Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Biomedical Engineering Page 1 of 5

First-Year Students Designing Real-World Solutions

In the first week of fall semester, four first-year engineering students, Sean Burrell, Teya Evans, Adam Kramer, and Eloise Sinwell, had a brainstorming session to determine how to create a set of physical therapy stairs designed for children with disabilities. Their goal was to construct something that provided motivation through reward, had variable step height, and could physically support the students. 

Evans explained, “The one they were using before did not have handrails and the kids were feeling really unstable.”

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Teya Evans is pictured stepping on the staircase her team designed and built. With each step, the lightbox displays different colors.

The team was extremely successful and the staircase they designed met all of the goals set out by their client, physical therapists. It provided motivation through the multi-colored lightbox, included an additional smaller step that could be pulled out to adjust step height, had a handrail to physically support the students and could even be taken apart for easy transportation.

This is a part of the Engineering 101 course all Pratt students are required to take. Teams are paired with a real client and work together throughout the semester to design and create a deliverable solution to the problem they are presented with. At the end of the semester, they present their products at a poster presentation that I attended. It was pretty incredible to see what first-year undergraduates were able to create in just a few months.

The next poster I visited focused on designing a device to stabilize hand tremors. The team’s client, Kate, has Ataxia, a neurological disorder that causes her to have uncontrollable tremors in her arms and hands. She wanted a device that would enable her to use her iPad independently, because she currently needs a caregiver to stabilize her arm to use it. This team, Mohanapriya Cumaran, Richard Sheng, Jolie Mason, and Tess Foote, needed to design something that would allow Kate to access the entire screen while stabilizing tremors, being comfortable, easy to set up and durable.

The team was able to accomplish its task by developing a device that allowed Kate to stabilize her tremors by gripping a 3D printed handlebar. The handlebar was then attached to two rods that rested on springs allowing for vertical motion and a drawer slide allowing for horizontal motion.

“We had her [Kate] touch apps in all areas of the iPad and she could do it.” Foote said. “Future plans are to make it comfier.”

The team plans to improve the product by adding a foam grip to the handlebar, attaching a ball and socket joint for index finger support, and adding a waterproof layer to the wooden pieces in their design. 

The last project I visited created a “Fly Flipping Device.” The team, C. Fischer, E. Song, L. Tarman, and S. Gorbaly, were paired with the Mohamed Noor Lab in the Duke Biology Department as their client. 

Tarman explained, “We were asked to design a device that would expedite the process of transferring fruit flies from one vial to another.”

The Noor lab frequently uses fruit flies to study genetics and currently fly flipping has to be done by hand, which can take a lot of time. The goal was to increase the efficiency of lab experiments by creating a device that would last for more than a year, avoid damaging the vials or flies, was portable and fit within a desk space. 

The team came up with over 50 ideas on how to accomplish this task that they narrowed down to one that they would build. The product they created comprised of two arms made of PVC pipe resting on a wooden base. Attached to the arms were “sleeves” 3D printed to hold the vials containing flies. In order to efficiently flip the flies, one of the arms moves about the axis allowing for multiple vials to be flipped that the time it would normally take to flip one vial. The team was very successful and their creation will contribute to important genetic research.

The Fly Flipping Device

It was mind-blowing to see what first-year students were able to create in their first few months at Duke and I think it is a great concept to begin student education in engineering through a hands-on design process that allows them to develop a solution to a problem and take it from idea to implementation. I am excited about what else other EGR 101 students will design in the future.

By Anna Gotskind


Inventing New Ways to Do Brain Surgery

This is the sixth and final 2019 post written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Patrick Codd is the Director of the Duke Brain Tool Laboratory and an Assistant Professor of Neurosurgery at Duke. Working as a neurosurgeon and helping with the research and development of various neurosurgical devices is “a delicate balance,” he said.

Patrick Codd

Codd currently runs a minimally invasive neurosurgery group. However, at Massachusetts General Hospital, he used to run the trauma section. When asked about which role was more stressful, he stated “they were both pretty stressful” but for different reasons. At Mass General, he was on call for most hours of the day and had to pull long shifts in the operating room. At Duke, he has to juggle surgery, teaching, and research and the development of new technology.

“I didn’t know I was going to be a neurosurgeon until I was in college,” Codd said. Despite all of the interesting specialties he learned about in medical school, he said “it was always neurosurgery that brought me back.”

Currently, he is exclusively conducting cranial surgery.

 Neurosurgeon U.S. Air Force Maj Jonathan Forbes,looks through loupes as he performs brain surgery at the Bagram Air Field in Afghanistan, Oct. 10, 2014. 

Though Dr. Codd has earned many leadership positions in his career, he said he was never focused on advancement. He simply enjoys working on topics which he loves, such as improving minimally invasive surgical techniques. But being in leadership lets him unite other people who are interested in working towards a common goal in research and development. He has been able to skillfully bring people together from various specialties and help guide them. However, it is difficult to meet everyone’s needs all of the time. What is important for him is to be a leader when he needs to be.

Dr. Codd said there are typically five to eight research papers necessary in to lay the groundwork for every device that is developed. However, some technologies are based on the development of a single paper. He has worked on devices that make surgery more efficient and less minimally invasive and those that help the surgical team work together better. When developing technologies, he tries to keep the original purpose of the devices the same. However, many revisions are made to the initial design plans as requirements from the FDA and other institutions must be met. Ironically, Dr. Codd can’t use the devices he develops in his own operating room because it would be a conflict of interest. Typically other neurosurgeons from across the country will use them instead.

Post by Andrew Bahhouth, NCSSM 2020

Designing Tomorrow, One Healthcare Innovation at a Time

Imagine a live, health-focused version Shark Tank open to the public: presentations from real health professionals, presenting real innovations they developed to address real health care issues. And yes, there are real money awards at stake.

It’s the 2019 Duke Health Innovation Jam.

At ten minutes ‘til show time, people gather in small groups clothed in suits, business attire, and white coats. They chat in low voices. The hum of comfortable conversation buzzes through the room. The sixth floor of the Trent Semans Center is quite the setting. Three sides of the room are encapsulated in glass and you can easily see an expansive view of both Duke’s West and Medical campuses, as well as luscious green trees comprising parts of Duke’s Forest. Naturally, there is a glorious view of the Chapel, basked in sunlight.

This light finds its way into the room to shine on various research posters at the back displayed on a few rows of mobile walls. Though a few strays meander through the stationary arrangements – stopping to look more closely at particular findings – most people make their way into the room and find a seat as the minutes dwindle away. The hum grows and there is a bit of anticipatory energy among those readying themselves to present.

At three minutes after 10, the program director of the Duke Institute for Health Innovation, Suresh Balu, takes position at the front of the room, standing before the small stage at center that is surrounded by lots of TV monitors. No seat in the room is a bad one. Balu indicates that it is time to begin and the hum immediately dissipates. He explains the general format of the event: six pitches total, five minutes to present, eight minutes to answer questions from investors, a show-of-hand interest from investors, and transition to the next pitch, followed by deliberation and presentation of awards.

After a round of thanks, introduction of the emcee – Duke’s Chief of Cardiology, Dr. Manesh Patel – the curtains opened – figuratively – on Duke’s fifth annual Innovation Jam.

Groups presented on the problems they were addressing, their proposed innovations, and how the innovations worked. There was also information about getting products into the market, varying economic analysis, next steps or detailed goals for the projection of the projects, and analysis of the investment they are currently seeking and for what purposes.

The first group pitched an idea about patient-centric blood draw and suggest a device to plug into existing peripheral draws to reduce the frequent poking and prodding that hospital patients often experience during their hospital stay when blood is needed for lab tests. Next up was a group who designed an intelligent microscope for automated pathology that has a programmable system and uses machine learning to automate pathological blood analysis that is currently highly time consuming. Third at bat was a group that made a UV light bag to clean surgical drain bags that frequently become colonized with bacteria and are quite frankly “nasty” – according to the presenter.

Batting cleanup was PILVAS – Peripherally Inserted Left Ventricular Vent Anticoagulation System – which is a device that would be accessory to VA ECMO support to reduce thromboembolism and stroke that are risks of ECMO. Fifth was the ReadyView and ReadyLift, a laparoscopic tool set that is much cheaper than current laparoscopic tools and methods, and because of its ability to be used with any USB compatible laptop, it would increase access to laparoscopic surgery in countries that have a high need for it. Last, but not least, was an innovation that is the first synthetic biometric osteochondral graft for knee cartilage repair that hopes to improve knee osteoarthritis surgical care as the first hydrogel with the same mechanical properties of cartilage.

Following a quick ten-minute break for investors to huddle around and discuss who should win the awards – $15,000 for Best Innovation and $15,000 for Best Presentation – the winners were announced. Drumroll, please.

ReadyView won Best Presentation and the synthetic osteochondral graft won Best Innovation. A pair of representatives from Microsoft were also in attendance – a first for the Innovation Jam – and awarded SalineAI, the group who designed the intelligent microscope with an independent award package.

Patel, the emcee, says we are in the midst of a fourth industrial revolution.

“What is the biggest cinema in the world?” Patel asked. “Netflix,” he says. Industries are reimagining themselves and healthcare is no exception.

What is the best healthcare system of the future going to look like? Of course, we really don’t know, but there are certainly people who are already doing more than just think about it.

Zapping Your Brain Is Dope

Emerging technology has created a new doping technique for athletic performance that is, as of now, perfectly legal.

Coined “neuro-doping,” this method sends electric current through one’s brain to facilitate quicker learning, enhanced muscular strength, and improved coordination. Use of this electronic stimulus has taken off in the sports world as a replacement for other doping methods banned by the World Anti-Doping Agency (WADA). Because it’s relatively new, WADA has yet to establish rules around neuro-doping. Plus, it’s virtually undetectable. Naturally, a lot of athletes are taking advantage of it.

Image result for doping

One specific method of neuro-doping is known as Transcranial Direct-Current Stimulation (tDCS). It works by sending a non-invasive and painless electrical current through the brain for around three to 20 minutes, in order to excite the brain’s cortex, ultimately increasing neuroplasticity (Park). This can be done commercially via a headset like device for $200.

Image result for transcranial direct current stimulation headset
The Halo Sport

Weight lifters, sprinters, pitchers, and skiers are just some of many types of athletes who can benefit from tCDS. By practicing with these headphones on, new neural pathways are constructed to help their bodies achieve peak performance. Dr. Greg Appelbaum, director of Opti Lab and the Brain Stimulation Research Center, says it’s especially useful for athletes where technique and motor skills triumph — such as a sprinter getting out of the blocks or an Olympic ski jumper hanging in the air. Top-tier athletes are pushing that fine limit of what the human body can accomplish, but neuro-doping allows them to take it one step further.

Neuro-doping has other applications, too. Imagine insanely skilled Air Force pilots, surgeons with exceptionally nimble hands, or soldiers with perfect aim. tCDS is being used to make progress in things like Alzheimer’s and memory function because of its impact on cognitive functioning in the forms of increased attention span and memory. You could even learn the guitar faster.

In this sort of context, it’s a no brainer that neuro-doping should be taken advantage of. But how ethical is it in sports?

The precedent for WADA to ban a substance or technique has been based on meeting two of the following three criteria: (1) drugs or tools that likely enhance performance to secure a winning edge; (2) drugs or tools that place athletes’ health at risk; (3) any substances or techniques that ruin the “spirit-of-sport” (Park). Lots of research has shown tCDS is pretty legit. As for health risks, tCDS is still in the experimental stage, so not much can be said about its side effects. Ethically, it causes a lot of controversy.

Many issues come into play when thinking about allowing athletes to neuro-dope. Given its similarities with other popular drugs, tCDS could introduce unfair advantages. Furthermore, not everyone may have access to the technology, and not everyone may want to use it. However, it’s important to note that sports already have unfair advantages. Access to things like proper coaching and nutrition may not be a reality for everyone. Sports are just inherently competitive.

Back when baseball players doped, it was awesome to watch them crush balls out of the park. Reintroducing performance enhancement through tCDS could mean we start seeing mountain bikers launching insane air and world records being smattered. The human body could achieve newfound heights.

Are the benefits worth it? Does neuro-doping ruin the “spirit of the sport?” Regardless of these important questions, tCDS is a fascinating scientific discovery that could make a difference in this world. So, what do you think?

Will Sheehan
Post by Will Sheehan

Park, Cogent Social Sciences (2017), 3: 1360462
https://doi.org/10.1080/23311886.2017.1360462

Gene-Editing Human Embryos: What, How, Why?

Every seat full. Students perched on the aisle stairs and lining the back walls.

What topic could possibly pull so many away from their final exams? Not “How to Stop Procrastinating” nor “How to Pass Life After Failing Your Exams” but rather “Gene-Editing Human Embryos: Unpacking the Current Controversy” on the Duke campus.

Since Chinese researcher He Jiankui announced at the Second International Summit on Human Genome Editing in Hong Kong that he made the world’s first genetically engineered babies, a debate on the ethical implications has raged on social media.

On December 6, the University Program in Genetics and Genomics and the Molecular Genetics and Microbiology department co-hosted a panel responding to He’s claims. Charles A. Gersbach from the Biomedical Engineering department lead the discussion of what exactly happened and then joined the panel which also contained Misha Angrist, a senior fellow in the Science & Society initiative;  Heidi Cope, a genetic counselor; Giny Fouda, an assistant professor in pediatrics; and Vandana Shashi, a genetic counselor.

Dr. He Jiankui announced he had used CRISPR to edit genes in twin embryos that were then born at full term.

But what exactly has He potentially done to these twin girls? Can they fly? Breathe underwater? Photosynthesize? Not exactly. He said he deleted a gene called CCR5 to increase their HIV resistance. Two percent of Northern Europeans naturally have a mutation that removes the CCR5 gene from their DNA and as a result do not display any traits other than increased HIV resistance.

Many researchers have explored blocking CCR5 activity as a potential HIV treatment. Using CRISPR-Cas9, a genetic engineering technology that can cut and paste specific sequences in the DNA, He targeted CCR5 during in vitro fertilization. According to his tests, he successfully removed both copies of the CCR5 gene in one of the girls. However, in the other girl, the CCR5 remained normal on one chromosome and on the other, CRISPR had deleted more than intended.  The effects of that additional deletion are unknown. 
Both the girls are mosaics, meaning the genetic change occurred in some of their cells and not in others, leading to still more uncertainties.

Researchers have conducted genetic engineering experiments on both somatic cells and human embryo cells that were never brought to term. (Somatic cells constitute all parts of the body other than the eggs and sperm.) But because He altered the twin girls as embryos and then they grew to full term, their children could inherit these changes. This alters their family line, not just a single individual, increasing the ethical implications.

According to Shashi, He’s experiment becomes difficult to justify. Additionally, embryos have not consented to these changes in their genetics, unlike a patient undergoing genetic therapy.

Many doctors, scientists, and journalists have also questioned He’s lack of transparency because he hid this work until his grand announcement, which caused China to arrest him. In addition, as Cope explained, “it is not typically the PI who does the informed consent process” as He did with these parents.

While He defends his work by saying that the girls’ father carries HIV and wished to increase the girls’ safety, the twins were not actually at great risk for HIV. Their father’s medical history does not increase their chances of contracting the virus, and the overall risk for HIV in China is low. As Fouda emphasized in the panel, “there was no justification for this experiment.” While He discussed the potential for genetic engineering to help society, for these two individuals, no medical need existed, and that increases the ethical dilemma.

A final concern of researchers is the current inability to ensure technical competency and accuracy. As seen by the additional deletion in one of the girls,  CRISPR-Cas9 still makes errors. Thus using it to alter not only a human being but all of that individual’s progeny would demand a much higher standard, something close to a life-or-death scenario.

But, the panelists also noted, if it hadn’t been He, it would have been somebody else. Perhaps somebody else may have done it more ethically with more transparency and a more traditional consent process, Angrist said.

While He’s claims have yet to be proven, the fact that they could reasonably be true has many concerned. The World Health Organization has announced that they will begin greater oversight of genetic engineering of the human germline.

On campus over the last weeks, I’ve heard mixed reviews on He’s work with some joking about future superhero babies while others have reacted with fear. The technology does live among us; however, the world is working on writing the guidebook and unrolling the yellow tape.

Post by Lydia Goff

Drug Homing Method Helps Rethink Parkinson’s

The brain is the body’s most complex organ, and consequently the least understood. In fact, researchers like Michael Tadross, MD, PhD, wonder if the current research methods employed by neuroscientists are telling us as much as we think.

Michael Tadross is using novel approaches to tease out the causes of neuropsychiatric diseases at a cellular level.

Current methods such as gene editing and pharmacology can reveal how certain genes and drugs affect the cells in a given area of the brain, but they’re limited in that they don’t account for differences among different cell types. With his research, Tadross has tried to target specific cell types to better understand mechanisms that cause neuropsychiatric disorders.

To do this, Tadross developed a method to ensure a drug injected into a region of the brain will only affect specific cell types. Tadross genetically engineered the cell type of interest so that a special receptor protein, called HaloTag, is expressed at the cell membrane. Additionally, the drug of interest is altered so that it is tethered to the molecule that binds with the HaloTag receptor. By connecting the drug to the Halo-Tag ligand, and engineering only the cell type of interest to express the specific Halo-Tag receptor, Tadross effectively limited the cells affected by the drug to just one type. He calls this method “Drugs Acutely Restricted by Tethering,” or DART.

Tadross has been using the DART method to better understand the mechanisms underlying Parkinson’s disease. Parkinson’s is a neurological disease that affects a region of the brain called the striatum, causing tremors, slow movement, and rigid muscles, among other motor deficits.

Only cells expressing the HaloTag receptor can bind to the AMPA-repressing drug, ensuring virtually perfect cell-type specificity.

Patients with Parkinson’s show decreased levels of the neurotransmitter dopamine in the striatum. Consequently, treatments that involve restoring dopamine levels improve symptoms. For these reasons, Parkinson’s has long been regarded as a disease caused by a deficit in dopamine.

With his technique, Tadross is challenging this assumption. In addition to death of dopaminergic neurons, Parkinson’s is associated with an increase of the strength of synapses, or connections, between neurons that express AMPA receptors, which are the most common excitatory receptors in the brain.

In order to simulate the effects of Parkinson’s, Tadross and his team induced the death of dopaminergic neurons in the striatum of mice. As expected, the mice displayed significant motor impairments consistent with Parkinson’s. However, in addition to inducing the death of these neurons, Tadross engineered the AMPA-expressing cells to produce the Halo-Tag protein.

Tadross then treated the mice striatum with a common AMPA receptor blocker tethered to the Halo-Tag ligand. Amazingly, blocking the activity of these AMPA-expressing neurons, even in the absence of the dopaminergic neurons, reversed the effects of Parkinson’s so that the previously affected mice moved normally.

Tadross’s findings with the Parkinson’s mice exemplifies how little we know about cause and effect in the brain. The key to designing effective treatments for neuropsychiatric diseases, and possibly other diseases outside the nervous system, may be in teasing out the relationship of specific types of cells to symptoms and targeting the disease that way.

The ingenious work of researchers like Tadross will undoubtedly help bring us closer to understanding how the brain truly works.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

 

MRI Tags Stick to Molecules with Chemical “Velcro®”

An extremely close-up view of Velcro

In the new technique, MRI chemical tags attach to a target molecule and nothing else – kind of like how Velcro only sticks to itself. Credit: tanakawho, via Flickr.

Imagine attaching a beacon to a drug molecule and following its journey through our winding innards, tracking just where and how it interacts with the chemicals in our bodies to help treat illnesses.

Duke scientists may be closer to doing just that. They have developed a chemical tag that can be attached to molecules to make them light up under magnetic resonance imaging (MRI).

This tag or “lightbulb” changes its frequency when the molecule interacts with another molecule, potentially allowing researchers to both locate the molecule in the body and see how it is metabolized.

“MRI methods are very sensitive to small changes in the chemical structure, so you can actually use these tags to directly image chemical transformations,” said Thomas Theis, an assistant research professor in the chemistry department at Duke.

Chemical tags that light up under MRI are not new. In 2016, the Duke team of Warren S. Warren’s lab and Qiu Wang’s lab created molecular lightbulbs for MRI that burn brighter and longer than any previously discovered.

A photo of graduate students Junu Bae and Zijian Zhou in front of a bookshelf.

Junu Bae and Zijian Zhou, the co-first authors of the paper. Credit: Qiu Wang, Duke University.

In a study published March 9 in Science Advances, the researchers report a new method for attaching tags to molecules, allowing them to tag molecules indirectly to a broader scope of molecules than they could before.

“The tags are like lightbulbs covered in Velcro,” said Junu Bae, a graduate student in Qiu Wang’s lab at Duke. “We attach the other side of the Velcro to the target molecule, and once they find each other they stick.”

This reaction is what researchers call bioorthogonal, which means that the tag will only stick to the molecular target and won’t react with any other molecules.

And the reaction was designed with another important feature in mind — it generates a rare form of nitrogen gas that also lights up under MRI.

“One could dream up a lot of potential applications for the nitrogen gas, but one that we have been thinking about is lung imaging,” Theis said.

Currently the best way to image the lungs is with xenon gas, but this method has the downside of putting patients to sleep. “Nitrogen gas would be perfectly safe to inhale because it is what you inhale in the air anyways,” Theis said.

A stylized chemical diagram of the hyperpolarization process

In the new technique, a type of molecule called a tetrazine is hyperpolarized, making it “light up” under MRI (illustrated on the left). It is then tagged to a target molecule through a what is called a bioorthogonal reaction. The reaction also generates a rare form of nitrogen gas that can be spotted under MRI (illustrated on the right). Credit: Junu Bae and Seoyoung Cho, Duke University.

Other applications could include watching how air flows through porous materials or studying the nitrogen fixation process in plants.

One downside to the new tags is that they don’t shine as long or as brightly as other MRI molecular lightbulbs, said Zijian Zhou, a graduate student in  Warren’s lab at Duke.

The team is tinkering with the formula for polarizing, or lighting up, the molecule tags to increase their lifetime and brilliance, and to make them more compatible with chemical conditions in the human body.

“We are now developing new techniques and new procedures which may be helpful for driving the polarization levels even higher, so we can have even better signal for these applications,” Zhou said.

15N4-1,2,4,5-tetrazines as potential molecular tags: Integrating bioorthogonal chemistry with hyperpolarization and unearthing para-N2,” Junu Bae, Zijian Zhou, Thomas Theis, Warren S. Warren and Qiu Wang. Science Advances, March 9, 2018. DOI: 10.1126/sciadv.aar2978

Post by Kara Manke

Growing “Mini Brains” To Understand Zika’s Effects

You probably remember what the Zika virus is because of the outbreak in 2015 that made global headlines.

microcephaly illustration

An infant with microcephaly (left) with a reduced head circumference, as compared to an infant born with a regular head circumference (right) Picture credit: https://commons.wikimedia.org/w/index.php?curid=63278345

The serious nature of the virus was apparent when hundreds of infants across South America were born with microcephaly – a condition characterized by a very small head circumference as a result of abnormally slow brain growth.

The sudden outbreak of Zika in South America led to a panic of the possibility of spread into the United States as well as beyond – and thus, research into learning more about the disease mechanisms of Zika expanded. However, one of the problems in studying a disease like Zika is the difficulty of modeling a complex organ like the developing brain.

Until now, the current way to model the brain was with a brain organoid – a brain grown in a lab. Organoid structures attempt to mimic whole developing organs – however, current brain organoid technology required the use of a large spinning bioreactor to facilitate nutrient and oxygen absorption to mimic the function of the vascular system in our brains. Large spinning bioreactors are expensive to run and bulky—they require large volumes of expensive media that mimic brain fluid. The size and cost has meant that only a few organoids can be grown and studied at once.

Guo-li Ming, University of Pennsylvania

Dr. Guo-li Ming, a professor of neuroscience from the Perelman School of Medicine at the University of Pennsylvania, set out to work on finding a way to solve this problem. She came down to Duke University last week to give a talk on her findings.  As she spoke, I could feel the minds of the audience firmly captivated by her words. It was truly fascinating stuff – Ming was actually growing brains in the lab!

The work began by finding a way to take the large spinning reactor that the existing brain organoid required and make it smaller. Three clever high school students working in her lab used a 3D printer and a small motor that involved spinning 12 tiny interconnected paddles within 12 small cell culture wells. Each of the wells contain a paddle that is spun by one gear.  All of the individual gears connect to a continually rotating central gear driven by a motor.

Bioreactor schematic

The Spin bioreactor. Source: http://www.cell.com/cell/abstract/S0092-8674(16)30467-6

After many optimizations, the final design was called SpinW,  which ultimately required a mere 2 ml of media per well, resulting in a net 50-fold reduction in media consumption, as well as dramatically reduced incubator space. The large number of wells, combined with dramatically reduced cost of the apparatus and media consumption, allowed for optimal conditions to run multiple test scenarios with ease – essentially meaning that 12 “mini brains” could be tested at the same time.

The design of SpinW costed a mere $400, while the commercial design costs over $2,000, with the added burden of consuming 50 times more media. The success of the design only serves to prove that age doesn’t matter when it comes to great ideas!

A brain organoid infected with Zika virus. ZIKV envelope protein is shown in green; neural progenitor cells marked by SOX2 are shown in red; neurons marked by CTIP2 are shown in blue.
CREDIT: Xuyu Qian/Johns Hopkins University

Dr. Ming and her team used the apparatus to model the Zika virus’s impact on the brain.

The findings indicate that Zika works by killing off neural stem cells, as well as causing a thinning of key brain structures. One of the observations was that, by day 18 of Zika infection of a brain organoid, there was an overall decrease in size, which points to the link of Zika causing microcephaly. The Zika infection of early-stage organoids corresponded to the first trimester of human fetal development.

The brain is the most complex organ in the body, and one of the least understood. The work Dr. Ming and her team has done goes a long way towards helping us understand the way the human brain develops and works, as well modeling its reaction to things like viruses. It was a pleasure and honor to hear Dr. Ming talk to us about her work –I am eager to hear about further developments in this field!

Post by Thabit Pulak

Anita Layton: A Model of STEM Versatility

Using mathematics to model the kidney and its biological systems is a field of study located at the intersection of two disciplines.

Anita Layton is a math professor at Duke. (Photo by Chris Hildreth, Duke Photography)

But for Duke’s Anita Layton, PhD, the Robert R. and Katherine B. Penn Professor of Mathematics and a professor of biomedical engineering, that just adds to the fun of it.

Growing up, with her father as the head of mathematics at her school, she was always told she was going to be a mathematician just like him. So she knew that was the last thing she wanted to do.

When Layton arrived as an undergraduate at Duke, she began a major in physics, but she seemed rather cursed when it came to getting correct results from her experiments. She settled for a BA in physics, but her academic journey was far from over. She had also taken a computer science course at Duke and fallen in love with it. If an experiment went wrong “things didn’t smell or blow up” and you could fix your mistake and move on, she said.

While pursuing her PhD in computer science at the University of Toronto, Layton was performing very math-oriented computer science, working with and analyzing numbers. However, it would be a while before biology entered the mix

While she was never good at dissections, she told me she was always good at understanding things that ‘flow’ and she came to the realization that blood is something that flows. She thought, “Hey, I can do that.

Anita Layton, Duke

Anita Layton, Ph.D.

Layton began creating programs that could solve the equations that model blood flow quickly, using her background in computer science. She then started learning about physiology, focusing on the renal system, and making models

It was a journey that took her to many different places, with pit stops and U-turns throughout many different fields. Had Layton stuck with just physics or computer science or math, she never would have ventured out and found this field that she is an expert in now.

It’s her interest in many different fields that has set Layton apart from many other people in the STEM field. In learning a wide variety of things, she has gotten better at computer science, mathematics, biology, physics, and more

When asked about what advice she would give her younger self, or any young person going into college, it would be to do just that: “Learn more things that you’re not good at.” She encouraged just taking a chemistry or biology class once in a while, or a philosophy course that makes you think in ways that you don’t normally. It’s often in those classes that you unearth things that can truly set your life in a completely different direction, Layton said, and she’s living proof of that.

Cecilia Poston, NCSSM

Cecilia Poston

Guest Post by Cecilia Poston, a senior at North Carolina School of Science and Math

Creative Solutions to Brain Tumor Treatment

Survival rates for brain tumors have not improved since the 1960s; NIH Image Gallery.

Invasive brain tumors are among the hardest cancers to treat, and thus have some of the worst prognoses.

Dean of the Pratt School of Engineering, Ravi Bellamkonda, poses for his portrait inside and outside CIEMAS.

Displaying the survival rates for various brain tumors to the Genomic and Precision Medicine Forum on Thursday, Oct. 26, Duke professor Ravi Bellamkonda noted, “These numbers have not changed in any appreciable way since the 1960s.”

Bellakonda is the dean of the Pratt School of Engineering and a professor of biomedical engineering, but he is first a researcher. His biomedical engineering lab is working toward solutions to this problem of brain tumor treatment.

Unlike many other organs, which can sacrifice some tissue and remain functional, the brain does not perform the same way after removing the tumor. So a tumor without clearly defined boundaries is unsafe to remove without great risk to other parts of the patient’s brain, and in turn the patient’s quality of life.

Bellakonda hypothesized that brain tumors have characteristics that could be manipulated to treat these cancers. One key observation of brain tumors’ behavior is the tendency to form along white matter tracts. Put simply, tumors often spread by taking advantage of the brain’s existing structural pathways.

Bellakonda set out to build a device that would provide brain tumors a different path to follow, with the hope of drawing the tumor out of the brain where the cells could be killed.

The results were promising. Tests on rats and dogs with brain tumors showed that the device successfully guided out and killed tumor cells. Closer examination revealed that the cells killed were not cells that had multiplied as the tumor grew into the conduit, but were actually cells from the primary tumor.

The Bellamkonda lab’s device successfully guided and killed brain tumors in rats.

In addition to acting as a treatment device, Bellakonda’s device could be co-opted for other uses. Monitoring the process of deep brain tumors proves a difficult task for neurooncologists, and by bringing cells from deep within the tumor to the surface, this device could make biopsies significantly easier.

Although the device presents promising results, Bellakonda challenged his lab to take what they have learned from the device to develop a less invasive technique.

Another researcher in the Bellakonda lab, Tarun Saxena, engaged in research to utilize the body’s natural protection mechanisms to contain brain tumors. Creating scar tissue around tumors can trick the brain into treating the tumor as a wound, leading to immunological responses that effectively contain and suppress the tumor’s growth.

Visiting researcher Johnathan Lyon proposed utilizing electrical fields to lead a tumor to move away from certain brain regions. Moving tumors away from structures like the pons, which is vital for regulation of vital functions like breathing, could make formerly untreatable tumors resectable. Lyon’s 3D cultures using this technique displayed promising results.

Another Bellakonda lab researcher, Nalini Mehta, has been researching utilizing a surprising mechanism to deliver drugs to treat tumors throughout the brain: salmonella. Salmonella genetically engineered to not invade cells but to easily pass through the extracellular matrix of the brain have proven to be effective at delivering treatment throughout the brain.

While all of these therapies are not quite ready to be used to treat the masses, Bellakonda and his colleagues’ work presents reasonable hope of progress in the way brain tumors are treated.

By Sarah Haurin

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