Solid-Phase Synthesis of Molecularly Imprinted Polymer Nanoparticles with a Reusable Template-"Plastic Antibodies"

Molecularly imprinted polymers (MIPs) are generic alternatives to antibodies in sensors, diagnostics, and separations. To displace biomolecules without radical changes in infrastructure in device manufacture, MIPs should share their characteristics (solubility, size, specificity and affinity, localized binding domain) whilst maintaining the advantages of MIPs (low-cost, short development time, and high stability) hence the interest in MIP nanoparticles. Herein, a reusable solid-phase template approach is reported (fully compatible with automation) for the synthesis of MIP nanoparticles and their precise manufacture using a prototype automated UV photochemical reactor. Batches of nanoparticles (30-400 nm) with narrow size distributions imprinted with: melamine (d = 60 nm, Kd = 6.3 x 10-8 M), vancomycin (d = 250 nm, Kd = 3.4 x 10-9 M), a peptide (d = 350 nm, Kd = 4.8 x 10-8 M) and proteins have been produced. The instrument uses a column packed with glass beads, bearing the template. Process parameters are under computer control, requiring minimal manual intervention. For the first time, the reliable re-use of molecular templates is demonstrated in the synthesis of MIPs (30 batches of nanoMIPs without loss of performance). NanoMIPs are produced template-free and the solid-phase acts both as template and affinity separation medium.