A traumatic brain injury can be a mysterious thing.
A mild concussion can’t be reliably captured by traditional diagnostic technologies like the MRI or CT scan, which are costly and not portable. Instead, physicians use a neurophysiological test that measures key indicators like balance, memory and cognitive skills, but it relies largely on the patient’s subjective answers to a series of questions.
The area of research to find better diagnostic tools languished until recently, when the military saw a spike in TBI rates among troops fighting in Afghanistan and Iraq—from 2001 to 2011, the annual number increased from 11,000 to 32,000.
In response, the Department of Defense has poured nearly a billion dollars into preventing, diagnosing and treating TBI. The funding has spawned more than 500 research projects, and developing a portable tool that can deliver an accurate diagnosis on the front lines has become an urgent mission.
“In the past, it was ‘Everybody gets better, be tough,’” says Col. Dallas Hack, director of the Army’s Combat Casualty Care Research Program. Now, with study after study showing the life-changing effects of a severe concussion, Hack says physicians are eager to identify the injured as soon as possible.
‘Needle in a Haystack’
The military is pursuing multiple technologies, but one of the most promising is a handheld device that tests TBI-related biomarkers found in the blood.
In particular, researchers have identified a few proteins released into the bloodstream after the brain is injured; the higher the concentration of these biomarkers in blood serum, the more severe the trauma. These proteins, however, are present in very low quantities, are difficult to measure and degrade quickly. Some can also lead to false positives as they’re associated not just with a brain injury, but also cancer or another bodily injury.
SFC Fluidics, a biomedical device company based in Fayetteville, Ark., is one of the outfits trying to solve this riddle. In 2009, it received a $5 million grant from the Army Medical Research and Materials Command to develop a TBI diagnostic tool for triaging on the front line. The company initially licensed a technology that used antibodies to isolate and quantify a specific protein biomarker from a drop of blood.
The method delivered a result within 30 minutes, but Dr. Sai Kumar, the company’s vice president of research and development, said it was less effective at protein concentrations of less than a billionth of a gram. What Kumar wants is a tool that can reliably measure at or below a picogram, or a few in a trillion. “It’s literally looking at a needle in a haystack,” he tells Txchnologist.
The company is also pursuing electrochemical biosensor chip technology, which has been billed as a “lab on a chip.” A clinician still uses a protein, but it is placed on a gold chip with an antibody. The device has two modes, one of which produces a signal from an electrochemical reaction, revealing the protein and its concentration. The detection happens in milliseconds, but the entire process, which involves separating and analyzing the plasma in blood, takes about an hour. Kumar is hoping to cut the time from blood draw to the result in half.
Many failures, few successes
TBI is a notoriously tough field to research—at least 30 phase-three drug trials have failed to effectively treat the injury. Few diagnostic tools have reached the clinical trial stage.
Kumar says researchers are all too aware of the risks. SFC Fluidics is focusing on the glial fibrillary acidic protein (GFAP), which preliminary studies have indicated as the most reliable, clinically useful TBI biomarker. Another biomarker, S100B, has been identified as a good negative predictor.
Kumar says that if researchers are successful in diagnosing through GFAP, the rest of the biomarkers will be a “piece of cake.” The company has its sights on other biomarkers, which are promising but can’t be disclosed yet.
If these devices find their way onto the front lines, they will be pocket ready. In hospitals, where they could be used to diagnose concussed athletes, car accident patients and seniors who have taken a nasty fall, they will be the size of a small printer that can be placed on a cart or carried by a nurse.
The company begins beta testing at its collaborators’ labs this fall and anticipates a clinical trial in early 2015. Kumar is hopeful that the results will be ready by the following year.
Though troops in Afghanistan are scheduled to withdraw in 2014 and presumably won’t require the capability for portable diagnostics in a combat zone, such a tool will still be vital for concussions sustained in training.
“Our long-term hope,” Col. Hack tells Txchnologist, “is to come up with things that prevent injuries in first place, or if they do have them, allow us to know how severe they are, then have something to help people recover.”
Top Image: Soldiers carry Pfc. Kristopher Sirnell between obstacles during a practice exercise for the Expert Field Medical Badge. Photo courtesy U.S. Army/Phil Sussman.