Enter the 2019 R&D 100 Awards!
Universal Bacterial Sensor was a 2018 R&D 100 Award winner and received a Special Recognition R&D 100 Gold Award in the Corporate Social Responsibility category. All of the R&D 100 Awardees were announced at the R&D 100 Awards Gala held in Orlando, Florida on Nov. 16, 2018.
The R&D 100 Awards have served as the most prestigious innovation awards program for the past 57 years, honoring R&D pioneers and their revolutionary ideas in science and technology.
Submissions for the 2019 R&D 100 Awards are now being accepted. Any new technical product or process that was first available for purchase or licensing between January 1, 2018 and March 31, 2019, is eligible for entry in the 2019 awards.
The human innate immune system is capable of detecting all pathogens quickly, sensitively and effectively. It does this by selectively recognizing and binding to pathogen-specific biomarkers—or bacterial calling cards—via a suite of immune receptors.
However, it isn’t always capable of fighting off every bacterial infection on its own.
Modern medicine can come to the rescue, but only if doctors know what to treat for. Current point-of-care detection technologies are largely focused on identifying a specific pathogen that can be detected in a single sample—a task that requires insight doctors don’t always have until symptoms progress.
As antimicrobial resistance surges, infectious diseases re-emerge and the impact of the gut microbiome on health is better understood, it is more important than ever for healthcare professionals to be able to detect unknown threats before symptom appear—and without having a specific pathogen in mind.
A team at Los Alamos National Laboratory (LANL) has created a possible solution. They’ve designed a Universal Bacterial Sensor—modeled after the human innate immune system—that mimics the biological recognition of all categories of bacterial pathogens. Requiring less than a drop of blood, it detects all pathogens without prior knowledge of what they might be, before symptom onset and within 15 to 30 minutes. The sensor retains its sensitivity to identify the pathogens even as the bacteria evolve, such as when they acquire antibiotic resistance. The innovation was a 2018 R&D 100 Award winner and received a Special Recognition R&D 100 Gold Award in the Corporate Social Responsibility category,
“Your innate immune system is a universal bacteria sensor; it has evolved to be one over hundreds and hundreds of years,” said Jessica Kubicek-Sutherland, PhD, one of the LANL researchers responsible for the innovation. “The innate immune system recognizes conserved signatures for different pathogens. For bacteria it is recognizing conserved components of the bacterial cell wall.”
“Other people have a hard time detecting these conserved signatures because they are lipids, that is their biochemistry, which makes them very difficult to work with—they are sticky, and they are greasy,” added Kubicek-Sutherland, who started working on the sensor as an undergraduate and then again as a post doctorate and is now a staff researcher at LANL in the Physical Chemistry and Applied Spectroscopy department. “Our group is very good at working with these lipid-type molecules. We basically developed a system where we can use lipids to capture lipids and then detect this conserved signatures just like the innate immune system would.”
There are three major classes of bacteria—Gram-positive, Gram-negative and Gram-indeterminate and within those classes each has conserved signatures. The LANL sensor can broadly detect all three of these classes and identify which class of bacteria an infection is from.
“Knowing which class a pathogen is from then guides treatment,” explained Kubicek-Sutherland. “You know if its bacteria or not to start, and then you know which class it is so you can give antibiotics based on the cell wall of the bacteria you are trying to treat.”
In addition to Kubicek-Sutherland, LANL researchers responsible for the bacterial sensor include; LANL team leader and deputy group leader Harshini Mukundan, PhD; LANL staff scientist Aaron Anderson, MS; Loreen Stromberg, PhD, a post-doctoral fellow at LANL; Rama Murthy Sakamuri, PhD, former post-doctoral fellow at LANL (currently a Research Scientist at Bako Diagnostics); and Basil Swanson, PhD, a retired LANL Fellow.
Understanding the market
The bacterial sensor has been a long time in the making, said Kubicek-Sutherland. The initial research was started by Swanson, who had developed an optical biosensor decades before. Roughly ten years ago, that work was redirected toward creating a sensor that identified bacteria.
In 2017 things began to move forward when the team was accepted in the the UC/Los Alamos Entrepreneurial Postdoctoral Fellowship program, an initiative designed to mentor new entrepreneurs and create new companies from R&D advancements. It is targeted at existing postdoctoral researchers at LANL to gain skills in entrepreneurship and commercializing technology. A presentation on this program was given at the 2018 R&D 100 Conference.
The program involved two phases. In the first phase, the postdoctoral teams were coached by experienced investors and entrepreneurs who helped them polish their research for presentation to funding partners, learn to refine their story and hone their pitch. The six-month phase one culminated in a live pitching event of the innovation to the community known as DisrupTECH. From there four postdoctoral teams, including the bacterial sensor team, went on to phase two. The second phase was designed to facilitate the exploration and evaluation of a Los Alamos technology for commercialization and included a focused six-month full-time fellowship aimed at creating a new business in northern New Mexico.
“During those six months we were tasked with completing 100 customer interviews. We had to really explore the commercial potential of our technology,” said Kubicek-Sutherland. “It was a fantastic experience. As a scientist it is not something that you are taught—how to really talk about your technology to the general public. Just learning how to describe your technology in a way that actually catches people’s interest and not just hammering them with technical detail.”
Customer feedback prompted the team to reevaluate how they should market their technology. Although the sensor can detect all different types of bacteria, they learned that their potential customers—doctors—were not all the interested in such a broad application.
“We had originally thought every doctor in every clinic would use our sensor to test every patient to determine whether they had a bacterial infection or a viral infection,” said Kubicek-Sutherland. “After talking to doctors in a variety of different fields we learned that doctors want to get through their patients quickly and they have their dogma that they practice, so adding a test like this is just not going to happen because it’s going to take time, it’s going to cost money and they just don’t feel like the benefit outweighs that.”
Based on this feedback, the team started investigating using the bacteria sensor for specific applications. One area that they determined there was a lot of need that the sensor could be utilized was in diagnosing sepsis—a life-threatening condition that is often a complication of an infection.
“After talking to doctors in the field we learned that sepsis is a disease that has very poor diagnostics and basically anything that can enter the market would be useful,” said Kubicek-Sutherland.
The bacterial sensor is being explored in several other applications in addition to sepsis diagnostics.
Following the Entrepreneurial Postdoctoral Fellowship program, the LANL team received a grant from the Department of Defense to automate their bacterial sensor so that anyone can use it regardless of expertise. The DOD has also asked them to develop assays to detect select agent pathogens in blood using the bacterial sensor.
There has also been a lot of work focused on using the sensor for tuberculosis (TB) diagnostics, said Kubicek-Sutherland. There is need for a TB diagnostic, especially for kids as they don’t produce sputum the standard way TB is identified in adults.
The LANL team has partnered with a clinical in Kenya, where they are working on using their bacterial sensor to diagnosis kids in low-income areas.
“We are trying to diagnosis diseases in these poor kids who are infected with a whole bunch of different things,” said Kubicek-Sutherland. “A lot of them have TB, a lot of them have HIV and they are usually malnourished. What kills them often is something like a salmonella or a staph infection because they couldn’t diagnosis it the background of all of these other things. We’ve put a lot of focus in being able to tease apart these different kinds of infections so that we can help guide treatments.”
Going forward the team is working to make their technology more accessible. In addition to the efforts to automate, they are working on developing a more rugged design, and pairing with apps that would allow the sensor to be run at a remote location. They are also working to create a complimentary sensor that can diagnosis viral infections in addition to bacterial.
“The thought is to put our sensor on the bench at any doctor’s office that would require it, in emergency rooms, in remote clinics in other parts of the world or to have one that a solider could carry in a backpack and have any untrained user be able to use this sensor at the point of need,” said Kubicek-Sutherland. “That’s our ultimate goal. We are all really interested in tackling global health.”