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Friday, April 19, 2024

UW-Madison researchers hope to decrease detection time for NEC

Portable device may be key to early recognition of necrotizing enterocolitis

Imagine holding a state-of-the-art research laboratory in the palm of your hand. The device can go anywhere you go, and nearly anyone can operate it. What would you do with it?

A team of scientists at the University of Wisconsin-Madison already have a plan. They hope to use the device to create a faster and cheaper diagnostic test for necrotizing enterocolitis, or NEC.

NEC is a medical condition that causes the death of intestinal tissue and is primarily seen in premature newborns. The condition is devastating because both its symptoms and diagnoses are ambiguous, and it progresses rapidly. In America, nearly 14 percent of very low-birth infants will be diagnosed with NEC. Worldwide, approximately 40 percent of preterm infant mortality can be attributed to NEC.

“It’s a multifactorial condition. People don’t really know what the cause is,” said Katie Brenner, a post-doctoral researcher in Douglas Weibel’s lab at UW-Madison. “When a baby leaves the sterility of the womb, it encounters a multitude of microorganisms including harmful bacteria. But in premature infants, the body is not mature enough. The immune system doesn’t recognize that there is a problem.”

Brenner has been tasked with finding a biomarker, or an indicator of necrotizing enterocolitis. She plans to do this by analyzing urine samples from preterm and normal infants in Madison.

“Bacteria in the gut metabolize nearly everything they come into contact with, and the products get excreted through urine,” said Brenner. “I am essentially looking for signs of NEC through the lens of metabolomics.”

Diagnosis of NEC happens after the infant starts to exhibit the condition’s superficial symptoms such as a distension of the stomach. By that point, however, the dangerous microbes are growing out of control and parts of the bowel have already been harmed. If the condition cannot be halted, immediate treatment is usually a resection of the intestine, which requires surgery.

These children will most likely never have a normal digestive system in their lives.

However, in resource-limited settings, caregivers without access to the lab and radiographic data necessary to identify NEC may not be able to administer treatment before the damage has been done.

The Weibel lab has engineered a portable, degassed plastic device that they hope will one day be used in these untrained and resource-limited environments to test for biomarkers of different diseases and conditions, especially the one for NEC. The device, smaller than a deck of cards, does not require any power to operate or connection to external technology. The cost of producing one cartridge is less than one dollar, and it can be disseminated easily.

By responding to pressure changes, the device can draw in fluid from a sample such as urine into its center chambers. The chambers are preloaded with reagents for specific assays and reactions. Because there are many chambers, many different tests to identify metabolites can be performed in parallel. The tests can be modified to change color or give off fluorescence based on the results. Essentially, the device does laboratory analysis without laboratory equipment.

After diagnosis, the device can also determine the next step: treatment. Most doctors usually administer a cocktail of antibiotics preemptively to kill the harmful microbes that cause NEC. But in doing so, the helpful bacteria are also destroyed, and their loss may further threaten the fragile state of newborns. If physicians can quickly identify what pathogens are actually present, they can tailor the set of antibiotics to do less harm to the internal environment.

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The device can act as a metabolomic survey and offer quick identification of the microbes in the system.

Earlier detection, diagnosis and treatment will give the preterm infants in America and around the world a better chance at survival and recovery.

“The main idea of our research is to leverage technology to diagnose something important, in matters where it could mean life or death,” said Brenner.

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