Water-Compatible Molecularly Imprinted Polymers Obtained via High-Throughput Synthesis and Experimental Design

Abstract

A technique allowing high-throughput synthesis and evaluation of molecularly imprinted polymer sorbents at a reduced scale (mini-MIPs) was developed and used for the optimization of MIPs for use in pure aqueous environments. The technique incorporated a 4-port liquid-handling robot for the rapid dispensing of monomers, templates, solvents and initiator into the reaction vessels of a 96-well plate. A library of 80 polymers, each ca. 50 mg, could thus be prepared in 24 h. The MIP rebinding capacity and selectivity could be rapidly assessed in the batch mode by quantifying nonbound fractions in parallel using a UV monochromator plate reader. This allowed a complete evaluation of the binding characteristics of an 80 polymer library in approximately 1 week. With the objective of optimizing a polymer imprinted with the local anaesthetic Bupivacaine for use in pure aqueous systems, a polymer library was prepared by varying the original poly(MAA-co-EDMA) MIP composition. The variable factors were the added amount of the hydrophilic comonomer, 2-hydroxyethyl methacrylate (HEMA), the cross-linking ratio, and the porogen. This optimization resulted in polymers showing high imprinting factors (IF = K(MIP)/K(NIP)) in water as a result, mainly, of reduced binding to the nonimprinted polymer. Normal scale batches of these materials showed strong retention of the template and low nonspecific binding when assessed as chromatographic stationary phases using pure phosphate buffer, pH 7.4, as mobile phase, by equilibrium batch rebinding experiments and as sorbents for extractions of the analyte from blood plasma samples.

From 3D to 2D: A Review of the Molecular Imprinting of Proteins

“…Dirion used a high-throughput synthesis and evaluation of MIP sorbents to optimize a MIP for the local anaesthetic bupivacaine in aqueous systems (40). The resultant MIPs showed high imprinting factors in water, attributed to reduced nonspecific binding to the imprinted polymer.…”

Imidazolium-based functional monomers for the imprinting of the anti-inflammatory drug naproxen: Comparison of acrylic and sol–gel approaches

“…This further precludes use of template molecules that are only soluble in aqueous media, which implies obvious limitations in the development of MIP for many environmental and biological applications. Although some promise has been shown for aqueous-based rebinding procedures, such results are rare and considerable progress is required to overcome this limitation [10,11].…”

Influence of salt ions on binding to molecularly imprinted polymers

“…More recently, several promising methods to approach the optimization problem in a more systematic way have been demonstrated. Chemometrical approaches, combinatorial synthesis, high-throughput screening, and computational methods have been applied to investigate factors of importance in the synthesis protocol and to expedite the optimization of polymer compositions towards high selective rebinding of the template [4][5][6][7][8][9][10][11][12][13][14][15].…”

“…Water may interfere with hydrogen bonds involved in the recognition and MIPs relying on non-covalent interactions to the template are therefore often prepared in aprotic organic media. Optimal rebinding is usually observed in similar aprotic organic solvents as the ones used during the imprinting, although several cases of successful rebinding in aqueous media have been reported [8,[16][17][18][19][20][21][22][23][24][25]. The pH and the ionic strength of the rebinding solvent mixture have been recognized as parameters affecting the binding capacity [16,19,26].…”