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Week in BioE (May 1, 2018)

To Bee or Not To Bee

beesYou might have heard reporting over the last few years that honeybees are dying at faster-than-usual rates. Over the last decade, colony collapse rates increased significantly, causing precipitous losses in the overall bee population. The consequences could be grave: in addition to providing honey, bee pollination is an important factor in agriculture, affecting major crops such as melons. squashes, and several kinds of nuts. Loss of this factor could substantially increase prices or even result in shortages.

 

To address this crisis, scientists at Washington State University focused on the role played by pesticides in colony collapse disorder. These poisons are particularly toxic to bees in tiny amounts, with the problem compounded by the ability of these toxins to build up in the bees’ bodies. A group of students led by Waled Suliman, PhD, a postdoctoral research associate in WSU’s Department of Biological Systems Engineering, developed a powder that acts like a magnet to draw pesticide out of the insects’ bodies. The bees then excrete the pesticide-laden particles like any other kind of waste.

 

The initiative, called Gaminus, has already tested its material in bees and found that the design works as planned. In coming months, they intend to continue their research by measuring toxin levels in the excreted particles.

Advances in Visualization

An important field within bioengineering is visualization, or the ability to use technology to enable scientists to see biological processes not normally visible to the naked eye. If you’ve seen a fetal ultrasound, for instance, then you’ve seen how one part of this area has advanced enormously in recent years. However, integrating visualization technologies with surgery remains a major challenge, particularly for minimally invasive surgeries. One key obstacle is that surgeons must rely on video screens during surgery, rather than being able to look down and feel the tissue with their hands.

 

A startup at the Cleveland Clinic is attempting to integrate perioperative visualization with HoloLens, a brand of smart glasses developed by Microsoft, to produce “mixed reality,” i.e., a combination of actual vision and virtual reality. With a grant from the National Heart, Lung, and Blood Institute awarded to Centerline Biomedical, the Cleveland Clinic startup, and to Karl West, Director of Medical Device Solutions at Cleveland Clinic and a staff member in the Lerner Research Institute’s Department of Biomedical Engineering, the integrated visualization device will be tested in a preclinical model of cardiac stent placement.

 

Elsewhere in the Midwest, Nathan Gianneschi, PhD, Professor of Chemistry, Biomedical Engineering and Materials Science and Engineering at Northwestern University, has been leading an effort to augment transmission electron microscopy (TEM). In its common form, TEM provides highly detailed images of submicroscopic organisms and structures and can provide visualization of nanomaterials as they grow. Gianneschi’s new approach, called liquid cell TEM (LCTEM), uses an irradiated region of a liquid cell to facilitate real-time visualization. The work is detailed in a recent article in ACS Central Science. You can see video posted online at the journal website.

Turning Red

Ultraviolet and infrared light appear beyond either end of the visible light spectrum. Past work using either ultraviolet or infrared light to activate fluorescent proteins can help visualize biochemistry in vivo, but it can also damage cells because of the activating light or the chemicals produced by illuminating the proteins. Recently, Young L. Kim, PhD,  Associate Professor of Biomedical Engineering at Purdue, led a team of scientists who produced red fluorescent silk to kill harmful bacteria when the protein is activated by external green light. Dr. Kim and his colleagues report their findings in Advanced Science. The silk requires further testing, but if ultimately proved successful, it could overcome a current limitation of the use light-activated fluorescent biomaterials in controlling pathogens, which is that the light itself, often in the ultraviolet part of the spectrum, comes with its own potentially negative effects on health.

Absorbable Stents for Cardiac Care

Vascular stents to reopen blocked coronary arteries are usually the treatments used for patients with mild coronary artery disease. These simple devices are a small tube, sometimes coated with a drug to prevent clotting, inserted into the artery to restore flow. Stents can fail over time, requiring reimplantation, and the stents may also narrow over time and reduce blood flow to the surrounding tissue. To overcome this problem, Donghui Zhu, PhD, Associate Professor in the Department of Biomedical Engineering at the University of North Texas, developed a stent that is fully biodegradable and disappears over time as the damaged tissue heals. Dr. Zhu recently won a $2 million grant from the National Institutes of Health to test the stent in a series of trials.

 

People and Places

Penn State University has won a research grant from the American Heart Association, which will be used to support its 10-week Penn State Summer Translational Cardiovascular Science Institute (STCSI). Led by Keefe Manning, PhD, Professor of Biomedical Engineering at Penn State, the STCSI will provide $4,000 stipends for undergraduate students to conduct summer research on cardiovascular disease.

 

Finally, here at Penn Bioengineering, we are immensely proud to announce that our PhD student Jina Ko was named one of 14 PhD candidates in the inaugural class of Schmidt Science Fellows. Schmidt Fellows are each awarded a $100,000 stipend to cover the cost of living while conducting postdoctoral research. Congratulations, Jina!
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Week in BioE (April 24, 2018)

Pushing the Limits of Imaging

7T-MRI
An image showing 7-tesla MRI of the human brain

Since the late 1970s with the advent of computed tomography (CT), medical imaging has grown exponentially. Magnetic resonance imaging (MRI) offers some of the clearest pictures of human anatomy and pathology, particularly as the strength of the magnetic field used (measured in units called Teslas) increases. However, MRI machines are expensive, and the costs increase as one uses a machine with higher field strength to ‘see’ the human more closely. Therefore, it is often more useful (and certainly less expensive) to modify existing MRI technology on hand, rather than acquire a new machine.

A recent example is the work of Tamer Ibrahim, PhD, Associate Professor of Bioengineering at the University of Pittsburgh. Dr. Ibrahim used a series of multiple NIH grants to develop a coil system for Pitt’s 7T-MRI — one of only approximately 60 worldwide — enabling it to more accurately image the brain’s white matter. Dr. Ibrahim is interested in seeing how hyperintensity in the white matter is related to depression, which is one of the highest-burden but least-discussed diseases in the world. Called a “tic-tac-toe” radiofrequency coil setting, the device that Dr. Ibrahim created is a network of antennas fitted to the head that minimize concerns such as coil heating and radiofrequency intensity losses, as well as safety concerns.

Dr. Ibrahim has more NIH funding on the way to continue optimizing his device and apply it in other psychiatric and neurological disorders. Rather than purchasing a new MRI machine with higher field strengths to achieve this image quality, Dr. Ibrahim’s coil design can be used on existing machines. One possible outcome is more clinicians using this new coil to study how changes in the brain’s white matter structure occur in a broad range of brain diseases, leading to both earlier detection anfor ad more effective treatment.

Smart Shunt for Hydrocephalus

Hydrocephalus, once more commonly known as “water on the brain,” is a condition marked by abnormal accumulation of cerebrospinal fluid (CSF) in the skull. If unchecked, the accumulation of fluid will create dangerous pressures in the brain that can result in brain damage. Hydrocephalus occurs in one in every 1,000 births, and nearly 400,000 adults in the US suffered at least on episode of hydrocephalus. For both infants and adults, hydrocephalus is often treated surgically with the installation of a shunt to channel the excess CSF out of the cranium. These shunts are simple but effective devices that operate mechanically. However, since they’re entirely mechanical, they fail over time. Being able to determine that such a failure was imminent could allow patients to receive a replacement shunt before complications arise.

To meet this clinical need, a group of scientists at the University of Southern California (USC)  updated existing shunt systems with microsensing technology, creating a “smart shunt” that can tell clinicians how an installed shunt is functioning and alert the clinician that a replacement is needed. The group, including Ellis Fan-Chuin Meng, PhD, Gabilan Distinguished Professorship in Science and Engineering, Dwight C. and Hildagarde E. Baum Chair, and Professor of Biomedical Engineering and Electrical Engineering-Electrophysics, has created a start-up called Senseer to produce these smart shunts.

The shunt currently measures pressure, flow, and occlusion using miniature microelectronics sensors. If device approval comes, the company hopes to move on to developing smart sensors for other organ systems.

DNA-based Drug Testing

Drug and alcohol testing is a controversial topic, partly because of the balance between individual rights to use legal drugs and potential for societal harm if these drugs are abused or if patients transition into illegal drug use and dependence. Inventing technology to determine when, and how much, a person has been drinking or using drugs (including tobacco) would probably increase, rather than decrease, the controversy involved in the topic.

New technology reported recently adds a new element to this discussion. According to Robert Philibert, MD, PhD, Professor of Psychiatry at the University of Iowa and an adjunct faculty member in the Department of Biomedical Engineering, his company’s tests, which rely on epigenetic markers of substance use, could be used, for example, to inform a primary care physician about the actual history of substance use, rather than relying solely on patients’ self-reported use.

Dr. Philibert’s tests are currently pending approval by the Food and Drug Administration. Marketing for the products will begin in the coming weeks.

People and Places

Recognizing the changing priorities in engineering and the growing role of data sciences, Boston University has decided to adapt its curriculum by adding data science requirements for all majors. According to John White, PhD, Chair of the Department of Biomedical Engineering, “Advances in data sciences and computing technology will allow us to make sense of all these data.”

The Biomedical Science Program at Howard Payne University in Brownwood, Texas, has received a $200,000 grant from  the James A. “Buddy” Davidson Charitable Foundation to endow a scholarship in Davidson’s name, as well as to refurbish the program’s Winebrenner Memorial Hall of Science.

Finally, we offer our congratulations this week to James C. Gee, PhD, Professor of Radiologic Science in Radiology at the University of Pennsylvania’s Perelman School of Medicine and a Graduate Group faculty member in Penn’s Department of Bioengineering.  Dr. Gee was named a fellow of the American Institute for Medical and Biological Engineering.

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Week in BioE (April 17, 2018)

Mosquito Bites Inspire Brain Implants

mosquitoesWe’ve talked before at this site about the difficulty involved in implanting devices in the brain. One chief problem is that any implant to record brain signals causes small amounts of damage that causes signal quality to deteriorate over time. One approach to overcoming this problem uses flexible materials that can move with brain tissue movement, rather than resisting the movement to cause damage.

One of the more recent designs was inspired by an NPR report on mosquitoes. Dr. Andrew Shoffstall, a postdoc in the lab of Jeffrey Capadona, PhD, Associate Professor of Biomedical Engineering at Case Western Reserve University (CWRU), saw the report and used the mechanism that mosquitoes use when biting people to design a new device, which the CWRU team describes in an article in Scientific Reports.

The authors studied the buckling force when mosquitoes puncture the skin, using this design to invent new microneedles for brain implant recordings. The group fashioned a 3D-printed plastic device to mimic the process used by the mosquito. They tested the device, first mechanically and then in rat brains, finding that the device could successfully implant a microelectrode in 8 out of 8 trials. Certainly the device will require much more rigorous testing, but if successful, it could change the way implants are inserted into human patients.

Big News About Small Things

Speaking of implants, they continue to decrease in size.  Scientists at Stanford University created a wireless device that is the size of a rice grain. Reporting in IEEE Transactions on Biomedical Circuits and Systems, the scientists, led by Amin Arbabian, PhD, Assistant Professor of Electrical Engineering at Stanford, and including Dr. Felicity Gore, a postdoc in the Department of Bioengineering, describe the design and fabrication of this implant. The implant was designed to stimulate peripheral nerves using either platinum electrodes connected directly to the nerve or light from a blue LED to stimulate optogenetic channels expressed in the neurons. The group conducted an in vivo experiment, using the device to stimulate the sciatic nerve of a frog, and they showed the device’s feasibility. Powered by ultrasound transmitted through the skin, the device has no external wire connections. The size of the implant, combined with its ability to target single nerves, could revolutionize how pain is treated, among other applications. 

Meanwhile, here at Penn, the creation of very small things is getting a very big boost. In a new collaboration among schools and centers, the university’s Center for Targeted Therapeutics and Translational Nanomedicine has established the Chemical and Nanoparticle Synthesis Core (CNSC). The director, Andrew Tsourkas, PhD, is a Professor in the Department of Bioengineering and the Undergraduate Chair. The mission of the CNSC is to provide a concierge level service for Penn faculty interested in synthesizing new molecules for therapy development, as well as new nanoparticles for advanced diagnostics.

A Leap Forward With Stem Cells

Over the last decade, stem cell research has resulted in significant contributions to medical science. One application is the modeling of organs and organ systems for studies before in vivo investigations. However, stem cell projects involving the heart have been limited by the inability to get these cells to a mature state.

However, in a letter published in Nature, researchers at Columbia University and the University of Minho in Portugal describe how they used electrical and mechanical stimulation of human induced pluripotent stem cells to create more mature cells. The authors, led by Gordana Vunjak-Novakovic, PhD, University Professor and Mikati Foundation Professor of Biomedical Engineering and Medical Sciences at Columbia, describe how, after four weeks of culturing under the described conditions, the cells displayed multiple characteristics of maturity, although some electromechanical properties of mature cells remained lacking. These findings show that engineering the physical environment that surrounds cells during development is a key factor for the engineering design of replacement tissue.

Individualizing First Aid

Personalized medicine has begun to affect the way that doctors treat several diseases with genetic bases, notably cancer. However, first aid has lagged a bit behind in personalization, in part because the urgency of first aid care emphasizes fast, practical solutions that work for everyone. However, in a presentation at Philadelphia’s Franklin Institute last month, Jonathan Gerstenhaber, PhD, Assistant Professor of Instruction in the Department of Bioengineering at Temple University, demonstrated a prototype device that uses 3D printing technology to produce personalized bandages when they are needed.

Dr. Gersternhaber created a 3D printer that will print bandages directly onto the skin of the patient. Customizing the fit of the bandage with the printing technology would make them last longer, and the ‘on demand’ production of the bandage provides a chance to individualize the bandage design even in the urgent care setting. The device uses electrospinning technology to create bandages from soy protein, which, as a natural substance, can actually speed healing. Having completed the prototype, Dr. Gerstenhaber has moved onto portable models, as well as a larger device that can make bandages across a larger surface area.

Solving Two Problems in Glaucoma Care 

Glaucoma is one of the earliest medical uses for cannabis, commonly known as marijuana. The cannabinoids in the cannabis plan have the effect of lowering intraocular pressure, which is the primary mechanism underlying glaucoma. However, the intoxicating effects of cannabis pose a problem for many patients. Thus, most patients still rely on eyedrops containing other drugs. Getting the dosage correct with eyedrops is tricky, however, because of the continual blinking and tearing of the eye.

Now, in a new article published in Drug Delivery and Translational Research, a team of researchers led by Vikramaditya G. Yadav, PhD, Assistant Professor of Chemical and Biological Engineering at the University of British Columbia, describes how they developed a nanoparticle hydrogel medication to deliver a cannabinoid. The authors tested the gel in situ, with good results. The authors imagine that such a gel could be used by patients at bedtime, and during the night, the drug would be dispensed by the gel and be gone by morning.
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Week in BioE (April 10, 2018)

‘Kelp’ Is on the Way!

kelp
Chondrus crispus, a common red algae from which carrageenan is extracted.

Medicine has made tremendous strides since the 1960s, as evidenced by the increased survival rates of combat soldiers since Vietnam. Nevertheless, blood loss remains the most common cause of death of soldiers on the battlefield. Finding a way for medics or soldiers to stop bleeding can significantly cut down on these deaths, but current approaches are either very expensive or not easy to use in combat.

According to a new paper published in Acta Biomaterialia, a solution to this problem could come from seaweed — or more precisely, from kappa-carrageenan, a type of polymeric carbohydrate produced by certain types of edible seaweed.  Akhilesh K. Gaharwar, PhD, Assistant Professor of Biomedical Engineering at Texas A&M, led a study team who developed and tested an injectable hydrogel nanoengineered from kappa-carrageenan.

The authors combined kappa-carrageenan with clay-based nanoparticles to yield a hydrogel that can be injected into wounds. When the gel solidifies, it both stanches the flow of blood and helps to generate new tissue. The gel performed well in in vitro experiments. The next step will be to test the gel in animal models of wounds.

A New Understanding of Anatomy

A group of scientists collaborating among Mount Sinai Medical Center, NYU, Weill Cornell Medical Center, and the University of Pennsylvania, including Penn Bioengineering secondary faculty member Rebecca Wells, MD, published a paper in Scientific Reports detailing the heretofore unknown extent of the human interstitium and providing a new understanding of these fluid-filled compartments beneath the skin surface. The study used confocal laser endomicroscopy, which can examine structures at depths of 60-70 µm, to look at human hepatobiliary tissue. They found a reticular pattern of fluid-filled sinuses not detected before, which is connected to the lymph nodes and similar to structures found in other organs and organ systems.

On the basis of their findings, the authors suggest that our current understanding of the anatomy might be revised. Much more research is necessary, but they also believe that the fluid-filled spaces might play important roles in cancer metastasis and a number of other disease processes.

Bringing Bioprinting to the Masses

Three-dimensional printing is one of the great innovations of the last decade, and it has transformed numerous fields inside and outside of science. In the health sciences, the ability to manufacture 3D biomaterials holds enormous promise. Unfortunately, the costs of 3D printing remain prohibitive; the available models range between $10,000 and $200,000 in cost, not including the raw materials, software, etc.  However, engineers at Carnegie Mellon University (CMU) might have devised a solution. In a paper published in HardwareX, Adam Feinberg, PhD, Associate Professor of Biomedical Engineering at CMU, and his coauthors describe their development of a syringe-pump large volume extruder (LVE).

Syringe pump extruders, which inject raw material into 3D printers, are already used to print biomaterials. However, achieving cheap, fast, and precise printing of 3D materials is a major technical challenge. The LVE, which is based on open-source hardware and software, significantly increases the size of the extruder without compromising speed, and it can print at sizes as small as 100 µm. The authors estimate that the materials necessary to build their bioprinter would cost less than $500 — orders of magnitude less than current models that are slower and unable to print using large volumes. Their source materials are online here.

People and Places

Missouri dominates this week’s news, with a new program at one institution and a symposium at another. At the University of Missouri, the College of Engineering has announced that it will begin offering an undergraduate program in biomedical engineering in the fall. Ninety miles away at Missouri University of Science and Technology,  a symposium will be held this week — the first to be convened on the topic of biomedical humanities. The event is a collaboration between Missouri S&T’s Center for Science, Technology, and Society and the Center for Biomedical Research.

Colorado State University’s Department of Biomedical Engineering is celebrating its 10th anniversary. In that time, the department has added more than 20 faculty members to its original cohort of 29.
 
Finally, we offer our congratulations to Jelena Kovačević, PhD, who has been named the new dean at NYU’s Tandon School of Engineering. A graduate of Columbia and the University of Belgrade, Dr. Kovačević, who is an electrical engineer with broad interest in biomedical applications, moves to NYU from CMU and is the first-ever female dean of Tandon. Congratulations Jelena!
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Week in BioE (April 2, 2018)

Beer Gets a Hand From Bioengineering

beerBeer is among the oldest beverages known to humankind. While we don’t know what the beer that the ancient Egyptians drank tasted like, there’s little question that the trend toward craft brewing over the past generation has resulted in a proliferation of brews with a range of colors and flavors. Beers with a strong flavor of hops are currently popular, resulting in high demand for the plant that bears them. Like many plants, however, the hop plant requires significant water and energy to produce, adding to the burden of global climate change.

Bioengineers from the University of California, Berkeley, might have found a solution to this problem. In an article recently published in Nature Communications, the Berkeley scientists, led by Jay D. Keasling, Ph.D., from the Department of Bioengineering, described how they engineered brewer’s yeast cells using DNA from mint, basil, and yeast to produce the terpenoid that produces the taste of hops. Taste testers found the beer made from the engineered yeast to be hoppier in flavor than two commercial beers.

The authors of the study acknowledge that a true hop flavor is likely subtler than the register of tastes they used to engineer their brewers yeast. That said, they believe their research could serve as a basis for the genetic engineering of plant products for a range of uses. In addition, the amount of saved money could be enormous — currently, the cost of growing an acre of hop plants is nearly $7,000, which is approximately 10 times that of corn.

Wearables Monitor Digestion

We may be getting a much closer look at certain aspects of digestion thanks to two wearable devices developed by engineers on two sides of the country. On the West Coast, bioengineers at the University of California, San Diego, led by Todd P. Coleman, PhD, professor in UCSD’s Department of Bioengineering,  developed a device to monitor the electrical activity of the stomach over a 24-hour period. Unlike other technologies, this approach doesn’t require the user to drink a barium solution or ingest a tiny camera. The device, which they describe in an article in Scientific Reports, consists of a series of wearable sensors based on EKG technology and an event-logging app for computers or mobile devices. In testing, the new device performed comparably to gastric manometry, a ‘gold standard’ in clinical care that requires insertion of a nasogastric tube. The authors believe their device could have use in gastric motility disorders.

Across the country at Tufts, Fiorenzo Omenetto, PhD, Frank C. Doble Professor in the Department of Biomedical Engineering, led a team of scientists in developing a tooth-mounted sensor that can monitor food intake. The device, which measures 4 square millimeters, is described in an article in Advanced Materials. The sensor could replace the much bulkier mouthguards used for such research in the past.

Painless Lupus Testing

Despite being among the more common autoimmune disorders, lupus is difficult to diagnose. Blood tests often do not provide conclusive results. Ultimately, a kidney biopsy is often necessary to confirm the diagnosis, an invasive procedure that can be problematic with sick patients.

Now, a research team at the University of Houston has developed a saliva test that might eliminate the need for kidney biopsy. Chandra Mohan, MD, PhD, Hugh Roy and Lillie Cranz Cullen Endowed Professor of Biomedical Engineering at UH, received an NIH grant to develop a new technology which identifies proteins in the saliva as biomarkers of lupus. An important aspect of the assay is that it can be used to monitor the disease, as well as diagnose it, so the efficacy of medication to treat the disease can be followed without having to obtain multiple kidney biopsies.

Fluid Shear Stress Affects Ovarian Cells

Like most cancers, survival rates for ovarian cancer have gone up in past decades. As with most cancers, early detection remains a key step to extending survival, but a large proportion of ovarian cancers are not diagnosed until they have metastasized to other organs. Therefore, understanding the process by which normal ovarian cells become cancerous and the mechanism underlying their metastasis could improve our ability to predict these cancers and perhaps detect them earlier.

In response to this issue, researchers at Virginia Tech have uncovered part of the mechanism by which ovarian cancer cells metastasize. Led in part by  Rafael V. Davalos, PhD, L. Preston Wade Professor of Biomedical Engineering and Mechanics, the researchers report in PLOS One that fluid-induced shear stress plays a key role. Ovarian cancer causes the accumulation of fluid in the abdomen, called ascites. Using a mouse model, the study authors found that benign ovarian cells actually became malignant, and malignant cells were more likely to metastasize under this stress. This knowledge could go a long way toward developing more effective treatments for ovarian cancer.

People and Places

Two universities have announced they will begin offering degree programs in biomedical sciences. Among three programs added by Loma Linda University in California is one with an emphasis on neuroscience, systems biology, and bioengineering. Enrollment begins in the fall. In Huntington, W.V., Marshall University has added a bachelor’s degree program in BME, also beginning in the fall.

The University of North Texas, near Dallas, broke ground on a new BME building. The college anticipates the building will open for the Fall 2019 semester.

Finally, we are very proud to report that Elsie Effah Kaufmann, PhD, who earned bachelor’s, master’s, and doctoral degrees from Penn Bioengineering, was honored last week at the 44th annual meeting of the National Society of Black Engineers in Pittsburgh, where she received the 2018 Golden Torch Award for International Academic Leadership. Congratulations!

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Week in BioE (March 26, 2018)

A New Theory of Robotics?

robotic catRobots have come a long way in the past few decades, but we’re still a long way off from one that can move like animals and humans. To date, programming movement for robots uses instructions to individual mechanical parts to mimic muscle activity. The main challenge is that the number of small, coordinated muscle movements in walking requires an enormous number of instructions to program. In addition, these instructions are often not very good at accommodating for different surfaces or changing landscapes.

 

One way around this issue might be to focus less on “muscles” and more on neurons for creating the instructions of walking. This is the approach being taken in the lab of Francisco Valero-Cuevas, PhD, Professor of Biomedical Engineering at the University of Southern California. A recent feature at Wired magazine details their construction of a robotic cat based on a network of artificial neurons.

 

The USC model uses reinforcement learning, which is a system whereby neurons of the spinal cord form networks on the basis of trial and error, using random firing of neurons until motion is produced. In this way, the need for an algorithm or complicated programming is eliminated. The cat, called Kleo, is a long way off from being able to land on its feet or use a litter box, but it might give us insight into new technologies that will help people with disabilities from spinal cord injury or motor neuron disease.

Less Neuronal Flexibility With Learning

One of the primary tasks of the brain is learning, but there’s still a lot we don’t know about what happens in the brain as learning occurs. Much of the past research examined changes at the level of individual neurons to explain learning. Newer research, however, has indicated that it is more insightful to examine larger populations of neurons during tasks to get a deeper insight into how the brain learns.

 

Using this principle, a team of engineers and scientists collaborating between Carnegie Mellon and the University of Pittsburgh submitted rhesus monkeys to a learning task and obtained neural recordings to determine how the task affected neuron populations. Their study, led by Steven Chase, PhD, and Byron Yu, PhD, both associate professors of biomedical engineering at CMU, was published in Nature Neuroscience. Drs. Matthew Golub and Penn alumnus Aaron Batista were also coauthors.

 

Contrary to previous thinking, the authors found the brain is less flexible during learning tasks. In part, this lack of flexibility explains why certain tasks take a long time to learn. The authors state that it remains unclear whether the brain changes detected occur at the level of the cortex or subcortex, so additional research will be necessary.

Preventing Bad Science

Academic science remains largely an environment of publish or perish, and this pressure on scientists has unfortunately resulted in an increased incidence of academic fraud. One form of fraud is recycling old images from past publications of successful experiments while presenting the results of newer research.

 

Recognizing that data science could be used to detect such episodes of fraud, Konrad Kording, PhD, a Penn Integrates Knowledge (PIK) Professor with appointments in the Departments of Bioengineering and Neuroscience, and his collaborators developed an algorithm that can compare images across journal articles and detect whether images have been repeated across two articles, even if they have been resized, rotated, or cropped. They describe their technique in a paper recently published on the BioRxiv preprint server. Among the next moves the authors are considering is licensing the algorithm to academic publishers, with the caveat that the possibility of false positive accusations has not been eliminated.

People and Places

Congratulations go to Judy Cezeaux, PhD, who has been named Dean of the Arkansas Tech University College of Engineering and Applied Sciences. A biomedical engineer with degrees from Carnegie-Mellon and Rensselaer Polytechnic Institute, Dr. Cezeaux was most recently chair of the Department of Biomedical Engineering at Western New England University.

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U.S. News Ranks Penn Bioengineering No. 4

U.S. NewsEvery year, U.S. News & World Report compiles the rankings of Bioengineering and Biomedical Engineering departments across the country. Today, U.S. News revealed its rankings for 2019. Penn Bioengineering placed 4th among almost two hundred programs. Tied now with programs that include MIT, UC Berkeley, and Stanford, Penn BE is the fastest rising program in the Top 10. The department also strengthened its position as the highest ranked science and engineering program at Penn in this year’s rankings.

“It was welcome news to know that we were evaluated so highly by our peers” says David Meaney, chair of Penn BE, “I really think it is a statement of the students we attract to Penn, our educational programs, and the cutting edge research done by our faculty”.

Penn Engineering also rose in the rankings, rising one spot to #18.  Computed based on scores from peers, recruiters, and research activity, the rankings show that Penn BE lives in a healthy engineering ecosystem!

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Week in BioE (March 14, 2018)

Nanotube Yarn Used for Neurological Applications

nanotubes
Microscopic image of carbon nanotube yarn.

Tapping into the autonomous nervous system – the control center for things like heartbeat and breathing – is a relatively new part of neurostimulation technologies to both record and direct organ function. Implants designed for stimulating peripheral nerves often fail because the protective tissue surrounding nerve bundles (the perineurium) is difficult to penetrate, and the body’s immune response often builds a scar around the implanted device.

Now, a team of scientists from Case Western Reserve University (CWRUL) has used carbon nanotubes to overcome these obstacles, reporting their findings in Scientific Reports. The authors, led by Dominique M. Durand, Ph.D., Director of the Neural Engineering Center and El Lindseth Professor of Biomedical Engineering, Neurosciences, Physiology and Biophysics at CWRU, fabricated yarn made of carbon nanotubes that was 10 to 20 µm in diameter. The yarn was then used to create electrodes, which were implanted into rats to monitor activity of the glossopharyngeal and vagus nerves.

The authors found that they could use the implants to monitor nerve activity under conditions of hypoxia and stomach distention. They report that the success of their experiments likely derives from the similarity of the nanotube yarn to the actual neural tissue surrounding the implant. The implants are a long way from being tried in humans, but the large number of functions controlled by just these two nerves indicates that such implants could find use in an enormous number of diseases.

Better Screening of Nanoparticle Delivery

As we discussed last week, the development of gene-based therapies is hindered by the sheer size of the human genome. The immense volume of information involved can quickly become difficult to manage, so one way in which scientists “keep track” of genetic information during the process of introducing new genetic material into an organism is DNA barcoding. This process attaches a small piece of DNA to the gene being studied; if and when the gene causes cells to replicate, these cells will bear the barcode, thus allowing the observer to be certain of the gene identities the whole time.

Seeking to determine whether DNA barcoding of lipid nanoparticles for injection into living models would outperform in vitro testing, a team of investigators at Georgia Tech and Emory University conducted a comparison of the two techniques, reporting their findings in Nano Letters. The authors, led by James Dahlman, Ph.D., Assistant Professor of Biomedical Engineering at GT/Emory, found that in vitro testing did not predict in vivo delivery. Further, they were able to track several dozen barcodes delivered by nanoparticles to eight different cell lines.

The authors believe that their technique, which they call JOint Rapid DNA Analysis of Nanoparticles (JORDAN), is superior to in vitro screening of nanoparticles to predict successful transplantation. They are offering JORDAN online as open source software so other scientists can use the technology to more accurately screen nanomaterials.

Synthetic Biologists Create Gene Circuits

Among the many types of molecules that regulate genetic expression in the body are microRNAs, non-coding strands of RNA that are responsible for gene silencing and other forms of gene expression regulation. The ability to harness and control the functions of microRNAs could have important implications for disease prevention and treatment.

In a recent article in Systems Biology and Applications, researchers at the University of Texas, Dallas, report on their engineering of a microRNA-based genetic circuit and its deployment in living cells. They created the circuit using strands of RNA from a variety of organisms, including viruses and jellyfish. The authors, led by Leonidas Bleris, Ph.D., Associate Professor of Bioengineering at UT Dallas, used the circuits to better understand how microRNAs change gene expression under different conditions.

More importantly, the authors found that their circuit had the ability to outproduce types of gene expression, which decreased as the number of gene replications increased.  The authors believe that their discoveries could have applications in a number of genetic disorders.

Discouraging Smoking at the Level of the Brain

Cigarette smoking is the single greatest contributor to negative health outcomes in the population.  Nicotine addiction often appears during the teenage years, and aggressive advertising has been used for the last couple of decades to encourage people to quit smoking and younger people not to start. Despite the widespread use of advertising to change human behavior, remarkably little is known on how the brain responds to advertising messages.

Danielle S. Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering at Penn, recently collaborated with faculty from Penn’s Annenberg School of Communication to determine the neuroscience underlying this outcome. The collaborators showed graphic warning labels to a cohort of smokers while they were subjected to functional magnetic resonance imaging, which images brain activity during specific tasks. They found that smokers whose brains showed greater coherence between regions in the valuation network were more likely to quit smoking. Determining why these brain regions acted as they did could yield even more effective smoking-cessation messaging.

Purdue Startup Working to Expand MRI

Engineers at Purdue, including Zhongming Liu, Ph.D., Assistant Professor of Biomedical Engineering and Electrical and Computer Engineering, have cofounded at startup company, called MR-Link, to develop and produce a coin-sized device that can be inserted into MRI machines, allowing them to perform multiple scans simultaneously.

The device could be useful in reducing the amount of electromagnetic force to which patients are exposed during an MRI scan. In addition, Dr. Liu and his colleagues believe the device will cost perhaps less than a tenth of what similar devices currently cost. Given the widespread use of MRI, the device could ultimately impact how a number of diseases and disorders are diagnosed and tracked.

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Week in BioE (March 7, 2018)

Online Tool for 3D Visualization of Gene Mutations

recon3d
DNA inside cell nuclei undergoing the process of mitosis.

Fifteen years ago marked a major milestone in the Human Genome Project: scientists successfully sequenced all of the base pairs in our 23 sets of chromosomes. Following this accomplishment, researchers assembled generations of mathematical models to understand how gene mutations result in disease. A key barrier in developing these models is the size of genome itself: a single human genome requires approximately 2 GB of storage, and many studies examine thousands of genomes to detect changes in a small number of patients. Both processing these large datasets and efficiently storing them create challenges. Making these model predictions accurate and complete is another challenge.

Scientists collaborating among several universities on three continents developed an online computational tool to help overcome these barriers. The scientists, who include Bernhard Palsson, Ph.D., Galletti Professor of Bioengineering at University of California, San Diego, as one of the lead authors, report on the resource in a recent issue of Nature Biotechnology.

Called Recon3D, the new resource provides a metabolic network model using approximately 17% of known human genes. The model combines data on the genes, metabolites, proteins, and metabolic reactions for human metabolism. In addition, as the model’s name implies, Recon3D accounts for the physical structure of model components, imporving significantly on past models that relied on linear, two-dimensional models. Although the model still has 83% of genes left to incorporate, it could ultimately unravel some of the mysteries underlying virtually any disease with a genetic cause, from inborn errors of metabolism to cancer.

Bioengineering for Refugees

As the war in Syria enters its seventh year, at least five million refugees have left the country to seek asylum elsewhere. Roughly 20% of the refugees are now in Lebanon, where many reside in refugee camps.  Although these refugees are now much safer than before, even in the best of circumstances, the conditions in refugee camps can compromise health and wellness.

Engineering can offer relief for some of these conditions. A three-week course offered in January at the American University of Beirut, co-designed and taught by Muhammad Zaman, Ph.D., Professor of Biomedical Engineering at Boston University, and entitled “Humanitarian Engineering: Designing Solutions for Health Challenges in Crises,” had students devising solutions to the issues facing these refugees.

Among the ideas generated by the students was “3D Safe Water” – a device designed to detect the contamination of water, decontaminate it, and deploy the technology in low resource settings. The device uses sensors to detect contamination and chlorine to decontaminate. With water-borne diseases taking an especially hard toll on camps like these, the device could significantly improve living conditions for refugees.

Placenta on a Chip

Organ-on-chip technologies use microfluidics to model organs or organ systems. So far, engineers have developed chip-based models of the lungs, heart, and kidneys, as well as the circulatory system.

The most recent addition to the organ-on-chip family is the placenta-on-a-chip, developed by Dan Huh, Ph.D., Wilf Family Term Assistant Professor of Bioengineering at the University of Pennsylvania. Modeling the organ that mediates and communicates between a pregnant woman and the fetus, Dr. Huh created a chip to study how drugs move from the bloodstream of the mother to the fetus. With this knowledge, one could determine more safely and more accurately how drugs taken by the mother can affect a pregnancy.

People and Places

Two colleges have announced new biomedical engineering programs.  George Fox University, a Christian college in Oregon, will offer a BME concentration for engineering majors starting this fall. On the other side of the country, Springfield Technical Community College in western Massachusetts will offer a two-year associate’s degree in BME technology.

The University of Arizona, in cooperation with the City of Phoenix, will launch a new medical technology accelerator program, to be called InnoVention. It will be located on UofA’s Phoenix Biomedical Campus. Frederic Zenhausern, PhD, MBA, Professor of Basic Medical Sciences and Director of the Center for Applied NanoBioscience and Medicine at Arizona, is among the people leading the effort.

Finally, Distinguished Professor Craig Simmons of the University of Toronto’s Institute of Biomaterials and Biomedical Engineering is among 10 awardees sharing a $3.5 million grant (approximately $2.7 million in U.S. currency) for the development of medical devices and technologies. Dr. Simmons, a former postdoc at Penn, will use his funding to investigate the use of stem cells to repair congenital heart defects in infants.

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Week in BioE (February 27, 2018)

Pain Relief Using Spearmint Aromatherapy

spearmintPain is the body’s way of telling you there’s something wrong. For most of us, the pain goes away after the body fixes itself. However, more than 10% of Americans suffer from chronic pain after the healing period. Many chronic pain patients need drugs to reduce their symptoms.  Given the pervasive use of opioid drugs to treat chronic pain, opioid addiction is common among chronic pain patients.

However, a remarkably clever and elegant cellular engineering technology may provide a new approach for treating chronic pain. Martin Fussenegger, Ph.D., a professor in the Department of Biosystems Science and Bioengineering at the Swiss Federal Institute of Technology, is the lead author of a new study published in Nature Biomedical Engineering combining cellular and genetic engineering to alleviate pain using cells as factories to produce spearmint. The strategy employed by the authors used engineered human cells to express huwentoxin IV, a blocker of sodium channels regulating pain signals in neurons, upon exposure to carvone, a terpenoid found in spearmint.

Testing their concept in a mouse model of pain, the authors found that mice exposed to spearmint both orally and via aromatherapy showed fewer signs of pain. Looking forward, Dr. Fussenegger and his colleagues believe that their technology, called AromaCell, should be tested next in human cell lines to alleviate concerns about immunological responses to the cells when implanted into patients.

Press Button to Bleed

Another recent article in Nature Biomedical Engineering details the work of the Boston-area biotech firm Seventh Sense Biosystems on their push-button blood collection device, called TAP. As we have discussed here before, currently used blood-drawing procedures are often uncomfortable to patients because of the sharp needle prick used to collect blood. TAP was designed to collect 100 microliters of whole blood using a device the size of a stethoscope bell in a “virtually painless” manner.

The scientists from Seventh Sense designed the patch using microneedle technology. With this approach, they designed TAP with multiple microneedles deployed at high velocity to collect blood from capillaries — the tiniest vessels that connect veins and arteries and that lie closest to the surface of the skin — rather than from a vein tied off with a tourniquet. Testing the device in 144 volunteers, the study authors found that the device was as accurate as current methods for obtaining blood to measure hemoglobin (important for diabetics) and was significantly less painful.

Seventh Sense predicts this disposable device will cost only $5 per use, but this is still almost double the materials cost for standard blood draws. However, the company believes that the pain-free nature of and time saved with TAP will offset the higher cost of the device.

Advances in Global Health

The positively epidemic nature of human papilloma virus (HPV), affecting nearly one quarter of all Americans, has drawn particular attention over the last decade or so. The clear association between HPV and cervical cancer (as well as head and neck cancers) has led to the development and deployment of vaccines (controversial due to the sexually transmitted nature of HPV) and to increased calls for more regular and accurate screening. In developing nations, implementing either effective vaccination or early screening programs remains an uphill struggle.

Responding to the need for more accessible screening technologies, Jessica Ramella-Roman, Ph.D., Associate Professor of Biomedical Engineering at Florida International University (FIU), and Purnima Madhivanan, Ph.D., an epidemiology professor at FIU, traveled to Mysore, India, to install a device developed by Dr. Ramella-Roman at the Public Health Research Institute of India. The device is a hand-held imaging tool that uses a technology called Mueller matrix imaging to provide high-resolution digital images of the cervix in about 5 seconds. The resolution of the images eliminates the need to use dyes or stains to detect malignant cells. The testing of the device is currently ongoing.

Elsewhere in global health, researchers at Google have teamed with medical faculty from Stanford to produce a machine learning algorithm that could examine the human retina and determine whether the person in question is at risk for cardiovascular disease. They report their findings in Nature Biomedical Engineering.

The technology is not ready for actual patients yet — the study authors concede that the algorithm does not outperform the currently available technologies. However, if improved with additional research and testing, the algorithm could be deployed virtually anywhere, including in patients’ homes.

People and Places

Yale University has launched a new Center for Biomedical Data Science, dedicated to collecting, studying, and managing big data. The interim directors are Mark Gerstein, Ph.D., Albert L Williams Professor of Biomedical Informatics, Molecular Biophysics, and Biochemistry, and Hongyu Zhao, Ph.D., Ira V. Hiscock Professor of Biostatistics and Professor of Genetics and Professor of Statistics and Data Science.

The University of Virginia has announced a partnership with Smithfield Bioscience, a subsidiary of Smithfield Foods, Inc. The goal of the partnership is to advance a variety of tissue engineering applications using tissue samples from pigs. George J. Christ, Ph.D., Professor of Biomedical Engineering and Orthopaedic Surgery, heads UVA’s $3 million Center for Advanced Biomanufacturing, which is involved in the partnership.

Finally, we offer our congratulations to Guoqiang Yu, Ph.D., Professor of Biomedical Engineering at the University of Kentucky and a former research faculty member in physics here at Penn, for being awarded a two-year $420,000 R21 research grant from the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Yu will use the money to develop a device to measure cerebral hemodynamics in neonatal ICU patients.