New Technology Could Help Diagnose Sepsis in Hours

Researchers have developed a microfluidics chip that detected mock-sepsis conditions within a few hours, instead of at least two days by currently used methods. As sepsis left untreated can be fatal in as little as two days, a rapid blood test would provide medical professionals with a critical window of time in which to begin early antibiotics treatment of diagnosed patients.

“Normally when you detect sepsis, you do it through bacterial culture; that takes two days on the short end to 15 days on the long end. Most people die of sepsis at two days. The detection currently is on the exact same time scale as mortality, so we’re trying to speed that up,” said Dimitri Pappas, associate professor of chemistry at Texas Tech University (Lubbock, TX, USA), “Instead of the bacteria, we’re looking at the body’s immune response to those bacteria, because that’s what you really care about: the bacteria cause the infection, but it’s the body’s response that causes sepsis.” It begins with a systemic inflammatory response then progresses into sepsis and eventually septic shock, in which blood pressure plummets and organs fail.

“In the elderly, in people who are immune-compromised – people who have had surgeries, for example, or burns or they’re already fighting off infection – and in children as well, you see a runaway immune response where the body’s act of saving itself can actually be lethal,” said Prof. Pappas. When not fatal, sepsis can result in amputation of a limb or prolonged hospitalization.

Sepsis is suspected by a patient’s abnormal body temperature and rapid heart and breathing rates. “Those are all incredibly crude measurements,” said Prof. Pappas, “It leads to a lot of false positives.” Because doctors know the bacterial culture likely will take longer than a septic patient’s life span, they often order treatment immediately. “The way they treat sepsis right now is through a massive antibiotic administration,” said Prof. Pappas “That’s good, actually, but if you do it prophylactically and when it’s not needed, you’re basically helping create drug-resistant bacteria. So there’s a need to detect sepsis and to treat it but not to over treat it.”

To successfully treat septic patients, doctors need two critical pieces of information: the microorganism causing the infection and whether it can be eradicated by antibiotics. “Waiting for that information over several days is one of the main problems and reasons for the devastating outcomes,” said Dr. John Griswold, professor and chair emeritus, Department of Surgery, TTU’s Health Sciences Center, “Dr. Pappas has developed a test that should give us at least the indication of bacterial invasion within a matter of hours as opposed to days. The sooner we have an indication of microorganism invasion, the sooner we are on the path to successful treatment of these very sick patients.” Prof. Griswold added that sepsis is considered one of the most costly diseases in healthcare.

Prof. Pappas and graduate student Ye Zhang recently filed a provisional patent for a microfluidics chip that can speed up detection. “We can take a blood sample, introduce it into this chip and capture one cell type or move fluids around and add chemicals to dye the cells certain colors and do diagnostic measurements,” said Prof. Pappas.

Using their chip, a sepsis diagnosis can be confirmed in just four hours. “That rapid detection will let doctors intervene sooner and intervene when necessary, but it also allows them not just to detect it but to follow up treatment,” said Prof. Pappas, “you can follow and retest them over time to make sure the body’s response is returning to normal.”

Another advantage is that the chip requires less than a drop of blood per test. “It’s so minimal we could do this multiple times throughout the course of the treatment of the patient. If they’re not septic at hour zero, but they still look septic by other methods, we could test them in six hours and see if they’ve progressed or not,” said Prof. Pappas.

The chips are designed to detect certain white blood cells activated by the immune system to fight the infection. To this point, all testing has been done with using transformed stem cells. “We have stem cells that we transform into white blood cells, then we trick them into thinking there’s an infection. We add those infection-response blood cells to human blood in the concentrations we want and the timeframe we want,” said Prof. Pappas. The blood is then tested to see if the chip registers it as septic. “That allows us to refine the technique to make sure it’ll work, because human samples are far more variable,” he said, “Before moving to humans, we had to show it’ll work in the first place.”

“Ultimately, this type of work – for it to be successful – has to be commercialized,” he said. “It has to be out there in the hands of physicians.” The next step is to test the chip with patient blood. In collaboration with Dr. Griswold, Dr. Pappas will now begin enrolling patients.

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