering Department, presented a paper at one of the conference sessions. Alongside presenters from MIT, Johns Hopkins, Berkeley, UCSD, UIUC, and Stanford, Sevile (see photo right) participated in a special sessions on curricular innovation held on Friday, October 13. Sevile did a great job explaining the innovations introduced to Penn’s undergraduate lab over the course of the last few years, and the presentation was very well received.

Next year’s BMES conference will be held in Atlanta on October 17-20, followed by the 2019 meeting in Philadelphia, to be co-chaired by Penn BE’s Jason Burdick.

September 19, 2017September 18, 2017

InnoWorks Academy Engages Local Teens

InnoWorks

The week of August 21-25, 20 students from area middle schools visited Penn to participate in InnoWorks, an educational initiative of the United InnoWorks Academy (UIA), a non-profit organization founded in 2003 by William Hwang, M.D., Ph.D., when he was an undergraduate engineering major at Duke. Today, InnoWorks offers programs at 20 colleges and universities in the U.S. and Caribbean. In the program, undergraduate student volunteers host middle schoolers from disadvantaged backgrounds to foster the teenagers’ interest in science and engineering.

InnoWorks Each day of the week, from 9:15 a.m. to 5:00 p.m., the group of teens attended presentations, conducted experiments, and competed against one another in activities designed to have them apply the principles they learned about. Each day was dedicated to different topics: materials science on Monday; biology on Tuesday; chemistry and earth science on Wednesday; physics and computer science on Thursday; and a wrap-up day on Friday. In addition, over the course of the week, the students were scored for their activities, with a winner announced at the end of the week.

For instance, on Friday, students participating in InnoWorks competed in the Egg Drop Challenge. Using materials provided for them, the students designed their own parachutes for eggs, which they used in dropping the eggs from the second floor of Skirkanich Hall to the ground floor. The students did so well that the competition had to be extended to the third floor.

On another day, Dr. Kushol Gupta, a research assistant professor at Penn conducting research on HIV and assistant director of the Penn Band, talked to the students about the physics of music. Sarah Tang and Monroe Kennedy of Dean Vijay Kumar’s GRASP lab discussed the current state of robotics and drones and showed video clips of some of their work. It was among the most popular popular parts of the week.

Here at Penn, the codirectors of the chapter are Jacqueline Valeri, a senior bioengineering major, and Monica Shen, a senior biology major. Asked about InnoWorks this year, Jackie said, “The InnoWorks program is a great camp to be involved with because the hands-on, interactive engagement really gets our students excited about science. We try to do really minimal lecturing time and maximize the opportunity for the students to actually do experiments, demonstrations, and design challenges. As codirector of this year’s program, it was really awesome to see what a great group of students we had this year and how they flourished throughout the week. This is my third year participating in Penn’s InnoWorks chapter and it has been one of the most rewarding, fun experiences that I’ve had at Penn!”

September 14, 2017September 14, 2017

Undergraduates Converge at Penn for REU

This past summer, 10 undergraduate from 10 colleges came to Penn for 10 weeks (May 30 to August 4) for the Summer Undergraduate Research Experience (SURE), also known as the Research Experience for Undergraduates (REU). During the program, the students were hosted in the laboratories of faculty in Penn’s Schools of Engineering and Applied Science (including Penn Bioengineering faculty Beth Winkelstein, Dan Huh, and Jason Burdick) and Arts and Sciences and the Perelman School of Medicine. These students were hosted under the aegis of the Center for Engineering MechanoBiology (CEMB), a National Science Foundation-funded collaboration among Penn, Washington University (WashU) in St. Louis, New Jersey Institute of Technology (NJIT), Alabama State University, Bryn Mawr College, Boston University, and the University of Texas at Austin.

The students all worked on individual research projects. At the end of the 10-week term, three abstracts from this research were chosen for presentation at the forthcoming annual meeting of the Biomedical Engineering Society (BMES), which will be held October 11-14 in Phoenix. The three students are Kimberly DeLuca (NJIT), John Durel (Univ. of Virginia), and Olivia Leavitt (Worcester Polytech).

The CEMB Web site at WashU has a nice page up featuring the program and this summer’s students.

https://cemb.wustl.edu/penns-2017-summer-undergraduate-research-experience-at-a-glance/

September 12, 2017September 12, 2017

Noordergraaf Fellows Conduct Summer Research

Each year, the Penn Department of Bioengineering chooses undergraduate students to receive fellowships for summer research. These fellowships, which provide a $3,500 stipend for use over 10 weeks, were endowed by the Abraham Noordergraaf Student Summer Bioengineering Research Fund. Dr. Noordergraaf, who died in 2014, was a founding member and first chair of the Penn BE Department. In keeping with Dr. Noordergraaf’s research focus on the cardiovascular system, fellows with a focus on this system are favored but not exclusively awarded.

The fellows for the summer of 2017 were Brianna Karpowicz, Jacqueline Valeri, and Alejandro Villasmil. Brianna is a junior bioengineering major working in the lab of Professor Yale Cohen. In her research, Brianna worked with Dr. Cohen in the Auditory Research Laboratory, examining the modeling of multisensory perceptual decision making and specifically seeking to better understand the mechanisms underlying the relationship between sensory information and perception.

Alejandro Villasmil

Alejandro Villasmil, who is a senior bioengineering major working in Professor Beth Winkelstein’s lab, used his Noordergraaf’s grant to study chronic pain in neck injury. To better understand this problem, Alejandro helped to model injury to the facet capsular ligament — one of the structures in the neck — by examining how painful and nonpainful stimuli affected the axonal structure. He found using fluorescence technology that uniaxial tension resulted in axonal changes resulting in pain.

Finally, Jacqueline Valeri is a senior bioengineering major doing research in the lab of Professor Jennifer Phillips-Cremins. In Professor Cremins’s lab, Jackie undertook research on stem cells, specifically examining the question of whether light could be used to control and modulate the fate of these cells — a field called optogenetics. She helped to design two light boxes to stimulate the interaction between two proteins as a first step toward ultimately attempting to control pluripotent stem cells using light, specifically determining what cell lines these stem cells ultimately produce.

We congratulate our Noordergraaf award winners!

August 22, 2017August 22, 2017

Pancreatic Cancer Detection With Micropore Chip

Pancreatic cancer remains one of the deadliest types of cancer, with one- and five-year survival rates of only 20% and 7%, respectively, according to the American Cancer Society. The mortality is so high because the disease does not typically cause symptoms until it is too late. Therefore, earlier detection could be the key to better survival rates.

In a new paper published by Lab on a Chip, a research team from the lab of David Issadore, assistant professor of Bioengineering, reports on its development of a micropore chip, callled the circulating tumor cell fluorescence in situ hybridization (CaTCh FISH) chip, that could detect circulating tumor cells (CTCs) from mice and patients with pancreatic cancer, even at very low, previously undetectable levels.

Jin A (Jina) Ko, who is a Ph.D. student in Bioengineering and first author on the paper, says that CTCs are a key mechanism underlying metastasis, which is another reason why pancreatic cancer has such a low survival rate. Not only can the chip that she helped design detect these cells, which circulate in the bloodstream, but more importantly, pancreatic tumors shed these cells even in their very early stages before any spread has occurred. Therefore, provided the test is performed early enough, the tumor can be detected and treated. Patients with family histories of pancreatic cancer or who have tested positive for certain gene mutations would likely benefit from this sort of test.

The study authors also tested the CaTCh FISH chip using blood samples from 14 patients with advanced pancreatic cancer and from healthy controls. They found that their micropore chip could detect several RNA markers of cancer in 10-mL samples — around 2 tsp. In addition, there were no false-negative results among the healthy controls, demonstrating a high level of reliability in that regard.

“We have developed a microchip platform that combines fast, magnetic micropore-based negative immunomagnetic selection with rapid on-chip in situ RNA profiling,” Jina said. “This integrated chip can isolate both rare circulating cells and cell clusters directly from whole blood and allow individual cells to be profiled for multiple RNA cancer biomarkers.”

August 21, 2017August 21, 2017

Sperry Wins BMES Design and Research Award

Megan Sperry, a Ph.D. student in the Department of Bioengineering, is a recipient of a Student Design and Research Award from the Biomedical Engineering Society (BMES). Megan works in the Spine Pain Research Lab of Beth Winkelstein, Ph.D., professor of Bioengineering and Vice Provost for Education at Penn’s School of Engineering and Applied Science, as well as with Eric Granquist, DMD, MD, an oral and maxillofacial surgeon at Penn Dental Medicine.

With Drs. Winkelstein and Granquist, Megan studies temporomandibular joint (TMJ) pain and osteoarthritis, the latter of which can develop as a long-term consequence of untreated TMJ dysfunction. There’s currently no way to determine which patients will progress to TMJ osteoarthritis, so Megan’s extended abstract, which was submitted to the BMES competition, detailed a study using 18F-EF5 PET, an imaging modality used mainly in oncology. Hypothesizing that hypoxia, or low oxygen, was a key factor in the development of TMJ osteoarthritis, Megan studied the relationship between hypoxia and persistent TMJ pain and found that hypoxia preceded reorganization of the cartilage of the TMJ, part of the process culminating in TMJ osteoarthritis (see image below).

“This project has been both fun and challenging because it brings together concepts and techniques from multiple fields, including orthopedics, neuroscience, and, with the use of 18F-EF5, radiation oncology,” Megan said. “I’m excited to have the opportunity to share my work at the BMES Annual Meeting and receive feedback as we continue to move the project forward.”

Each year, BMES awards up to five graduate students the Student Design and Research Award from dozens of submissions. Congratulations to Megan for this elite recognition of her research!

August 16, 2017

BMES at Penn Wins Outreach Award

BMES

The chapter of the Biomedical Engineering Society (BMES) at the University of Pennsylvania has won the Student Outreach Achievement Award from the society. This is the second time in three years that BMES at Penn has won the award, for which more than 60 other chapters compete.

The award acknowledges the efforts of Penn BMES to establish relationships with the surrounding community. For instance, Junior Beta Day, held in the spring semester, saw Penn BE students hosting approximately 60 local middle school students for a day on campus, during which they interacted with members of the faculty and engaged in activities centered on bioengineering. In addition, the Penn BMES chapter has participated in local neighborhood revitalization initiatives and acted as mentors.

“I’m very proud of our group’s outreach initiatives within the both the greater Philadelphia and campus communities,” said Sonia Bansal, who is one of the outreach chairs for the chapter. “Our partnerships with iPraxis and SPARK help us break down bioengineering concepts into approachable activities for middle school students. We hope that our programming shows students that they too can go on to be engineers and scientists, and its an incredibly rewarding experience to see students get excited about STEM.”

Founded in 1968, BMES is a 501(c)(3) nonprofit professional association acting as a lead society for 7,000 members and 115 student chapters.

July 21, 2017July 25, 2017

Secondary Projects From Ghana: Group 4

While brainstorming and writing a proposal for a device to detect pediatric tuberculosis has been extremely valuable, we recognize the challenge of developing our devices as undergraduate/graduate students. This acknowledgement led us to try to identify a healthcare problem in Ghana and to come up with a solution that undergraduates could potentially pursue. The process began after we arrived in Ghana, with each student independently identifying a problem and brainstorming a solution. Next, we played an entrepreneurial game, in which each student gave a pitch for an idea, and everyone gave hypothetical money to his or her favorite idea. The ideas with the most hypothetical monetary investments would move on to the next round. After two rounds of pitches, we narrowed our list down to two ideas: Big Data and the Multi-Cot. Splitting up our group between the two ideas, we then prepared a presentation to give to Kumasi Center for Collaborative Research in Tropical Medicine (KCCR) researchers. Yesterday and today, we present the summaries of our ideas.

Ghana group 4-1 — The Multi-Cot aims to tackle the issue of limited space in large regional hospitals within Ghana and other similar situations of overcrowding.

Kate Panzer (gave first-round pitch) ’18, Katharine Cocherl ’20, Kaila Helm ’20, Hope McMahon ’18

Throughout our time in Ghana, we had the opportunity to visit many hospitals and smaller health clinics. While visiting Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, we noticed that there was a poster on a pediatrician’s wall for the “One Baby One Cot” initiative. We soon learned that there is very limited space per patient at the large regional hospitals — certainly not enough space for each individual baby to occupy his or her own cot. For example, in some hospitals, there can be up to eight babies in one cot! This can be problematic when trying to prevent the spread of infection but also difficult for mothers who have little to no space to watch over their newborns when they stay at the hospital to breastfeed.

There are several implications of having multiple babies in a single cot that we would like to address. First, the risk of hospital-acquired infections greatly increases because of the close contact of the babies. This close contact also makes it difficult for nurses and caretakers to monitor each baby. In addition, many babies may need to be transported to other hospitals because of a lack of bed space, moving the patients and their caretakers farther from home.

Ghana 4-2 — The horizontal sliding mechanism of the Multi-Cot allows each newborn to be safely removed from the structure, regardless of the cot level.

After learning about this problem, we began thinking of ways to decrease the complications associated with having multiple newborns in one cot. During the brainstorming session, the key element that led to our solution was actually how we view the problem. We started to see the issue as a lack of horizontal space – meaning the inability to add more cots horizontally without physically expanding the newborn ward. If expanding the horizontal space is not possible, then why not try to make better use of the vertical space that is already available? This concept of vertical space led us to the idea of the Multi-Cot, which involves three smaller newborn cots stacked vertically, with space between each cot to provide proper airflow. With clear plastic sides and an open top, each baby would be easily seen from every direction. Finally, to ensure safety when removing newborns from the lower levels, we added a sliding mechanism to our design to allow the lower cots to slide horizontally and eliminate any vertical obstructions when picking up the baby.

As we anticipate developing the Multi-Cot, we must consider multiple factors. Our main consideration is safety, which includes the Multi-Cot’s stability, the visibility of every child, and the ability to be sanitized. Other factors to be considered include the cost, as well as the ease of physical construction and dismantling; however, we would address these details later in the design process.

July 20, 2017July 25, 2017

Secondary Projects From Ghana: Group 3

While brainstorming and writing a proposal for a device to detect pediatric tuberculosis has been extremely valuable, we recognize the challenge of developing our devices as undergraduate/graduate students. This acknowledgement led us to try to identify a healthcare problem in Ghana and to come up with a solution that undergraduates could potentially pursue. The process began after we arrived in Ghana, with each student independently identifying a problem and brainstorming a solution. Next, we played an entrepreneurial game, in which each student gave a pitch for an idea, and everyone gave hypothetical money to his or her favorite idea. The ideas with the most hypothetical monetary investments would move on to the next round. After two rounds of pitches, we narrowed our list down to two ideas: Big Data and the Multi-Cot. Splitting up our group between the two ideas, we then prepared a presentation to give to Kumasi Center for Collaborative Research in Tropical Medicine (KCCR) researchers. Today and Friday we present the summaries of our ideas.

Big Data: Deciphering Acoustic Trends in Tuberculosis, Pneumonia and Healthy Coughs

David Pontoriero (gave first-round pitch) ’18, Kathleen Givan ’20, Jason Grosz ’19, Danielle Tsougarakis ’20, Ethan Zhao ’19

Our goal was to think of a project that a team of undergraduates at Penn could complete in one year to produce something of value to KCCR in the scope of Ghanaian healthcare. We turned our attention toward big data science and the difficulties in tuberculosis diagnosis. One of the difficulties identified was the lack of diagnostic tools in more remote arms of the healthcare system. This lack leads to unnecessary and numerous referrals to larger care centers, inconveniencing the patient and placing a burden on the efficiency of the healthcare system.

Specifically, the only standard-of-care diagnostic ubiquitous throughout all clinics was patient-reported symptoms — the most notable of which is prolonged coughing. Moreover, this symptom can often be confused with asthma or pneumonia. However, asthma involves bronchial constriction, and TB and pneumonia have different sputum distribution profiles. We theorized that this difference would correlate with differentiated sound profiles for patient coughs or baseline breathing and, subsequently, measurable biomarkers. The idea proposed was that, if blind data could be collected from KCCR with sound recordings of patients coughing and breathing, along with their demographics and final diagnoses, then analyses could be run to produce an algorithm capable of differentiating between each cough or breath. This algorithm could then be extended to a phone app that could be used to more empirically diagnose patients in any setting and increase overall healthcare efficiency.

July 19, 2017

Primary Projects From Ghana: Group 2

Throughout the Spring 2017 semester, our professor, Dr. David Issadore, taught us (a class of eight undergraduates students and one graduate student) about microfluidics and point-of-care diagnostics. The next phase of the course was to come up with a new diagnostic for pediatric tuberculosis. At the end of the semester, our final assignments included submitting an NIH Research Project Grant (R01) proposal and giving a 20-minute presentation for our devices. These assignments greatly prepared us for our trip to Ghana, as we were able to ask questions and get feedback on our proposed devices by speaking to healthcare professionals at Ghanaian hospitals, clinics, and research facilities. The semester course was mainly focused on the technical design of our devices, which enabled us to hone in on the practical and real-world implementation of the devices while in Ghana. This week, the BE Blog will publish our summaries.

The LAMinator: Urine Diagnostic for Pediatric Tuberculosis

Danielle Tsougarakis ’20, Ethan Zhao ’19, Jason Grosz ’19, Kate Panzer ’18

Current devices that detect Mycobacterium tuberculosis include chest X-ray, smear microscopy, and GeneXpert. Although the combination of these techniques can lead to a proper diagnosis for adults, there are three main limitations of their use: (1) necessary infrastructure; (2) required sputum samples; and (3) time. First, many clinics in rural Ghana do not currently have the infrastructure or electricity sources to support these machines. Second, both smear microscopy and the GeneXpert rely on analyzing sputum samples (bacteria-containing phlegm), but children have difficulty providing sufficient samples. Finally, since sputum samples are best taken in the morning, these techniques often require patients to go home and return the next day to provide a sample.

ghana group 2-1 — Since all biological molecules are inherently non-magnetic, these magnetic nanoparticles can be attached to ManLAM using aptamers to allow for detection by the spin-valve sensor.

To address these limitations in our own design, we proposed a diagnostic device that does not require electricity, relies on a urine sample instead of a sputum sample, and is anticipated to take one hour to obtain a diagnosis. By incorporating these three characteristics, we propose a device that can be used to more easily diagnose children during their first initial visit at any healthcare facility in Ghana.

ghana group 2-2 — This overview of our device shows how the biomarker will be magnetically labeled, pushed through microfluidic channels, captured on the surface, and detected by the spin-valve sensor.

After doing a literature search of publications on pediatric tuberculosis, we learned that M. tuberculosis sheds a glycolipid called lipoarabinomannan (ManLAM) that is excreted in the urine. Therefore, ManLAM is the biomarker we hope to detect. Next, after learning that biology is inherently nonmagnetic, we figured that we could detect ManLAM specifically and sensitively if we could label it magnetically. Our proposed design does this labeling by adding magnetic nanoparticles (MNPs) to the ManLAM. This magnetic labeling involves aptamers, which are synthetic oligonucleotides that can be created to bind to a specific target. By combining the MNPs with aptamers that bind only to ManLAM, we can ultimately give the urine biomarker a magnetic property.

ghana group 2-3 — The LAMinator has a reusable box component to house the electronics as well as a disposable cartridge to hold the microfluidic chip and disposable wells to avoid sample contamination.

Therefore, the first step of our device is treating the urine sample with the custom aptamer-bound MNPs. The electronic components of our diagnostic device consist of specialized sensors, called spin-valve sensors, that can detect the presence of magnetic particles. Small fluid channels containing the urine sample traverse the surface of these sensors. If ManLAM is present in the urine as it passes by the spin-valve sensors, the surface-bound aptamers bind to the magnetically labeled ManLAM and capture them on the surface. The presence of these magnetic particles activates the spin-valve sensors and produces a change in voltage that can be detected by computer-like microprocessors. If ManLAM is not in the sample, then nothing will bind to the capture aptamers and no TB will be detected.

ghana group 2-4 — The microfluidic chip design has two channels to allow for two urine samples to be analyzed at the same time.

We would like to thank Penn Engineering and everyone who has helped to make this program possible. As you can see from our blog posts, our time in the classroom and the month in Ghana have been an unforgettable academic and cultural experience. The APOC program has been an amazing opportunity to get out of our comfort zones and to see the potential of engineering solutions in the world around us.