Sample Preparation Using Molecularly Imprinted Polymers

Despite the advances in the development of new instruments and highly sensitive analytical methods based on gas, liquid or supercritical fluid chromatography coupled to various detectors including high resolution mass spectrometry that can be associated with different ionization sources, a pre-treatment is usually necessary in order to extract and isolate the analytes of interest from complex samples before their determination. Solid-phase extraction (SPE) is routinely used for the extraction or purification of compounds from liquid samples or solid matrix extracts. Despite their attractive features, the classical SPE sorbents retain analytes by non-selective hydrophobic or polar interactions that lead to partial co-extraction of interfering substances that may cause matrix effects even with a specific detector such as a mass spectrometer. To enhance the extraction selectivity of the target analytes, new materials involving a mechanism of molecular recognition were developed. They include immunosorbents or oligosorbents based on the use of immobilized antibodies or aptamers, respectively. Nevertheless, the development of an immunosorbent is time-consuming and relatively expensive and despite their high potential, a limited number of aptamer sequences is, to date, available. An alternative is to develop molecularly imprinted polymers (MIPs). These sorbents are synthetic polymeric materials possessing specific cavities designed for a template molecule involving a retention mechanism based on molecular recognition. The MIPs have been already successfully used in several fields, such as sensors, biomimetic catalyst in organic synthesis, drug delivery, and separation of structural analogs or enantiomers in liquid chromatography and capillary electrophoresis. The use of MIPs as selective sorbents for sample pretreatment was described for the first time by Sellergren and co-workers in 1994 and concerned the development of a MIP for the solid-phase extraction of pentamidine from urine, there has been a growing interest in these polymers for extraction purposes. Initially mainly developed for the selective recognition of small molecules, such as drugs, pesticides or other environmental pollutants, they are now developed, as illustrated in recent reviews, for the recognition of proteins or even microorganisms. While the nature of the targets for which MIPs have been developed has evolved, so has the format of the extraction devices. Indeed, although MIPs have been mainly applied to the selective extraction or cleaning of target analytes from various complex samples by introducing them in a cartridge to carry out off-line SPEs, a strong trend towards miniaturized extraction devices has been observed over the past decade. The tendency is to develop new synthesis pathways to obtain particles of controlled sizes, fibers, stir-bars or membranes thus allowing their use in dispersive SPE, solid-phase microextraction or stir bar sorptive extraction. This change of format is not only a reduction in size, but also implies changing the polymerization modes, which, despite the small size of the devices, must make it possible to maintain sufficient binding capacity. The modification of the polymerization conditions is also required when developing MIPs for proteins because of their lack of stability in conventional polymerization solvents. Based on the works published over the past two years for numerous target molecules, this paper aims to review the new strategies of development of MIPs in different formats dedicated to various extraction methods often treated independently in the previously mentioned reviews, for both small organic molecules and proteins for which there are high expectations for replacing antibodies.