Latest NIH award aims for instrument capable of detecting botulinum, ricin, anthrax, other agents of concern

 First, in the early 1990s, came MicroChemLab. Then, in the early-to-mid 2000s, the “saliva device” and a follow-up technology, RapiDx. Those microfluidics-based platforms eventually led to SpinDx, unveiled earlier this summer as the latest in a line of medical diagnostic tools developed at Sandia. Many were created under the guidance of Anup Singh (8620), acting senior manager for the biological science and technology group located at the Labs’ California and New Mexico sites.

With that string of successes, it was hardly a surprise when Sandia was awarded another

major award recently — nearly $4 million over four years — from the National Institute of Allergy and Infectious Diseases at NIH. NIH has funded a number of projects at Sandia over the past few years.

“This was our plan: to build on our successes, hire good people, and not rest on our laurels,” Anup says.

With the latest NIH award, Anup says the objective is very clear: His team is tasked with producing a point-of-care instrument — one ready for the Food and Drug Administration’s (FDA) approval — that can detect a suite of biothreat agents, including anthrax, ricin, botulinum, shiga, and SEB toxin.

“This is currently an unmet need for the nation’s biodefense program,” says Anup. “A point-of-care device does not exist.”

The device, once developed, approved by FDA, and commercialized, would most likely be used in emergency rooms in the event of a bioterrorism incident.

“This will take things to the next level,” Anup says. In addition to the broader suite of toxins and bacterial agents that the device would test for, the other unique aspect of the project is that comprehensive testing with animal (mouse) samples will be conducted.

“Before, with other instruments we’ve developed, we would purchase blood, spike it with toxins, then test the blood. Now, we will take a live animal specimen, feed it botulinum and other toxins, then screen the blood of the mice to see if it can be detected. For shiga toxin, we will also try to get samples from naturally infected humans to test.”

Closer to the translational elements of research

This is an important step, Anup says, since toxins may behave differently in live animals and humans than they do in laboratory blood samples. “We are getting closer and closer to translational elements of research, which involves testing in animal and clinical facilities. This is part of the maturation of our bioresearch activities,” he says.

The project will also expand the technical capability of the SpinDx platform.

“When you look for bacterial agents, you don’t want to rely solely on proteins because you won’t get the detection sensitivity you need,” explains Anup. “So we are also using other methods that may lead to better detection limits and additional confirmation.”

The new NIH project includes collaborators possessing both animal modeling and device manufacturing expertise.

The University of Texas Medical Branch, with whom Sandia enjoys a years-long partnership, together with the US Department of Agriculture’s Western Regional Research Center in Albany, Calif., will provide Sandia with expert insight into toxins as well as animal lab facilities and expertise on diseases. Bio-Rad, a manufacturer and distributor of a variety of devices and laboratory technologies, will serve as a consultant on the project and will help evaluate plans for product development, assist with manufacturers’ criteria on the device that is developed, and provide important feedback on building a prototype device.

Although the latest NIH award represents a continuing success story for Sandia’s microfluidics/bioresearch work, Anup stresses that it was part of a thoughtful strategy that has been followed for several years.

“You’ve got to keep innovating and coming up with the next thing,” says Anup. “Every technology has its lifecycle. As good as SpinDx is, we know there will be other technologies, better technologies, that come along in the next few years. We have to continue to innovate to meet the needs of our customers, understand what other competing technologies are being designed to solve the problems, and develop technologies that provide an improvement.”

The need for diagnostic devices in the biodefense area is not going away any time soon, Anup says, since there are always new diseases springing up for which good diagnostic assays aren’t available.

“Plus, we want these devices to be dual-use,” he adds. “We’re not just going to wait for the next anthrax letter incident to happen for our devices to be used and tested; we want to be useful for other things as well, like infectious diseases. We ask ourselves: Can we use something like this [SpinDx or other, yet-to-be-developed devices] for the next SARS? What about the next swine flu outbreak? When we think of bio-threats, we think of man-made problems. But what about nature-made problems?”

Those two areas, he says, will keep Sandia’s bioresearch efforts engaged for years to come.

“That’s where the value of the national labs really comes in. With long-term problems that require a sustained effort, our capabilities and culture are a very good fit. Sponsors like NIH have begun to realize this, which is what they’re essentially telling us with this latest award. It takes more than one grant to solve big problems like these.”

A team success

Like so many complex Sandia technical efforts, the SpinDx project would not be a success without important contributions from a number of important team members.

Chung-Yan Koh (8621) leads the development of the assays in SpinDx, while Matt Piccini (8621) leads the design and development of the device and its full functionality. Post-doc Scott Moen (8621) set up a testing facility at the University of Texas Medical Branch, and UTMB’s Johnny Peterson and Michael Leffelholz provided access to facilities and samples for testing of SpinDx.

The US Department of Agriculture (USDA) and University of Massachusetts-Dartmouth have also been key collaborators on the SpinDx project. Larry Stanker and Luisa Cheng at USDA have provided antibodies and animal samples for testing, while BR Singh and Easwaran Ravichandran at UM-Dartmouth have provided substrates and animal samples.

Finally, SpinDx never would have gotten off the ground without the efforts of former Sandians Greg Sommer and Ulrich Schaff, who led the early development of the technology. Greg and Ulrich are both on entrepreneurial leave and have founded a company to commercialize the technology.