title: Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation.
abstract: Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (≤1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.
authors.affiliation: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, Prince Consort Road, London, SW7 2AZ, UK. ingekherrmann@gmail.com m.stevens@imperial.ac.uk.
authors.forename: I K
authors.initials: IK
authors.lastname: Herrmann
authors.forename: S
authors.initials: S
authors.lastname: Bertazzo
authors.forename: D J P
authors.initials: DJ
authors.lastname: O'Callaghan
authors.forename: A A
authors.initials: AA
authors.lastname: Schlegel
authors.forename: C
authors.initials: C
authors.lastname: Kallepitis
authors.forename: D B
authors.initials: DB
authors.lastname: Antcliffe
authors.forename: A C
authors.initials: AC
authors.lastname: Gordon
authors.forename: M M
authors.initials: MM
authors.lastname: Stevens
mesh_terms: D000818:Animals; D001419:Bacteria / Q000302:isolation & purification*; D002449:Cell Aggregation; D055252:Cell-Derived Microparticles / Q000382:microbiology*; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D006801:Humans; D046210:Microfluidic Analytical Techniques; D009504:Neutrophils / Q000382:microbiology; D051381:Rats; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology