By Patti Koning
The botulinum toxin, caused by the bacteria clostridium botulinum, is the most toxic substance known to man — a miniscule quantity can deliver a lethal dose. Despite remarkable scientific advances, laboratory mice remain the only reliable means of testing for botulism.
DISK JOCKEY — Ulrich Schaff holds a prototype SpinDx, a portable instrument for running assays for toxins and other substances. The SpinDx botulinum assay outperformed the current “gold standard” botulinum test, mouse bioassays, and has the potential to become a powerful biodefense diagnostic tool. (Photo by Randy Wong)
“The mouse bioassay is primitive, but remains the gold standard due to its sensitivity,” says Greg Sommer (8621). “Our SpinDx botulinum assay vastly outperformed the mouse bioassay in head-to-head tests, and requires absolutely no animal testing. Plus there are a lot of advantages in terms of cost and speed. Our test can be run in under 30 minutes, compared with days for the mouse bioassay.”
The botulinum assay uses the same lab-on-a-disk platform (SpinDx) as the radiation biodosimeter developed by Greg, Ulrich Schaff, and Chung-Yan Koh (both 8621). That device can perform protein measurements, white blood cell counts, and DNA testing, giving a rapid and detailed picture of radiation exposure (see Lab News, May 6, 2011).
The project received National Institutes of Health funding to adapt the lab-on-a-disk platform for toxin diagnostics. While botulism is quite rare — only about 145 cases are reported in the United States each year, according to the Centers for Disease Control and Prevention — the lethality of the toxin makes it an attractive candidate for bioterrorism.
“A very small amount in the food system could harm a lot of people,” says Greg. “This isn’t an assay with a large commercial market, therefore it’s not something that industry is going to take on. So this is where we, as a national lab, step in and fill the gap.”
There are several reports of botulinum having been weaponized by terrorists and nations at war, most notably by terrorists in Japan in the early 1990s as well as by Iraq during the Persian Gulf War. While the toxin has not yet been successfully deployed as a bioweapon, those working in national security are trying to get ahead of the problem with vaccines and therapeutics, as well as diagnosis and prevention. Additionally, botulinum is being used more frequently for therapeutic and cosmetic uses (Botox), creating greater risk for misuse.
Remarkably simple platform
The goal, says Greg, is to create a handheld, point-of-care device that can be used in the field by emergency responders. The SpinDx platform has several advantages for such a scenario. For one, it’s remarkably simple.
The device works just like a CD player, using a spinning disk to manipulate a sample.
“You just mix your sample and spin, says Ulrich. The device is very reproducible and reliable.”
Another advantage is the ability to process samples in virtually any form, which is especially important when testing for a food-borne toxin. If you prepare your sample correctly, this device can read it,‖ says Chung-Yan.
In a recent demonstration, he was challenged to test what was basically a continental breakfast — milk, half-and-half, yogurt, honey, hot chocolate mix, cinnamon, canned meat, peanut butter, and a raspberry vinaigrette salad dressing. “Milk and honey are difficult because they are viscous and opaque, plus honey has bee proteins that can interfere,” he adds. “Foods with a lot of fat — again, milk as well as peanut butter — are also traditionally hard to work with.”
Through a lot of trial and error, Chung-Yan made improvements to the assay that enabled it to handle thick, viscous food substances and increased its sensitivity under these challenging conditions. Collaborators at the USDA provided high-quality botulinum antibodies that bind with high affinity, enabling the higher sensitivity.
That ability to process so many food substances makes the device relevant for food safety testing. About 15 percent of botulism cases are food borne, usually related to home canning. In 2007, 14 people in seven states contracted botulism from hot dog chili sauce due to faulty manufacturing equipment at a food plant in Augusta, Ga.
“Food processing plants are looking for something that can be integrated into their assembly lines,” says Greg. “Our device will be suitable because it’s fast, inexpensive, and simple to operate.”
Tip of the iceberg
But botulism is just the tip of the iceberg. With proof-of-concept on the botulinum toxin, the team is turning its attention toward other toxins as well as pathogens, bacteria, and viruses. While the focus is on biodefense, Greg also sees the SpinDx device becoming a regular medical diagnostic tool.
“Ideally, this device would have a routine clinical application so medical personnel use it regularly,” he says. “The disks are consumable and assay-specific, so in an emergency you would just switch to the right toxin disk.”
The team is currently developing a deployable prototype to run the assays. The goal is a fully integrated, automated device ready for field testing.“We’ve done most of our testing in a benchtop setting, where we spin the sample on the disk and then read it out on a microscope,” he says. “The next step is to automate those processes and get the system into users’ hands. This technology has a lot of potential for so many applications.” - Patti Koning
By Nancy Salem
Every year, mechanical engineering students at the University of New Mexico build a serious race car. And every year, Sandia’s Imane Khalil guides them to the heart of the job — the engine.
“It’s a blast. We love working with her,” says Garrett Kuehner, project manager of this year’s UNM Formula SAE (FSAE) race car team. “Everyone recommends her course.”
SANDIA ENGINEER Imane Khalil and project manager Garrett Kuehner work together on the University of New Mexico’s 2012 Formula SAE race car. Imane teaches engine theory to the student team led by Kuehner. This year’s car is a few weeks away from completion. It will compete in June against cars built by undergraduate student teams from across the country.
Imane, manager of Structural and Thermal Analysis Dept. 6233, is an adjunct professor in the UNM mechanical engineering department. Her class, High Performance Engine, is one of several that comprise the optional FSAE capstone design course for seniors. Students who opt for FSAE work as a team to build, from the ground up, a race car that competes against entries from universities worldwide.
“My class covers the theory of the engine and how to improve the engine’s performance,” Imane says. “It brings together everything they have learned in four years.”
FSAE, started in 1979, is a student design competition for university undergraduates organized by SAE International, formerly the Society of Automotive Engineers. Its concept is that a fictional manufacturing company has contracted a design team to develop a small Formula-style race car to be evaluated for its potential as a production item. The target customer is the non-professional weekend autocross racer.
Each student team designs, builds, and tests a prototype based on a set of rules. The car then competes in one or more of seven international competitions in static and dynamic tests. Static tests are design, cost, and business presentation. Dynamic tests are acceleration, skid pad, autocross, endurance, and fuel economy.
FSAE encompasses all aspects of the engineering industry including research, design, manufacturing, management, development, testing, marketing, and finances.
UNM has entered cars in North American FSAE competitions since 1997. In 1998, the program came under the wing of Professor John Russell, a retired Air Force colonel, who made the project an accredited course.
Its cars generally finish in the top 25 percent of all US and world divisions, despite having an operating budget in the lower 50 percent of teams. The UNM team has finished as high as 14th in the world and 10th in the US, and last year was eighth in design and ninth in autocross, its best showing ever in those events.
This year’s competition will be in Lincoln, Neb., June 20-23. “We’re getting better and better each year,” Kuehner says. “It’s an evolutionary design process. Each team builds on the previous year.”
The program is set up for about 25 students who work on the race car over three semesters, or 18 months. Design begins in the spring and runs through summer. Manufacturing starts in the fall and wraps up the following spring, allowing for some overlap as the incoming team begins design work for its car. The team then prepares for the summer competition.
The team divides into groups that work on different parts of the car: chassis, suspension and steering, brakes, engine, drivetrain, and aerodynamics. Each group uses complex software during the design phase, and their input goes into creating a detailed CAD model of the car.
“This is the flagship project in the mechanical engineering program where students get hands-on design and manufacturing experience in a professional engineering setting,” Kuehner says. “The program is run similarly to a small business, mimicking the type of work found in industry. Considering team members are also balancing other courses, work, and personal lives, there are many sleepless nights spent working on the project.”
The estimated annual budget for the program is $55,000. About $18,000 goes to raw materials, as 95 percent of the vehicle is made at UNM. Sandia is a key sponsor, donating $10,000 a year through Community Involvement. “Sandia is doing a lot to help this program excel in terms of money and intellectual resources,” Imane says. “We really want to help the science and engineering at UNM.”
Imane’s one-semester class covers engine theory, including thermodynamics, heat transfer, and fluids, and works with Ricardo software — used by Ford, GM, and other auto manufacturers — to model the high-performance engine: 500 cc, dual overhead cam, 5 valve per cylinder. It runs on 85 percent ethanol.
“We buy an engine and by using computer modeling and simulations, we come up with improvements that optimize the engine for speed,” says Imane, who has been teaching the class six years ago.
Program director Russell says Imane’s contribution has been invaluable. “Much of the reason for our continued success can be attributed to Dr. Khalil’s dedicated support,” he says.
Imane says she is proud of the students, most of whom continue on to graduate school. Some have been hired by auto heavyweights like Ford, Chrysler, Toyota, and Honda.
“I love teaching and academia,” Imane says. “It’s my way of giving back to the community. I want to help UNM and help students excel at what they’re doing.”
Imane was born and raised in Lebanon during that country’s violent civil war. She moved to the US in 1989 and studied mechanical engineering at the University of California at San Diego, where she earned bachelor’s and master’s degrees and a doctorate in fluid and gas dynamics. She was hired at Sandia eight years ago.
Imane worked four years in California building airplane engines, a job that qualified her to teach in the FSAE program at UNM.
“It’s fun to work with the students,” she says. “I love science so teaching this class is not work to me. I leave the classroom feeling grateful to have this opportunity. It is very fulfilling.”
Imane says she feels strongly about mentoring young people because she had a mentor in her life.
“My graduate advisor, professor David Miller, gave me invaluable guidance and support which I attribute to the successes I’ve had,” Imane says. “In addition to teaching, I have had many opportunities for mentoring. The students are very receptive to the help a practicing engineer can provide. I have seen some of my students, with a little push, go much farther in their careers than they expected.” -- Nancy Salem
A former DARPA robot developed at Sandia is now serving an educational purpose at New Mexico Highlands University (NMHU).
About a decade ago, Sandia developed the Multi-function Utility Logistics Equipment Vehicle, or MULE, robot. The project was sponsored by DARPA — the Defense Advanced Research Projects Agency — Lockheed Martin, and Sandia to help troops haul heavy equipment across a variety of terrains, and could negotiate one-meter steps. But once the MULE had served its purpose, it was parked in a garage at Sandia’s Robotic Vehicle Range and left alone until the summers.
SANDIA PROGRAM MANAGER Jake Deuel (6532) joins Logan Herrera, a senior undergraduate computer science major at NMHU, Sandia senior staff scientist Wendy Amai (6532), NMHU computer science graduate student Miguel Maestas, and chair of NMHU’s computer and mathematical sciences department Gil Gallegos. (Photo by Rick Loffredo/NMHU)
For the past two summers, students and Gil Gallegos, chair of the computer and mathematical sciences department at Highlands, worked with the MULE as part of DOE’s FAST, or faculty/student program, which pairs students with professors for research projects.
Gallegos and NMHU students added hardware and software to expand the MULE’s capabilities.
“Every summer, we’d dust this off, and students would get very excited to work on it for the summer,” says Jake Deuel (6532), manager of the Robotic and Security Systems group. “We realized we weren’t doing anything with it, and found a way to donate it to NMHU for two years.”
Gallegos says the goal of having the MULE at the university’s lab is to help generate thesis topics for graduate students in the computer science department and for undergraduate senior capstone projects. He adds that it will be a valuable recruiting tool to encourage students to pursue STEM careers.
“We’re very appreciative of Sandia allowing us to use this. It really does improve our program, and it’s very exciting to have the robot in the lab and to have students excited about it,” Gallegos says.
Miguel Maestas earned his bachelor’s degree in computational engineering from NMHU two years ago and is now in his second semester as a master’s student. He says the MULE will be instrumental to his thesis work, and is anxious to start working with it. He will first run diagnostics to ensure all electronic parts are intact, and has plans to integrate a 3-D image capture function. Eventually, this would help with object and possibly facial recognition to enhance the robot’s navigational capabilities.
Currently, four undergraduate and three graduate students are signed up to work with the MULE, but Gallegos expects that having the robot on campus will continue to generate interest. Other projects in the works include software development to communicate with motors that control the MULE’s six wheels and shoulders and installing microcontrollers for individual joints, shoulders, and wheels.
“I’m hopeful that this will help recruit other students into the computer sciences department. It’s very exciting to be able to work with the MULE and to know that it has been used to help develop other projects that are state-of-the-art,” Maestas says. -- Stephanie Hobby