Thursday, November 21, 2024
11/21/2024
Program Director/Principal Investigator (Last, First, Middle): Anker, Jeffrey N. Abstract Our goal is to fabricate and validate a novel immunosensor which attaches to implanted medical devices to detect and monitor local infection biomarker concentrations using standard-of-care X-ray imaging. While implanted medical devices improve patient quality of life and extend life expectancy, they both reduce the number of bacteria needed to cause an infection and provide a haven for growth biofilms that tolerate both antibiotics and host immune system. Thus, over half of the 2 million hospital-acquired infections in the US are associated with implanted medical devices, with 90,000 annual attributed deaths and staggering costs. Early detection is key to treatment as it allows interventions before tissue damage or progression to systemic infection and sepsis. Likewise, during treatment it is important to monitor infections for eradication to ensure success of device replacements. However, systemic blood biomarkers are ineffective at early stages or during antibiotic treatment when the infection is localized near the device. Fluid aspiration is performed when needed, but not appropriate for screening or repeated monitoring as it is invasive, painful, can cause inflammation, and for areas such as hip is performed by a radiologist under fluoroscopy. By contrast, our device will be attached during implantation or surgical irrigation & debridement and noninvasively read with X- rays which are already acquired as the standard of care during followup and emergency visits. Previously, we demonstrated proof-of-concept for X-ray readout of radiodense dials for mechanical strain in cadaveric and sheep models, and pH measurements in cadaveric and a rat peritonitis models. Here, we will extend the concept for the first time to an antigen-responsive immunosensor, and specifically to detecting alpha- defensin an infection-specific biomarker released by activated neutrophils. To do this we will have to control the synthesis conditions, optimize device shape for sensitive readout at the clinical alpha-defensin threshold, and add mechanical gain mechanisms to the gauge. We will also study sensor stability over 1 month and more. We will develop a prototype and fasteners that attach it to a hip prosthesis and peritoneal dialysis tube. We will characterize the hip-attached sensor in human cadaver models and the peritoneal dialysis tube- attached sensor in a live rat model. The proposed research is significant because it develops a noninvasive method to detect, monitor, and study infection biomarkers in situ with the ultimate potential for reducing morbidity, mortality and associated cost from implant infections. Additionally, the approach can be generalized to a wide range of other antigens on implanted devices or injected sensors which would broaden what we can detect with X-rays and enable new tools for biomedical research and clinical practice. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
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