RESUMEN

Sepsis following burn trauma is a global complication with high mortality, with ∼60% of burn patient deaths resulting from infectious complications. Diagnosing sepsis is complicated by confounding clinical manifestations of the burn injury, and current biomarkers lack the sensitivity and specificity required for prompt treatment. There is a strong rationale to assess circulating extracellular vesicles (EVs) from patient liquid biopsy as sepsis biomarkers due to their release by pathogens from bacterial biofilms and roles in the subsequent immune response. This study applies Raman spectroscopy to patient plasma-derived EVs for rapid, sensitive, and specific detection of sepsis in burn patients, achieving 97.5% sensitivity and 90.0% specificity. Furthermore, spectral differences between septic and non-septic burn patient EVs could be traced to specific glycoconjugates of bacterial strains associated with sepsis morbidity. This work illustrates the potential application of EVs as biomarkers in clinical burn trauma care and establishes Raman analysis as a fast, label-free method to specifically identify features of bacterial EVs relevant to infection amongst the host background.

Asunto(s)

Biomarcadores , Quemaduras , Vesículas Extracelulares , Sepsis , Espectrometría Raman , Humanos , Quemaduras/complicaciones , Quemaduras/metabolismo , Espectrometría Raman/métodos , Vesículas Extracelulares/metabolismo , Sepsis/metabolismo , Sepsis/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Femenino , Masculino , Adulto , Persona de Mediana Edad

RESUMEN

Sepsis following burn trauma is a global complication with high mortality, with ~60% of burn patient deaths resulting from infectious complications. Sepsis diagnosis is complicated by confounding clinical manifestations of the burn injury, and current biomarkers markers lack the sensitivity and specificity required for prompt treatment. Circulating extracellular vesicles (EVs) from patient liquid biopsy as biomarkers of sepsis due to their release by pathogens from bacterial biofilms and roles in subsequent immune response. This study applies Raman spectroscopy to patient plasma derived EVs for rapid, sensitive, and specific detection of sepsis in burn patients, achieving 97.5% sensitivity and 90.0% specificity. Furthermore, spectral differences between septic and non-septic burn patient EVs could be traced to specific glycoconjugates of bacterial strains associated with sepsis morbidity. This work illustrates the potential application of EVs as biomarkers in clinical burn trauma care, and establishes Raman analysis as a fast, label-free method to specifically identify features of bacterial EVs relevant to infection amongst the host background.

RESUMEN

Surface enhanced Raman scattering (SERS) is a powerful tool for vibrational spectroscopy, providing orders of magnitude increase in chemical sensitivity compared to spontaneous Raman scattering. Yet it remains a challenge to synthesize robust, uniform SERS substrates quickly and easily. Lithographic approaches to produce substrates can achieve high, uniform sensitivity but are expensive and complex, thus difficult to scale. Facile solution-phase chemical approaches often result in unreliable SERS substrates due to heterogeneous arrangement of "hot spots" throughout the material. Here we demonstrate the synthesis and characterization of a homogeneous gold nanofoam (AuNF) substrate produced by a rapid, one-pot, four-ingredient synthetic approach. AuNFs are rapidly nucleated with macroscale porosity and then chemically roughened to produce nanoscale features that confer homogeneous and high signal enhancement (~109) across large areas, a comparable performance to lithographically produced substrates.