For instance, RNA-sequencing (RNA-seq) is an NGS technology that examines the presence and quantity of RNA in biological samples, and it requires bioinformatics analysis to make sense of it all. However, there are hundreds of bioinformatics tools with different data analysis pipelines that result in various results for the same dataset. This can significantly hinder the ability to reliably reproduce RNA-seq related research and applications, especially for the regulatory approval process by the U.S. Food and Drug Administration (FDA). 

Choosing the right analysis model and tool to do the proper job for high throughput data analysis remains a great challenge. So the FDA invited a team of researchers at the Georgia Institute of Technology to conduct a comprehensive investigation of RNA-seq data analysis pipelines for gene expression estimation to recommend best practices. 

“No common standard for selecting high throughput RNA-seq data analysis tools has been established yet. This has been a huge challenge for studying hundreds of tools that form tens of thousands of analysis pipelines,” noted May Dongmei Wang, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University who led the investigation.

Wang and her colleagues presented their results in the journal Nature Scientific Reports. In their study, the researchers developed three metrics – accuracy, precision, and reliability – and systematically evaluated 278 representative NGS RNA-seq pipelines. 

“We demonstrate that those RNA-seq pipelines performing well in gene expression estimation will lead to the improved downstream prediction of disease outcome. This is an important discovery,” said Wang, corresponding author of the paper, “Impact of RNA-seq Data Analysis Algorithms on Gene Expression Estimation and Downstream Prediction.”

She added, “Because the FDA is a regulatory agency for approving novel medical devices for NGS-genomics to be utilized in daily clinical practices for personalized and precision medicine and health, it is critical to see whether gene expression generated from RNA-seq acquisition and analysis pipeline are reproducible and reliable.”

The team’s comprehensive investigation revealed that the high throughput RNA-seq data quantification modules – mapping, quantification, and normalization – jointly impacted the accuracy, precision, and reliability of gene expression estimation, which in turn affected the downstream clinical outcome prediction (as shown in two cancer case studies of neuroblastoma and lung adenocarcinoma).

“Clinicians and biomedical researchers can use our findings to select RNA-seq pipelines for their clinical practice or research,” Wang said. “And bioinformaticians can use these benchmark datasets, results, and metrics to develop and evaluate new RNA-seq tools and pipelines.”

But one size does not fit every need, as in any machine learning paradigm, Wang noted. 

“The machine learning and algorithms are heavily dependent on goals,” she said. “Thus, based on our extensive experience in biomedical big data analytics and AI for almost two decades, we suggested that the FDA identify top goals for clinical genomics applications first. Based on different needs, different RNA-seq pipelines will be selected to achieve the optimal performance.”

In addition to Wang, the research team included lead author Li Tong, Po-Yen Wu, John H. Phan, Hamid R. Hassazadeh, Weida Tong, and members of the FDA’s Sequencing Quality Control project (Wendell D. Jones, Leming Shi, Matthias Fischer, Christopher E. Mason, Sheng Li, Joshua Xu, Wei Shi, Jian Wang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Falk Hertwig, Frank Berthold, Barbara Hero, Yang Liao, Gordon K. Smyth, David Kreil, Pawel P. Tabaj, Dalila Megherbi, Gary Schroth, and Hong Fang).

This work was supported by grants from the National Institutes of Health (U54CA119338, R01CA163256, and UL1TR000454), the National Science Foundation (EAGER Award NSF1651360), Children's Healthcare of Atlanta and Georgia Tech Partnership Grant, Giglio Breast Cancer Research Fund, the Centers for Disease Control and Prevention (CDC), and the Carol Ann and David D. Flanagan Faculty Fellow Research Fund.

CITATION: Li Tong, et al., “Impact of RNA-seq Data Analysis Algorithms on Gene Expression Estimation and Downstream Prediction.” (Nature Scientific Reports 2020)

Writer: Jerry Grillo

The tension between awareness and fatigue can lead to case-count plateaus, shoulder-like dynamics, and oscillations as rising numbers of deaths cause people to become more cautious before they let down their guard to engage once again in behaviors that increase risk for transmission, which, in turn, leads to rising death counts — and renewed awareness.

“Epidemics don’t necessarily have a single peak after which the risk subsides,” said Joshua Weitz, Patton Distinguished Professor of Biological Sciences and founding director of the Interdisciplinary Ph.D. in Quantitative Biosciences at the Georgia Institute of Technology. “People’s behaviors are both influenced by and influence epidemic dynamics, potentially driving plateaus, and oscillations in incidence.”

A paper describing the connection between human behavior and viral spread was published this month in the journal Proceedings of the National Academy of Sciences. It was authored by researchers at Georgia Tech, McMaster University, Princeton University, and Texas A&M.

In the early days of the pandemic, many scientists turned to traditional epidemiological studies, which showed epidemic cases could rise to a peak and then fall smoothly as immunity to the infection reached high levels in a population in the absence of large-scale interventions. Public health messages urged the population to “flatten the curve” to prevent disease from overwhelming hospitals.

“We were concerned that a focus on ‘the peak’ was potentially misguided because it implied that the shape was a feature of the disease alone without considering the consequence of behavior,” Weitz said. “In reality, there does not have to be a single peak during an epidemic.”

“If people are aware of the severity of the epidemic, they may change their behavior, and if they change their behavior, there will be fewer severe outcomes,” Weitz said. “But if awareness is short-term, individuals may tire of public health regulations and the virus will come roaring back. Instead of a single peak in cases, there can be plateaus or oscillations balanced between cautious behavior and relaxation.”

The research team analyzed data from the early phase of the epidemic and found evidence that the decrease in fatalities after a peak was slower than the rise toward it. However, in contrast to simple models of awareness-driven behavior, the research team also found evidence that individuals tended to increase their activity — as measured by mobility indicators — before epidemic severity waned. This means that individuals may have grown fatigued, worsening the epidemic severity. The study also found that other preventive measures, like mask wearing, have the potential to avert worst-case outcomes in disease transmission even as mobility increases in light of fatigue.

“This study underlines the importance of human behavior in driving epidemic outcomes,” said Jonathan Dushoff from the Department of Biology at McMaster University. “To make good predictions beyond the short term, we need to understand all of the factors driving human responses to the virus — fear, fatigue, information, misinformation, and so forth. We have a long way to go.” 

Weitz and Dushoff share optimism as well as concerns on the potential effects of anticipation of imminent vaccine distribution on behavior associated with transmission.

“It’s hard to be sure what impacts vaccine distribution will have on behavior,” Dushoff said. “There is concern in public health circles that people who think the vaccine is just around the corner could relax their guard. Human behavior is complicated.”

Lessons for future public health responses may help focus on the role of human behavior as well as communications that make disease impacts personal, fostering long-term awareness and changes in behavior that can reduce collective transmission.

Weitz and Dushoff coauthored the study with Sang Woo Park from the Department of Ecology and Evolutionary Biology at Princeton University and Professor Ceyhun Eksin from the Department of Industrial and Systems Engineering at Texas A&M.

This research was supported by the Simons Foundation (SCOPE Award ID 329108), the Army Research Office (W911NF1910384), National Institutes of Health (1R01AI46592-01), and National Science Foundation (1806606 and 1829636). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

CITATION: Joshua S. Weitz, Sang Woo Park, Ceyhun Eksin, and Jonathan Dushoff, “Awareness-driven Behavior Changes Can Shift the Shape of Epidemics Away from Peaks and Towards Plateaus, Shoulders and Oscillations.” (Proceedings of the National Academy of Sciences, 2020) https://doi.org/10.1073/pnas.2009911117

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The possible treatment, which could become the first non-drug, non-surgical, long-acting therapy for glaucoma, uses the injection of a natural and biodegradable material to create a viscous hydrogel — a water-absorbing crosslinked polymer structure — that opens an alternate pathway for excess fluid to leave the eye. 

“The holy grail for glaucoma is an efficient way to lower the pressure that doesn’t rely on the patient putting drops in their eyes every day, doesn’t require a complicated surgery, has minimal side effects, and has a good safety profile,” said Ross Ethier, professor and Georgia Research Alliance Lawrence L. Gellerstedt Jr. Eminent Scholar in Bioengineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “I am excited about this technique, which could be a game-changer for the treatment of glaucoma.”

The research, which was supported by the National Eye Institute and the Georgia Research Alliance, was published Dec. 7 in the journal Advanced Science. The research was conducted in animals, and shows that the approach significantly lowered the intraocular pressure.

As many as 75 million people worldwide have glaucoma, which is the leading cause of irreversible blindness. Glaucoma damage is caused by excess pressure in the eye that injures the optic nerve. Current treatments attempt to reduce this intraocular pressure through the daily application of eyedrops, or through surgery or implantation of medical devices, but these treatments are often unsuccessful.

To provide an alternative, Ethier teamed up with Mark Prausnitz, professor and J. Erskine Love Jr. Chair in the School of Chemical and Biomolecular Engineering at Georgia Tech, to use a tiny hollow needle to inject a polymer preparation into a structure just below the surface of the eye called the suprachoroidal space (SCS). Inside the eye, the material chemically crosslinks to form the hydrogel, which holds open a channel in the SCS that allows aqueous humor from within the eye to drain out of the eye through the alternative pathway.

There are normally two pathways for the aqueous humor fluid to leave the eye. The dominant path is through a structure known as the trabecular meshwork, which is located at the front of the eye. The lesser pathway is through the SCS, which normally has only a very small gap. In glaucoma, the dominant pathway is blocked, so to lessen pressure, treatments are created to open the lesser pathway enough to let the aqueous humor flow out.

In this research, the hydrogel props open the SCS path. A hollow microneedle less than a millimeter long is used to inject a droplet (about 50 microliters) of the hydrogel-precursor material. That gel structure can keep the SCS pathway open for a period of months.

“We inject a viscous material and keep it at the site of the injection at the interface between the back of the eye and the front of the eye where the suprachoroidal space begins,” Prausnitz said. “By opening up that space, we tap a pathway that would not otherwise be utilized efficiently to remove liquid from the eye.”

The injection would take just a few minutes, and would involve a doctor making a small injection just below the surface of the eye in combination with numbing and cleaning the injection site. In the study, the researchers, including veterinary ophthalmologist and first author J. Jeremy Chae, did not observe significant inflammation resulting from the procedure.

The pressure reduction was sustained for four months. The researchers are now working to extend that time by modifying the polymer material — hyaluronic acid — with a goal of providing treatment benefits for at least six months. That would coincide with the office visit schedule of many patients.

“If we can get to a twice-a-year treatment, we would not disrupt the current clinical process,” Prausnitz said. “We believe the injection could be done as an office procedure during routine exams that the patients are already getting. Patients may not need to do anything to treat their glaucoma until their next office visit.”

Beyond extending the time between treatments, the researchers will need to demonstrate that the injection can be repeated without harming the eye. The procedure will also have to be tested in other animals before moving into human trials.

“The idea of having a ‘one-and-done’ treatment that lasts for six months would be particularly helpful for those whose access to healthcare is non-optimal,” Ethier said. “Having a long-acting therapy would have an additional advantage during times of pandemic or other disruption when access to healthcare is more difficult.”

This research was supported by a grant from the National Eye Institute (R01 EY025286) and by the Georgia Research Alliance. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Mark Prausnitz serves as a consultant to companies, is a founding shareholder of companies, and is an inventor on patents licensed to companies developing microneedle-based products (Clearside Biomedical). These potential conflicts of interest have been disclosed and are being managed by Georgia Tech. J. Jeremy Chae, Jae Hwan Jung, Ethier, and Prausnitz are listed as co-inventors on an IP filing related to this study.

CITATION: J. Jeremy Chae, et al., “Drug-free, Non-surgical Reduction of Intraocular Pressure for Four Months After Suprachoroidal Injection of Hyaluronic Acid Hydrogel.” (Advanced Science, 2020) https://doi.org/10.1002/advs.202001908

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Researchers at the Georgia Institute of Technology and Emory University have received a landmark commitment to accelerate the scope and impact of Parkinson’s disease studies and to position Georgia as a hub for collaborative research on this and other neurological diseases.

The multiyear commitment from the McCamish Foundation will drive transformational research that harnesses science, engineering, and technology at Georgia Tech and Emory to better analyze the complexities of the brain and transform the treatment of Parkinson’s and other disorders of the nervous system. The Wallace H. Coulter Department of Biomedical Engineering (BME), an academic collaboration between Georgia Tech and Emory, is uniquely positioned to lead this new kind of translational neuroscience discovery driven by engineering innovation.

“For 22 years, Georgia Tech and Emory University have collaborated to improve the lives of individuals diagnosed with many of the world’s most challenging diseases. Through the sustained support of transformational philanthropy, the Coulter Department of Biomedical Engineering has become a national model for academic partnerships,” said Georgia Tech President Ángel Cabrera. “This visionary and generous commitment from the McCamish Foundation will allow us to expand and accelerate collaboration and discovery to the point that an exciting new treatment for Parkinson’s disease and other neurological disorders could be within our reach.”

Emory President Gregory L. Fenves added, “This generous commitment will enable Emory and Georgia Tech to build on our powerful biomedical partnership as we work to combat Parkinson’s and other devastating neurological diseases. New treatments and cures require a deep commitment — I am grateful for our friends at the McCamish Foundation who will help us make the progress and find the answers that patients and families so urgently need.”

Gordon Beckham Jr. has felt the impact of Parkinson’s personally, with the loss of his father, Hank McCamish, to the disease. Beckham now sits on the board of directors of the Parkinson’s Foundation and works to raise awareness to beat the disease. He said his goal is to build a strong research community in Georgia that will create new frontiers in the treatment of the degenerative disease.

“The McCamish Foundation has been in discussions on and off with Georgia Tech, since my dad’s passing, about innovative approaches to dealing with Parkinson’s,” said Beckham, CEO of the Atlanta-based McCamish Group LLC and president of the McCamish Foundation. “We have always been impressed by the amazing depth of talent at Tech.”

The McCamish name is well-known at Georgia Tech. Alumnus Hank McCamish, IM 1950, is the namesake of Tech’s basketball arena, McCamish Pavilion. Over the years, the family has supported numerous causes at Georgia Tech. This commitment is one of the largest in the Institute’s history and is the first of its kind for the Institute.

“More recently, we met Susan Margulies and learned of the formal biomedical engineering collaboration between Tech and Emory, two of the top institutions in the country in their respective fields,” Beckham said. “At the same time, the University of Georgia (UGA) is making major investments in Parkinson’s research. Given all this momentum within the state of Georgia, with BME as a nexus, the McCamish Foundation felt the timing was right to try something new at Tech and Emory while also leveraging the existing powerful collaboration between Tech, Emory, and UGA.”

“We already participate in robust research collaborations with Georgia Tech and Emory,” said UGA President Jere W. Morehead. “We look forward to expanding our partnerships in order to leverage the complementary strengths of our three institutions to bring new hope to those who suffer from this terrible disease.”

Beckham said The McCamish Foundation dreams of a day when all Parkinson’s related conversations begin with, “Remember when.”

The McCamish commitment will support faculty research on neurological diseases, including establishing a seed fund to support high-risk, high-reward research ventures. It will also provide fellowships for graduate students and create regular interactions among researchers at Tech, Emory, and UGA, including an annual national conference focused on Parkinson’s disease. The idea is to give researchers space to collaborate and brainstorm unconventional ideas that hold the greatest promise for significant discoveries.

“Our vision is to create the next frontier in neuroscience and neurotechnology by confronting the enormous complexities of the dynamic brain and nervous system,” said Susan Margulies, the Wallace H. Coulter Professor and Chair in the Coulter Department of Biomedical Engineering. “Our brains engage with, adapt to, and are influenced by the world around us. Studying the changing chemical and electrical brain dynamics is a direct path to detecting and treating Parkinson’s disease and other neurological disorders.”

###

About the Wallace H. Coulter Department of Biomedical Engineering

The Wallace H. Coulter Department of Biomedical Engineering is a partnership between Georgia Tech and Emory University. Combining the best of research and education, the department is dedicated to improving health and well-being by creating medical breakthroughs driven by engineering innovation and translational research. To learn more, visit bme.gatech.edu

Hundreds of millions of doses will have to distributed nationwide and kept cold until healthcare professionals can administer not one, but two doses to each person. And enough skeptical members of the population will have to be persuaded to receive the vaccine to slow virus transmission.

Beyond those challenges, the distribution effort will have to adapt to unexpected and uneven demand; accommodate recipients who may not return on time for a second dose; train hundreds of thousands of staff from clinics, pharmacies, doctor’s offices, and hospitals; prioritize serving high-risk groups first while encouraging others to wait — all while under tremendous pressure to get the much-anticipated vaccines into use as case counts and the death toll continue rising.

“Time is of the essence because the virus is already so widespread,” said Pinar Keskinocak, the William W. George Chair and professor in the H. Milton Stewart School of Industrial and Systems Engineering (ISyE) and director of the Center for Health and Humanitarian Systems at the Georgia Institute of Technology. “With the pressure on our timeline, knowledge of how quickly the disease is spreading, and the broad U.S. and global need, I can’t think of a comparable public health initiative that has ever been undertaken.”

Shipping and Keeping Hundreds of Millions of Doses Cold

Three vaccines, produced by Moderna, Pfizer and its German partner BioNTech, and Oxford-AstraZeneca, are expected to be available first. The Pfizer-BioNTech vaccine will need to be kept ultra-cold — minus 94 degrees Fahrenheit — on its journey to individual Americans. The Moderna drug won’t have such demanding conditions, but both it and the Pfizer vaccine will tax the existing “cold chain” that keeps vaccines and other temperature-sensitive products in a narrow range of conditions during transport and storage. 

The Oxford-AstraZeneca vaccine will have much less stringent requirements and faster ramp-up in capacity, though early testing suggests its efficacy may be lower than the others. That will create tradeoffs between efficacy versus access and speed in distribution.

Plans already exist to get the vaccines from manufacturers to the states, each of which has developed its own distribution plan. Keskinocak worries mostly about “last mile” plans — getting the vaccines to where they will be injected — and getting individuals to those locations.

“Access is going to be a challenge,” she said. “You may be able to get it to locations where it can be distributed, but you have to make sure the people who really need the vaccine can easily access those locations.”

Cold chain transportation, tracking, tracing, and storage already exist in most areas, but refrigeration could be challenging for rural areas that may be at the end of the chain, especially for the vaccine requiring very cold temperatures beyond the capability of freezers found in most doctor’s offices and clinics. And cold can sometimes be too cold, Keskinocak said.

“We often think about keeping it cold, but sometimes it may be too cold, which is not good. It’s not just whether the temperature exceeded the required level, but also whether it went below that. It is important to keep the vaccine exactly at the required temperature level.”

Pfizer has developed a shipping container that includes a temperature tracking device — and 50 pounds of dry ice to maintain the right temperature during transit. Because it is contained in small vials and the liquid vaccine is diluted for use, the overall volume being shipped will be relatively small, limiting the number of packages that will be moved and stored, Keskinocak noted.

Ultimately, the cold chain may play a significant role in vaccine effectiveness. Currently, the vaccines being produced by Pfizer/BioNTech and Moderna are reported to have a higher efficacy than the Oxford-AstraZeneca vaccine — but only if they can be maintained at the proper temperatures. The timing, magnitude, and duration of temperature fluctuations during transport and before administration could affect that in ways that may be difficult to assess.

“Our current modeling shows that a vaccine that is less effective but that can be distributed more quickly and more widely might work better in some settings than a more effective vaccine, thereby reducing the total number of infections in the population,” Keskinocak said.

If You Build It, Will They Come?

Expectations are that the nation is hungry for a vaccine to escape the horrors of Covid-19. But a recent Gallup survey shows that only 58% of respondents said they planned to receive the vaccine when it becomes available. Boosting that percentage will require a massive communications effort to overcome vaccine reluctance and concerns fueled by the uneven nature of the U.S. pandemic response.

“If we can get the vaccine to locations where people can access it, and we have the necessary syringes, supplies, and PPE, as well as the healthcare staff to administer the injections, it’s not clear that people will come to receive it in large enough numbers,” Keskinocak said. “That’s one major component missing from a lot of the plans that I see at the state level.”

The communications program will have to run in parallel to the vaccine distribution, and they have to be coordinated so that supply meets demand.

“Public health communication and dissemination of information at the right time and in the right language is going to be at least as important and challenging as the logistics of distributing the vaccine,” Keskinocak said. “Communication is going to shape demand to a large extent. If one is more effective than the other, we will have a mismatch between demand and supply.”

Different demographic populations have different levels of trust for medicine in general and vaccines in particular, she said, so communications campaigns will have to focus on issues of concern to those groups. Unexpected variations in vaccine demand caused by these concerns could also create logistical uncertainties.

“We can try to forecast demand, and ship supplies to those locations,” she said. “But historically, we have seen that demand can exceed supply in one location while inventory builds up in another location. We need to avoid this situation of unmet demand and unused vaccine.”

Another issue will be the two doses necessary for the vaccine. The second dose must be received within a narrow range of time for the two-dose vaccine to be effective. Should a second dose be reserved for every person receiving a first dose, or should the goal be to get as many doses out as possible?

“Some people may never show up to be vaccinated, while others will receive the first dose, but may not come back for the second dose,” she said. 

Getting the Program Started

The first available doses will likely go to healthcare workers and first responders who are on the front lines of battling Covid-19. That is expected to be the easier part of vaccination logistics, and the lessons learned there should help with the much more massive vaccination campaign for high-risk individuals and the general public.

As vaccine production and distribution capacity ramp up, other groups will be next in line. While distributing small batches as manufacturers produce it can create some supply challenges, that also allows the system to more easily adjust to unexpected demand.

Even though distributing and administering vaccines is something the U.S. healthcare system does routinely, the size and timeline of this project are unprecedented, Keskinocak noted.

Beyond the logistical and communications needs, the vaccination program will also have a strong information technology component. Administration will likely be by appointment, and each injection will have to be reported to a vaccine registry to provide a record of which vaccines people have received and when.

Vaccinating People Who May Already Be Immune

It’s estimated that the number of reported Covid-19 cases may be just 10% of the actual number of infections in the U.S. Assuming recovery from the virus confers immunity for some period of time means there may be quite a few people who don’t actually need the vaccine right away to be protected. But there are currently no plans to determine whether recipients are already immune before they receive the vaccine.

“There are a lot of people out there who have some level of immunity to the coronavirus,” Keskinocak said. “The plans I’ve seen don’t include the serological testing that would be needed to identify people with some level of immunity, which could be around 30% of the population by the time the vaccine gets out to the general public.”

Testing for immune antibodies could be done ahead of the vaccination program, but that would create an extra step in a process that is already quite complicated. Healthcare systems such as the U.S. Department of Veterans Affairs or certain private insurance plans could include that step, especially if vaccine supplies lag behind demand.

“The big complexity is timing,” she said. “Once vaccines become available, you’ll want to deliver them as quickly as possible to as many people as possible in a very short time frame.”

Annual vaccination campaigns for the seasonal flu set ambitious goals for the population levels they want to reach, but the time challenges will be much greater for the coronavirus vaccine.

“The seasonal flu vaccine becomes available months before the virus spreads broadly, so we have quite a bit of time to administer it before we get into the peak of the flu season,” she said. “We have been in the midst of the Covid-19 pandemic for several months now. We are really late in the game, so we don’t have the luxury of time.”

Keskinocak is cautiously optimistic that the challenges will ultimately be addressed.

“There are certainly still lots of unknowns,” she said. “But the state plans I have seen look reasonable from a supply chain standpoint. Some of the decisions will be made once the states receive the vaccine, and exactly how they do it will be somewhat up to the local jurisdictions. There are still many things that need to be decided to make this unprecedented initiative live up to its goals.”

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Biochemical information about the body most commonly comes from analysis of blood — which represents only 6% of bodily fluids — but valuable information may also be found in other bodily fluids that are traditionally hard to get. Researchers have now developed a way to extract dermal interstitial fluid (ISF), which circulates between cells in bodily tissues, using a simple through-the-skin technique that could provide a new approach for studying the metabolic products of cells, obtaining diagnostic biomarkers, and identifying potential toxins absorbed through the skin. Because the dermal interstitial fluid doesn’t clot like blood, the microneedle-based extraction could offer a new approach for continuous monitoring of glucose and other key health indicators.

Results of a human trial on the microneedle-based ISF sampling is reported Nov. 25 in the journal Science Translational Medicine. The study, conducted by researchers from the Georgia Institute of Technology and Emory University, was supported in part by the National Institutes of Health and Children’s Healthcare of Atlanta.

“Interstitial fluid originates in the blood and then leaks out of capillaries to bring nutrients to cells in the body’s tissues. Because interstitial fluid is in direct communication with the cells, it should have information about the tissues themselves beyond what can be measured from testing the blood,” said Mark Prausnitz, Regents Professor and J. Erskine Love Jr. Chair in Georgia Tech’s School of Chemical and Biomolecular Engineering. “This microneedle-based technique could provide a minimally invasive and simple way to access this interstitial fluid to make it available for medical diagnostic and research applications.” 

ISF has been difficult to sample. Indwelling instruments for monitoring glucose in ISF already exist, and other researchers have used surgically implanted tubing and vacuum-created blisters to extract ISF through the skin, but these techniques are not suitable for routine clinical diagnostic use. 

The researchers, led by first author Pradnya Samant, used a patch containing five solid stainless steel microneedles that were a hundredth of an inch in length. By pressing the patch at an angle into the skin of 50 human subjects, they created shallow micropores that reached only into the outer layer of skin containing ISF. The researchers then applied a suction to the area of skin containing the pores and obtained enough ISF to do three types of analysis. For comparison, they also took blood samples and obtained ISF using the older blister technique.

To accurately determine the biomarkers available in the ISF, the researchers needed to avoid getting blood mixed with the ISF. Though major blood vessels don’t exist in the outer layers of skin, capillaries there can be damaged by the insertion of the microneedles. In their studies, the researchers found that if they slowly ramped up the suction after inserting the microneedles, they could obtain fluid clear of blood.

The overall extraction procedure took about 20 minutes for each test subject. The procedure was well tolerated by the volunteers, and the microscopic pores healed quickly within a day, with minimal irritation.

The extracted fluid was analyzed at Emory University using liquid chromatography-mass spectrometry techniques to identify the chemical species it contained. Overall, there were about 10,000 unique compounds, most of which were also found in the blood samples. However, about 12% of the chemical species were not found in the blood, and others were found in the ISF at higher levels than in the blood.

“The skin is metabolically active, and it is full of cells that are changing the fluid,” Prausnitz said. “We found that some of the compounds were unique to the ISF, or enriched there, and that is what we were hoping to find.”

While not all the compounds unique to the ISF could be analyzed, the research team identified components of products that are applied to the skin — such as hand lotions — and pesticides that may enter the body through the skin. This discovery could set the stage for use of the microneedle technique for dermatological and toxicology studies.

“If you want to look at what accumulates in the skin over time, this may provide a way to obtain information about those kinds of exposures,” Prausnitz said. “These are materials that may accumulate in the tissues of our body, but are not found in the bloodstream.”

The researchers also determined the pharmacokinetics of caffeine and the pharmacodynamics of glucose — both small molecules — from the ISF, indicating that that dynamic biomarker information could be obtained from the technique. Those measurements suggested that ISF could provide a means for continuously monitoring such compounds, taking advantage of the fact that the fluid does not clot.

“We were encouraged that we found a good correlation between the blood and interstitial fluid glucose, which suggests we might be able to have a continuous glucose monitoring system based on this technology,” Prausnitz said. A microneedle-based system could provide a less invasive alternative to existing implantable glucose sensors by allowing the sensing components to remain on the surface of the skin.

In future research, Prausnitz would like to reduce the time required to extract the ISF and simplify the process by eliminating the vacuum pump. Additional study of the compounds found in the fluid could also show whether they have medical diagnostic value.

“We’d like to make this microneedle-based technique available to the research community to make ISF routinely available for study,” he said. “Tissue interstitial fluid could be a novel source of biomarkers that complements conventional sources. This research provides a means to study this further.”

The research team also included Nicholas Raviele and Juan Mena-Lapaix from Georgia Tech; and Megan M. Niedzwiecki, Douglas I. Walker, Gary W. Miller, Vilinh Tran, Eric I. Felner, and Dean P. Jones from Emory University.

CITATION: Pradnya P. Samant, "Sampling interstitial fluid for human skin using a microneedle patch." (Science Translational Medicine, 25 November 2020) https://stm.sciencemag.org/content/12/571/eaaw0285

This work was supported in part by the U.S. National Institutes of Health (U2CES026560, P30ES020953, R01ES023485, P30ES019776, S10OD018006) and by Children’s Healthcare of Atlanta. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Mark Prausnitz is an inventor of patents licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products, and is a founder/shareholder of companies developing microneedle-based products (Micron Biomedical). This potential conflict of interest has been disclosed and is managed by Georgia Tech. Pradnya P. Samant and Prausnitz are inventors on a patent application (WO2019126735A1) submitted by Georgia Tech Research Corporation that covers ISF collection methods presented in this study.

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Writer: John Toon

When faced with the spread of Covid-19, Georgia Tech’s entire community sprang into action to develop and implement a way to test the campus community. The extensive and ambitious saliva-based surveillance test is conducted entirely on campus. Everything, from packing test kits and self-administering tests to analyzing samples and providing incentives to encourage testing, was developed and executed by faculty, staff, students, and partners. Last month, Georgia Tech surpassed 100,000 cumulative tests, a figure that has helped the Institute identify positive cases and take appropriate action to slow the transmission of the virus.

Here, we introduce you to a handful of the hundreds of people who have been working day in and day out to ensure that the testing program runs smoothly. These dedicated individuals are among the many who took part in developing and scaling the test so that Georgia Tech can collect and test hundreds of samples a day. They are the people who pack the test kits and drive them across campus to the Institute’s on-site testing facility. They are the people who stand by to assist students, faculty, and staff who show up each week at one of several on-campus testing locations. Each of their contributions represents a critical component of Tech’s testing program — one that speaks directly to Georgia Tech’s commitment to solving challenges through innovation around the world and right here at home.

Greg Gibson

Greg Gibson knew testing had to be part of the solution to managing the coronavirus on campus, but he didn’t imagine we would be doing it on the large scale that we are. “Testing on campus seemed to be the obvious thing to do but no one was doing it,” Gibson explains. He credits senior research scientist Anton Bryskin for pushing him to use the technology we already had in place on campus to help combat Covid-19. Gibson says the science came together easily, but the logistics were difficult. He acknowledges individuals like Mike Shannon of GTRI and JulieAnne Williamson, executive director of Sustainability and Building Operations, for scaling up the testing model.

"This could be done anywhere but it was done at Georgia Tech because of the will of everyone here." - Greg Gibson. Professor, School of Biological Sciences and School of Physics. Research led for development of the coronavirus testing program.

Joshua Weitz

Weitz, a professor at Georgia Tech, focuses on epidemics and their behavior. His interest lies in how modeling transmissions, coupled with crowd control and testing, can lead to improved disease mitigation tactics. “A virus may be small, but it can reshape populations and ecosystems on different scales,” Weitz explains. He believes he was able to make a difference on campus and in public health, but maintains, “This is only possible with many people working together with a common purpose.” Now his goal is to take lessons learned at Tech to help others protect themselves and their communities.

"A virus may be small, but it can reshape populations and ecosystems on different scales." - Joshua Weitz. Professor, School of Biological Sciences and School of Physics. Research focused on modeling the spread of viral infectious diseases.

Read the remainder of the story here. 

As Covid-19 outbreaks surge in several states, the choice to see family this holiday season gets more complicated by the day. Thankfully, there’s a tool—developed by Georgia Tech faculty, scientists, GIS specialists, and graduate students—that can help estimate the potential risk of exposure involved with a trip home for a turkey dinner. 

Joshua S. Weitz, Patton Distinguished Professor in the School of Biological Sciences, and Clio Andris, assistant professor in the Schools of City and Regional Planning and Interactive Computing, created the “Covid-19 Event Risk Assessment Planning Tool.”

They launched the tool in July, and since then it has generated more than 2 million unique visitors, been featured in national and international media, and spurred the development of related sites in Spanish and Italian. A multi-authored scientific article describing the tool was published in Nature Human Behaviour on November 9, 2020.

“We are starting to see the traffic ramp up again as people plan for the holidays,” Andris said.

A Useful Spatial Tool

The tool breaks down the risk of attending events, no matter the size, based on county-level Covid-19 case reports in the U.S. and parts of Europe. Users can select the county they are interested in and the size of the event they wish to attend.

Weitz, the founding director of Tech’s Quantitative Biosciences Graduate Program, and an ardent Atlanta United fan, was having trouble deciding whether or not to go to a home game when the Mercedes-Benz stadium in Atlanta reopened after the Covid-19 lockdown.

He developed a statistical model based on the odds of encountering one infected individual amongst many. Weitz quickly realized that the model would also be useful in the form of an interactive map.

“I reached out to Andris, given her expertise in spatial visualization and analysis,” he said. 

“Clio and I were already collaborating on modeling Covid-19 epidemic spread in Georgia. I knew she would be an ideal partner, particularly given the strong visualization background of her team of Master of Science in Geographic Information Science and Technology students.”

Andris’ Friendly Cities Lab works on a number of Covid-19 projects meant to assist cities and the people that live in them. 

“At that point in the summer, and even now, the Covid-19 case rates change based on location,” she said. “Early on, people only had national-level data, and we wanted to drill down to the county level. This allows people to decide whether to attend an event based on the risk level in their locality.”

While the interactive tool works well for large-scale events, users can also select smaller event sizes like 10 or 15 people—the size of many family gatherings during the holidays. 

Read the rest of the story on the website of the School of City and Regional Planning.

Academia and industry. Campus vs. corporate. Exploration for new knowledge — or to move a company or industry forward.

But for many College of Engineering faculty, such shorthand dichotomies are false. Every day, they show up for work to conduct sophisticated research, teach classes, mentor students and serve on committees. They live the life of the scholar-instructor, yet they bring something extra: the experience of working in the private sector, in all its relentless pursuit of fast results and shareholder value.

This experience, they say, generated reward in several forms. Time spent in industry yields valuable lessons to share in classrooms and labs. Here are a few.

Emily Grubert
Assistant Professor, School of Civil and Environmental Engineering
Right now: Big decisions are made in operating big infrastructure like energy, water and transportation systems. Grubert’s research combines decision-support tools with opinion research to improve how those big decisions are made. She generates a deeper, clearer picture of various options, making it easier to compare one against another.

Her time in industry: Stints at McKinsey and Pacific Gas & Electric gave Grubert an up-close look at massive infrastructure systems and helped her develop scenario-based models to guide decision making. “I chose McKinsey because I wanted to work with refineries, power plants, mining companies and other big infrastructure [entities] in a way that didn’t require me to go work for them,” she says. “So, in my interview, I let them know I would quit in a couple of years to get a Ph.D.”

Takeaways from the private sector: “On the academic side, we tend to under-value process and governance in decision-making,” Grubert says. “We focus on a few facts — we’ll do an analysis and say, ‘option X is 20% better.’ But that doesn’t mean that the 'better' option will be what someone in industry will choose because there are other considerations. There’s a whole lot more to decision making on the private sector side.”

The perfect-fit field: “Interdisciplinary” is an important word to Grubert, and she was glad to find that Georgia Tech embraced a multi-disciplinary view of research. “I view engineering as a way to apply science to help people thrive in the world, and that includes social science,” says Grubert. “Once you start working in civil and environmental engineering, it’s amazing how important social science is, because you’re working with so many people.”

David Frakes
Associate Professor, Wallace H. Coulter Department of Biomedical Engineering and School of Electrical and Computer Engineering
Right now: The Frakes Lab at Georgia Tech is brand-new — he arrived at his alma mater in the summer of 2020 — but its focus is to explore and model new kinds of medical devices. One noteworthy niche: He aims to design devices that fit and work across a population of patients by testing the devices on thousands of virtual people. “Machine learning is in everything these days,” he says. “If you have data, you have a big advantage.”

His time in industry: In the early days, it was hedge fund management on Wall Street. Later came a five-year stop at Google, where he spearheaded mobile imaging projects. Most recently, Frakes led an Apple team that developed algorithms driving the camera software inside the iPhone 11. Along the way, he even started two companies.

Takeaways from the private sector: Frakes runs his lab like a startup: with quarterly objectives, “go and no-go” decisions and a sense of urgency. “In academia, there may not be a clear finish line on the calendar or work plan,” he observes, “but in a startup, your time is not infinite. You only have so much runway.” This entrepreneurial approach to research, he adds, is appealing to students. “It’s just fun to have skin in the game in the lab every day.”

The ‘village in the room’: At Arizona State, Frakes helped launch the BRAIN Center, an industry-university research collaborative to develop neurotechnologies. He’s applied for NSF funding to do the same at Georgia Tech. The new center would engage multiple companies with a large group of faculty from engineering and other disciplines. “It takes a village to go after certain problems,” he says. “With this center, we’ll be getting a lot of subject matter experts in the room to work on problems too big for any one of them to solve alone.”

Blair Brettmann
Assistant Professor, School of Chemical and Biomolecular Engineering and School of Materials Science and Engineering
Right now: Brettmann develops new technologies and materials to make it possible for products with many different components to be customizable quickly. “In industry, to make a small change to a product, you have to address many issues. So, just changing that one item can take huge amounts of time. A lot of what I’m doing is looking at ways to pair with a computational person to make it faster.” Her research has widespread implications for materials and processes in manufacturing.

Her time in industry: Working for the French materials company Saint-Gobain, Brettmann led R&D projects for new coatings, surface treatments and other functional materials. “I didn’t do much in the lab — it was really more managerial,” she says. A desire to stay engaged in technical work and to mentor students led her back to campus.

Takeaways from the private sector: “One of the best things to come out of my industry work is project management,” Brettmann says. “As a principal investigator, I now have seven different research projects. But as a postdoc I only had to focus on one or two things at a time. My industry experience helped me manage better.”

Some say the grass is greener: “I like to joke that when you’re in industry, you see academics as rich because of the fancy equipment they have. And academics see industry as rich because they have more money to pay people. Also, university researchers focus on getting their name out there, getting funding, helping students. In industry, there’s a lot of time pressure to get a product out the door.”

Mohit Singh
Associate Professor, H. Milton Stewart School of Industrial & Systems Engineering
Right now: Singh conducts research to improve decision making, employing a highly mathematical approach. A large part of his exploration involves designing algorithms to arrive at discrete decisions using fixed variables to decide this-or-that, very quickly. Significantly, he’s moving the field into new ways of using open-data variables to inform the algorithms, thus bridging the separate worlds of “discrete and continuous optimization.”

His time in industry: In a seven-year stint for Microsoft, Singh worked to optimize the process for deciding how data from cloud computing customers should be distributed across computer servers. Factoring in high-demand times, storage needs and other variables, he helped develop frameworks that determined server access, optimizing for both the client and server performance.

Takeaways from the private sector: Industry inspires much of Singh’s research. “I’m currently working on a lot of optimization problems,” he says, “and apart from being fundamental and theoretical in nature, so many of them are motivated by what comes in practice. I want to look at relevant problems.”

The difference is the students: A major motivating factor in Singh’s decision to come to Georgia Tech was the opportunity to guide and mentor students. Most undergraduates don’t do much research, “but you see them grow and develop their own vision.” Graduate students can work on problems for several years. However, in industry, “you only have interns, and you don’t get to see them grow over time.”

Joseph Oefelein
Professor, Daniel Guggenheim School of Aerospace Engineering
Right now: Oefelein uses ultra-powered computing and algorithms to create highly sophisticated simulations of propulsion and power systems such as liquid rocket engines. His simulations and models reveal the interplay between turbulence and the complex physical processes in combustion. The goal is to find new ways to optimize these systems.

His time in industry: Seventeen years with a national laboratory may sound like a government job, but Oefelein’s career with Sandia National Laboratories had him in constant partnership with private industry, working with researchers in energy science to improve the predictability of combustion models. During this time, he always kept an eye on how those models could inform the design of different types of piston, gas turbine and rocket engines manufactured for automobiles, trucks and aviation and space vehicles.

Takeaways from the private sector: “In the classroom, a lot of times I can just naturally answer a question like, ‘Why do I need to learn this?’” Oefelein says. “Not only can I share real-world experience and observations with students, I can give a perspective right away, and in a natural way.” Like the other engineering faculty, the ability to work with students was a motivating factor to return to a campus.

You can’t learn if you don’t share: Having experienced academia, government and industry, Oefelein has a perspective on how all three can work together to address some of the intractable problems facing humankind. “Understanding comes from sitting down with colleagues in different sectors and being able to appreciate all the pros, cons and constraints,” he says. “The more communication that occurs, the better off everyone will be.”

“This stimulation harnesses our brain’s natural tendency to entrain to stimuli, to then manipulate neural activity, recruit the brain’s immune system, and clear pathogens,” Singer explained to a virtual audience in her recorded video presentation.

The work is based on previous animal studies by Singer and her colleagues, in which they discovered that a light flickering at 40 hertz (40 cycles per second) stimulates gamma waves, significantly cutting down on amyloid beta, an Alzheimer’s pathogenic hallmark. Gamma waves are associated with high-level cognitive functions, like perception and memory. Disruptions to these kinds of brain waves have been found in various neurological disorders.

“We found that one hour of gamma stimulation reduced amyloid beta and recruited microglia, the primary immune cells of the animals’ brains,” said Singer, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. She added that the treatment, “even rescued spatial memory behavior in mice. That led to our next key question. Does this translate to humans?”

To answer that question, Singer initiated the Phase I feasibility trial with James Lah, principal investigator of the study for Emory, where he is associate professor and vice chair in the Department of Neurology and director of the Cognitive Neurology Program.

“We went into this preliminary pilot study with the primary goal of learning whether or not sustained use of this device would be tolerable in humans, and whether or not people would use it,” Lah explained. “The results were promising. Everybody tolerated the devie and we were able to tune it to the level of light and sound that was not only tolerable, but successfully provoked the underlying brain response that was desired.”

The initial feasibility study, an eight-week trial entitled, “Gamma Sensory Flicker for Patients with Prodromal Alzheimer’s Disease: A Phase I Trial,” involved 10 people who were organized into two groups of five each. One group underwent no flicker treatments for the first four weeks, followed by four weeks of treatment. The other group received eight weeks of flicker treatments.

First, the research team assessed the safety of treatment, which required participants to wear an experimental visor and head phones that exposed them to 40 Hz of light and sound. There were no overall severe adverse events among participants during pre-trial screening, in the study, or during the 10-month open label extension (some patients volunteered to continue being monitored and assessed). There were some mild adverse effects that could be flicker related (dizziness, tinnitus, headache, worsened hearing loss). But overall, Singer said, the safety profile was excellent.

Of major concern to the researchers was whether participants would tolerate the treatment, and stick with it over eight weeks or more. Again, Singer and her team were satisfied with the results: Most participants tolerated it well, and adherence was greater than 88 percent among all participants.

The researchers found that there were no clear changes in the presence of Alzheimer’s pathogens (amyloid beta and p-Tau), but saw strong EEG entrainment (brain wave synchronization) at 40 Hz when gauging participants’ neural responses during flicker, and a significant increase in neural network functional connectivity (which is weakened in Alzheimer’s) after eight weeks.

Also, as they had previously observed in studies with mice, the researchers noted the activity of cytokines (small proteins used in cell signaling), which indicated that flicker is also engaging the brain’s immune system in humans.

“These are interesting but preliminary biological effects of gamma flicker,” Singer said. “All of this is gearing us up for our next larger and longer study coming soon.”

The study was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (R01-NS109226-01S1), by the Packard Foundation, the Friends and Alumni of Georgia Tech, the Lane Family, the Wright Family, and Cognito Therapeutics. Any findings, conclusions, and recommendations are those of the researchers and not necessarily of the sponsors.

Competing interests: Annabelle Singer owns shares in Cognito Therapeutics, which funded the human study at Emory Brain Health Center. Cognito aims to develop gamma stimulation-related products. These conflicts are managed by Georgia Tech’s Office of Research Integrity Assurance.

And over the past couple of months, he’s been quite busy. 

In a story widely carried by major media outlets, last month NASA announced that a study published in the journal Nature Astronomy shows evidence of water on the sunlit portions of the moon, through an effort involving the use of the NASA SOFIA flying observatory. Orlando is one of the study’s co-authors — he’s been working on the lunar water issue for many years and some of his research group’s modeling was critical to the paper.  

Orlando is also principal investigator for the Radiation Effects on Volatiles and Exploration of Asteroids and Lunar Surfaces (REVEALS) team based at Georgia Tech, part of a NASA project which is researching not only water on the moon, but also how to better protect astronauts from the dangers of space exploration. Orlando collaborates with University of Notre Dame colleagues on this project, and last month he learned he would be featured in a short “infomercial” about the research, which ran during halftime of the NBC national telecast of the Nov. 7^th Notre Dame-Clemson game. 

He’s also the recent winner of a major award from the American Vacuum Society (the national surface science society) for his work on integrating surface chemistry and physics into planetary science. The award is named for an un-official mentor who Orlando collaborated with in the early 1990’s. Add to that the renewal of Department of Energy funding for his research looking into minimizing the dangers of nuclear waste storage, and other NASA projects on future astronaut habitats, and you’ve got the makings of a busy 2021 for Orlando.

Add to that the renewal of Department of Energy (DOE) funding for his research looking into minimizing the dangers of nuclear waste storage, and other NASA projects on future astronaut habitats, and you’ve got the makings of a busy 2021 for Orlando.

Other than finding molecular water on the Moon, all of these projects gravitate towards Orlando’s fascination with radiation: either protecting astronauts from it in space, or finding new ways to deal with nuclear waste radiation on Earth. 

“My emphasis has always been on understanding radiation, how it affects surfaces and interfaces,” Orlando says. “For decades now, we have been moving these tools we’re using in different scientific communities to try and unravel what happens when you’re in a star-forming region, or on the Moon, and being irradiated by solar wind, or anywhere where you’re not protected from radiation.

“A big part of my portfolio is a strange mixture of atomic and molecular physics mixed in with surface physics and chemistry,” he says. “In fact, the program at DOE is all of these. The safe storage of nuclear waste, which is a very important environmental and potential national security issue, is essentially a very complicated solid-liquid interface problem that gets worse when you add radiation.”

An award honoring a mentor, research partner

Orlando, who has an adjunct appointment with the School of Physics, is the winner of the 2021 Theodore E. Madey Award, presented by the American Vacuum Society (AVS) and the Polish Vacuum Society. Madey, a physicist and longtime professor at Rutgers University, was a pioneer in expanding physics and chemistry to include the study of surfaces. 

According to the AVS website, the Madey Award is presented to scientists showing “outstanding theoretical and/or experimental research in areas of interest to the AVS and PVS, including surface science.” In Orlando’s case, the Madey Award is primarily for integrating surface physics and chemistry with planetary sciences – the kind of research Orlando is conducting with REVEALS.

Orlando will travel to Poland for a series of lectures in the summer of 2022; typically the Madey Award winner would make those appearances in 2021, but Orlando says the pandemic has forced changes to the schedule.

For Orlando, the Madey award represents a truly unique honor; it’s named for someone Orlando knew and worked with, a former colleague he called “a gifted and kind person.” They met when Orlando was a postdoctoral fellow at Sandia National Laboratory in New Mexico. Soon after they would begin research together, with Orlando helping Ted Madey organize conferences such as the Desorption Induced by Electronic Transitions (DIET) conference held in Callaway Gardens, Georgia, in April 2009 — an event that ultimately occurred some months after Madey’s death in summer 2008.  

“We were doing work on inelastic electron scattering, and I’ve never stopped doing it since then,” Orlando says. “But what I’ve done is move the tools necessary to study this, and that problem (electron-bombarded surfaces and interfaces) to the planetary sciences community. Ted did sort of the same thing, but towards the latter part of his career. He was very interested in planetary science. He, I, and a few others were sort of moving this area of surface science forward by directly linking it to problems in space science.”

REVEALS gets the NBC spotlight

Orlando has recently made significant progress in moving that combination of surface physics, chemistry, and planetary sciences: He currently leads the REVEALS team of scientists from Georgia Tech and other higher education institutions in its mission of finding potential resources such as water on the Moon. His team is also researching new materials and technologies to protect future astronauts from radiation bombardment as they explore the Moon, Mars, or near-Earth asteroids. 

One of those partner institutions is Notre Dame, which helped create a recent NBC video that aired during its nationally-telecast November 7^th football game with Clemson.

Notre Dame professor Jay LaVerne is a good friend of Orlando’s, which is how LaVerne ended up as a part of the original REVEALS team. “He’s the first guy I thought of when I wanted to simulate cosmic rays and the proton bombardment coming from solar winds,” Orlando says. “We can simulate the low energy part of this, but he can simulate the high energy part better. Together we can do a very good and comprehensive study.”

NBC is focusing mostly on the Notre Dame Radiation Laboratory, but did bring a crew to Georgia Tech’s Marcus Nanotechnology Building to shoot an interview with Orlando. The NBC crew observed all campus virus protection protocols during videotaping, so it did not shoot in Orlando’s REVEALS lab, which is in tighter quarters. Instead, he’s given time to speak in the video about the project’s mission.

“Developing a spacesuit is a multi-decade process, and it’s really complicated,” he says. “If it doesn’t stand up to radiation, it’s pretty useless. We’re looking at using nanocomposite materials, which offer stronger protection, but also lighter weights and more flexibility. The suits that we want to make will be good for protecting them from radiation, but also protecting them from dust. That’s also a serious problem when astronauts go exploring. The philosophy is risk mitigation,” he adds. The suit work is carried out in collaboration with other GT-REVEALS researchers in the School of Chemistry and Biochemistry, School of Materials Science and Engineering, and School of Physics and is indeed a multidisciplinary effort.

Orlando shares that, eventually, he and the REVALS team hope to develop and use materials that will turn the entire spacesuit into a radiation detector.  

Water, water everywhere – even on the moon

The recent discovery of molecular water on the moon also ties into REVEALS. The “V” in REVEALS refers to volatiles — molecules like hydrogen or water that are needed and can be produced by the bombardment of lunar regolith (the fine, fragmented soil that covers lunar bedrock) by solar wind or micrometeorites. REVEALS studies how this process could happen. If there are enough useful volatiles, could they somehow be ‘mined’ by astronauts to be used on site? This is critical for long term human exploration and presence on the moon, which is the goal of the NASA Artemis program.

Orlando explains that that’s why the October Nature Astronomy research paper is so important. “We’re very, very active in understanding how water is formed on the moon, how water moves on the moon, how water is lost from the moon, and how it’s kept on the moon,” he says. “The paper says water is kept in higher abundances than what most people think — and subsurface too. It (the research) does really contribute significantly to the overall possibility of extracting water and using it as a resource for a longer-term presence.”

The researchers discovered this by asking for observation time from SOFIA – the Stratospheric Observatory for Infrared Astronomy, that NASA flies on a modified Boeing 747 so it can observe space above the clouds.  

That fact, and SOFIA’s Faint Object Infrared Camera, were the primary factors in helping to find evidence of water on the moon, Orlando says. “When you’re above the cloud layer, you automatically subtract out your water background (from the clouds), so you could do a real mapping of what’s on the moon with the telescope without water interference. That’s number one, a background-free measurement.”

The second factor is the infrared camera’s ability to capture optics on a particular 6 micron-based spectrum that helped show evidence of actual molecular water, and not just its separate components of hydrogen and oxygen. As the Nature paper puts it, water has been detected before by other spacecraft, but “whether the hydration is molecular water (H₂O) or other hydroxyl (OH) compounds is unknown, and there are no established methods to distinguish the two using the 3 µm (microns) band of specialized telescopes and spectroscopes. However, a fundamental vibration of molecular water produces a spectral signature at 6 µm (microns) that is not shared by other hydroxyl compounds.” Using SOFIA, observations reveal “a 6 µm feature at high lunar latitudes, due to the presence of molecular water on the lunar surface.”

“It (SOFIA) was mostly used for astrophysics. We’d never pointed it at the moon before to look for water,” Orlando says. Co-author Paul Lucey and graduate student Casey Honniball (first author of the study) were awarded time on SOFIA. Orlando and Brant Jones, a Georgia Tech REVEALS co-investigator, did computer modeling to help explain the results and to determine how much water could be there — either on the soil grains, trapped between the grains, or in the grains themselves. Jones and Orlando are measuring this directly, now, in Orlando’s Electron and Photon Induced Chemistry on Surface (EPICLS) Lab.

Radiation waste on Earth, radioactive-free habitats in space

Orlando’s interest in radiation is also a part of a Department of Energy Office of Science contract that funds the Pacific Northwest National Laboratory Interfacial Dynamics in Radioactive Environments and Materials (IDREAM2) Energy Frontier Research Center (EFRC). IDREAM2 is looking into the fundamental physics and chemistry associated with the storage of nuclear wastes across the DOE complex. This includes relics of Cold War weapons production.

Orlando is the science lead on the radiation cross cutting theme in IDREAM2. “Safe storage, treatment and monitoring the radioactive waste legacy is an important problem set the DOE is dealing with,” he says. “We look very carefully at what happens at the interfaces. We (Georgia Tech) have been active in this for a very long time.” An important waste issue is the production of molecular hydrogen and the radiation induced damage of water and the waste forms. “It is actually the reverse of what we’re doing for NASA. It’s the splitting and breaking up of water and the buildup of hydrogen, and that needs to be understood and controlled.”

Orlando is hoping that his team’s studies will help scientists predict how nuclear waste will behave and ‘age’ so that governments can know how to best deal with the longer term storage and treatment options.

His interest in radiation also explains his involvement in another NASA program, HOME (Habitats Optimized for Missions of Exploration). This program involves interdisciplinary groups of scientists at seven universities, all with the goal of designing and manufacturing what NASA is calling “SmartHabs,” fully autonomous habitats that will “keep astronauts alive while they are resident, and keep the vehicle/habitat alive (operational) while they are not,” according to Georgia Tech’s HOME website. 

Artificial cilia apparatus setupThat is where a team of Georgia Tech researchers, which includes Professor Alexander Alexeev, Professor Peter Hesketh, and recent Ph.D. graduate Srinivas Hanasoge, comes in. The group has successfully engineered synthetic biomimetic cilia, and developed a mechanism for manipulating them using magnetic fields in a way that mimics their natural motion. Their results were recently published in ACS Applied Materials & Interfaces in an article titled “Metachronal Actuation of Microscale Magnetic Artificial Cilia.”

“Cells utilize highly complex biomechanical machinery to actuate cilia,” explains Alexeev. “Such machinery is inaccessible in synthetic systems, so the challenge was figuring out how to design relatively simple microscopic devices that can closely mimic the complex three dimensional motion of cilia that can still be fabricated using our current microfabrication technology.”

In their work, the group demonstrated several methods to create arrays of magnetic artificial cilia that are capable of producing metachronal waves. They also showed that they could control the direction of the waves using different types of magnetic actuation.

Cilia being activated by a magnetic field

“The most surprising result was that our relatively simple system that is composed of anchored magnetic filaments and a rotating magnet can produce complex motion that resembles the beating of biological cilia,” said Alexeev.

At large scales in everyday life, fluid mixing does not pose particular challenges, but at the microscale it is a significant obstacle. Alexeev and his collaborators are hoping their findings can be applied to micro and nano devices that operate with extremely small amounts of fluids, including organ-on-a-chip and lab-on-a-chip systems.

The group is also optimistic that their findings will lead to an improved understanding of how cilia functionthat they can be reproduced and manipulated artificially.

“The ability to produce different types of metachronal motion using our synthetic cilia opens a possibility to systematically investigate the effects of ciliary activity and metachrony on different functions performed by biological cilia such as fluid and particulate transport,” explains Alexeev. “This is important for better understanding the biological function of cilia and devising new ways to manipulate minute amounts of fluids at the microscale.“

This research was sponsored by the USDA NIFA (Grant #11317911) and the NSF (CBET-1510884). The cleanroom fabrication was assisted by the staff of Georgia Tech IEN.

CITATION: Srinivas Hanasoge, Peter J. Hesketh, and Alexander Alexeev, “Metachronal Actuation of Microscale Magnetic Artificial Cilia,” (ACS Applied Materials & Interfaces, 2020, 12, 41, 46963–46971). https://doi.org/10.1021/acsami.0c13102

They all gathered, from a distance, for the CNEP’s first annual online retreat (September 25-26). The online event – which drew 18 grad students (trainees), 11 faculty members, two staff members, and three advisory board members from the neurotech industry – was sponsored by the Georgia Tech and Emory Neural Engineering Centers, and the Laney Graduate School at Emory.

The wide ranging of retreat foci took in science, technology, neuro-ethics, diversity and inclusion, with time for a neuro-themed quiz show. Meanwhile, second year PhD students – that new generation – presented their research, which focused on, among other things, topics such as machine learning methods for decoding brain activity, and brain imaging techniques for understanding Alzheimer’s disease. And a neuro-ethics exercise sparked a lively discussion about the societal impact of brain-enhancing technologies, with real-world examples.

In spite of the physical distance between the attendees, they found a sense of community, with plenty of break-out sessions that promoted multiple interactions. This included a team Jeopardy event over home-delivered pizza (which took some nifty coordination), and an interactive session on identity development, intersectionality, and privilege, and the affect how these things can have on professional, academic, and personal lives.

The retreat is just one facet of the training program currently being carried out remotely, according to the CNEP leadership team: Garrett Stanley and Lena Ting, professors in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory; Chris Rozell, professor in Georgia Tech’s School of Electrical and Computer Engineering; and Michael Borich, assistant professor in Emory’s Department of Rehabilitation Medicine, Division of Physical Therapy (all four also are members of the Petit institute for Bioengineering and Bioscience at Georgia Tech).

Trainees and faculty are also taking part in monthly workshops and weekly seminars that focus on technical training and professional development.

With an award from NIBIB of nearly $1 million, CNEP was designed to take advantage of the explosive development of new tools for measurement and manipulation of nervous system function, with the goal of addressing challenges posed by the growing threat of neurological diseases and disorders on an expanding senior population. The program supports the development of PhD students in Biomedical Engineering at Georgia Tech and Emory, as well as Bioengineering, Electrical and Computer Engineering, and Machine Learning at Tech, leveraging  the growing strength of Neural Engineering at both universities.

“SfN is honored to recognize this stellar group of neuroscientists for both their groundbreaking research and their leadership in advancing women in neuroscience,” said SfN President Barry Everitt. “These women are dedicated to both innovative, creative approaches to scientific questions and mentoring, advocating, and being role models for young female and minority scientists. They have all already made significant contributions to their fields, developing new tools for research or therapeutic approaches.”

The Trubatch Award recognizes early-career researchers who have demonstrated great originality and creativity in their work. Singer, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and a member of the Petit Institute for Bioengineering and Bioscience at Georgia Tech, was called out for her unique research in addressing Alzheimer’s disease.

Singer’s groundbreaking insights into the interaction between neural activity and immune function is providing a possible new therapeutic approach, utilizing flickering auditory and visual stimulation at specific frequencies to affect not only sensory areas but memory circuits, too. These oscillations trigger biochemical signals that mobilize the brain’s immune cells to help clean up molecular hallmarks of Alzheimer’s disease, like amyloid and hyperphosphorylated tau. Repeated stimulation also improved memory in mouse models.

Because of the non-invasive nature of the procedure, it is considered a promising candidate for treatment (Singer recently presented the results of a preliminary clinical trial in humans).

Also receiving a Trubatch Award was Markita Landry (assistant professor of chemical and biochemical engineering at the University of California-Berkeley), who developed probes that can measure chemical communication between neurons. Winners of the Trubatch Award receive a $2,000 prize.

Other SfN award winners were: Carmen Maldonado-Vlaar (University of Puerto Rico) and Barbara Shinn-Cunningham (Carnegie Mellon University), who won the Bernice Grafstein Award for Outstanding Accomplishments in Mentoring; Courtney Miller (Scripps Research Institute) and Ghazeleh Sadri-Vakili (Harvard Medical School), who won the Louise Hanson Marshall Special Recognition Award; and Kristen Harris (University of Texas-Austin) and Yasmin Hurd (Addiction Institute of Mount Sinai), who won the Mika Salpeter Lifetime Achievement Award.

The Society for Neuroscience is an organization of nearly 36,000 basic scientists and clinicians who study the brain and the nervous system.

“High compliance with voluntary quarantine – where the entire household stays home if there is a person with symptoms or risk of exposure in the household – has a significant impact on reducing the spread,” said Pinar Keskinocak, the William W. George Chair and professor in the H. Milton Stewart School of Industrial and Systems Engineering (ISyE) and director of the Center for Health and Humanitarian Systems at the Georgia Institute of Technology. “Shelter-in-place (SIP) puts the brakes on the spread for some time, but if people go back to ‘business as usual’ after SIP, the significant impact is lost, so it needs to be followed up by voluntary quarantine and other physical distancing measures.”

Utilizing data from the state of Georgia, the study determined that a combination of non-pharmaceutical interventions, with various levels of compliance that change over time, could in some instances cut cumulative infections in half and reduce the peak number of infections to about a third of what could have been seen, “flattening the peak” to avoid overwhelming a state’s healthcare system. 

The study compared actual statistics to revised models of what could have happened in the state during the past seven and a half months without the physical distancing. As Covid-19 cases increase toward what may be a new peak this fall, the study could help public health officials evaluate the benefits of potential intervention strategies, for example, in the debate around K-12 school closure.

The study modeled the number of Covid-19 infections and resulting severe outcomes, and the need for hospital capacity under social distancing, particularly, school closures, shelter-in-place, and voluntary quarantine. 

“As one would expect, there is variation across the state in the observed data, which depends in large part on people’s behaviors,” said Nicoleta Serban, who is the Joseph C. Mello chair and professor in ISyE. “For example, mobility increased faster in some counties compared to others, which is likely to be correlated with increased physical and social interactions, and therefore faster spread of the coronavirus.”

The team, including Georgia Tech ISyE Ph.D. students Buse Eylul Oruc and Arden Baxter, developed and used an agent-based simulation model to project the infection spread. “This is a sophisticated mathematical model which mimics what might happen in practice – under different scenarios – by capturing the progression of the disease in an individual, as well as the interactions between people in the household, in peer groups such as schools or workplaces, or in community groups such as grocery stores,” Oruc said.

The model utilizes parameters specific to Covid-19 and data from Georgia on population interactions and demographics. The study covered a period starting February 18, evaluating different social distancing scenarios, including baselines in which no intervention would have taken place or the only intervention would have been K-12 school closure, comparing them to combinations of shelter-in-place and voluntary quarantine with different timelines and compliance levels. 

Outcomes were compared at the state and community level for the number and percentage of cumulative and daily new symptomatic and asymptomatic infections, hospitalizations, and deaths; Covid-19-related demand for hospital beds, ICU beds, and ventilators. 

The number of hospitalizations in Georgia turned out to be fewer than models last spring had forecast, but “models accurately predicted which hospital regions of the state that would have the largest gaps between number of people with severe outcomes and available care capacity – and therefore face potential shortages of ICU beds, hospital beds, and ventilators,” Baxter said. 

The results suggest that shelter-in place followed by voluntary quarantine reduced peak infections to less than a third of what we would have seen if no intervention had taken place and to less than a half if only schools had been closed. The models predicted correctly that the interventions would delay the peak from April to sometime between late July to mid-September, reducing the daily strain on health care systems.

According to the study, increasing shelter-in-place duration from four to five weeks yielded between 2% to 9% and 3% to 11% decrease in cumulative infection and deaths, respectively. Regardless of the shelter-in-place duration, increasing voluntary quarantine compliance decreased daily new infections and cumulative infections by about 50%. The cumulative number of deaths ranged from 6,660 to 19,430 under different scenarios. 

As infection rates rise in the United States during late October, the study could help public health officials select the best techniques for addressing the viral threat. Georgia’s total population is approximately 10.5 million, and Covid-19 related deaths have exceeded 7,600.

“The study further highlighted and quantified the impact of how compliance with public health measures impact infectious disease spread,” Keskinocak said. “The takeaway message is that each of us have the power to control our health by making the right choices.”

“As individuals and as a nation, we often expect technological or medical fixes or cures to health problems, whereas many of these problems, whether they are at the individual level or the public health level, are caused by or exacerbated by our choices and behaviors,” Keskinocak said. “For many of them, we don’t need a new fancy device, drug, or technology to make things better. As individuals, or households, or communities, we have the power and the responsibility to impact and improve our own health, and the public health, by making healthy choices.”

This research was supported in part by the William W. George endowment, the Virginia C. and Joseph C. Mello endowments, a National Science Foundation Graduate Research Fellowship (DGE-1650044), an NSF grant to support the high performance computing facilities at Georgia Tech (MRI-1828187), and research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following Georgia Tech benefactors: Andrea Laliberte, Joseph C. Mello, Richard “Rick” E. & Charlene Zalesky, and Claudia & Paul Raines. The funders played no role in the study design, data collection, analysis, interpretation, or in writing the manuscript.

CITATION: Pinar Keskinocak, Buse Eylul Oruc, Arden Baxter, John Asplund, and Nicoleta Serban, “The impact of social distancing on COVID19 spread: State of Georgia case study.” (PLOS ONE, 2020) https://doi.org/10.1371/journal.pone.0239798

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Writer: John Toon

At this particular gathering, Gleason gave a presentation of his work – a safe, low-cost, easy-to-use (and develop) 3D camera (utilizing an X-Box gaming system) to assess the risk of obstructed labor for patients in Ethiopia. But after hearing Yeo’s presentation about wearable device technology, Gleason approached him and said, “’What if we use your technology to monitor the health of neonates in Africa?’ In a minute we came up with this idea.”

The idea is to use Yeo’s wireless, wearable device for continuous health monitoring of neonates (infants under four weeks of age), who have the highest risk of mortality, particularly in the developing world. Yeo is developing the soft electronic sensor system for the project.

“Over the last 20 to 30 years, we’ve done a pretty good job at reducing childhood mortality rates, but actually if you look at the neonatal mortality rates, they’ve almost flatlined,” said Gleason, an associate professor in both the Wallace H. Coulter Department of Biomedical Engineering (BME) at Georgia Tech and Emory University and the George W. Woodruff School of Mechanical Engineering at Tech.

“This first month of life period is when about half of all child mortality happens and most of these neonatal deaths occur in the first week of life,” Gleason adds.

Yeo, assistant professor in the Woodruff School and the Coulter Department, has developed a small, wireless, wearable electronic device that would adhere on an infant’s chest like a Band-Aid and communicate to a tablet or smartphone to offer real-time, continuous monitoring of temperature, heart rate, respiratory rate, and blood oxygen concentration, with alarms for high risk conditions. It could provide timely indication to mothers and health care workers regarding hypothermia, apnea, asphyxia, respiratory distress, hypoxemia, oxygen oversaturation, neonatal infections, and sepsis. 

“The hospitals we work with in Ethiopia really don’t monitor [the infants] very often – there are often too few probes, and healthcare workers must go to each neonate and take measurements of heart rate and blood/oxygen as they have time,” said Gleason. “So, I thought if we have a device like this that can continuously monitor four key parameters – heart rate, respiration rate, blood/oxygen level, and temperature – we could identify at-risk neonates while there is still time to intervene. This could reduce neonatal mortality in low-resource settings like Ethiopia.”

The funding will support a clinical pilot study among 50 neonates in the Neonatal Unit at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, where Gleason and his research team will work with clinicians, engineers, and hospital staff to collect essential data, assess the efficacy, improve usability and participant acceptability, and assess the feasibility, market, and cost of local manufacturing of this all-in-one wearable device.

Leading the Ethiopian team are clinical researchers Asrat Demtse, who is a neonatologist, and Abebaw Fekadu, who heads up the Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa, a sub-awardee on the Gates grant).

“We’re going to pilot this in hospitals, but I think the long-term version for this could be a first seven day-of-life baby monitor for at-risk newborns that a mother has connected to an app on her phone,” said Gleason. “That would be amazing. There’s a little bit of research between now and then to get that to work, but it can totally be an application. And even here in the U.S., we have sudden infant death syndrome, sleep apnea, etc. and this device could potentially catch all those things. I think this is an opportunity to save the lives of many babies.”

Margulies was selected for her work "identifying how and why injuries occur in children’s brains and lungs through the development and use of novel platform technologies and models, and for translating basic discoveries of three therapies in pre-clinical trials," according to the Academy. She is only the second person from Georgia Tech to receive the honor. The late Bob Nerem, founding director of the Petit Institute for Bioengineering and Bioscience, is the other.

Margulies is the Wallace H. Coulter Professor and Chair in the Wallace H. Coulter Department of Biomedical Engineering (BME) at Georgia Institute of Technology and Emory University, a shared department between the two schools. She is also a Georgia Research Alliance Eminent Scholar in Injury Biomechanics. Her research interests center around traumatic brain injury in children and ventilator-induced lung injury with a focus in these areas on prevention, intervention and treatments.

“We are incredibly proud and offer our warmest congratulations to Susan Margulies as she is named to the 2020 class of the National Academy of Medicine,” said Steven W. McLaughlin, provost and executive vice president for Academic Affairs at Georgia Tech. “This well-deserved distinction is a testament to her as an exemplary scholar, leader, and collaborator.”

New NAM members are elected by current members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health.

Margulies came to Georgia Tech and Emory in 2017 from the University of Pennsylvania. She now leads a BME department that is consistently ranked as one of the nation's most prominent programs of its kind in both graduate and undergraduate education. In 2020, U.S. News & World Report ranked BME’s graduate program (based at Georgia Tech) No. 2 in the U.S., and  the joint Georgia Tech/Emory BME graduate program was also ranked No. 2. It is the largest BME department in the country, with 68 faculty on two campuses and more than 1,500 undergraduate and graduate students.

Margulies, also a member of the Petit Institute, earned her BSE in Mechanical and Aerospace Engineering at Princeton University and a PhD in Bioengineering from the University of Pennsylvania. She completed a postdoctoral fellowship at Mayo Medical School. Earlier this year, in February, Margulies was also elected to the National Academy of Engineering (NAE), which is among the highest professional distinctions conferred to an engineer.

Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine and related policy and inspires positive actions across sectors.

National Academy of Medicine Elects 100 New Members

The conversation will take place Monday, Oct. 19, from 1 to 2 p.m. via Microsoft Teams, with a maximum capacity of 250 attendees, limited to those logged in with a Georgia Tech email address. Attendees will have the chance to ask questions, and a recording will be made available on the Petit website following the event.

In addition to the many research angles of Covid-19 — including therapeutics, diagnoses, co-morbidities, public health, public policy, and healthcare systems — this session will highlight the health disparities associated with Covid-19, providing an additional perspective into this public health crisis.

The discussion has been planned and organized by a committee for diversity, equity, and inclusion within the Petit Institute. The group was formed in September following a June town hall and a collective desire within the community to take action following national race-related tragedies.

“The goal of our committee is to create a safer, more inclusive, and more highly prosperous environment for our historically underrepresented minority faculty, trainees, and staff,” said Ed Botchwey, committee chair and associate professor in the Coulter Department. “We hope to maintain a focus on anti-racism action within our Institute.”

In support of this goal, the group began hosting town halls within the Petit community on ways to think about systemic racism across disciplines.

“We must confront the routines, biases, and contradictions that preserve the status quo,” Botchwey said. “This town hall is a fresh call to antiracist action in the bioengineering and bioscience community. I’m looking forward to our conversation as we look for ways in which all of our members can answer the call.”

Other committee members include:

• Nettie Brown, BME, predoctoral representative
• María Coronel, ME, postdoctoral representative
• Andrés García, ME, Petit Institute executive director
• Milan Riddick, BME, undergraduate representative
• Lakeita Servance, Petit Institute, staff representative

Looking like any other small vial of clear liquid, these programmable drugs would communicate directly with our biological systems, dynamically responding to the information flowing through our bodies to automatically deliver proper doses where and when they are needed. These future medicines might even live inside us throughout our lives, fighting infection, detecting cancer and other diseases, essentially becoming a therapeutic biological extension of ourselves. 

We are years away from that, but the insights gained from research in Gabe Kwong’s lab are moving us closer with the development of ‘enzyme computers’ — engineered bio-circuits designed with biological components, with the capacity to expand and augment living functions.

“The long-term vision is this concept of programmable immunity,” said Kwong, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, who partnered with fellow researcher Brandon Holt on the paper, “Protease circuits for processing biological information,” published Oct. 6 in the journal Nature Communications. The research was sponsored by the National Institutes of Health.

The story of this paper begins two years ago when, Holt said, “our lab has a rich history of developing enzyme-based diagnostics; eventually we started thinking about these systems as computers, which led us to design simple logic gates, such as AND gates and OR gates. This project grew organically and we realized that there were other devices we can build, like comparators and analog-digital convertors. Eventually this led to the idea of taking an analog-to-digital converter and using that to digitize bacterial activity.”

Ultimately, they assembled cell-free bio-circuits that can combine with bacteria-infected blood, “with the basic idea that it would quantify the bacterial infection — the number of bacteria — then calculate and release a selective drug dose, essentially in real time,” said Holt, a Ph.D. student in Kwong’s Laboratory for Synthetic Immunity and lead author of the paper. 

The researchers sought to construct bio-circuits that use protease activity to process biological information under a digital or analog framework (proteases are enzymes that break down proteins into smaller polypeptides and amino acids). The team built its analog-to-digital converter with a tiny device, made only of biological materials, that changed signals from bacteria into ones and zeroes. Then, the circuit used these numbers to choose the proper dosage of drugs needed to kill the bacteria without overdosing.

That’s the traditional approach — bio-circuits digitizing molecular signals, allowing operations to be carried out by Boolean logic. The second part of the team’s new paper takes a more nuanced approach, with a focus on analog circuits as opposed to digital. “We treat protease activity as multi-valued, signals between one and zero,” Holt said. 

That multi-valued approach led to yet another idea, and ultimately to the bigger picture of analog bio-circuits.

“We got tempted by this idea of fuzzy logic, where you can think about what happens if there’s a signal between zero and one,” he added. “That’s more like an analog circuit. We were really inspired by this concept, so we decided to build analog bio-circuits with the same basic materials as before — proteases and peptides. And we were able to solve a mathematical oracle problem, Learning Parity with Noise.”

The ability to process information from the biomolecular environment with an analog framework is critical, according to Kwong.

“Fuzzy logic is interesting because biology doesn’t think in zeroes and ones,” he said. “Biology operates as a spectrum. So if you think about enzymatic activity, it’s never just on and off. It’s on, and the activity can be anywhere between zero and one. So the long term goal is to recognize that biology is not as simple as a digital electronic circuit. You actually need some capacity to work with analog signals.” 

This work was funded by an NIH Director’s New Innovator Award (Award No. DP2HD091793) as well as an R01 from the NCI (GR10003709). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NIH.

Competing interests: Gabe Kwong is co-founder of and consultant to Glympse Bio, which is developing products related to the research described in this paper. This study could affect his personal financial status. The terms of this arrangement have been reviewed and approved by Georgia Tech in accordance with its conflict of interest policies. Holt and Kwong are listed as inventors on a patent application pertaining to the results of the paper. The patent applicant is the Georgia Tech Research Corporation. The application 24 number is PCT/US19/051833. The patent is currently pending/published (publication no. WO 25 2020/061257). The biological analog-to-digital converter and the analog protease circuits are covered in the patent. 

CITATION: Brandon Holt, Gabe Kwong. “Protease circuits for processing biological information.” (Nature Communications, 2020)  (https://www.nature.com/articles/s41467-020-18840-8)

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Writer: Jerry Grillo

The measles outbreak that began in west Texas in late January 2025 continues to grow, with 400 confirmed cases in Texas and more than 50 in New Mexico and Oklahoma as of March 28.

Public health experts believe the numbers are much higher, however, and some worry about a bigger resurgence of the disease in the U.S. In the past two weeks, health officials have identified potential measles exposures in association with planes, trains and automobiles, including at Washington Dulles International Airport and on an Amtrak train from New York City to Washington, D.C. – as well as at health care facilities where the infected people sought medical attention.

Measles infections can be extremely serious. So far in 2025, 14% of the people who got measles had to be hospitalized. Last year, that number was 40%. Measles can damage the lungs and immune system, and also inflict permanent brain damage. Three in 1,000 people who get the disease die. But because measles vaccination programs in the U.S. over the past 60 years have been highly successful, few Americans under 50 have experienced measles directly, making it easy to think of the infection as a mere childhood rash with fever.

As a biologist who studies how viruses infect and kill cells and tissues, I believe it is important for people to understand how dangerous a measles infection can be.

Underappreciated Acute Effects

Measles is one of the most contagious diseases on the planet. One person who has it will infect nine out of 10 people nearby if those people are unvaccinated. A two-dose regimen of the vaccine, however, is 97% effective at preventing measles.

When the measles virus infects a person, it binds to specific proteins on the surface of cells. It then inserts its genome and replicates, destroying the cells in the process. This first happens in the upper respiratory tract and the lungs, where the virus can damage the person’s ability to breathe well. In both places, the virus also infects immune cells that carry it to the lymph nodes, and from there, throughout the body.

What generally lands people with measles in the hospital is the disease’s effects on the lungs. As the virus destroys lung cells, patients can develop viral pneumonia, which is characterized by severe coughing and difficulty breathing. Measles pneumonia afflicts about 1 in 20 children who get measles and is the most common cause of death from measles in young children.

The virus can directly invade the nervous system and also damage it by causing inflammation. Measles can cause acute brain damage in two different ways: a direct infection of the brain that occurs in roughly 1 in 1,000 people, or inflammation of the brain two to 30 days after infection that occurs with the same frequency. Children who survive these events can have permanent brain damage and impairments such as blindness and hearing loss.

Yearslong Consequences of Infection

An especially alarming but still poorly understood effect of measles infection is that it can reduce the immune system’s ability to recognize pathogens it has previously encountered. Researchers had long suspected that children who get the measles vaccine also tend to have better immunity to other diseases, but they were not sure why. A study published in 2019 found that having a measles infection destroyed between 11% and 75% of their antibodies, leaving them vulnerable to many of the infections to which they previously had immunity. This effect, called immune amnesia, lasts until people are reinfected or revaccinated against each disease their immune system forgot.

Occasionally, the virus can lie undetected in the brain of a person who recovered from measles and reactivate typically seven to 10 years later. This condition, called subacute sclerosing panencephalitis, is a progressive dementia that is almost always fatal. It occurs in about 1 in 25,000 people who get measles but is about five times more common in babies infected with measles before age 1.

Researchers long thought that such infections were caused by a special strain of measles, but more recent research suggests that the measles virus can acquire mutations that enable it to infect the brain during the course of the original infection.

There is still much to learn about the measles virus. For example, researchers are exploring antibody therapies to treat severe measles. However, even if such treatments work, the best way to prevent the serious effects of measles is to avoid infection by getting vaccinated.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

They are Margaret E. Kosal, an associate professor in the Sam Nunn School of International Affairs, and Juan D. Rogers, professor and associate chair in the School of Public Policy.

Rogers was selected for his contribution to “the development of new models and tools for impact assessment of R&D programs.” Kosal was chosen for her work helping develop “testable frameworks to explore the relationships between science, technology, and security and to explain their impacts on geopolitics,” according to the AAAS.

Founded in 1848, AAAS says it is the world’s largest general scientific society. It seeks to advance science through programs that include science policy as well as education and public engagement.

“This year’s class of fellows are the embodiment of scientific excellence and service to our communities,” said Sudip S. Parikh, the organization’s chief executive officer and executive publisher of Science journals. “At a time when the future of the scientific enterprise in the U.S. and around the world is uncertain, their work demonstrates the value of sustained investment in science and engineering.”

Kosal’s work focuses on explaining the intersection of emerging science and technology and security, especially in the areas of reducing threats from the proliferation of weapons of mass destruction and the relationship of emerging science and technology and geopolitics.

“My research is driven by scholarly, theoretically grounded discourse and discovery; by a commitment to bridging the academic/scholarly-policy gap; and by a dedication to advancing and championing research by students and young scholars that bridges the physical, life and social sciences, and engineering,” Kosal said.

"I'm honored and humbled to be selected as a fellow and look forward to further work bridging across disciplines," Kosal said.

Rogers’ work addresses the design, implementation, and evaluation of public policies that focus on science and technology, especially the uses of science and technology to address special social or economic needs. He has developed models for the evaluation of research and development processes and a framework for public expenditure reviews, including public policy functional analysis, evaluation of the impacts of R&D policies and scientific research, and technology transfer and diffusion policies for science and technology.

“I feel honored and humbled to be recognized for my research work by AAAS,” he said. “It is very rewarding to see that others find value in my contributions and, at the same time, feel responsible for communicating the importance of the research enterprise in today's world.”

Rogers and Kosal join five other Georgia Tech faculty in being selected for the honor this year. AAAS also chose Krista S. Walton and Chaouki T. Abdallah in the College of Engineering, Wilbur Lam and Anant Madabhushi in the Wallace H. Coulter Department of Biomedical Engineering, and Daniel I. Goldman in the College of Sciences.

In all 32 other Georgia Tech faculty members are active AAAS fellows, according to the organization’s website. This includes four in the Ivan Allen College: Diana Hicks, Kaye Husbands Fealing, retired Associate Professor Cheryl Leggon, and Aaron Levine, all in the School of Public Policy.

For more information on the other Georgia Tech recipients, see the campuswide announcement. For more information on the AAAS and this year’s class of fellows, visit the AAAS website.