Blood Test May Help Doctors Catch Pancreatic Cancer Early

A blood test may be able to detect the most common form of pancreatic cancer while it is still in its early stages while also helping doctors accurately stage a patient’s disease and guide them to the appropriate treatment. A multidisciplinary study found the test—known as a liquid biopsy—was more accurate at detecting disease in a blinded study than any other known biomarker alone, and was also more accurate at staging disease than imaging is capable of alone. The team, which includes researchers from the Perelman School of Medicine, the Abramson Cancer Center, and the School of Engineering and Applied Science, published their findings in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third leading cause of cancer deaths. The overall five-year survival rate is just 9%, and most patients live less than one year following their diagnosis. One of the biggest challenges is catching the disease before it has progressed or spread. If the disease is caught early, patients may be candidates for surgery to remove the cancer, which can be curative. For locally advanced patients—meaning patients whose cancer has not spread beyond the pancreas but who are not candidates for surgery based on the size or location of the tumor—treatment involves three months of systemic therapy like chemo or radiation, then reassessing to see if surgery is an option. For patients whose disease has spread, there are currently no curative treatment options.

“Right now, the majority of patients who are diagnosed already have metastatic disease, so there is a critical need for a test that can not only detect the disease earlier but also accurately tell us who might be at a point where we can direct them to a potentially curative treatment,” says the study’s co-senior author Erica L. Carpenter, director of the Liquid Biopsy Laboratory and a research assistant professor of medicine. The study’s other co-senior author is David Issadore, an associate professor of bioengineering and electrical and systems engineering.

Read more at Penn Medicine News.

Read more about Penn’s pancreatic cancer research here. 

Penn Bioengineering and COVID-19

A message from Penn Bioengineering Professor and Chair Ravi Radhakrishnan:

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.

RESEARCH

Novel Chest X-Ray Contrast

David Cormode, Associate Professor of Radiology and Bioengineering

Nanomedicine and Molecular Imaging Lab

Peter Noel, Assistant Professor of Radiology and BE Graduate Group Member

Laboratory for Advanced Computed Tomography Imaging

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).

Immunotherapy

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering

Mitchell Lab

Mike Mitchell is working with Saar Gill (Penn Medicine) on engineering drug delivery technologies for COVID-19 mRNA vaccination. He is also developing inhalable drug delivery technologies to block COVID-19 internalization into the lungs. These new technologies are adaptations of prior research published Volume 20 of Nano Letters (“Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering” January 2020) and discussed in Volume 18 of Nature Reviews Drug Discovery (“Delivery Technologies for Cancer Immunotherapy” January 2019).

Respiratory Distress Therapy Modeling

Ravi Radhakrishnan, Professor, and Chair of Bioengineering and Professor of Chemical and Biomolecular Engineering

Radhakrishnan Lab

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).

Diagnostics

Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine

Syd Shaffer Lab

Arjun Raj, Professor of Bioengineering

Raj Lab for Systems Biology

David Issadore, Associate Professor of Bioengineering and Electrical and Systems Engineering

Issadore Lab

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

Litt Lab

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.

BE Labs COVID-19 Efforts

BE Educational Labs Director Sevile Mannickarottu & Staff

BE Educational Labs staff members Dana Abulez (BE ’19, Master’s BE ’20) and Matthew Zwimpfer (MSE ’18, Master’s MSE ’19) take shifts to laser-cut face shields.

The George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace staff have donated their PPE to Penn Medicine. Two staff members (Dana Abulez, BE ’19, Master’s BE ’20 and Matthew Zwimpfer, MSE ’18, Master’s MSE ’19) took shifts to laser-cut face shields in collaboration with Penn Health-Tech. Dana and Matthew are also working with Dr. Matthew Maltese on his low-cost ventilator project (details below).

Low-Cost Ventilator

Matthew Maltese, Adjunct Professor of Medical Devices and BE Graduate Group Member

Children’s Hospital of Philadelphia Center for Injury Research and Prevention (CIRP)

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.

Face Shields

David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean

Molecular Neuroengineering Lab

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

Auditory Research Laboratory

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

The Hammer Lab

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.

Neuromatch Conference

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

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.

Neuromatch Academy

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

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

Spine Pain Research Lab

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 ksas@seas.upenn.edu.

 

 

Penn is fighting pancreatic cancer

A microscopic view of pancreatic adenocarcinoma. (Image: Emma Furth)

Swept up in a pancreatic cancer diagnosis is inevitably a sense of fear and sadness.

But at Penn, researchers are bringing new hope to this disease. And with patients like Nick Pifani, it’s clear that they’re moving in the right direction.

Pifani, from Delran, New Jersey, first noticed some lingering stomach upset in February 2017. He called his family doctor, concerned—especially given that he was an otherwise healthy marathon runner who was only 42. He was sent to a gastrointestinal specialist. A few weeks later, some crippling stomach pain sent him back to the emergency room and he received an MRI that showed a mass on his pancreas—Stage Three, inoperable, he was told.

He was treated with chemotherapy, along with radiation and, eventually, and after receiving advice from doctors at Penn, his tumor was removed. Thereafter, he realized he had a PALB2 mutation—a cousin of the BRCA gene mutation. At that moment, his long-term needs changed and he found himself seeking specialized care at Penn, where he met Kim Reiss Binder, assistant professor of medicine at the Hospital of the University of Pennsylvania (HUP).

“I’m a planner; I want to understand what [my] potential options are,” Pifani says. “[Reiss Binder] asked why I was there to see her and I explained and quickly I could tell she was—outside of her being remarkably intelligent—a great listener and a compassionate doctor.”

“I have a feeling she worries about me more than I do,” he laughs.

Pifani has now been in remission for two years and four months; he sees Reiss-Binder every three months for checkups. His survival story is inspiring and a sign of momentum, even if a world without pancreatic cancer is still frustratingly out of reach.

Pancreatic cancer at Penn

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, outmatched only by lung cancer (No. 1) and colorectal cancer (No. 2). A person diagnosed with pancreatic cancer is still unlikely to survive past five years—only 9% of survivors do, giving it the highest mortality rate among every major cancer.

In short, pancreatic cancer seldom paves the way for optimistic narratives. Some of the hope that has surfaced, though, is thanks to some talent, dedication to the cause, and hard work at Penn.

A key point of progress in the battle against the disease was made in 2002, when former Assistant Professor of Medicine David Tuveson established a standard model for examining human development of this disease in mice. This model has allowed for a reliable way to study the disease and has influenced progress made here at Penn and elsewhere since.

“There’s been a burst of activity in translational research, from bench to bedside,” explains Ben Stanger, the Hanna Wise Professor in cancer research and director of the Penn Pancreatic Cancer Research Center (PCRC) at the Abramson Cancer Center.

“And there’s a lot of momentum with community building, a dramatic increase in patient volumes, and a dramatic increase in what we know about the cancer,” he says of the status of pancreatic cancer today.

Reiss Binder, meanwhile, explains that one mark of progress at Penn and beyond has been learning about people like Pifani, who have the PALB2 gene, and why they respond differently to treatments than those without it. Platinum-based chemotherapies, for example, are especially effective for people with the PALB2 gene who are battling pancreatic cancer. An ongoing trial at Penn has tested and found some success with using PARP inhibitors—taken orally as an enzyme that fixes single-stranded breaks of DNA—as a maintenance therapy in that same PALB2 demographic after they’ve had chemotherapy. These are less toxic than chemotherapy for patients with the same mutations.

It’s all been slow progress toward better treatments, but there has been progress.

“This is the tip of the iceberg for a disease that we historically have treated with perpetual chemotherapy,” Reiss Binder says. “We owe it to patients to find better options to suppress the cancer but not ruin their quality of life.”

Catching cancer earlier

The consensus on why pancreatic cancer is so deadly? It just can’t be spotted fast enough.

Pancreatic cancer often presents well after it has developed and metastasized, and does so in a way that is not easy to recognize as cancer. Common symptoms include, for example, stomach upset and back pain. And by the time a harder-to-ignore symptom of the cancer surfaces, a sort of yellowing of the skin (a result of a bile duct blockage), it’s likely too late to stop the cancer in its tracks.

One approach to improved detection being tested at Penn, by Research Assistant Professor of Medicine Erica Carpenter, is a liquid biopsy—drawn from a standard blood test. Current means to test for pancreatic cancer—imaging through an endoscopic tube—are invasive and expensive, meaning a common liquid test could transform how many cases are detected early.

Carpenter explains that circulating tumor cells (CTCs) can shed from a tumor that’s adjacent to the wall of a blood vessel; what’s shed then shows up in a blood test. The cells, if detected, can explain more about the nature of the tumor, giving doctors an opportunity to examine characteristics of cancerous cells and decide how to effectively treat a tumor if it can’t be surgically removed. It also allows interpretations of disease burden and the effectiveness of medications—through genome sequencing—that imaging does not.

Ultimately, this gives doctors the potential to track the growth of a tumor before it’s fully developed, all through one tube of blood—detected through an innovative use of technology.

 

David Issadore, Ph.D.

David Issadore, associate professor of bioengineering and electrical and systems engineering in the School of Engineering and Applied Science, has worked since 2017 to develop a chip that detects cancer in the blood, using machine learning to sort through literally hundreds of billions of vesicles and cells, looking for these CTCs. The chip retrieves data and the machine learning developed interprets that data, attempting to make a diagnosis that not only finds pancreatic cancer but also provides information about its progression—and, importantly, whether a patient might benefit from surgery.

Read the full story at Penn Today. Media contact Brandon Baker.

Six Penn Engineers Receive Tenure

Brian Chow, David Issadore, Dongeun (Dan) Huh, Linh Thi Xuan Phan, Amish Patel and Aleksandra Vojvodic

The School of Engineering and Applied Science has granted tenure to six faculty members, including three from the Department of Bioengineering.

Tenured faculty at Penn Engineering demonstrate teaching excellence and international leadership in their fields of study and research collaborations.

Brian Chow
Associate Professor in Bioengineering
Chow’s research focuses on the discovery and engineering of photoreceptors and sensory proteins for manipulating and monitoring the physiology of genetically targeted cells, and the application of these tools to reveal principles of cellular dynamics. His work has advanced the rational design of light activated proteins and the use of optogenetic reagents to study cell signaling.

David Issadore
Associate Professor in Bioengineering
Issadore’s research combines microelectronics, microfluidics, and nanomaterials to create miniaturized platforms for the diagnosis of disease. His work has the potential to radically change the way we diagnose and treat diseases by bringing the technologies out of the lab and directly to the point of care.

Dongeun (Dan) Huh
Associate Professor in Bioengineering
Huh’s research aims to develop innovative bioengineering tools and technologies using biologically inspired design principles and micro- and nano-scale engineering techniques to create systems that mimic the structure and function of human physiological systems.

Linh Thi Xuan Phan
Associate Professor in Computer and Information Science
Phan’s work focuses on making cyber-physical systems (CPS) safer, faster, and more secure, both by strengthening the theoretical foundations and by developing practical solutions. Her recent projects include a cloud platform with real-time capabilities, a new diagnosis technique for timing-related faults, and new ways to defend CPS against attacks from insiders and/or external attackers.

Amish Patel
Associate Professor in Chemical and Biomolecular Engineering
Patel’s research strives to achieve a molecular-level understanding of solvation and transport in aqueous and polymeric systems, with applications ranging from the prediction of protein interactions to the design of advanced materials for water purification and energy storage. His group combines principles of statistical mechanics and liquid state theory with state-of-the-art molecular modeling and atomistic simulation techniques to study these biological, nanoscopic and polymeric systems.

Aleksandra Vojvodic
Associate Professor in Chemical and Biomolecular Engineering
Vojvodic’s research focuses on theory and computation-driven materials design. Her lab uses computational frameworks to obtain fundamental understanding of surface and interface properties of complex materials that can be used to develop theoretical models for chemical transformations and energy conversion. These models have been used to predict new catalyst materials for several chemical reactions which have been experimentally synthesized and tested, validating the desired properties of the computationally predicted catalyst material.

Originally posted on the Penn Engineering Medium blog.

Brian Chow, Dan Huh, and David Issadore Promoted to Tenured Positions as Associate Professors in Penn Bioengineering

by Sophie Burkholder

We would like to congratulate Penn Bioengineering faculty members Brian Chow, Ph.D., Dongeun (Dan) Huh, Ph.D., and David Issadore, Ph.D., on all of their recent promotions to tenured positions as Associate Professors. Both Chow and Issadore taught the second half of the foundational course in the Penn Bioengineering undergraduate curriculum, Bioengineering Modeling, Analysis, and Design Laboratory, in which students form lab groups to complete modules in microfluidics, synthetic biology, bioelectrical signal analysis, and bioanalytical spectroscopy.

Chow R01
Brian Chow, Ph.D.

Outside of the classroom, Chow’s research focuses on the creation of dynamic input and output interfaces for cells through the use of optogenetics, synthetic biology, genomics, and device engineering. The Chow lab’s current projects include the exploration of functional diversity of photoreception, engineering optically active genetically encoded tools, and their applications in neuroscience and mammalian synthetic biology. His research is supported by the NIH and he is the recipient of a 2017 NSF CAREER Award. Chow also supports undergraduate innovations in research by hosting the annual Penn team for the International Genetically Engineered Machine (iGEM) competition, a program which he helped to create during his time as a graduate student at MIT. One group of Bioengineering students under Chow’s mentorship used the iGEM project as a springboard to create an accessible, open-source plate reader.

David Issadore, Ph.D.

The Issadore lab at Penn focuses on the use of microelectronics and microfluidics for medical diagnostics. In projects that combine elements of bioengineering, electrical engineering, chemical engineering, and applied physics, Issadore and his team use an interdisciplinary approach to create miniaturized low-cost platforms for disease diagnosis. His company Chip Diagnostics received the JPOD @ Philadelphia QuickFire Challenge Award last month. Earlier this year, Issadore taught the Penn Engineering course Appropriate Point of Care Diagnostics (APOC), which culminated in a service trip to Ghana (read blog posts written by participating students here). This fall, he will take over the core Bioengineering undergraduate course in Bioengineering Signals and Systems, which focuses on applications in ECG signaling, cochlear implants, and biomedical imaging.

organ-on-a-chip
Dan Huh, Ph.D.

Dr. Huh is the principal investigator of the BIOLines Lab at Penn, which is best known for its work on bioinspired engineering systems that Huh calls “organs-on-a-chip.” Using design and engineering principles based on microfluidics and biomimicry, the Huh lab creates microengineered systems that can reconstitute the structural and functional complexity of healthy and diseased human physiological systems in ways not possible using traditional cell culture techniques. His research has been featured in TEDx, and he has won several prestigious honors and awards including the Bernard Langer Distinguished Lectureship, Lush Prize, the McPherson Distinguished Lectureship, CRI Technology Impact Award, John J. Ryan Medal, Design of the Year Award and Best Product of the Year Award from London Design Museum, NIH Director’s New Innovator Award, and Analytical Chemistry Young Innovator Award. This fall, Huh will teach a graduate level course in biomicrofluidics that will cover the use of microfluidics for biomedical application.

Chip Diagnostics receives the JPOD @ Philadelphia QuickFire Challenge Award

By Erica K. Brockmeier

Chip Diagnostics is the awardee of the JPOD @ Philadelphia QuickFire Challenge sponsored by Johnson & Johnson Innovation — JLABS. The Challenge was designed to accelerate healthcare innovation and commercialization within the greater Philadelphia area.

David Issadore (center) was announced as the awardee of the JPOD @ Philadelphia QuickFire Challenge by Katherine Merton (right), head of JLABS New York City, Boston, and Philadelphia, at last week’s BIO 2019 International convention. (Photo: Johnson & Johnson Innovation)

Chip Diagnostics is a Philadelphia-based device company founded in 2016 based on research from the lab of David Issadore, Assistant Professor of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science. The startup combines microelectronics, microfluidics, and nanomaterials with the aim to better diagnose cancer. The company is developing technologies and digital assays for minimally-invasive early cancer detection and screening that can be done using mobile devices.

There has been a long interest in diagnosing cancer using blood tests by looking for proteins, cells, or DNA molecules shed by tumors, but these tests have not worked well for many cancers since the molecules shed tend to be either nonspecific or very rare.

Issadore’s group aims to target different particles called exosomes: Tiny particles shed by cells that contain similar proteins and RNA as the parent cancer cell. The problem, explains Issadore, is that because of the small size of the exosomes, conventional methods such as microscopy and flow cytometry wouldn’t work. “As an engineering lab, we saw an opportunity to build devices on a nanoscale that could specifically sort the cancer exosomes versus the background exosomes of other cells,” he explains.

After Issadore was approached by the IP group at PCI Ventures in the early stages of their research, Chip Diagnostics has since made huge strides as a company. Now, as the awardee of the JPOD @ Philadelphia QuickFire Challenge, Chip Diagnostics will receive $30,000 in grant funding to further develop the first-in-class, ultra-high-definition exosomal-based cancer diagnostic. The award also includes one year of residency at Pennovation Works as well as access to educational programs and mentoring provided by Johnson & Johnson Family of Companies global network of experts.

Originally posted on the Penn Engineering Medium Blog. Continue reading at Penn Today.

Junior Bioengineering Students Complete Their Laboratory Course with Creatively Designed Spectrophotometers

by Sophie Burkholder

To finish the second half of Bioengineering Modeling, Analysis, and Design (BE MAD) Laboratory – the hallmark laboratory course of Penn’s Bioengineering program – instructors Dr. Brian Chow and Dr. David Issadore tasked junior undergraduate students with creating their own spectrophotometers for potential use in detecting water-borne pathogens in a design process that involved rapid prototyping techniques, the use of low-cost optoelectronics, and the incorporation of automation software and a graphical user interface for data acquisition. The final projects were assessed for both the creativity of the structural design of the device, and their abilities to measure optical properties of fluorescein, a chromophore used in clinical diagnostics, to determine each device’s accuracy, sensitivity, precision, and dynamic range.

For the final project of the year, many groups planned adventurous structural innovations to house their spectrophotometer circuits. Some of this year’s highlights included a fish tank complete with flashing lights and goldfish, a motorized arm that could successfully shoot a ball into a miniature basketball hoop with every spectrophotometer reading, a guitar with the ability to actually play music, and a working carousel. “My group decided to make a version of the Easy Bake Oven, using an LED oven light bulb, and a motor to open the door,” said junior Alina Rashid. “Of course, it didn’t actually cook anything because of the spectrophotometer inside, but maybe next time!” All of these designs involved the use of CAD-modeling to create sketches and parts that could then be laser-cut or 3D-printed into physical structures. The Department of Bioengineering also allotted each group with a budget for students to purchase any additional parts they required for their designs that were not already available in the lab.

On Demo Day for the spectrophotometer projects, instructors, lab staff, and friends came to the Stephenson Foundation Bioengineering Educational Laboratory and Bio-MakerSpace to assess final designs and celebrate the end of the semester. Given three solutions of unknown concentrations, students used their completed spectrophotometers to create standard curves using Beer-Lambert’s Law and attempt to determine the concentrations of the provided solutions. “I always love Demo Day because that’s when all separate aspects of the project – the mechanical design, the code, the circuitry – come together to make a device that actually works the way we planned and wanted it to all along,” said junior Jessica Dubuque. After nearly a month of working on the projects, each lab group went into Demo Day with designs they were proud of, and ended the semester on a high note with many new insights and lab skills under their belt for the beginning of their Senior Design projects in the fall.

Junior Bioengineering Students Filter ECG Signals for Use in Astronaut Fatigue-Monitoring Device

by Sophie Burkholder

Every undergraduate student pursuing a B.S.E. in Bioengineering participates in the Bioengineering Modeling, Analysis, and Design Laboratory I & II courses, in which students work together on a series of lab-based design challenges with an emphasis on model development and statistical analysis. Recently, junior undergraduates enrolled in this course taught by Dr. Brian Chow and Dr. David Issadore (both of whom recently received tenure) completed a project involving the use of electrocardiography (ECG) to innovate a non-invasive fatigue-monitoring device for astronauts that tend to fall asleep during long operations in space.

Using ECG lead wires and electrodes with a BioPac M-35 data collection  apparatus, students collected raw data of their own heart and respiration rates, and loaded the data into MATLAB to analyze and calculate information like the heart rate itself, and portions of it like the QT-interval. “I think it was cool that we could measure signals from our own body and analyze it in a way that let us use it for a real-world application,” said junior Melanie Hillman about the project.

After taking these preliminary measurements, students used a combination of circuitry, MATLAB, and data acquisition boards to create both passive and active filters for the input signals. These filters helped separate the user’s breathing rate, which occurs at lower frequencies, from the heart rate, which occurs at higher frequencies, allowing for the data to be read and analyzed more easily. In their final design, most students used an active filter circuit chip that combined hardware with software to create bandpass filters of different frequency ranges for both input signals.

“It was nice to be able to do a lab that connected different aspects of engineering in the sense that we both electronically built circuits, and also modeled them theoretically, because normally there’s a separation between those two domains,” said junior Emily Johnson. On the final day of the project, Demo Day, groups displayed their designs ability to take one input from the ECG cables connected to a user, and filter it out into recognizable heart and respiration rates on the computer. This project, conducted in the in the Stephenson Foundation Bioengineering Educational Laboratory here at the University of Pennsylvania’s Department of Bioengineering, is just one of many examples of the way this hallmark course of the bioengineering curriculum strives to bring together all aspects of students’ foundational engineering coursework into applications with significance in the real world.

Week in BioE (February 28, 2019)

by Sophie Burkholder

Louisiana Tech Sends First All-Female Team to RockOn

A team of faculty and students from Louisiana Tech University will participate in RockOn, a NASA-sponsored workshop on rocketry and engineering. Mechanical Engineering Lecturer Krystal Corbett, Ph.D., and Assistant Professor of bioengineering Mary Caldorera-Moore, Ph.D., will work together to lead the university’s first team of three all-female students at the event. At the program, they will have the chance to work on projects involving components of spacecraft systems, increasing students’ experience in hands-on activities and real-world engineering.

Refining Autism Treatments Using Big Data

Though treatments like therapy and medication exist for patients with autism, one of the biggest challenges that those caring for these patients face is in measuring their effects over time. Many of the markers of progress are qualitative, and based on a given professional’s opinion on a case-by-case basis. But now, a team of researchers from Rensselaer Polytechnic Institute (RPI) hopes to change that with the use of big data.

Juergen Hahn, Ph. D., and his lab recently published a paper in Frontiers in Cellular Neuroscience discussing their findings in connecting metabolic changes with behavioral improvements in autistic patients. Their analysis looks for multiple chemical and medical markers simultaneously in data from three distinct clinical trials involving metabolic treatment for patients. Being able to quantitatively describe the effects of current autism treatments would revolutionize clinical trials in the field, and lead to overall better patient care.

Penn Engineers Can Detect Ultra Rare Proteins in Blood Using a Cellphone Camera

One of the frontiers of medical diagnostics is the race for more sensitive blood tests. The ability to detect extremely rare proteins could make a life-saving difference for many conditions, such as the early detection of certain cancers or the diagnosis of traumatic brain injury, where the relevant biomarkers only appear in vanishingly small quantities. Commercial approaches to ultrasensitive protein detection are starting to become available, but they are based on expensive optics and fluid handlers, which make them relatively bulky and expensive and constrain their use to laboratory settings.

Knowing that having this sort of diagnostic system available as a point-of-care device would be critical for many conditions — especially traumatic brain injury — a team of engineers led by Assistant Professor in the Department of Bioengineering, David Issadore, Ph.D., at the University of Pennsylvania have developed a test that uses off-the-shelf components and can detect single proteins with results in a matter of minutes, compared to the traditional workflow, which can take days.

Read the full story on Penn Engineering’s Medium blog.

Treating Cerebral Palsy with Battery-Powered Exoskeletons

Cerebral palsy is one of the most common movement disorders in the United States. The disorder affects a patient’s control over even basic movements like walking, so treatments for cerebral palsy often involve the use of assistive devices in an effort to give patients better command over their muscles. Zach Lerner, Ph.D., is an Assistant Professor of Mechanical Engineering and faculty in Northern Arizona University’s Center for Bioengineering Innovation whose research looks to improve these kinds of assistive devices through the use of battery-powered exoskeletons.

Lerner and his lab recently received three grants, one each from the National Institute of Health (NIH), the National Science Foundation (NSF), and the Arabidopsis Biological Resource Center, to continue their research in developing these exoskeletons. Their goal is to create devices with powered assistance at joints like the ankle or knee to help improve patient gait patterns in rehabilitating the neuromuscular systems associated with walking. The team hopes that their work under these new grants will help further advance treatment for children with cerebral palsy, and improve overall patient care.

People & Places

David Aguilar, a 19-year-old bioengineering student at Universitat Internacional de Catalunya made headlines recently for a robotic prosthetic arm that he built for himself using Lego pieces. Due to a rare genetic condition, Aguilar was born without a right forearm, a disability that inspired him to play with the idea of creating his own prosthetic arm from age nine. His design includes a working elbow joint and grabber that functions like a hand. In the future, Aguilar hopes to continue improving his own prosthetic designs, and to help create similar versions of affordable devices for other patients who need them.

This week, we would like to congratulate two recipients of the National Science Foundation’s Career Awards, given to junior faculty that exemplify the role of teacher-scholars in their research. The first recipient we’d like to acknowledge is the University of Arkansas’ Kyle Quinn, Ph.D., who received the award for his work in developing new image analysis methods and models using the fluorescence of two metabolic cofactors. Dr. Quinn completed his Ph.D. here at Penn in Dr. Beth Winkelstein’s lab, and received the Solomon R. Pollack Award for Excellence in Graduate Bioengineering Dissertation Research for his work.

The second recipient of the award we wish to congratulate is Reuben Kraft, Ph.D., who is an Assistant Professor in Mechanical and Biomedical Engineering at Penn State. Dr. Kraft’s research centers around developing computational models of the brain through linking neuroimaging and biomechanical assessments. Dr. Kraft also collaborates with Kacy Cullen, Ph.D., who is a secondary faculty member in Penn’s bioengineering department and a member of the BE Graduate Group faculty.

Finally, we’d like to congratulate Dawn Elliott, Ph.D., on being awarded the Orthopaedic Research Society’s Adele L. Boskey, PhD Award, awarded annually to a member of the Society with a commitment to both mentorship and innovative research. Dr. Elliott’s spent 12 years here at Penn as a member of the orthopaedic surgery and bioengineering faculty before joining the University of Delaware in 2011 to become the founding director of the bioengineering department there. Her research focuses primarily on the biomechanics of fibrous tissue in tendons and the spine.

APOC Ghana 2018: Day 4

By Xuanjie (Lucas) Gong, Biotechnology MS ’19; Shihan Dong, Biotechnology MS ’19; and Princess Aghayere, Health & Societies ‘19

Ghana 2018
MUAC tape

Today, we all went to the Maternal and Child Health Hospital in Rural Kumasi. The main purpose of the visit was to observe malnutrition cases in children and to interact with doctors and nurses who treat children suffering from malnutrition.

Ghana 2018
RUTF

While visiting the clinic, the nutrition group asked the questions that we prepared yesterday. It turns out that the situations here match up with our research. Doctors and nurses use WHO standards to determine the nutrition status of the kids. Also, they use MUAC tape to determine the severe acute malnutrition. Children who have MUAC less than 11.5 cm will be sorted into a severe acute malnutrition group.

As for solutions or treatments, they do know about and have RUTF (Ready-to-Use Therapeutic Food). We also learned that they have therapeutic milk, F-75 and F-100, to treat malnourished children in different phases. They have F-75 to use at the starting phase of treatment. If F-75 helps to stabilize the children, they move onto F-100, and they use diluted F-100 for children under 6 months.

We had 2 cases that we mainly focused on. The first case was of a 3-year-old girl who suffered from Kwashiorkor, Marasmus, and Marasmic Kwashiorkor. All 3 diseases are signs of severe acute malnutrition. She had been there for 3 weeks for treatment, and her condition was not improving. The doctors attributed her declining condition to poverty and the mother’s psychiatric problems. The patient’s mother has already lost two children to the same condition. The doctors describe the girl’s status as unstable because she often vomits and isn’t gaining weight. The second patient is a child exposed to HIV as a result of her mother being positive for the disease. Because she is only 3 months old, blood cannot be drawn, and testing cannot be done to ensure her HIV status.

Ghana 2018
F-75 therapeutic milk

In the evening, we went to a church to give a presentation to local women with little to no education. We started by asking them what they eat everyday, and luckily we received a lot of responses. From their responses, we could clearly see that their diet lacked components of vegetables and fruits. Then, we delivered a brief speech containing basic nutrition knowledge, mainly based on the six essential nutrients. We explained the function of these nutrients and some local sources to obtain them. Surprisingly, one of the female audience members said that this was her first time hearing about vitamins and minerals.

During the question and answer segment of our presentation, some women asked about the different types of sources for minerals and vitamins. In particular, one woman asked about the foods that she could eat to help with her hypertension. To our surprise, another women asked whether her intake of fruits was excessive. This question made us think about people’s awareness of obesity and other diseases related to overeating. At the end of the presentation, the audience was happy about what we presented today and looked forward to learning more on our next visit.