Given the closing of schools in response to the coronavirus pandemic, professors teaching lab-based courses were forced to make some changes. One such course, the Department of Bioengineering’s Medical Device Development (BE 472) taught by Matthew R. Maltese, Ph.D., usually requires students to develop a medical device and learn how to lead a startup venture for it. Over the semester, students design prototypes for unmet needs in the medical device community, and then go on to learn about business-related aspects of the project, like fundraising, regulations, teamwork, and leadership. Maltese often encourages junior engineering students to take the course, in the hopes that their projects might become launchpads for their senior design projects the following year.
But with the pandemic’s interruptions to education restricting access to the lab, or even to some of the schematics for their earlier designs, Maltese’s Spring 2020 students had to re-focus on the business side of their projects.
Fortunately, the shift to online learning came late enough in the semester that most students had already come up with solid project ideas. Maltese then shifted gears to the less hands-on parts of the course. “There’s lots of elements to this course that are not focused on putting hands on hardware,” he says. “They’re focused on distilling and disseminating information about your endeavor to people that are interested.”
While some of those more hands-off assignments originally had some face-to-face aspects, like the final pitch competition, they’re also easy to transition to an online format. Maltese had students record videos of their pitches, which he notes is perhaps more akin to what they might have to do for external pitch competitions. And even though students couldn’t make their physical prototypes, Maltese says that they were all able to make virtual prototypes through CAD or other modeling software.
In his opinion, this renewed focus on out-of-lab prototype models might be a good thing for real-world experience. Investors and stakeholders often want the full picture of a device or startup before they even have to start working with physical material, for the sake of cost efficiency.
Students had already been working on their projects for a couple of months before the pandemic started to affect classes, so most of them stuck to their original ideas instead of adapting them to meet the needs of the current medical crisis. “Next year, I think we’re going to focus the class on COVID-19 ideas though,” says Maltese.
In fact, Medical Device Development will likely be one of many Penn Bioengineering courses that adapts its curriculum to the challenges the pandemic presented. “As a medical device community, a pharmaceutical community, a healthcare community, we were not ready for this,” Maltese notes, “but history teaches us that some of our greatest innovations emerge from our greatest trials.” He is excited for the future.
Some medical conditions, like diabetes or limb amputation, have the potential to result in wounds that never heal, affecting patients for the rest of their lives. Though normal wound-healing processes are relatively understood by medical professionals, the complications that can lead to chronic non-healing wounds are often varied and complex, creating a gap in successful treatments. But biomedical engineering faculty from the University of Connecticut want to change that.
Ali Tamayol, Ph.D., an Associate Professor in UConn’s Biomedical Engineering Department, developed what he’s calling a “smart” bandage in collaboration with researchers from the University of Nebraska-Lincoln and Harvard Medical School. The bandage, paired with a smartphone platform, has the ability to deliver medications to the wound via wirelessly controlled mini needles. The minimally invasive device thus allows doctors to control medication dosages for wounds without the patient even having to come in for an appointment. Early tests of the device on mice showed success in wound-healing processes, and Tamayol hopes that soon, the technology will be able to do the same for humans.
A New Patch Could Fix Broken Hearts
Heart disease is by far one of the most common medical conditions in the world, and has a high risk of morbidity. While some efforts in tissue engineering have sought to resolve cardiac tissue damage, they often require the use of existing heart cells, which can introduce a variety of complications to its integration into the human body. So, a group of bioengineers at Trinity College in Dublin sought to eliminate the need for cells by creating a patch that mimics both the mechanical and electrical properties of cardiac tissue.
Using thermoelastic polymers, the engineers, led by Ussher Assistant Professor in Biomedical Engineering Michael Monaghan, Ph.D., created a patch that could withstand multiple rounds of stretching and exhibited elasticity: two of the biggest challenges in designing synthetic cardiac tissues. With the desired mechanical properties working, the team then coated the patches with an electroconductive polymer that would allow for the necessary electrical signaling of cardiac tissue without decreasing cell compatibility in the patch. So far, the patch has demonstrated success in both mechanical and electrical behaviors in ex vivo models, suggesting promise that it might be able to work in the human body, too.
3-D Printing a New Tissue Engineering Scaffold
While successful tissue engineering innovations often hold tremendous promise for advances in personalized medicine and regeneration, creating the right scaffold for cells to grow on either before or after implantation into the body can be tricky. One common approach is to use 3-D printers to extrude scaffolds into customizable shapes. But the problem is that not all scaffold materials that are best for the body will hold up their structure in the 3-D printing process.
A team of biomedical engineers at Rutgers University led by Chair of Biomedical Engineering David I. Schreiber, Ph.D., hopes to apply the use of hyaluronic acid — a common natural molecule throughout the human body — in conjunction with polyethylene glycol to create a gel-like scaffold. The hope is that the polyethylene glycol will improve the scaffold’s durability, as using hyaluronic acid alone creates a substance that is often too weak for tissue engineering use. Envisioning this gel-like scaffold as a sort of ink cartridge, the engineers hope that they can create a platform that’s customizable for a variety of different cells that require different mechanical properties to survive. Notably, this new approach can specifically control both the stiffness and the ligands of the scaffold, tailoring it to a number of tissue engineering applications.
A New Portable Chip Can Track Wide Ranges of Brain Activity
Understanding the workings of the human brain is no small feat, and neuroscience still has a long way to go. While recent technology in brain probes and imaging allows for better understanding of the organ than ever before, that technology often requires immense amounts of wires and stationary attachments, limiting the scope of brain activity that can be studied. The answer to this problem? Figure out a way to implant a portable probe into the brain to monitor its everyday signaling pathways.
That’s exactly what researchers from the University of Arizona, George Washington University, and Northwestern University set out to do. Together, they created a small, wireless, and battery-free device that can monitor brain activity by using light. The light-sensing works by first tinting some neurons with a dye that can change its brightness according to neuronal activity levels. Instead of using a battery, the device relies on energy from oscillating magnetic fields that it can pick up with a miniature antenna. Led in part by the University of Arizona’s Gutruf Lab, the new device holds promise for better understanding how complex brain conditions like Alzheimer’s and Parkinson’s might work, as well as what the mechanisms of some mental health conditions look like, too.
People & Places
Each year, the National Academy of Engineering (NAE) elects new members in what is considered one of the highest professional honors in engineering. This year, NAE elected 87 new members and 18 international members, including a former Penn faculty member and alumna Susan S. Margulies, Ph.D. Now a professor of Biomedical Engineering at Georgia Tech and Emory University, Margulies was recognized by the NAE for her contributions to “elaborating the traumatic injury thresholds of brain and lung in terms of structure-function mechanisms.” Congratulations, Dr. Margulies!
Nimmi Ramanujam, Ph.D., a Distinguished Professor of Bioengineering at Duke University, was recently announced as having one of the highest-scoring proposals for the MacArthur Foundation’s 100&Change competition for her proposal “Women-Inspired Strategies for Health (WISH): A Revolution Against Cervical Cancer.” Dr. Ramanujam’s proposal, which will enter the next round of competition for the grant, focuses on closing the cervical cancer inequity gap by creating a new model of women-centered healthcare.
In response to the unprecedented challenges presented by the global outbreak of the novel coronavirus SARS-CoV-2, Penn Bioengineering’s faculty, students, and staff are finding innovative ways of pivoting their research and academic projects to contribute to the fight against COVID-19. Though these projects are all works in progress, I think it is vitally important to keep those in our broader communities informed of the critical contributions our people are making. Whether adapting current research to focus on COVID-19, investing time, technology, and equipment to help health care infrastructure, or creating new outreach and educational programs for students, I am incredibly proud of the way Penn Bioengineering is making a difference. I invite you to read more about our ongoing projects below.
Novel Chest X-Ray Contrast
David Cormode, Associate Professor of Radiology and Bioengineering
The Cormode and Noel labs are working to develop dark-field X-ray imaging, which may prove very helpful for COVID patients. It involves fabricating diffusers that incorporate gold nanoparticles to modify the X-ray beam. This method gives excellent images of lung structure. Chest X-ray is being used on the front lines for COVID patients, and this could potentially be an easy to implement modification of existing X-ray systems. The additional data give insight into the health state of the microstructures (alveoli) in the lung. This new contrast mechanics could be an early insight into the disease status of COVID-19 patients. For more on this research, see Cormode and Noel’s chapter in the forthcoming volume Spectral, Photon Counting Computed Tomography: Technology and Applications, edited by Katsuyuki Taguchi, Ira Blevis, and Krzysztof Iniewski (Routledge 2020).
Computational Models for Targeting Acute Respiratory Distress Syndrome (ARDS). The severe forms of COVID-19 infections resulting in death proceeds by the propagation of the acute respiratory distress syndrome or ARDS. In ARDS, the lungs fill up with fluid preventing oxygenation and effective delivery of therapeutics through the inhalation route. To overcome this major limitation, delivery of antiinflammatory drugs through the vasculature (IV injection) is a better approach; however, the high injected dose required can lead to toxicity. A group of undergraduate and postdoctoral researchers in the Radhakrishnan Lab (Emma Glass, Christina Eng, Samaneh Farokhirad, and Sreeja Kandy) are developing a computational model that can design drug-filled nanoparticles and target them to the inflamed lung regions. The model combines different length-scales, (namely, pharmacodynamic factors at the organ scale, hydrodynamic and transport factors in the tissue scale, and nanoparticle-cell interaction at the subcellular scale), into one integrated framework. This targeted approach can significantly decrease the required dose for combating ARDS. This project is done in collaboration with Clinical Scientist Dr. Jacob Brenner, who is an attending ER Physician in Penn Medicine. This research is adapted from prior findings published in Volume 13, Issue 4 of Nanomedicine: Nanotechnology, Biology and Medicine: “Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions” (May 2017).
Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine
Arjun Raj, David Issadore, and Sydney Shaffer are working on developing an integrated, rapid point-of-care diagnostic for SARS-CoV-2 using single molecule RNA FISH. The platform currently in development uses sequence specific fluorescent probes that bind to the viral RNA when it is present. The fluorescent probes are detected using a iPhone compatible point-of-care reader device that determines whether the specimen is infected or uninfected. As the entire assay takes less than 10 minutes and can be performed with minimal equipment, we envision that this platform could ultimately be used for screening for active COVID19 at doctors’ offices and testing sites. Support for this project will come from a recently-announced IRM Collaborative Research Grant from the Institute of Regenerative Medicine with matching funding provided by the Departments of Bioengineering and Pathology and Laboratory Medicine in the Perelman School of Medicine (PSOM) (PI’s: Sydney Shaffer, Sara Cherry, Ophir Shalem, Arjun Raj). This research is adapted from findings published in the journal Lab on a Chip: “Multiplexed detection of viral infections using rapid in situ RNA analysis on a chip” (Issue 15, 2015). See also United States Provisional Patent Application Serial No. 14/900,494 (2014): “Methods for rapid ribonucleic acid fluorescence in situ hybridization” (Inventors: Raj A., Shaffer S.M., Issadore D.).
HEALTH CARE INFRASTRUCTURE
Penn Health-Tech Coronavirus COVID-19 Collaborations
Brian Litt, Professor of Bioengineering, Neurology, and Neurosurgery
In his role as one of the faculty directors for Penn Health-Tech, Professor Brian Litt is working closely with me to facilitate all the rapid response team initiatives, and in helping to garner support the center and remove obstacles. These projects include ramping up ventilator capacity and fabrication of ventilator parts, the creation of point-of-care ultrasounds and diagnostic testing, evaluating processes of PPE decontamination, and more. Visit the Penn Health-Tech coronavirus website to learn more, get involved with an existing team, or submit a new idea.
Dr. Maltese is rapidly developing a low-cost ventilator that could be deployed in Penn Medicine for the expected surge, and any surge in subsequent waves. This design is currently under consideration by the FDA for Emergency Use Authorization (EUA). This example is one of several designs considered by Penn Medicine in dealing with the patient surge.
David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean
Led by David Meaney, Kevin Turner, Peter Bruno and Mark Yim, the face shield team at Penn Health-Tech is working on developing thousands of rapidly producible shields to protect and prolong the usage of Personal Protective Equipment (PPE). Learn more about Penn Health-Tech’s initiatives and apply to get involved here.
Update 4/29/20: The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Dr. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold. Read the full post on the Penn Engineering blog.
OUTREACH & EDUCATION
Student Community Building
Yale Cohen, Professor of Otorhinolaryngology, Department of Psychology, BE Graduate Group Member, and BE Graduate Chair
Yale Cohen, and Penn Bioengineering’s Graduate Chair, is working with Penn faculty and peer institutions across the country to identify intellectually engaging and/or community-building activities for Bioengineering students. While those ideas are in progress, he has also worked with BE Department Chair Ravi Radhakrishnan and Undergraduate Chair Andrew Tsourkas to set up a dedicated Penn Bioengineering slack channel open to all Penn Bioengineering Undergrads, Master’s and Doctoral Students, and Postdocs as well as faculty and staff. It has already become an enjoyable place for the Penn BE community to connect and share ideas, articles, and funny memes.
Undergraduate Course: Biotechnology, Immunology, Vaccines and COVID-19 (ENGR 35)
Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering and Chemical and Biomolecular Engineering
This Summer Session II, Professor Dan Hammer and CBE Senior Lecturer Miriam R. Wattenbarger will teach a brand-new course introducing Penn undergraduates to a basic understanding of biological systems, immunology, viruses, and vaccines. This course will start with the fundamentals of biotechnology, and no prior knowledge of biotechnology is necessary. Some chemistry is needed to understand how biological systems work. The course will cover basic concepts in biotechnology, including DNA, RNA, the Central Dogma, proteins, recombinant DNA technology, polymerase chain reaction, DNA sequencing, the functioning of the immune system, acquired vs. innate immunity, viruses (including HIV, influenza, adenovirus, and coronavirus), gene therapy, CRISPR-Cas9 editing, drug discovery, types of pharmaceuticals (including small molecule inhibitors and monoclonal antibodies), vaccines, clinical trials. Some quantitative principles will be used to quantifying the strength of binding, calculate the dynamics of enzymes, writing and solving simple epidemiological models, methods for making and purifying drugs and vaccines. The course will end with specific case study of coronavirus pandemic, types of drugs proposed and their mechanism of action, and vaccine development.
Update 4/29/20: Read the Penn Engineering blog post on this course published April 27, 2020.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording facilitated Neuromatch 2020, a large virtual neurosciences conferences consisting of over 3,000 registrants. All of the conference talk videos are archived on the conference website and Dr. Kording has blogged about what he learned in the course of running a large conference entirely online. Based on the success of Neuromatch 1.0, the team are now working on planning Neuromatch 2.0, which will take place in May 2020. Dr. Kording is also working on facilitating the transition of neuroscience communication into the online space, including a weekly social (#neurodrinking) with both US and EU versions.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording is working to launch the Neuromatch Academy, an open, online, 3-week intensive tutorial-based computational neuroscience training event (July 13-31, 2020). Participants from undergraduate to professors as well as industry are welcome. The Neuromatch Academy will introduce traditional and emerging computational neuroscience tools, their complementarity, and what they can tell us about the brain. A main focus is not just on using the techniques, but on understanding how they relate to biological questions. The school will be Python-based making use of Google Colab. The Academy will also include professional development / meta-science, model interpretation, and networking sessions. The goal is to give participants the computational background needed to do research in neuroscience. Interested participants can learn more and apply here.
Journal of Biomedical Engineering Call for Review Articles
Beth Winkelstein, Vice Provost for Education and Eduardo D. Glandt President’s Distinguished Professor of Bioengineering
The American Society of Medical Engineers’ (ASME) Journal of Biomechanical Engineering (JBME), of which Dr. Winkelstein is an Editor, has put out a call for review articles by trainees for a special issue of the journal. The call was made in March 2020 when many labs were ramping down, and trainees began refocusing on review articles and remote work. This call continues the JBME’s long history of supporting junior faculty and trainees and promoting their intellectual contributions during challenging times.
Update 4/29/20: CFP for the special 2021 issue here.
Are you a Penn Bioengineering community member involved in a coronavirus-related project? Let us know! Please reach out to email@example.com.
What originally drew me to this field was a “Women in Engineering Day” I attended at a local college while in high school. I had the opportunity to hear incredible women speak about their research regarding biomaterials and tissue engineering. This event showed me the impact this field can have on the world. This drove me to pursue an undergraduate degree in Biomedical Engineering, which only strengthened my passion. As I furthered my studies and began working full-time at a biotechnology company, I learned more about bioengineering. With encouragement from my coworkers and family, I decided to pursue my Master’s in Bioengineering and am delighted to have the opportunity to study at Penn.
What kind of research do you conduct, and what do you hope to focus on for your thesis?
I am actually a part-time student, who works full-time at a drug packaging and medical device company out in Exton, PA. Though I am not doing research on campus, my coursework has tied into previous research projects I have participated in at my job. My latest project entailed understanding different material properties used in container closure systems for mAb-based biologics and how they interact. This work was done to support an understanding of how to pick appropriate vial/syringe systems for various drug products in development.
What’s your favorite thing to do on Penn’s campus or in Philly?
My favorite thing to do is trying all the new restaurants and incredible foods this city has to offer. I think Philadelphia is so unique and has such rich cultural influences. With so many different neighborhoods and restaurant options you really can’t go wrong.
What did you study for your undergraduate degree, how does it pair with the work you’re doing now, and what advice would you give to your undergraduate self?
My undergraduate degree was in Biomedical Engineering. It has supported my graduate coursework very well and has given me a great opportunity to dive deeper into certain parts of my studies.
My advice to my younger self would be to take your time! It took me a little while to evaluate different graduate programs and choose which was right for me. Though it took some time, I ultimately decided what was best for me and couldn’t be happier with my choices.
What are you thinking about doing after graduate school?
Currently, I work full-time as an Associate Packaging Engineer at West Pharmaceutical Services in Exton, PA. I hope to take my degree to further my career and to help support my future aspirations at this company.
At the end of April, the graduating seniors in the Penn Department of Bioengineering‘s B.S.E. (Bachelor of Science in Engineering) program presented their Senior Design projects. Developed over the course of their final two semesters in the undergraduate program, these projects are developed in teams of three or four as the students are guided through choosing and understanding an impactful biomedical problem, defining the characteristics of a successful design solution to eliminate or mitigate a problem or fulfill a need, identifying constraints, and creatively developing potential design solutions. Over the course of two days, the students then present their projects to faculty and students from across the Penn Engineering community.
Congrats to all of our graduating students on their innovative projects. Check out some photos from the 2019 BE Senior Design presentations and read the full list of this year’s abstracts below.
Group A: BreatheSmart
Caroline Atkinson, Sarah Cai, Rebecca Kellner, Harrison Troché
In the United States, more than 51 million people have been diagnosed with either asthma or chronic obstructive pulmonary disorder (COPD) as of 2016. These conditions result in swelling of the airways, making it difficult to breathe, but the symptoms are commonly managed through the use of a pressurized metered dose inhaler (pMDI), which dispenses aerosolized medication to the lungs, and are currently used by 78% of asthma patients in the US. However, a recent study showed up to 90% of pMDI users incorrectly use their inhalers, reducing the efficacy of medication . Our solution guides patients through the proper technique for using inhalers while providing real-time feedback so patients can correct their technique. This was accomplished by tracking flow rate data converted from a pressure sensor and a smartphone app that provides real-time visual feedback to the user. We were successful in our four design goals as the final device is: (1) lightweight and compact (78 grams with inhaler and 2.5”x1.5”x3.5”), (2) accurate in flow rate measurements (±8.7% error), (3) easy-to-use, with 95% of users surveyed able to use the app successfully without assistance (n=20), and (4) low cost, with the total cost being $76. To improve the design, we will improve accuracy and compactness, and reduce cost. Some ways this could be achieved are through the use of a smaller, custom microcontroller, and a more sensitive pressure sensor. Next steps would include a clinical trial to demonstrate the effectiveness of our device.
Group B: RIPT
Toren Arginteanu, Anna Mujica, Justin Mills, Kayla Prezelski
The tourniquet is the gold standard for treating traumatic extremity bleeding in pre-hospital emergency scenarios. Existing pneumatic tourniquets are safer than non-pneumatic alternatives, minimizing nerve damage and loss of limb function. However, current emergency pneumatic tourniquets are costly and delicate and prone to leaking, punture, and abrasion. Therefore, there is need for an emergency pneumatic tourniquet that is low-cost, highly durable, and easily applied by laypeople. Our design, the Rapidly Inflating Pneumatic Tourniquet (RIPT), consists of an internal bladder made of tough rubber, a durable outer covering made of ballistic nylon, and a pneumatic inflation mechanism involving an inflator valve, pressurized CO 2 cartridge, and pressure relief and regulator valves that maintain a safe and sufficient internal pressure of 250 mmHg. RIPT is tightened around the injured limb and secured with a spring-loaded, automatically locking PLA and aluminum clasp. RIPT’s average application time was 20 ± 0.4 s, which is significantly shorter than that of the Combat Application Tourniquet (CAT): 32 ± 2.9 s. RIPT’s internal bladder pressure reached 250 ± 4.8 mmHg. RIPT packs up to 87.5 in 3 and weighs 18.8 oz. RIPT has comparable circumferential pressure distribution to CAT and superior axial pressure gradient. RIPT’s raw material cost is $65.62. In the future, the clasp mechanism will be modified to improve ease-of-use and minimize size and weight. RIPT will be tested with trauma surgeons at Penn Presbyterian Hospital, and user feedback will indicate ease-of-use and pain of application relative to the CAT.
Group C: Proscopy
Abigail Anmuth, John Forde, Sarah Raizen, Rohit Shinde
Robotically-assisted surgery is a rapidly evolving technology that is expanding the capabilities of surgeons and improving patient outcomes in fields ranging from cardiothoracic surgery to urology. However, as this technology becomes more widely used, there are distinct limitations that impact the safety of surgical maneuvers, largely because of the lack of haptic feedback in the robotic arms of these surgical systems. In the case of prostatectomies, this can lead to the unintentional penetration of the rectal wall and cause pervasive infection, a condition known as rectal injury (RI). Proscopy is a novel real-time proximity sensor that monitors the distance between robotic surgical tools and a patient’s rectal wall to reduce the incidence of RI. This two-part preventative solution consists of a Hall Effect sensor-embedded brace at the tip of the surgical arm and a magnetized flexible insert. The Hall Effect sensors convert magnetic field strength to distance from the rectal wall. In lieu of haptic feedback, Proscopy provides visual feedback within the robot control console as the surgical robot arm nears the rectal wall, displaying information that cannot be perceived from the laparoscopic camera itself. Proscopy gives surgeons the ability to detect the rectal wall with a precision of 0.1±.05mm, rendering it a highly effective and streamlined mechanism for RI prevention during robotically-assisted prostatectomies.
Group D: CerviAid
Dana Abulez, Dayo Adetu, Lamis Elsawah, Yueqi Ren
Cervical insufficiency is premature dilation of the cervix in pregnant women without active labor, and if not addressed, can lead to the loss of pregnancy in the second trimester. This condition results in a protrusion of the amniotic sac out of the uterus and into the cervix, which must be pushed back to extend the pregnancy. In the cervical cerclage procedure, the only treatment for this condition, the cervix is sutured shut to prolong pregnancy. If the cerclage is completed after 14 weeks of pregnancy or if the cervix is more than 3 cm dilated, the procedure is termed an emergency cerclage, which has a higher rate of pregnancy loss due to amniotic sac puncture than regular cerclage procedures. Cerclage procedures are dependent on surgeon experience and utilize no standard method to push back the amniotic sac, which makes this procedure even more high risk. To combat this issue, CerviAid is a device that aims to increase the success rate of emergency cerclages, for which no standardized method exists. The device pushes up the amniotic sac gently with a silicone head and can accommodate a variety of cervix diameters found in patients. The head of the device is controlled by a rack and pinion with a locking mechanism to secure the device and firmly support the sac while the surgeon places the suture. Evaluations of CerviAid with a realistic model of the cervix and amniotic sac produced a 96.15% success rate, in which no membranes were ruptured after pushing through a model cervix. Future steps include further stakeholder evaluations and decreasing manufacturing costs.
Risk of surgical fire increases with use of surgical energy like electrocautery, which presents a source of ignition in an operating room setting with elevated percent oxygen saturation in the air and abundant flammable materials. To address this problem, the FDA recommends human factors strategies, such as heightening awareness, and training on use of surgical energy, which is available yet not standardized across the field. ArcAlert offers a real-time risk management solution for data-driven prevention of surgical fires during use of da Vinci robot electrocautery. The system includes an oxygen sensor device that detects percent oxygen saturation at the surgical field, a machine vision algorithm that detects electrical arcing, and a user-friendly web application. ArcAlert consolidates and assesses risk factor information so that if the oxygen sensor device’s reading exceeds a dangerous threshold or the machine vision algorithm detects arcing, an alert appears on the web application describing the risk, which facilitates improvements to equipment usage by operating room personnel. The oxygen sensor device acquires reliable readings over the timespan of a procedure with an accuracy within +/- 1% for 97% of readings. The machine vision algorithm detects approximately 80% of arcing incidences with only 20% falsely labeled, achieves spatial localization on the order of under 1 centimeter, and executes full pipeline implementation in under half a second. The current design is indicated for transoral surgeries, so future generations will diversify the types of procedures with which the system is compatible, in addition to going fully wireless.
Group F: Grip Glove
Kathryn Khaw, Matthew Rosenwasser, Vidula Kopli
Soft robotics offers many advantages over traditional robotics as an assistive and rehabilitative technology due to its cost-effectiveness and ability to mimic physiological movements. Because of the importance of grip on a patient’s quality of life, we leveraged soft robotic technology to create a flexible, exoskeleton glove for both therapy and assisting daily living for patients with hand impairments. Our device targets muscular dystrophy patients because these patients have a limited selection of devices for their needs. Our design consists of soft robotic actuators attached to a glove that mimic finger movement by bending upon inflation and surface electromyography (SEMG) sensors on the arm to predict the user’s intention to grip or release. Our device effectively recapitulates the forces generated during the grip of a healthy individual using three soft robotic actuators, with each actuator generating 2.83 ± 0.44 N (n = 6). The actuation frequency is 0.2 Hz (12 grips/minute) due to delays in deflation. The EMG sensors, MyoWare and OYMotion Analog EMG Sensor, were not sensitive enough to pick up graded changes in muscle activity, meaning we could only replicate an on-off response through a thresholded spike detection of processed EMG signals in two muscle groups that corresponded to grip and release. Going forward, we will use more sensitive EMG sensors, such as the Biosignalsplux Electromyography Muscle Sensor, increase actuation frequency by actively deflating actuators and include a pressure – solenoid feedback system to have controllable grips.
Group G: SpotOn
Julian Mark, Chase Rapine, Jared Rifkin
In this paper, we discuss SpotOn: a novel bioengineering solution to improving anterior cruciate ligament (ACL) tear recovery. ACL tears are very prevalent injuries and typically take 6-9 months to heal . Physical therapy during recovery is costly and time-intensive, and current knee braces for patients do not provide active support to protect the patient. With SpotOn’s dual-faceted smart mirror and dynamic knee brace technology, patients can begin strengthening the ligament and joint sooner after surgery with less risk of re-injury. When the patient exercises with SpotOn, the smart mirror provides feedback on the patient’s exercise form. If the mirror detects an error, it notifies the user and sends a signal to activate the knee brace and straighten the user’s knee. Key specifications for success include latency of knee brace activation, maximum supported load by the brace, and total cost. Latency and cost met specification goals with a delay less than 0.1s (target under 3s) and total cost of $343.25 (target under $600), but maximum torque output of 18.26ft-lbs was short of the 101.25ft-lbs load goal. Future directions for our design include tracking additional metrics besides squat form, increasing maximum torque output of the knee brace, and lastly adding an on-board battery to the brace to improve portability. Our product was not tested clinically, so the next step to implement our solution would be to reach out to clinicians who are treating injured patients and move forward with gathering clinical data.
Group H: TBx
Daphne Cheung, Gabriel Koo, Shelly Teng, Ethan Zhao
Caused by bacterial strain Mycobacterium tuberculosis, tuberculosis (TB) remains one of the world’s deadliest diseases, with over 10 million new cases and 1.3 million deaths in 2017. Currently, the gold standard for TB diagnosis is to sequence a patient sputum sample using a PCR machine called the GeneXpert. Although this method demonstrates high sensitivity and specificity, it is not ideal in low-income developing countries because it is too expensive and inaccessible, priced at $32,000 for equipment, and $17/test. Thus, diagnosis is most widely determined through smear microscopy. However, this method shows low sensitivity and specificity at only 60% and 81%, respectively. Our solution is TBx, a urine-based diagnostic protocol that offers greater diagnostic power than smear microscopy, while maintaining affordability at only a fraction of the price of the GeneXpert. TBx detects the presence of lipoarabinomannan (LAM) in urine, a glycolipid that is specific to active TB cases. Under TBx protocol, LAM is tagged using photoacoustic dye (IR Dye 800CW) and immunoprecipitation beads via anti-LAM antibodies. Samples are then spun down using a centrifuge to wash out excess dye, concentrated by resuspension in only 5mL 1x PBS, and imaged in a 96-well plate. The photoacoustic dye thermally expands and produces photoacoustic signal in response to photoexcitation at λ = 800nm. Compared to smear microscopy, TBx has higher sensitivity (67%, n = 31) and specificity (92%, n = 31). TBx also only costs $1,500 in equipment, and around $12/test. With further refinements to the TBx protocol and point-of-care packaging, TBx shows promise in developing countries to improve the TB diagnosis landscape, especially with its combination of increased sensitivity and specificity, as well as affordability.
Group I: Sensei “The Cast Master”
Carolina Ferrari, Kristen Ho, Blake Thomas, Alfredo Tovar
Acute compartment syndrome (ACS) occurs in 26,500 people in the US each year and is a result of capillary blood flow becoming compromised when tissue pressure exceeds 30 mmHg. The consequences of ACS are extremely severe if it is not immediately diagnosed. ACS can result in permanent muscle damage, nerve damage and/or amputation, and 70% of cases can be traced back to fractures. The current diagnostic method requires invasive pressure measurements if a patient’s primary symptom assessment is inconclusive. Thus, we have designed SENSEI, a non-invasive device that constantly monitors pressure and can diagnose ACS underneath a cast post-fracture. The device interacts with an Android application via bluetooth to let the user know if they are at risk in real time. SENSEI currently measures compartmental pressure of the forearm within a range of 20-40 mmHg with 91% accuracy. In the future, we plan on improving our pressure sensors so that SENSEI can diagnose ACS with 100% confidence. Other potential additions to SENSEI include designing a sleeve for the lower leg and developing an iOS application to capture more market share.
Group J: UrineLuck: Artificial Urinary Sphincter
Jason Grosz, Richard Adamovich-Zeitlin, Teddy Wang, Sally Pennacchi
Urinary incontinence (UI) is a debilitating ailment that impacts the lives of millions of men. Caused by urinary sphincter damage, prostate issues, or overactive bladder muscles, UI can render men homebound and ruin their social and professional lives. The current gold standard intervention for severe UI is the AMS 800, which consists of a pressure regulated cuff surrounding the urethra and a manual pump in the scrotum. The AMS 800 requires an invasive surgery for implantation and is extremely expensive – around $37,000 for the device, surgery, and hospital stay. It also suffers from a high failure rate, around 33% within three years, due to infections, mechanical failures, and tissue atrophy from the cuff blocking perfusion. In this paper, we fabricate and validate a silicone endourethral valve to treat UI in a less expensive, less invasive, and user-friendly way. These valves are inserted into the penile urethra and mimic the mechanics of bite valves commonly found in water bottles, whereby force applied perpendicularly to a slit enables flow. They are cheap, around $0.08 per device in material costs, do not occlude blood perfusion, and can be inserted at home or in an outpatient clinic with a catheter. Through validation in a PDMS model that recapitulates penile mechanics and geometry, we demonstrated that these valves enable strong flow, 4.99 mL/s, minimal leakage, 0.43 drops, and resistance to cyclic stress. With further cytotoxicity and biofilm testing and insertion protocol development, we hope that this design can improve quality-of-life and prognoses for incontinent men.
Group K: Automated Pathology
Olivia Lang, Joseph Maggiore, Prithvi Pendekanti, Olivia Teter
Clinical and laboratory staining protocols are typically an inefficient use of money, resources and manhours. The highly repetitive and standardized nature of this work poses an opportunity for automation. An automated system would allow a physician or clinician the ability to dedicate their time elsewhere, use less staining fluid, and potentially save on thousands of dollars when compared to similar alternatives. Hemauto is an automated diagnostic device as a proof of concept for a lowcost instrument that combines staining, image acquisition, and image analysis capabilities. Hemauto’s first use case is the detection of Malaria. Malaria, despite being highly treatable, is currently an epidemic in African lowresource regions, disproportionately affecting children. The high incidence rate can be attributed to a lack of standardized and effective earlydetection methods. Providing a lowcost, highthroughput device capable of giving a quantitative diagnosis with limited userinput is critical for these regions because current detection methods are either too hightech, not accurate enough, or are too expensive to be administered frequently. Hemauto’s solution synchronizes the actions of motors and computer technology to deliver a diagnosis. It uses two axes of motion controlled by independent stepper motors to follow the standard Giemsa staining protocol. The stained slide is then automatically focused and imaged in front of a 100x objective lens, where the captured images are analyzed to provide a quantified diagnosis. This proof of concept offers incredible promise for future automated pathology devices across many disease areas.
Group L: Preventear
Matt Riley, Jasmine Wang, Mary Zhuo Ke
Adolescent female athletes are at a high risk of Anterior Cruciate Ligament (ACL) tears as a result of improper form and training techniques. ACL tear prevention training programs are designed to reduce one’s future risk of a tear, but these programs are expensive and not available everywhere. PREVENTEAR is our proposed solution. PREVENTEAR is a self-guided jump training system involving a wearable sock and companion mobile app that like a personal trainer, provides instantaneous feedback on your technique, but is inexpensive and portable. The three main parameters important to jump training are knee angle, knee-to-knee distance, and foot landing technique. The ideal form is to have a knee angle between 30 and 90 degrees with respect to the vertical, have a knee-to-knee distance of greater than 60% with respect to hip width, and land on the ball of the foot before the heel. PREVENTEAR uses bluetooth to communicate with the sensors woven into the sock to a phone app and aims to give feedback on the quality of an athlete’s jump as accurately as ACL tear prevention training programs like Sportsmetrics. The app-reported feedback was compared to true values measured by an observer, phone application, and measuring tools to evaluate performance. PREVENTEAR overall provides a means for ACL tear prevention training by being portable and low cost in comparison to Sportsmetrics, and flexible for adolescent female athletes of varying sizes. PREVENTEAR hopes to further improve accuracy and expand to other forms of training important in reducing risk of ACL injury such as strength, flexibility, and plyometric training in the future.
Group M: Autonomous Home Urinalysis
Saumeel Desai, Anand Prabhu, Eshwar Inapuri
Urinalysis is a crucial diagnostic component of managing heart failure, kidney failure, pre-eclampsia and several other medical conditions. Urinalysis currently requires patient willingness, effort, time and money as patients must travel to a lab, wait for results and rely on caregiver support in order to comply with required follow-ups. Current at-home alternatives, such as dipsticks, lack proper controls and cannot reliably be used by physicians to guide therapy. Moreover, patients are opposed to handling urine, leading to low adherence rates. The goal of this design project was to create an autonomous home urinalysis device that greatly reduces the barriers to diagnostic data collection, enabling detection of deterioration and guidance of therapy with higher efficiency. To meet this goal, the proposed design needed to be affordable, fit on top of a toilet tank, take three or fewer simple steps to use and be capable of rapidly and quantitatively measuring urine volume as well as creatinine, sodium, glucose and albumin concentrations in published clinical reference ranges with a coefficient of variance less than 5%. The solution developed can perform urinalysis within two minutes with only three user steps and is quantitative, controlling assay conditions such as light, volume and time. Each of the initial design requirements have been met, but there is still room for improvement in reducing variation, improving usability and design for manufacturing. This work is a successful starting point upon which future iterations can build to successfully meet patient and provider needs in the urinalysis space.
Group N: BubbleBed
Eden Harris, Candace Jasper, Faith Taliaferro, Sandy Tang
Each year, the U.S. healthcare system spends over $11 billion towards the treatment of pressure ulcer. While pressure ulcers commonly occur in long-term care facilities, they are also prevalent in hospitals, with 700,000 patients admitted to U.S. acute care hospitals developing pressure ulcers each year . The current Braden diagnostic questionnaire assesses risk of ulcers development but fails quantify their locations without nurses having to inspect and rotate patients every two hours. Expensive sensing mats exist, but they offer no pressure relief, and smart-feedback beds offer no information about patient bodily pressure. Thus, we combine pressure sensing capabilities with smart feedback technology . We have developed Bubblebed: a mattress-like device capable of visualizing the user’s bodily pressure as well as responding to areas in need of pressure alleviation, as a means of preventing pressure ulcer development. This device increases or decreases pressure in a specified air cushion (or air cell) based on pressure readings received every ten minutes, actuating until all air cells are restored to safe values, the latter of which was drawn from empirical studies . Our final prototype consists of four air cells controlled by an Arduino algorithm that reads in pressure values within the air cell and opens the corresponding valve to either inflate or deflate a given cell. This prototype serves as a proof-of-concept, demonstrating the efficacy of our pressure-sensing feedback loop and workflow. Future clinical applications would necessitate expanding this to a full hospital bed-size mattress overlay with an associated monitor to visualize pressure ulcer risk.
New Vascularized Patches Could Help Patient Recovery from Heart Attacks
Heart attacks are the result of a stoppage of blood flow to the heart – an interruption to normal function that can result in severe tissue damage, or even tissue death. This loss of healthy tissue function is one of the biggest challenges in treating patients that undergo heart attacks, as the damaged tissue increases their risk of having future attacks. One of the main solutions to this issue right now is the creation of cardiac tissue scaffolds using stem cells to create a platform for new and healthy tissue to grow in vivo. A group of biomedical engineers at Michigan Technological University hopes to expand on this basis by focusing not just on cellular alignment in the scaffold but on that of microvessels too. Led by Feng Zhao, Ph.D., Associate Professor of Biomedical Engineering, the team hopes that this new attention on microvessel organization will improve the vasculature of the scaffolds, and thus improve the success of the scaffolds in vivo, allowing for a better recovery from heart attacks.
Some Stem Cells May Be More Fit Than Others
Stem cells are one of the hottest research areas in the field of bioengineering today. Widely known as the cells in the human embryo that have the ability to eventually transform into specific cells for the brain, lung, and every other organ, stem cells are also of recent interest because researchers found ways to reverse this process, transforming organ-specific cells back to the pluripotent stem cell level. This achievement however, is mostly applicable to individual stem cells, and doesn’t fully encapsulate the way this process might work on a larger population level. So Peter Zandstra, Ph. D., a bioengineering faculty member at the University of British Columbia, decided to research just that.
Using mouse embryonic fibroblasts (MEFs), Zandstra and his lab attempted to track the cells throughout their reprogramming, to more clearly trace each back to its respective parent population. Surprisingly, they found that after only one week of reprogramming, nearly 80% of the original cell population had been removed, meaning that most of the parent generation was not “fit” enough to undergo the process of reprogramming, indicating that perhaps some stem cells will have a better chance of survival in this process than others. This research may suggest that not all cells have the capacity to undergo reprogramming, as many researchers originally thought.
A New Microdevice Will Help Model Bronchial Spasms
The difficulty in breathing associated with asthma is the result of bronchial spasms, which are a kind of muscle contraction in the airways. But little was known about just how these spasms occurred in patients, so Andre Levchenko, Ph.D., Professor of Biomedical Engineering at Johns Hopkins, and his lab created a microdevice to model them. Calling the device a “bronchi on a chip,” Levchenko and his team used a microphysiological model to look at some of the biochemical and mechanical signals associated with these kinds of muscle contractions. They found that the contractions operate in a positive feedback system, so that those caused by disturbance from allergens will subsequently cause even more contractions to occur. But surprisingly, they also found that a second contraction, if triggered at the right time during the initial contraction, could actually stop the process and allow the muscles to relax. Because asthma is a notoriously difficult disease to translate from animal to human models, this new device opens the door to understanding different mechanisms of asthma before taking research to clinical trials.
New CHOP Research Center to Focus Research on Pediatric Airway Disorders
A new bioengineering lab at the Children’s Hospital of Philadelphia called the Center for Pediatric Airway Disorders will specialize in a variety of airway procedures for pediatric patients such as tracheal reconstruction and recurrent laryngeal nerve reinnervation. This new lab will be one of the first to give a unique focus to the application of bioengineering to pediatric laryngology. The interdisciplinary center brings together students and researchers from all different fields, including materials science and microbiology, to find new ways of repairing tissue and regenerating organs related to respiratory disorders. Specific areas of research will involve the modeling of children’s vocal cords, understanding the mechanisms of fibrosis, and improving surgical procedures.
Deeper Understanding of Sickle Cell Anemia Could Lead to New Treatments
Though sickle cell anemia is a common and well-known disease, a new study of its causes at the nanoscale level might reveal previously unknown information about the assembly of hemoglobin fibers. Using microscopes with the ability to visualize these molecules at such a small level, researchers at the University of Minnesota found that the beginning organizations that lead to sickle cell anemia are much less ordered than originally thought. Led by Associate Professor of Biomedical Engineering David Wood, Ph.D., the team of researchers used this higher level of microscopy to find that hemoglobin self-assembly process, which was originally thought to be 96% efficient, is actually only 4% efficient. Wood hopes that this new knowledge will help allow for the development of new and better treatments for patients with sickle cell anemia, as there are currently only two FDA-approved ones on the market.
People & Places
Penn Today asked five Penn researchers about the women in STEM who have been a source of inspiration and encouragement throughout their own careers. Their responses include active researchers who have paved the way for better inclusion in STEM and famous female scientists from the past who broke boundaries as they made strides with their research.
This week, we want to congratulate Joel Boerckel, Ph.D., Assistant Professor of Orthopaedic Surgery and Bioengineering, and his lab on receiving a second R01 Grant from the National Institute of Arthritis and and Musculoskeletal Skin Diseases for their work on defining the roles of YAP and TAZ in embryonic bone morphogenesis and mechanoregulation of fracture repair. Dr. Boerckel is a member of the McKay Orthopaedic Research Laboratory.
We would also like to congratulate Christopher Yip, Ph. D., on being appointed as the new dean of the University of Toronto’s Faculty of Applied Science and Engineering. A professor in both the Department of Chemical Engineering and Applied Chemistry the Institute of Biomaterials and Biomedical Engineering, Dr. Yip’s research involves the use of molecular imaging to understand the self-assembly of proteins.
Tulane Researchers Use Cancer Imaging Technique to Help Detect Preeclampsia
Preeclampsia is potentially life-threatening pregnancy disorder that typically occurs in about 200,000 expectant mothers every year. With symptoms of high blood pressure, swelling of the hands and feet, and protein presence in urine, preeclampsia is usually treatable if diagnosed early enough. However, current methods for diagnosis involve invasive procedures like cordocentesis, a procedure which takes a sample of fetal blood.
Researchers at Tulane School of Medicine led by assistant professor of bioengineering Carolyn Bayer, Ph.D., hope to improve diagnostics for preeclampsia with the use of spectral photoacoustic imaging. Using this technique, Bayer’s team noticed a nearly 12 percent decrease in placental oxygenation in rats with induced preeclampsia when compared to normal pregnant rats after only two days. If success in using this imaging technology continues at the clinical level, Bayer plans to find more applications of it in the detection and diagnosis of breast and ovarian cancers as well.
New CRISPR-powered device detects genetic mutations in minutes
This new chip eliminates the long and expensive amplification process involved in the typical polymerase chain reaction (PCR) used to read DNA sequences. In doing so, the CRISPR-Chip is much more of a point-of-care diagnostic, having the ability to quickly detect a given mutation or sequence when given a pure DNA sample. Led by Kiana Aran, Ph.D., the research team behind the CRISPR-Chip hopes that this new combination of nanoelectronics and modern biology will allow for a new world of possibilities in personalized medicine.
New Method of Brain Stimulation Might Alleviate Symptoms of Depression
Led by Flavio Frohlich, Ph.D., who has an adjunct appointment in biomedical engineering, this team of researchers based this new solution on information from each patient’s specific alpha oscillations, which are a kind of wave that can be detected by an electroencephalogram (EEG). Those who suffer from depression tend to have imbalanced alpha oscillations, so Frohlich and his team sought to use tACS to restore this balance in those patients. After seeing positive results from data collected two weeks after patients in a clinical trial receives the tACS treatment, Frohlich hopes that future applications will include treatment for even more mental health disorders and psychiatric illnesses.
University of Utah Researchers Receive Grant to Improve Hearing Devices for Deaf Patients
Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Scholar in the Department of Materials Science and Engineering and Secondary Faculty in Bioengineering, has been named the recipient of the 2018–19 George H. Heilmeier Faculty Award for Excellence in Research for “for pioneering multi-scale models of nanomaterials and biological systems.”
The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for George H. Heilmeier, a Penn Engineering alumnus and overseer whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.
We would also like to congratulate Jay Goldberg, Ph.D., from Marquette University on his election as a fellow to the National Academy of Inventors. Nominated largely for his six patents involving medical devices, Goldberg also brings this innovation to his courses. One in particular called Clinical Issues in Biomedical Engineering Design allows junior and senior undergraduates to observe the use of technology in clinical settings like the operating room, in an effort to get students thinking about how to improve the use of medical devices in these areas.