Sepsis is a life-threatening condition caused by bacterial infection of the bloodstream that threatens nearly twomillion lives in the U.S. annually. Risk of death escalates quickly once bacteria or fungi enter the bloodstream;thus, quick and accurate detection of bloodborne pathogens is critical to inform immediate tailored treatment.However, the current standard practice to detect bloodborne bacteria and fungi requires in vitro culture tomeasure microbial growth, a process which takes 12-120 hours, with times to a confirmed negative sometimestaking as long as 5 days. Positive cultures then undergo additional tests to determine bacterial identity andantimicrobial susceptibility. This protracted process, which includes significant pre-analytical delays caused bysample transport to off-site microbiology labs and long culture times, represents a critical bottleneck in thediagnostic laboratory workflow, creating significant economic and labor burden to the healthcare system andprolonging the time that patients may be receiving inappropriate treatment (broad spectrum antimicrobial drugsinstead of targeted therapy). Aincobio is developing a rapid, near patient in vitro diagnostic test, the BactoPhore,that can be deployed outside of the centralized lab to isolate and detect intact and viable low-concentrationbacteria and fungi in blood specimens in 2 hours. BactoPhore achieves enhanced analytical sensitivity by rapidlyconcentrating pathogens for detection to deliver a positive result quickly. To do this, BactoPhore incorporates a"lab-on-a-chip" system that can isolate microbes from 0.5 mL whole blood using dielectrophoresis (DEP) anddetect metabolic signatures using electrochemical impedance spectroscopy (EIS) within a low-cost consumable.A diagnostic prototype of the BactoPhore isolates >90% of target bacteria in 30 minutes and can detect 100CFUs of E. coli within 2 hours. Further, target microbes pre-concentrated from 10 mL of whole blood can betrapped by DEP in <30 minutes, demonstrating the potential for processing clinically relevant volumes. In thisPhase I SBIR, Aincobio will demonstrate feasibility of commercializing the BactoPhore test for label-free,antibody-independent, and culture-independent detection, concentration, and isolation of low abundance andviable bacterial and fungal pathogens by 1) evaluating the integrated BactoPhore prototype with commonpathogens spiked into whole blood, and 2) demonstrating that BactoPhore enables rapid and sensitivedownstream sequencing of the target microbe by depleting host DNA prior to extraction and library preparation.Completion of these aims will establish proof-of-concept that BactoPhore has analytical sensitivity to confirminfection from whole blood within 2 hours and significantly improve time-to-results for the entire diagnosticworkflow from positive result to pathogen identification.
Public Health Relevance Statement: PROJECT NARRATIVE
Bloodstream infections are the primary cause for sepsis, a life-threatening condition that requires rapid and
accurate detection, identification, and analysis of the causative pathogen to inform immediate tailored treatment
plans. Current diagnostic workflows include long in vitro culture times and a number of pre-analytical sample
transport delays. Aincobio is developing a rapid "lab-on-a-chip" diagnostic test that will detect presence of
pathogens from whole blood within two hours and significantly improve time-to-result for the entire diagnostic
workflow, which will save lives and reduce the use of broad-spectrum antimicrobials.
Project Terms:
