11/15/2024 Lilli Bresnahan
Written by Lilli Bresnahan
Illinois’ Grainger College of Engineering Jump ARCHES Research Program awarded funds to the detection of E. coli bypassing blood culture. This project is led by investigators Rashid Bashir, the Dean for The Grainger College of Engineering and professor of Bioengineering at UIUC, Enrique Valera, Research Assistant professor in Department of Bioengineering at UIUC, and John J. Farrell, Chair and Medical Director of Infection Control and Prevention at OSF HealthCare Saint Francis Medical Center.
Jump Applied Research in Community Health through Engineering and Simulation (ARCHES) Research Program was established in 2014. This program is an endowment partnership between Jump Trading Simulation & Education Center at OSF HealthCare and The Grainger College of Engineering at U. of I. It aims to provide direct access and grants to engineers and clinicians to fight against problems within health care.
The researchers believe “this project will provide a new diagnostic tool that will help eliminate the blood culture barrier,” according to the project’s executive summary.
The blood culture barrier refers to the blood culture laboratory test that is performed to detect bacteria in a blood sample by growing the initial few pathogens. According to FDA requirements, the blood culture is run up to five days for a confirmed negative. This is a problem because delaying the prescribed antibiotics, even for a few hours, leads to a significantly higher mortality rate for patients with potential sepsis. The risk of mortality increases 4-9% every hour treatment is delayed.
Normally, in current clinical practices, if an infection is suspected, broad-spectrum antibiotics are prescribed immediately, before the results of the blood culture.
“Therefore, what is needed is to provide a diagnostic tool that does not depend on blood culture to detect low concentrations of bacteria in a few hours,” Valera said.
Along with the patient’s information, such as their history, physical examination, and routine investigations, recognizing low detections of bacteria could quicken the clinical decisions for early detection of bacteremia and sepsis.
Recognizing the low detections of bacteria through a diagnostic tool that does not depend on blood culture is especially useful in “remote or under-resourced regions where access to bulky and expensive instrumentation can be extremely limited,” Valera said.
The researchers have three aims. First, they will combine their CRISPR cascade signal amplification method with their biphasic reaction— presence of a solid dried blood phase and a liquid solution phase— to allow for purification-free CRISPR-based diagnostics from whole blood. This process of combining means inhibitors, molecules present in the blood that interfere with the detection of bacterial DNA, are physically trapped in the solid-phase dried blood matrix. In the meantime, amplification reagents, molecules added to cause a detection reaction, can move into the solid porous area and begin the amplification. When blood is dried, a porous structure is formed, which the reagents needed for amplification can travel to, to find the bacterial DNA.
Aim 2 is the detection of E. coli from clinical samples obtained through OSF HealthCare in Peoria. Researchers will analyze 30 anonymous clinical blood samples, using the CRISPR cascade-based two-phase molecular detection reaction through the approved IRB protocols.
In Aim 3 the researchers plan to transfer their CRISPR cascade-based biphasic reactions to OSF HealthCare and design a small clinical study to assess the viability of their approach in the clinic. They will test E. coli positive and negative samples from patients at OSF HealthCare in Peoria.