Optimizing benzenesulfonic acid derivatives as functional monomers for imprinting of surfactant protein A (SP-A) epitopes in an electrochemical sensor.

We investigated electropolymerizable derivatives of benzenesulfonic acid - 2-aminobenzenesulfonic acid (MSDS), 3-aminobenzenesulfonic acid (MSAN), 2,5-diaminobenzenesulfonic acid (DABS), and 2-amino-5-methylbenzenesulfonic acid (PTMS) - as functional monomers for molecular imprinting. These monomers were electropolymerized on indium tin-oxide (ITO) electrodes in the presence of various peptide epitopes of surfactant protein A (SP-A) to form films of peptide-imprinted polymers (PIPs). SP-A in body fluids is a clinically significant biomarker for pulmonary diseases. Hence, precise quantification of SP-A in these fluids is diagnostically essential. Epitope molecular imprinting offers advantages over imprinting the whole SP-A molecule, including lower cost and greater accessibility of molecularly imprinted cavities within the PIP. However, choosing water-soluble monomers that can form conductive polymers with an affinity selective for SP-A epitopes remains a significant challenge. Herein, we systematically optimized monomer-to-template ratios and the hydropathy of the selected epitopes to enhance the electrochemical response of PIP film-coated ITO electrodes. The resulting chemosensors exhibited a broad linear dynamic concentration range of ∼0.001 to 10.0 pg/mL and an exceptionally low limit of detection of 0.05 pg/mL for SP-A. These SP-A epitope-templated PIP-based electrochemical sensors demonstrated strong potential for application in SP-A sensing in human serum.