Fighting Ebola: Sandia models and improves Liberia’s clinical sample transport system
As Monear Makvandi (6825) climbed the rickety staircase to the top of a guard tower to view Island Clinic Ebola Treatment Unit in Monrovia, Liberia, the infectious disease epidemiologist hesitated momentarily about whether to grab the rail for safety or to avoid touching it, even though the scientist in her knew there was no chance she could be exposed to the deadly Ebola virus.
Emerging from the stairwell, Monear, project lead for a Defense Threat Reduction Agency and United States Strategic Command Center for Combating Weapons of Mass Destruction (DTRA/SCC-WMD)-sponsored project to model and assess the blood sample transport system in Liberia, looked down on a courtyard where three adults and two children sat listlessly in plastic lawn chairs waiting for word that they were free of the virus.
Later, outside the Ebola treatment unit’s gate, Monear, manager Jen Gaudioso (6825) and complexity scientist Tom Moore (6132), watched from an SUV as a survivor was discharged from the clinic. They were told the man’s possessions were burned when he was admitted, so he was provided with clean hospital scrubs to wear, a week’s worth of beans and rice, and $10 for his journey home. No one was there to meet him. Due to lack of communications, his family likely did not know whether he was still alive.
Seeing the suffering, Monear hoped Sandia’s assessment of how patients’ blood samples are transported from Ebola clinics to diagnostic laboratories for testing would result in quicker reporting of diagnoses and shorter waits for patients.
In the project’s first month, the Sandia team developed a set of performance requirements for a new nationwide sample delivery system that is being adopted by the Liberian Ministry of Health, says Jen, manager of Sandia’s International Biological and Chemical Threat Reduction program.
“Prior to our analysis, samples were being transported from treatment units to labs on an ad-hoc basis. We developed a system and the country is implementing our system,” she says.
Reducing wait time key in controlling Ebola
When Liberians suspect they have Ebola, they check into large, open waiting rooms, usually lined with beds, called Ebola treatment units (ETUs). Their blood is drawn and they wait, sometimes for days, to learn their fate. During that wait, patients afflicted with less serious diseases might mix with Ebola sufferers and contract the virus there, exacerbating the epidemic.
While Sandia’s work is only one project among many that provide international assistance in Liberia, it’s important to help control the epidemic because patients get the care they need faster. The sooner public health professionals can identify Ebola carriers, the sooner they can locate people outside the clinic who had contact with a carrier and might be infected, say Tom and Pat Finley (6131), who led the computer modeling effort.
The project also enhances US national security. “Fundamentally, there’s the concern that Ebola will come to the US. The only way to prevent that from happening is to control the disease at the source,” Jen says. “The other fundamental national security interest, in countries that are already challenged, is stability. If the disease continues to progress in an uncontrolled fashion, that will lead to further instability in these countries in areas where there are active terrorist groups seeking haven.”
Fast, operational response to a dynamic situation
Monear, who has a cousin who was born in Liberia, was eager to put Sandia’s resources to work to help control the Ebola outbreak.
“I made a conscientious choice to come work at a national lab and focus on biological threat reduction and global health security. With our national security mission, we’re able to make a difference and identify small projects that contribute to the overall response effort,” she says.
The request from DTRA/SCC-WMD came in October. Sandia had done sample transport modeling for DTRA/SCC-WMD and the State Department before, Jen says. “They knew we understood the realities of working in a country like Liberia, so that we could come up with a realistic system and not an idealized version,” she says.
Jen quickly assembled the team.
Typically, modeling efforts like this take six to 12 months, but the fight against Ebola was a race against time, so Sandia needed to figure out a solution for Liberia in a matter of weeks.
“We really had this tremendous cooperation, working across centers, different departments, and programs. When the chips were down, the Labs let go of a lot of the day-to-day stove-piping, and we were allowed to get in there and do what we needed to do,” Pat says.
Pat’s group had experience modeling disease and logistics in developing countries. They immediately decided that their normal serial approach would be too slow, so they had to work the four tasks simultaneously, he says.
Leo Bynum (6132), the geospatial analytics lead, and his team collected data and transformed it into maps, a task made more difficult by incomplete, anecdotal, and, at times, incorrect data.
Pat and Tom worked on creating a model and simulation of Ebola treatment in Liberia that aimed to reduce travel times of the samples from the ETUs to the labs for testing, thus decreasing the time patients with and without Ebola were together.
Operations research analyst Jared Gearhart (6131) and his team developed algorithms to determine the optimal locations for labs and the best transportation routes, while accounting for such obstacles as a national curfew, poor infrastructure, lab capacity, and other factors.
And Jen, Monear, and Tom travelled to Liberia in November to interview healthcare workers in the field, international agencies working in the country, and Ministry of Health representatives so they could supply Sandia’s model with the latest data.
Culture changed by disease
The Sandians arrived for the six-day trip on a lone plane at the national airport in Monrovia and saw immediately how Ebola had changed Liberia. Before officially entering the country, Monear says they washed their hands in bleach on the tarmac outside the airport terminal and had their temperatures taken, a process repeated by guards outside buildings, restaurants, and hotels during their stay.
The team had no exposure to Ebola patients. All three say they felt safe the entire time they were in Liberia.
Sandia, which elevated the risk level for travel to Ebola-affected countries, including Liberia, extensively prepared the travelers on what precautions to take and provided a risk assessment based on a detailed itinerary of their trip. They also followed Centers for Disease Control and Prevention and state health department guidelines, which include a check at the US border for symptoms before re-entry and a requirement to monitor their temperatures and maintain daily contact with a public health worker for 21 days after their return.
“If you approached somebody with your hand extended, they would jump back,” Tom says, adding that elbow bumps in the air are the equivalent of a handshake in Liberia now.
The peak of the epidemic had passed when they arrived; the markets had just reopened, but people were fearful of physical contact, Monear says.
They found that getting a lab test result that takes a day or even several hours in the US could take as many as four days from remote areas of a country the size of Tennessee.
Prior to Sandia’s project, samples were taken to labs that were thought to be the closest or just because health care workers knew someone there, with little thought to lab capacity, travel difficulties, or other factors, Jen says. In one case, the team learned about samples carried on foot to a waterway, then brought by canoe to a bridge that connects with a “highway,” which is similar to a US hiking trail.
Sandia’s analysis helped influence where new diagnostic labs would be located, including one in Greenville in southeastern Liberia. “That’s been the area where we’ve had the most impact by helping Liberian stakeholders become aware of and overcome the challenges of providing lab results quickly in the remote region,” Jared says.
Motorcycles the vehicles of choice
Sandia’s model also showed the fastest options for transporting blood samples from patients, many in remote jungles, to diagnostic labs. Motorcycles are the vehicles of choice because they can move through traffic in more populated areas and are more easily pulled out when stuck on muddy roads, Monear says.
The model is flexible, so that when an outbreak occurs in one area of the country, ETUs can quickly adjust where to send samples to avoid a backlog at one lab. The model considered the capacity of labs and recommended multiple daily deliveries of samples to maintain a constant workflow, rather than delivering samples an hour before the end of the work day, the team says.
Sandia was uniquely suited for the project due to its computer modeling capabilities combined with its decades of experience in global health security. While in Liberia, Sandia’s team could reach back to the rest of the team to provide updated analyses, Jen says.
When Jen, Monear, and Tom attended meetings in Liberia, they would communicate any questions back to Pat, Jared, and others in New Mexico. The time difference worked in their favor. While the travelers slept, their colleagues answered the questions and incorporated changes into the model before work started in Liberia the next day.
With so many agencies involved in the response and the disease declining, it’s difficult to say exactly how Sandia’s sample transport system is affecting wait times in the ETUs, but Sandians say they were asked many times why they hadn’t brought their capabilities sooner to West Africa.
“It was taking two days to get samples. Now the system being implemented can help get results back in the same day or overnight and that will reduce interaction time,” Jen says.
Jen says Sandia’s modeling can help with questions of where to station healthcare workers, how to resupply labs, how to administer clinical trials of vaccines in Ebola-stricken countries, and many other logistics challenges. Discussions are ongoing about how to provide this expertise.
And a second DTRA/SCC-WMD-funded project in which Sandia will serve as a lab coordinator for a diagnostic lab staffed by contractors in Sierra Leone is underway, Jen says. A Sandian will visit that country in early 2015 to integrate the lab into the Ebola response system under the leadership of Sierra Leone’s Ministry of Health.
-- Heather Clark
Direct measurement of key molecule will increase accuracy of combustion models
by Holly Larsen
Sandia researchers are the first to directly measure hydroperoxyalkyl radicals — a class of reactive molecules denoted as “QOOH” — that are key in the chain of reactions that controls the early stages of combustion. This breakthrough has generated data on QOOH reaction rates and outcomes that will improve the fidelity of models used by engine manufacturers to create cleaner and more efficient cars and trucks.
A paper describing the work, performed by John Savee, Ewa Papajak, Brandon Rotavera, Haifeng Huang, Arkke Eskola, Leonid Sheps, Craig Taatjes Judit Zádor, and David Osborn (all 8353) and Oliver Welz of the University of Duisburg-Essen (and former Sandia postdoc), at Sandia’s Combustion Research Facility, is featured in the Feb. 6 edition of Science.
Thousands of chemical reactions are involved in the conversion of a fuel’s chemical energy into mechanical work in an automobile engine. The fleeting molecules that initiate, sustain, and then increase combustion are radicals: short-lived molecules that readily react and form new chemical bonds. Although many aspects of combustion are well established, a veil still covers ignition, the early stage of this process, and the chemistry that determines whether a fuel-air mixture will ignite rapidly, react slowly, or extinguish.
Decades of research worldwide have shown that QOOH must be a central connection in the network of ignition reactions. Researchers learned this by studying the products of ignition chemistry, looking at this web of reactions from its perimeter and working inward, gradually deducing the nature of the “reactive intermediate” molecules that must lie at the center.
Unlocking combustion’s secrets
Nearly 10 years ago, Sandia researchers designed a new instrument, the Multiplexed Photoionization Mass Spectrometer (MPIMS), to directly probe all kinds of intermediates, including the species that are at the center of important webs of reactions. In 2012, the Sandia team, together with colleagues from the University of Manchester and Bristol University in England used the MPIMS to directly measure reaction rates and products of the “Criegee intermediate,” a crucial reactive molecule in the web of reactions that occur in atmospheric chemistry.
“We not only measured the Criegee intermediates and provided fundamental knowledge about Criegee reactions,” says Craig, manager of Sandia’s combustion chemistry department. “We also disclosed to other researchers the process for generating and measuring the intermediates on their own. The impact has been enormous, as others have taken this knowledge and put it to work.”
QOOH was next in line.
But even with processes and tools in place, creative thinking was called for, says David, the chemist who headed the Sandia team. “We needed a specialized strategy to create enough QOOH radicals to detect, and we needed to determine the spectral fingerprint of a QOOH molecule, so that we would recognize it if we created it.”
The path to QOOH
Chemist John Savee came up with that strategy. Putting his knowledge of combustion chemistry to work, John helped pinpoint the best fuel for producing a detectable QOOH. He chose cycloheptadiene, a molecule with seven carbon atoms arranged in a ring.
Initial experiments seemed to prove John’s ideas were right, and the team turned to its computational experts, Ewa and Judit, who used quantum chemistry to predict what the experimentalists should have observed. Agreement between the two approaches would aid in confirming the discovery.
For the direct measurements, the team moved the MPIMS to the Advanced Light Source, a synchrotron user facility at Lawrence Berkeley National Laboratory. The intense tunable light created by the synchrotron allowed the team to measure spectral fingerprints of molecules, deducing the particular arrangement of atoms that gives a molecule its identity.
They confirmed that the spectrum of the radical they observed matched that predicted by Ewa and Judit, showing that it was in fact a QOOH molecule, rather than some other possible arrangement of the same atoms. Once again, the coupling of experimental results with computational verification gave the team confidence that they had detected and were measuring QOOH.
This teamwork was essential, says David. “Everyone on our team sits under one roof in the Combustion Research Facility. This means we can quickly marshal experts from different fields to attack a problem on multiple fronts, leveraging ideas and sparking creativity. When we confirmed we were seeing the center of the early combustion web, and could measure how QOOH was created and consumed, that was a thrill.”
The particular QOOH radical the team detected has a relatively long lifetime, reacting much more slowly with oxygen than any previous estimates. The impact of this class of QOOH radicals, which the team predicts will all have long lifetimes, is not yet clear, and their data will be incorporated into the latest combustion models to test its impact.
Interestingly, the same class of QOOH radicals has recently been proposed as a key intermediate that converts hydrocarbons in the atmosphere into small aerosol particles that impact health, visibility, and climate. Present models of atmospheric aerosol formation can’t match the rate and size growth of these particles, and the QOOH intermediate may help bring observations and models into agreement.
Knowledge is growing
With work done at Sandia and elsewhere, knowledge is growing about the chemical pathways of hydrocarbon oxidation. “We’ve been working on this reaction network from all sides for many years,” says Craig. “Now that we have directly measured reaction rates for a QOOH radical, we’ve filled in a large part of the picture.”
The researchers acknowledged there is still much to do to create a complete and accurate model of ignition or atmospheric oxidation. For example, measurements of other, more reactive QOOH species will be important for predicting ignition and oxidation behavior of a range of fuels.
“We know from our experience with the Criegee intermediate that researchers around the world will make great use of this information,” adds David. “And because these oxidation processes are important in many areas, including atmospheric studies, the impacts are likely to reach far beyond combustion.”
This research was funded by the Office of Basic Energy Sciences in DOE’s Office of Science.
-- Holly Larsen
Anthrax detector takes home national tech transfer award
by Nancy Salem
Sandia won the national Federal Laboratory Consortium’s (FLC) 2015 Award for Excellence in Technology Transfer for a credit card-sized device that can detect bacteria that cause anthrax.
BaDx (Bacillus anthracis Diagnostics) works in places with no power, refrigerated storage, or laboratory equipment. It requires minimal or no training and makes anthrax testing safer, easier, faster, and cheaper.
The award recognizes employees of FLC member laboratories and non-laboratory staff who have accomplished outstanding work in the process of transferring federally developed technology. A panel of experts from industry, state and local government, academia, and the federal laboratory system judge the nominations.
A Laboratory Directed Research and Development (LDRD) project in Sandia’s International Biological Threat Reduction Program led to BaDx. While a large team helped develop the detector, the FLC award recognizes Thayne Edwards (1714), Melissa Finley (6825), and Jason Harper (8631). They will receive the award April 29 at the FLC national meeting in Denver, Colo.
The technology was licensed to Aquila, a New Mexico woman-owned small business that specializes in the design and manufacture of technologies and services for nuclear security and international safeguards.
“It has been a remarkable experience to not only work with a Sandia research team in developing cool technology, but also with dedicated business partners to transfer that technology to,” Thayne says. “The awards that have recognized these efforts are another reminder to me of the great people I get to work with and the reward of solving difficult problems together.”
Jackie Kerby Moore, manager of Technology and Economic Development Dept. 1933 and Sandia’s representative to the FLC, says the competition for this year’s award was especially tough. “Sandia’s BaDx technology transfer recognition was one of only three selected across all of the Department of Energy laboratories for successful technology development and deployment,” she says. “It is very satisfying to be recognized by our peers.”
A deadly bacteria
Bacillus anthracis, the anthrax bacteria, is found in soils worldwide and can cause serious, often fatal, illness in humans and animals. It can survive in harsh conditions for decades. Humans can be exposed through skin contact, inhalation of spores, or eating contaminated meat.
Currently, samples must be propagated in a laboratory that uses specialized tools requiring a consistent power supply not always available in the developing world, says Melissa, who helps veterinary labs in less-developed countries improve safety, security, and efficiency at diagnosing infectious diseases. “Working with dangerous samples like B. anthracis spores places laboratory staff at risk,” she says. “Concentrating many positive test samples in a lab could also tempt someone to steal positive anthrax samples for nefarious uses.”
Another barrier is cost. “Farmers in many developing countries don’t make a lot of money, so they don’t pay for diagnostic testing often,” Melissa says. “When they do, they can’t afford to pay a lot for it.”
The most common diagnostic test for anthrax costs around $30, which is out of the reach of many farmers, perhaps discouraging them from testing animals they suspect as infected, Melissa says. The new device, which is like a pocket-sized laboratory, could cost around $5-$7 and does not require specialized tools.
Complex, sensitive, but simple to operate
BaDx needs no battery or electric power or special laboratory equipment. It’s hardy against wide temperature variation and can detect very small numbers of
B. anthracis spores. A field technician puts a sample swab into the amplification chamber, which contains selective growth media. The device then uses a lateral flow assay, similar to a common pregnancy test, to detect the B. anthracis. Magnetically operated valves allow the sample to advance from stage to stage to complete the testing process. A colored line appears on the device several hours later if the test is positive for the bacteria.
The technician can then initiate a chemical process that sterilizes the device, avoiding the risk of positive samples accumulating and falling into the wrong hands. “The device amplifies the B. anthracis so it can detect as few as 100 spores instead of the typical 1-10 million required for detection,” Jason says.
Jason and Thayne developed the microfluidics platform with the patent-pending magnetic valves that move the sample through the testing process. Bioscientist Bryan Carson, with technologists Jackie Murton and Bryce Ricken (all 8631), developed the selective media, and worked on building and testing the device, as well as helping to develop the decontamination strategy. Nanotechnology researchers George Bachand (1132) and Amanda Carroll-Portillo (8631) are working on improved strips for the lateral flow assay. Bill Arndt (6825), a researcher in the International Biological Threat Reduction Program, who regularly works in the developing world, provided guidance on device design.
“This is a wonderful example of where very sophisticated technology has enabled a practical solution to a very important problem” says Pete Atherton, senior manager of Industry Partnerships Dept. 1930. “Aquila has been a great partner for several years and their commercializing of this technology will help us fulfil our mission of serving the public good.”
The FLC is a nationwide network of about 300 members that provides the forum to develop strategies and opportunities for linking laboratory mission technologies and expertise with the marketplace.
The FLC Awards Program annually recognizes federal laboratories and their industry partners for outstanding technology transfer efforts and has become one of the most prestigious honors in technology transfer. Since its establishment in 1984, the FLC has presented awards to more than 200 federal laboratories.
-- Nancy Salem
Sandia sisters show school kids that they, too, can be engineers
by Nancy Salem
When twins Imani and Shauna Adams wrap up work as subsystem and components surety engineers at Sandia Labs, their day is hardly over. Most evenings — and weekends — they go from their jobs to their “kids,” middle and high schoolers who need a nudge on the path to careers in science, technology, engineering, and mathematics (STEM).
“They see our faces a lot,” says Shauna (422). “They think they can’t do math, and we say, ‘Why not? Here’s a problem. Just try. There, you did math.’ It’s an awesome experience to see the light bulb come on, to see someone who thought they couldn’t do math, who made all the excuses in the world, finally have a breakthrough. By the end of the day they accomplished something. They learned it’s not really that hard if you just try.”
Shauna and Imani (426) work with about 200 Albuquerque students a year through HMTech, sponsored by Sandia’s Black Leadership Committee, competitions with the National Society of Black Engineers (NSBE), and other STEM outreach programs. HMTech exposes students to such subjects as anatomy, physics, fractals, robotics, coding, computer programming, and life skills including personal finance and resume-writing. NSBE sponsors national contests in science and math, robotics, and renewable energy.
Shauna and Imani, who are two of the advisers to the Greater Albuquerque junior chapter of NSBE, spend countless hours tutoring, organizing workshops, helping with contests, and mentoring students in engineering. They help them prep for the ACT and SAT college entrance exams. “We introduce our kids to career aspects and point out their options,” Imani says. “We look at their class schedules and make sure they are on the right track. We show them where to find scholarships and push them to take advantage of summer opportunities through different STEM organizations.”
In the process, they serve as powerful role models. “When they see you and hear you talk to their class, they say, ‘She is an engineer. And guess what? She looks just like me,’” Shauna says. “Engineers look like all of us. When we go out and talk about engineering, it’s good for students to see people who look like them and have similar backgrounds. They say, ‘I can do this, too.’”
Gravitated to STEM
Shauna and Imani once stood in those shoes growing up in Hampton, Virginia, looking for a direction in life. They were latch-key kids — their father owned a business and their mother worked in community development and public housing — who came home to studies and science shows on TV like “Bill Nye the Science Guy” and “Zoom.” They had been exposed to engineering by volunteers in the schools who worked at nearby research labs and companies such as Lockheed Martin Corp. and Boeing Co.
“Our parents weren’t scientists, but we were always involved in science and math activities,” Imani says. “You gravitate to what you’re good at, and we were good at that.”
In middle school, the twins were in gifted programs and part of the Cooperating Hampton Roads Organization for Minorities in Engineering, or CHROME, which supported STEM awareness and opportunities. “We hung around with like-minded people,” Shauna says.
Their high school had an engineering focus, and they joined Project Lead the Way, a national nonprofit that offers resources and educational aid to K-12 students who want to enter STEM fields. Imani and Shauna took college-credit engineering courses through the program. They also did internships at NASA Langley through its Summer High School Apprenticeship Research Program, or SHARP, and attended the Hampton University Summer Transportation Institute focused on civil engineering.
“Our schools had many opportunities if you chose to take advantage of them,” Shauna says. “We had a lot of positive role models.”
In 11th grade, they had to decide whether to become math teachers, which they had in mind since childhood, or engineers. They didn’t know which way to go. “When our pre-calculus teacher heard that he said, ‘Why do you want to be a math teacher? Why not be an engineer?’” Imani says, “He said an engineer can always teach math, but a math teacher can’t necessarily be an engineer. When he put it that way it made sense. Engineering allows you to do both.”
Work and graduate school
The twins chose North Carolina Agricultural and Technical State University for college, majoring in mechanical engineering. North Carolina A&T is one of the country’s Historically Black Colleges and Universities and a top engineering school. “We loved it,” Shauna says. “It offered tremendous opportunities. It was an amazing experience.”
Imani and Shauna were Thurgood Marshall and Intel Corp. scholars and attended national conferences in New York City and San Jose, California. They interned as systems engineers at Pratt & Whitney in Connecticut through the Tuskegee Airmen Golden Eagle Scholarship. One summer was spent apart, with Shauna at Proctor & Gamble in Ohio as a product engineer and Imani at Exxon Mobile in Louisiana as a technical engineer.
They heard about Sandia through their involvement with NSBE and the American Society of Mechanical Engineers, and from Labs recruiters who visited North Carolina A&T. They wanted to attend graduate school and learned of Sandia’s Master’s Fellowship Program, which allows people to be hired by the Labs, work summers, and attend graduate school during the academic year.
“We were introduced to the concept of working and going to school, and that sounded great,” Shauna says. “You don’t run across that kind of opportunity often.”
They joined Sandia in 2011 and earned master’s degrees in mechanical engineering two years later from Ohio State University.
Inspiring the next generation
Imani works in quality for batteries and power sources. “It allows me to understand the components and the requirements that go into the design,” she says. “I work across components and weapon systems and get a good global aspect of the work at the Labs.”
Shauna works on various subsystems for both the B61 and W88 programs. “We make sure that what we’re building is being built according to requirements. Verification and validation methods are built into the design and testing,” she says. “Surety engineers are involved every step of the process. We’re one of the last signatures on the system.”
They work on multiple projects and it’s challenging, but they take the time to inspire the next generation, living by the NSBE code to excel academically, succeed professionally, and positively impact the community.
“I stand on the shoulders of a lot of other people,” Shauna says. “They sacrificed and opened doors for me to get where I am today.”
Imani says the opportunities she and her sister had growing up came from volunteers. “Someone was there to show us the way,” she says. “It’s our responsibility to do the same for someone else.”-- Nancy Salem