Molecularly Imprinted Polymer Waveguides for Direct Optical Detection of Low-Molecular-Weight Analytes

New composite layer architecture of 3D hydrogel polymer network that is loaded with mole­cularly imprinted polymer nanoparticles (nanoMIP) is reported for direct optical detection of low‐molecular‐weight compounds. This composite layer is attached to the metallic surface of a surface plasmon resonance (SPR) sensor in order to simultaneously serve as an optical waveguide and large capacity binding‐matrix for imprinted target analyte. Optical waveguide spectroscopy (OWS) is used as a label‐free readout method allowing direct measurement of refractive index changes that are associated with molecular binding events inside the matrix. This approach is implemented by using a photo‐crosslinkable poly(N‐isopropylacrylamide)‐based hydrogel and poly[(ethylene glycol dimethylacrylate)‐(methacrylic acid)] nanoparticles that are imprinted with l‐Boc‐phenylalanine‐anilide (l‐BFA, molecular weight 353 g mol−1). Titration experiments with the specific target and other structurally similar reference compounds show good specificity and limit of detection for target l‐BFA as low as 2 × 10−6 m. A new approach to direct detection of low‐molecular‐weight compounds that utilizes optical waveguide spectroscopy (OWS) and molecularly imprinted polymer nanoparticles (nanoMIP) is reported. It is based on a highly open composite architecture of a photo‐crosslinked hydrogel network and embedded nanoMIPs that simultaneously serves as an optical waveguide and large‐capacity binding‐matrix.