Sepsis is one of the leading causes of death around the world. The condition occurs when a local
infection overcomes the host natural defense mechanism and suddenly spreads into the circulatory system, triggering a vigorous, self-injurious inflammatory host response. The pathogenesis of
sepsis is relatively well known, one of the most potent immuno-activator being bacterial
lipopolysaccharide (LPS) - also known as '
endotoxin'. Tests exist to detect
endotoxin in bodily fluids, but are expensive, not necessarily user-friendly and require reporter molecules. In addition, the situation for safe and effective anti-
endotoxin therapy is problematical. At the present time,
endotoxin removal through cartridge
hemoperfusion is one of the better alternatives to combat
sepsis. The capability to both measure
endotoxemia levels and offer an adapted response treatment in a timely manner is crucial for better management and improved prognosis, but is currently unavailable. In this context, we describe herein preliminary research towards the development of an alternative LPS biosensor and an innovative LPS neutralization cartridge to be eventually combined in an all-integrated configuration for the
theranostic, personalized treatment of blood
endotoxemia/
sepsis. LPS detection is performed in a real-time and label-free manner in full human blood plasma, using ultra-high frequency acoustic wave sensing in combination with ultrathin, oligoethylene glycol-based mixed surface chemistry imposed on piezoelectric
quartz discs. Biosensing platforms are functionalized with
polymyxin B (PMB), a
cyclic peptide antibiotic with high affinity for LPS. Analogous surface modification is used on glass beads for the therapeutic cartridge component of the combined strategy. Incubation of LPS-spiked whole blood with PMB-bead chemistry resulted in a significant decrease in the production of pro-inflammatory TNF-α
cytokine. LPS neutralization is discussed in relation to the perturbation of its supramolecular chemistry in
solution.