Abstract: Described herein are biosensors for early, pre-symptomatic detection of infectious agents and methods for their use. In particular, this disclosure describes biosensors that utilize toll-like receptor (TLR) binding domains to detect pathogen-associated molecular patterns (PAMPs). Also provided herein are methods of detecting and/or capturing a PAMP from a biological sample using the disclosed biosensors.

Abstract: It has been found that moieties containing a lipophilic domain, e.g., lipophilic pathogen activated molecular patterns (PAMPs), insert into the lipid bilayer on a cell membrane to facilitate antigen recognition by the innate immune response receptors. This changes the basic understanding of antigen recognition by the innate immune system. A sensor platform for the ultra-sensitive and specific detection of moieties containing such a lipophilic domain, e.g., PAMPs, that are associated with a disease, has now been developed. To date, this approach has been validated with Lipoarabinomannan (LAM) from Mycobacterium tuberculosis and lipopolysacharide (LPS), associated with gram-negative bacteria. This approach may be extendable to all lipophilic targets associated with pathogens and thus, is the basis of a very simple and specific sensing platform. In addition, novel applications for this technology in the selection of recognition ligands by mass spectroscopy have been identified.