A Solution for Liver Testing for 10 Dollars

Brianna Wronko (left) and Guyrandy Jean-Gilles (right)

One of the Penn Bioengineering Department’s senior projects was the work of a two-person team: Brianna Wronko and Guyrandy Jean-Gilles. The result of their work was the MultiDiagnostic, a microfluidics platform that the two students describe as “A Fast, Inexpensive, and Accessible Diagnostic Solution.”

Brianna says that the project was originally conceived as a way for HIV clinics and treatment centers to test biological parameters such as viral load. However, the inability of Brianna and Guy to handle HIV-infected blood in the lab, as well as the desire to generate a product that could both serve patients directly and have a commercial focus. They decided their first offering would consist of liver function tests.

Manufactured by an automated process, the MultiDiagnostic is a paper microfluidics platform with a software component that can be run on a computer or cell phone. When a bodily fluid is placed into the platform, it diffuses into separate chambers of the platform, where colorimetric analysis is then conducted and data communicated via the software’s graphical user interface to the user.

The students currently have the platform in preclinical trials for the testing of aspartase aminotransferase and alkaline phosphatase; the ability to test alanine aminotransferase, bilirubin, and total protein are in the prototyping stage. Their current model is priced at a $10 customer price, which is considerably less expensive than competing technologies already on the market.

Among the most interesting aspects of this senior project team, other than the product itself, was that it had only two members. Asked how this fact affected their work, Brianna admitted that it posed a bit of an obstacle at first. However, she said, “we decided to break up the concept into parts, with me doing the wet lab parts, in which I have a background and Guy, whose background is in software, doing those parts.” In the end, they’re very happy with their final product.

Students Receive Awards for the Year

students receiving awards
Students in the BE Department have received several awards

Every year the Penn Bioengineering Department presents several awards to students. In addition to the Senior Design Awards, which will be featured over the course of the month, students were awarded for their service, originality, leadership, and scholarship.

The Hugo Otto Wolf Memorial Prize, endowed more than a century ago by the Philadelphia architect Otto Wolf, in memory of his son, was given to Margaret Nolan and Ingrid Lan. The Herman P. Schwan Award, named for a former faculty member in Bioengineering, was given to Elizabeth Kobe and Lucy Chai.

The Albert Giandomenico Award, presented to four students who “reflect several traits that include teamwork, leadership, creativity, and knowledge applied to discovery-based learning in the laboratory,” was given to Justin Averback, Jake Budlow, Justin Morena, and Young Shin.

In addition, Sushmitha Yarrabothula received the Bioengineering Student Leadership Award and four students — Hayley Williamson, Amey Vrudhula, Jane Shmushkis, and Ikshita Singh, won the Penn Engineering Exceptional Service Award.

Finally, the Biomedical Applied Science Senior Project Award, presented annually to the students who have “best demonstrated originality and creativity in the integration of knowledge,” was awarded to Derek Yee and Andrea Simi.

“These awards recognize many aspects of our students: their high academic achievement,  exceptional collaborative spirit, and leadership abilities,” said BE department chair David Meaney. “However, these traits are not limited to the only these students. Every single one of our undergraduates at Penn pushes themselves well beyond the classroom and into the community to make a unique difference.”

Creativity, Curiosity, and Engineering

by Dave Meaney and Dani Bassett

James Dyson
James Dyson

One can easily see that many of the world’s greatest challenges — producing enough food for the world population, providing each person with a set of fundamental human rights, or creating a sustainable environmental footprint as our societies move forward — must tap into two uniquely human traits: creativity and curiosity. In the fields of science and engineering, one can look at history and easily find creative and curious pioneers who ranged from Leonardo de Vinci (pioneered the field of human physiology), Grace Hopper (invented computer compilers), and Sir James Dyson (brought elegance to common household tools – the vacuum cleaner, the fan, the hand dryer, and the hair dryer).

Grace Hopper
Grace Hopper

Although we can look around and identify creative people, a natural question would be: What events in these individuals’ lives led to this creativity? We may see people around us who are creative and curious, but we often simply shrug and say ,“Wow, pretty ingenious person there.” Maybe we even think of this with a bit of yearning: “Boy, I wish I could think of things like that.”  We often make the observation and get back to our daily lives, accepting that creative people are born or “just happen.” In other words, we are either struck by lightning, or we are not. Nothing could be further from the truth.

Leonardo da Vinci
Leonardo da Vinci

Creative and curious people are not genetically wired differently than others. Curiosity and creativity are not rare skills conferred by serendipity. Instead, creative and curious people have benefited from mentors who pushed them to ask “Why?” at the right time in their lives: perhaps being in the right science class with the right teacher in middle school or reading a novel that made them imagine a world they could not see.

What does all of this have to do with engineering?  Well, some research suggests that many U.S. engineering undergraduates are weaker than their international counterparts in divergent and convergent thinking, which are two critical ingredients for creativity. These two thinking modalities may be propelled by different sorts of curiosity. Assessment tests for creative thinking traits often measure the ability to synthesize ideas, observations, and other information to make something new. From many possibilities, only one emerges as the ideal solution. This process is generally referred to as convergent thinking.  A second creativity trait is the raw ability to generate ideas, given a particular problem.  For example, one could be asked to generate as many possible uses of a brick that one can think of, and the resulting ideas are scored — both in terms of the number of ideas generated and the distinctiveness of each idea separately. This assessment, known as the alternative use test, measures divergent thinking. Ideally, engineers would have high ability in both divergent and convergent thinking, which would mean that they could both think of many possible solutions and pick the best among them.  However, one study performed almost a decade ago showed that half of the engineering undergraduates in the U.S. showed deficiencies in both convergent and divergent thinking — troubling, to say the least.

Adapted from an image in: Hany EA, Heller KA, “Entwicklung kreativen Denkens im kulturellen Kontext,” in Entwicklung und Denken im kulturellen Kontext, Mandl H, Dreher M, Kornadt H-J, eds (Toronto: Hogrefe Verlag für Psychologie, 1993), pp. 99-118. Reprinted with generous permission of Hogrefe Verlag.

However, all is not lost. Many changes have occurred over the last decade for engineering education in the U.S. We embraced the laboratory as a platform for problem-based learning, which cultivates the ideation phase of creativity and the convergence to a solution. We have also ‘tipped’ and ‘flipped’ the classroom to introduce more methods of open-ended problems as teaching tools, again using this change to reinforce that there are many ways and, rarely, one best way to solve a particular problem.

Yet with all of these very positive changes, we still don’t have a good road map for how ideas form in the mind, how we trade off one idea versus another, and how we decide which is the best idea. Our tools for creativity are based on countless efforts to try different methods, measure whether they have an effect, and take the most successful empirical methods and transform them into practice. Until recently, we had no idea what was going on in the mind during the creative process.

Fortunately, we now have ways to both interrogate and model how the mind works when we think and create.  Inspired by the principle that blood flow will increase to areas of the brain with high neural activity (side note: the brain is a remarkable energy hog for the body, representing less than 3% of body mass but consuming nearly 20% of its energy resources), researchers are measuring how flow to different areas of the brain change when people are asked to perform specific tasks. Early work showed these beautiful, color-coded images of how one task would increase blood flow to one area, while another task would increase blood flow to a different area.

Patterns of connectivity in the brain can be represented as
dynamic networks, which change in their configuration as
humans change mental states or cognitive processes while
performing a task.

However, scientists began to realize, that instead of looking at one pattern of brain activation at one time, we needed to study how the pattern changed over time. Analyzing these changes over time allowed us to estimate the brain areas that activated simultaneously with another during a mental task. If they activated together frequently, we assumed that they would have a functional connectivity between them. Simply put, areas that fire together are wired together, metaphorically speaking.  Very quickly, we saw maps of the brain’s own functional network emerge when volunteers would work on math problems, navigate a maze, and even when they were asked to just daydream.

Where does this lead us? Well, we stand on the cusp of learning and predicting the coordinated steps that our mind takes when we imagine different ideas and pick one as ‘the best.’  Not only can we map this process in real time, but we can also develop new theories about how to ‘steer’ from one brain network state to another. We can also apply this new knowledge to individuals on a case-by-case basis, rather than relying on the one-size-fits-all approach that is the current and common practice in cultivating divergent and convergent thinking.  In practice, this means that we would move away from prescribing the same creativity training exercise for everyone — with a large variation in the results — to a far more customized, efficient cognitive exercise. In fact, we could directly test the possibility that some of these exercises work for some people and not others because of an individual’s brain wiring map.  Science fiction? Nope, just modern day bioengineering at work.

David F. Meaney, Professor of Bioengineering and Neurosurgery

Danielle S. Bassett, Associate Professor of Bioengineering and Electrical and Systems Engineering

Hey, it’s Hey Day! Penn Juniors Become Seniors

Since 1916, University of Pennsylvania undergraduates have celebrated their last class day as juniors to mark Hey Day. While initially conceived as something solemn and rather formal, today it is an opportunity for students to get decked out in red T-shirts and novelty straw hats and bamboo canes (fashions from 1916) and celebrate.

This year, Hey Day was on April 27, and it was no exception to previous years. Several of our rising seniors were celebrating with everyone on College Green.

Hey Day for Penn Juniors
Penn BE students celebrating Hey Day

In addition to the gathering of students to be “officially” be made seniors by University President Amy Gutmann (see video here) and a passing of the gavel to next year’s junior class president, some students dropped in on their favorite teachers and staff members to say hello.

Sevile on Hey Day
BE Lab director Sevile Mannickarottu with Penn juniors

Dan Huh Receives Ryan Medal

Ryan Medical recipient Dan Huh
Professor Dan Huh

A professor in the Penn Department of Bioengineering, Dongeun (Dan) Huh, PhD, has been awarded the John J. Ryan Medal, which is given annually by the Royal College of Surgeons in Ireland (RCSI).

Every year this honor recognizes a scientist who has made major contributions to developing innovative biomedical technologies with the potential to have a broad impact on the life sciences. Dr. Huh, who is Wilf Family Term Endowed Chair in the BE Department, received the medal at an RCSI Research Retreat on March 9 on the RCSI campus in Dublin, and he delivered the John J. Ryan Distinguished Lecture.

“As an engineer, I am honored to have been selected by a group of biologists and clinicians for this prestigious award that recognizes significant contributions to biomedical research,” Professor Huh said. “It is truly rewarding and encouraging to experience strong support and enthusiasm for our pursuit of innovative biomedical technologies.”

Penn BE Lab Associate Wins Goldwater Scholarship

Michael Duong
Michael Duong

One of two Penn students recently awarded Barry Goldwater Scholarships is sophomore Michael Tran Duong, who works in the lab of Bioengineering Department faculty member Jennifer Phillips-Cremins.

“It is a wonderful honor for Michael to receive this extremely competitive award,” Professor Phillips-Cremins said. We are fortunate that Michael landed in a lab within Bioengineering at Penn, as this award indicates he has a very bright future well beyond Penn.”

Barry Goldwater
Senator Barry Goldwater (R-AZ)

Michael said, “I feel honored to receive this award and really appreciate the mentorship of Dr. Phillips-Cremins and her 3D Genome Folding and Neurobiology lab. Conducting research with Dr. Cremins as a high school student and undergraduate and receiving this award have strengthened my resolve to help patients with brain disease as a physician-scientist.”

The Goldwater Scholarship, named for the late U.S. Senator and Republican presidential candidate Barry Goldwater is awarded annually to 240 students who intend to pursue careers in math or science research. The amount of the award is as much as $7,500.


Tissue Engineering Makes Spinach Leaf Beat Like a Heart

Bestill my beating spinach leaf!

One of the more interesting tissue engineering stories to emerge this past month was the successful finding of a team at Worcester Polytechnic Institute (WPI), which used the veins in spinach leaves as a scaffold that was then recellularized with stem cells that produce heart muscle cells. After three weeks, the transplanted cells showed the ability to contract like the heart does when it beats.

“Proper vascularization of artificial living tissues has been one of the most critical challenges of tissue engineering for decades. This is particularly problematic when the size of the engineered tissue increases.,” said Dongeun (Dan) Huh, PhD, Wilf Family Term Assistant Professor in the Department of Bioengineering at the University of Pennsylvania “This work takes an unusual yet ingenious approach to solving this long-standing problem.”

Below you can watch a short video of some of the investigators on the study talking about it.

Cockroaches Give Undergrads a Leg Up in Designing Biomechatronic Prostheses

Penn Bioengineering students in Biomechantronic Lab
Biomechatronic lab students at Penn

When ABC premiered The Six Million Dollar Man more than 40 years ago, the idea of replacing or augmenting human limbs with fully functional biomechanical/biomechatronic versions probably seemed a distant possibility. In fact, the concept had already been in development for decades, but research in this area is only now coming to fruition. Three years ago, researchers in Chicago reported in the New England Journal of Medicine that they had fitted a 31-year-old amputee with a robotic leg that the patient could control with electromyographic, or EMG, signals from salvaged nerves.

Reflecting these developments, undergraduate students in the Department of Bioengineering (BE) have spent the last few weeks developing their own prosthetic devices, although both the mechanics and the “patient” are a bit cruder. Over the course of five lab sessions, these students are creating an “HCMI” — a human-cockroach machine interface that can translate an individual’s own nerve signals into ones that can control a cockroach leg.
The students performing these experiments are enrolled the first of two lab courses that BE students take as juniors. In the George H. Stephenson Foundation Undergraduate Bioengineering Laboratory, the students spend the first few sessions familiarizing themselves with cockroach anatomy. Each group then attaches an individual cockroach leg to a mechanical motor interface, creating a biomechatronic prosthesis, i.e., one that combines electronic, mechanical, and biological systems.

This part of the experiment was considered successful when the students were able to write the letters “BE” with the cockroach leg, using signals generated by computer. This is a more difficult task than it might seem, both because each cockroach leg responds at slightly different frequency-voltage ranges.

Why a cockroach leg?

“They’re easily attainable and easy to deal with,” says Sevile Mannickarottu, who is director of the Stephenson lab. “They’re also relatively large, which makes accessing their legs easy.”

The cockroach’s nervous system is also much simpler than those of birds or mammals, thus simplifying the process of creating the HCMI.

Once the students can write with the biomechantronic device, the final step of the experiment begins. Using human input, students are required to combine two devices to move the prosthetic. One of the devices is an EMG electrode; the other device is up to the student, and it can be a microphone, a motion sensor, or a range of other devices. Working directly with EMG signals is a challenge according to Mannickarottu, who described it as “incredibly noisy and difficult to interpret into meaningful data.”

After choosing their human input device, students send the signals from the device to a computer, which then converts the signal into an EMG signal, which is sent back out to the prosthetic leg. The students tried several different approaches to get the leg to move, including a musical keyboard, a force sensor, and a flex sensor. One group chose to use a Myo armband, a gesture recognition device produced by Thalmic Labs that is commonly used for video games.

With human prostheses and brain-machine interfaces rapidly advancing, overcoming a bit of entomophobia was a worthwhile endeavor for these undergrads.

Nine BE Students Receive NSF Research Fellowships


Nine students in the Department of Bioengineering (BE) have received fellowships from the National Science Foundation (NSF) Graduate Research Fellowship Program.

Six of the students — Zakary Beach, Nicolette Driscoll, Lindsey Fernandez, Jessica Hsu, Jinsu Kim and Ryan Leaphart — are current doctoral students in Bioengineering who earned undergraduate degrees from other top BE programs. Three of the awardees — Lucy Chai, Jake Hsu and Karren Yang — are BE graduating seniors in the Class of 2017. Lucy will spend next year on a Churchill fellowship at Cambridge before starting her NSF fellowship, while Jake has an internship with Genentech‘s Manufacturing Sciences and Technology department, and Karren will attend MIT.

“We are extremely fortunate to attract the very best graduate students in the country,” says David F. Meaney, Solomon R. Pollack Professor and Chair of BE. “This is an external recognition of the high quality of our students across the board.”

The Graduate Research Fellowship Program of the National Science Foundation recognizes and supports outstanding graduate students in NSF-supported science, technology, engineering, and mathematics disciplines who are pursuing research-based master’s and doctoral degrees at accredited United States institutions. For the 2017 competition, the NSF received more than 13,000 applications.