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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.

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Week in BioE (February 20, 2018)

Modeling Hemostasis With Microfluidics

hemostasis
Electronic scanning microscopic image of red blood cells forming a clot

Hemostasis is the process by which blood stops flowing from damaged blood vessels. It is a complex process involving multiple molecules and forces, and our current understanding is limited by our inability to test these factors simultaneously in the laboratory. Some tests, for instance, can tell us much about clotting — a part of hemostasis — but little about the other elements at play. In particular, the role in hemostasis of the endothelium, which is the cell layer that lines the blood vessels, has generally been omitted from previous studies.

However, a new article in Nature Communications details the use of microfluidics technology, which is often used to model organ systems outside the body, to engineer a more complete model of hemostasis. Led by Wilbur A. Lam, M.D., Ph.D., Assistant Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, the study authors fabricated microfluidics devices and then seeded vascular channels in the devices with human aortic and umbilical vein cells to simulate the endothelium.

Using the device, the authors were able to visualize hemostatic plug formation with whole blood and with blood from subjects with hemophilia. Although the authors concede that their model best represents capillary bleeding, rather than bleeding from larger vessels, they are confident that their model reliably represents the interaction of the endothelium with multiple varieties of blood cells.

Shedding Light on Cancer Response and Resistance

Penn’s founder, Benjamin Franklin, has a famous axiom: “an ounce of prevention is worth a pound of cure.” If Franklin were alive today, he would likely agree with two common axioms in cancer treatment: 1) if you can’t see it, you can’t treat it; and 2) if you treat it, treat all of it. Recent publications from investigators at Columbia and the University of Maryland reveal how imaging technologies can help predict to  outcomes and how nanotechnology is offering a new therapeutic tools for fighting cancer.

Using diffuse optical tomography (DOT), which employs near-infrared spectroscopy to obtain three-dimensional images, scientists at Columbia have shown in an article in Radiology that treatment response could be predicted as early as two weeks after the start of therapy. The authors, led by Andreas H. Hielscher, PhD, Professor of Biomedical Engineering, Electrical Engineering, and Radiology at Columbia, applied DOT in 40 women with breast cancer undergoing chemotherapy. They found that DOT imaging features were associated, some very strongly, with treatment outcomes at 5 months.  Given their positive findings, the authors intend to continue testing DOT in a larger cohort prospective study.

Another major issue in cancer chemotherapy is multidrug resistance (MDR),  a highly frustrating complication resulting from lengthy treatment. In MDR, cancer types can find ways to overcome the effects of chemotherapy, resulting in relapse, often with deadly consequences. Therefore, among the challenges that oncologists face is the need to predict MDR, preferably before treatment even begins.

Based on the knowledge that adenosine triphosphate (ATP), a common organic molecule in energy generation, is involved in MDR, scientists at the University of Maryland engineered nanoparticles that could target cancer cells and, when exposed to near-infrared laser irradiation, reduce the amount of ATP in the cells . The scientists, led by Xiaoming Shawn He, Ph.D., Professor of Bioengineering at Maryland, published their findings in Nature Communications.

Dr. He’s team tested their nanoparticles in vitro and subsequently in mice and found decreased tumor sizes in mice treated with the particles, as well as more deaths of cancer cells. In addition, two of seven mice treated with the nanoparticles plus light experienced complete tumor eradication. The findings offer hope that MDR could be overcome with direct delivery of targeted treatment to resistant tumors.

Preserving the Tooth

A frustrating problem often encountered by dentists is the growth of new cavities around existing fillings. Microbes are often critical catalysts for these new cavities. Using antimicrobial agents at cavity-repair sites could make a real difference. However, mesoporous silica has proved suboptimal for this purpose.

However, help might be on the way. A study in a recent issue of Scientific Reports, written by a trio of authors led by Benjamin D. Hatton, Ph.D., Assistant Professor at the Institute of Biomaterials & Biomedical Engineering of the University of Toronto, reports the successful synthesis of 500-nm nanocomposite spheres combining silica with octenidine dihydrochloride, a common antiseptic. The newly synthesized nanospheres outperformed earlier attempts with mesoporous silica. The authors will continue to develop these nanoparticles to deliver other drugs for longer periods of time.

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Week in BioE (February 12, 2018)

Engineering Recovery?

opioidsThe introduction of morphine in the 19th century to alleviate pain revolutionized medicine in a way few innovations do, but it brought with it a grave unintended consequence: addiction. In today’s society, opioid addiction is creating the biggest health crisis of the last half century. Affecting nearly 1 in 100 people, opioid addiction occurs more than type 1 diabetes, multiple sclerosis, or a number of other diseases. The addiction crisis also appears in global affairs and impacts our national security: heroin production in Afghanistan over the last 40 years has been critical to funding military actions by insurgent groups against both the US and, in the past, the Soviet Union.

However, bioengineers at Stanford have begun to tackle the issue of production and might have begun to tackle the issue of addiction. In the lab of Christine Smolke, Ph.D., Professor of Bioengineering at Stanford, they have been genetically engineering yeast to produce opioids. They described the process in a 2015 article from Science. Now, in a recent interview in Fast Company, Dr. Smolke discusses the possibility of using the yeast producing method she pioneered to produce opioids without addiction potential. These alternative drugs are very expensive to produce, and Dr. Smolke’s process could provide safer, less addictive compounds to people in need.

Breaking the Barrier

Among the challenges faced by bioengineers working on therapies for brain disease is the blood-brain barrier (BBB), a tightly regulated boundary between the circulatory system and the brain that prevents all but the tiniest molecules from getting into the brain. The poor permeability of the BBB to many molecules means that one needs to use higher drug dosages to reach the brain, which is one of the reasons why most psychiatric medications have a broad array of side effects.
One way of circumventing this issue is to deliver the drugs directly to the brain, rather than using oral or intravenous delivery methods that need to cross the BB. Here, the challenge is one of size — unless a needle used to administer such a drug is very small, it will invariably damage brain tissue, which can have devastating consequences. Answering this call has been Robert Langer, Ph.D., David H. Koch Institute Professor at MIT, whose lab has successfully microfabricated delivery cannulas as small as 30 microns, about one-third the diameter of human hair. As they report in Science Translational Medicine, the new cannula can target brain areas as small as 1 cubic millimeter.
Dr. Langer and his colleagues used the new cannula to create an implantable device, called the miniaturized neural drug delivery system (MiNDS), that they subsequently tested in rats and rhesus monkeys. They found that the device could modulate neuronal activity in both animals. In addition, MiNDS could also record and transmit information from the treatment site to enable feedback control. Going forward, the study authors envision the use of non-metallic materials to fashion cannulas and hydrogel coatings to facilitate MR imaging and increase biocompatibility.

Unlocking the Mystery of IPF

Idiopathic pulmonary fibrosis (IPF) is a lung disease that causes permanent scarring of the lung tissue. The disease affects around five million people worldwide, mainly people 50 or older, and the five-year mortality rate is very high. Although risk factors, such as cigarette smoking, have been identified, as the word “idiopathic” implies, the cause is unknown, making it difficult to create effective therapies other than ones that merely slow the progression of the disease.
However, thanks to a new discovery, we might be closer to effective treatments. In an article in the Journal of Clinical Investigation Insight, a team of scientists from Yale University report that the tissue lesions that constitute IPF are made up of roughly one-fifth pericytes — a type of contractile cell that plays an important role in the proper function of capillaries, including those in the lungs.
The study authors, led by Anjelica Gonzalez, Ph.D., Donna L. Dubinsky Associate Professor of Biomedical Engineering at Yale, found that IPF caused  pericytes to take on the properties of myofibroblasts, a cell type that is important to the wound-healing process. They found further that treatment of these myofibroblast-like pericytes with nintedanib, a drug approved for IPF treatment, reversed this effect. Armed with this knowledge, we come a step closer to designing and producing more effective therapies for IPF, as well as for diseases with similar effects.

People and Places

Washington University in St. Louis has announced it will launch a Ph.D. program in imaging science, to enroll its first cohort this fall. The program will be headed by Mark Anastasio, Ph.D., Professor of Biomedical Engineering and a 1993 recipient of an MSE from Penn.  WashU’s program is only the second such program in the country, following the program at the Rochester Institute of Technology.
Closer to home, Johns Hopkins is the recipient of a $50 million donation from the United Arab Emirates. The money will be used to create the Sheikh Khalifa Stroke Institute, which will unite faculty members from biomedical engineering, neurology, and rehabilitation medicine to advance research into stroke.
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Week in BioE (February 2, 2018)

Broccoli + Yogurt = Cancer Prevention?

broccoliGeorge H.W. Bush refused to eat it, but maybe he should start. It turns out that broccoli, combined with bioengineered yogurt, could provide effect cancer prevention. We’ve known for some time that compounds in certain fresh vegetables can increase chemoprevention, but the levels are usually too low to be effective, or they can’t be assimilated optimally by the body.  However, scientists in Singapore found that engineered bacteria, when ingested by mice with colorectal cancer, had anticancer effects. The bacteria caused the secretion of an enzyme by the cancer cells that transformed glucosinolates — compounds found in vegetables — into molecules with anticancer efficacy. The scientists report their findings in Nature Biomedical Engineering.

The authors programmed an E. coli cell line to bind to heparan sulfate proteoglycan, a cell surface protein that occurs in colorectal cancer cells. Once the engineered bacteria bound to the cancer cells, the bacteria secreted myrosinase, an enzyme that commonly occurs in many plants to defend them against aphids. In the cell model employed by the authors, myrosinase caused the conversion of glucosinolates into sulforaphane, which in turn could inhibit cancer cell growth.

The scientists then applied their system in a mouse model of colorectal cancer, feeding the mice yogurt infused with the engineered bacteria. They found that the mice fed broccoli plus the yogurt developed fewer and smaller tumors than mice fed broccoli alone. Additional testing is necessary, of course, but the study authors believe that their engineered bacteria could be used both as a preventive tool in high-risk patients and as a supplement for cancer patients after surgery to remove their tumors.

The Gates of CRISPR

About two years ago, software giant Microsoft unveiled Azimuth, a gene-editing tool for CRISPR/Casa9 that it had developed in collaboration with scientists at the Broad Institute. Now, in response to concerns that CRIPR may edit more of the genome than a bioengineer wants, the team has introduced a tool called Elevation. A new article in Nature Biomedical Engineering discusses the new tool.

In the article, the team, co-led by John C. Doench, Ph.D., Institute Scientist at the Broad Institute, describes how it developed Azimuth and Elevation, both of which are machine learning models, and deployed the tools to compare their ability to predict off-target editing with the ability of other approaches. The Elevation model outperformed the other methods. In addition, the team has implemented a cloud-based service for end-to-end RNA design, which should alleviate some of the time and resource handicaps that scientists face in using CRISPR.

Reducing Infant Mortality With an App

Among the challenges still faced in the developing world with regard to health care is high infant mortality, with the most common cause being perinatal asphyxia, or lack of oxygen reaching the infant during delivery. In response, Nigerian graduate student Charles C. Onu, a Master’s student in the computer science lab of Doina Precup, Ph.D., at McGill University in Montreal, founded a company called Ubenwa, an Igbo word that means “baby’s cry.”

With Ubenwa and scientists from McGill, Onu developed a smartphone app and a wearable that apply machine learning to instantly diagnose birth asphyxia based on the sound of a baby’s cry. In initial testing, the device performed well, with sensitivity of more than 86% and specificity of more than 89%. You can read more about the development and testing of Ubenwa at Arxiv.

People and Places

Several universities have announced that they are introducing new centers for research in bioengineering. Purdue University secured $27 million in funding from Semiconductor Research Corp. for its Center for Brain-inspired Computing Enabling Autonomous Intelligence, or C-BRIC, which opened last month. The center will develop, among other technologies, robotics that can operate without human intervention.

In Atlanta, Emory University received a $400 million pledge from the Robert W. Woodruff Foundation for two new centers — the Winship Cancer Institute Tower and a new Health Sciences Research Building. The latter will host five research teams, including one specializing in biomedical engineering. Further north in Richmond, Virginia Commonwealth University announced that it will begin construction on a new $92 million Engineering Research Building in the fall.  The uppermost floors of the new building will include labs for the college’s Department of Biomedical Engineering.

Finally, North Carolina’s Elon College will introduce a bachelor’s degree program in engineering in the fall. The program will offer concentrations in biomedical engineering and computer engineering. Sirena Hargrove-Leak, Ph.D., is director of the program.

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Week in BioE (January 24, 2018)

Using AI to Better Understand Cancer Immunology

ImmunoMap
A T cell with receptors highlighted in red

T lymphocytes in the immune system play a vital role in the body to recognize invasion by an outside element. When foreign bacteria enter the body, receptors on the T cell surface detect antigens associated with the bacteria and send a signal deploying phagocytes to attack and defeat the invading bacteria. While evolution and vaccination make the immune system very efficient, the inability of T cell receptors (TCRs) to detect cancer makes normal T cells relatively ineffective in resisting cancer. One of the ways to overcome this limitation of the immune system is to better understand how the TCRs respond to antigens. Analyses of the proteins involved in TSR responses are useful but limited by several factors, including the dizzying amount of data involved. Data analysis techniques have been helpful but have offered little information about the general reactions of TSRs, rather than how they react to specific antigens.  

A possible solution to this obstacle is ImmunoMap, developed by scientists collaborating between Johns Hopkins University and Memorial Sloan Kettering Cancer Center. In a study recently published in Cancer Immunology Research, the authors, led by Jonathan P. Schneck, M.D., Ph.D., a professor of pathology at Johns Hopkins associated with the university’s Institute for Cell Engineering and Institute for Nanobiotechnology, describe their creation and deployment of ImmunoMap, a group of artificial intelligence algorithms that use machine learning to process large amounts of sequencing data and compare data from different antigens with each other.

The authors trained ImmunoMap initially using data from a mouse model of melanoma, in which the algorithm demonstrated significantly better performance than traditional methods. Subsequently, ImmunoMap was applied to patient response data from a melanoma clinical trial of the chemotherapy agent nivolumab. The algorithm discovered a new group of patients that would respond positively to nivolumab treatment — a finding missed by popular past methods. More testing of ImmunoMap is necessary, but the technology could make significant contributions to the monitoring of cancer patients receiving chemotherapy. In addition, it could to help to better predict response in patients before they begin specific chemotherapy regimes.

Wearables Improving Health

Among the most troubling health disparities related to global wealth inequality is the higher rate of mortality among children suffering from cancer. Fever is a common symptom of children undergoing cancer treatment, and this symptom may indicate more serious health issues that require the attention of a doctor. However, continuously monitoring skin temperature in children from low resource settings is difficult. Seeking to help remedy this problem, undergraduate engineering students at Harvard collaborated with the Dana-Farber/Boston Children’s Cancer & Blood Disorders Center’s Global Health Initiative to develop tools for earlier fever detection and treatment.

In a course taught by David Mooney, Ph.D., Robert P. Pinkas Family Professor of Bioengineering at Harvard, students developed a wearable device that sounds an alarm when the wearer needs medical help. The app can send patients’ recorded messages to their doctors, who can then review the temperature data and messages from the children before responding. Fashioned like a wristwatch, the extra-durable and waterproof device will next move into pilot testing among a larger patient population.

Meanwhile, at Northwestern, John A. Rogers, Ph.D., the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering, and Neurological Surgery in Northwestern’s McCormick School of Engineering, has partnered with cosmetics giant L’Oréal to create the world’s smallest wearable. The device, which is smaller than an adult fingernail, measures UV sun exposure for the wearer and can tell when they should go back inside instead of risking overexposure. Unsurprisingly, it’s solar powered, and it was demonstrated a couple of weeks ago at a consumer electronics show in Las Vegas.

 

Growing Hydrogels Like Human Tissue

Scientists at Carnegie Mellon University and Nanyang Technological University in Singapore have collaborated in a process to create polyacrylamide gels that grow in a manner resembling natural tissue. K. Jimmy Hsia, Ph.D., Professor of Biomedical Engineering at Carnegie Mellon, is co-lead author of a new study in PNAS describing this new growth mode.

In the study, Dr. Hsia and his coauthors report that, in the same way that growth factors secreted by a living organism affect the generation of new tissue, oxygen can be modulated to control how hydrogels grow. Moreover, while growth is under way, the process could be continued to efficiently manage the mass transfer of nutrients from cell to cell. Finally, the authors detail the mechanical processes that help to shape the final product. With this new process, the ability to design and create materials for applications such as robotics and tissue engineering comes a step closer to resembling living tissue as closely as possible.

People and Places

Engineers at Virginia Tech have been awarded a $1.1 million grant from the Virginia Research Investment Committee to develop a device that uses low-energy electric fields for the treatment of brain tumors. Rafael Davalos, Ph.D., L. Preston Wade Professor of Biomedical Engineering and Mechanics, is the chief investigator on the grant.

The Department of Biomedical Engineering has announced the appointment of Kam W. Leong, Ph.D., as the Samuel Y. Sheng Professor of Biomedical Engineering. Dr. Leong earned his Ph.D. in chemical engineering from the University of Pennsylvania and taught at Duke and Johns Hopkins before arriving at Columbia in 2006. He was previously the James B. Duke Professor of Biomedical Engineering at Duke. Congratulations to Dr. Leong!