Friday, May 9, 2025
5/9/2025
Rapid Culture-Independent Detection of Sepsis Causing Microorganism Directly from Blood - ABSTRACT Sepsis is a rapid-developing and life-threatening condition and is one of the most common causes of death in hospitalized patients in the US. Sepsis is generally caused by bacterial, fungal, or viral infection. For well over half a century, blood culture has been the main diagnostic method, but can only inform us of the presence of microorganism growth. Although empirical antibiotic treatments are usually started as soon as patients presenting with signs of severe sepsis, gaps remain in our ability to rapidly identify sepsis-causing pathogens to guide treatment with higher precision. Studies have shown significant risks to septic patients associated with delayed results and inappropriate therapy, with each hour of delay in administration of appropriate antibiotics associated with increased mortality. Although molecular diagnostic technologies are available to improve identification accuracy, they still rely on a positive blood culture result which may take 12 to 48 h or even longer if the initial culture is unsuccessful. In this MIRA R35 project, we propose to develop novel nanopore- and click- chemistry-based approaches for accurate detection of sepsis-causing pathogen independent of blood culture in about 2 hours to support the early administration of source-directed antibiotics. To fit in the clinical sepsis treatment procedure, we will employ rapid automatic sample preparation and assay methods. Our methodology will target proteomic biomarkers, such as outer membrane proteins and virulence factors released into circulation, as they are less prone to interference of blood components compared to bacterial genomic materials, and are only secreted by viable microorganisms. The PI will accomplish the proposed goal by engineering nanopore biosensors meet clinical needs of sepsis causing pathogen detection and developing multiplex click chemistry amplified nanopore sensing for sepsis causing microorganism detection and prognosis. The scientific and clinical promises of our research lie in the innovative biosensing mechanism with unprecedented sensitivity for detecting sepsis causing pathogen protein biomarkers directly in blood; the user-friendly device prototype readily applicable in clinical settings; and the discovery of potential prognosis value of virulence factors. In the past years, the PI has established a successful research trajectory by mentoring a postdoctoral fellow and six PhD students, publishing high-impact research papers, and securing competitive research grants. We will utilize our group’s diverse expertise on biochemistry, proteomics, nanotechnology, and microelectronics in conjunction with our collaborators’ expertise on high specificity high affinity binding ligands and sepsis clinical diagnosis and treatment to ensure the success of proposed research. The nanopore biosensing platform resulting from this project will also benefit the general in vitro diagnostics field by offering a sensitive, user-friendly, cost-effective, and robust method for assaying protein biomarkers in biological samples.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).