Molecular Imprinting

Molecular imprinting is a process that allows for the synthesis of artificial receptors for a given target molecule based on synthetic polymers. The target molecule acts as a template around which interacting and cross-linking monomers are arranged and co-polymerized to form a cast-like shell. In essence, a molecular memory is imprinted in the polymer, which is now capable of selectively binding the target. Molecularly imprinted polymers (MIPs) thus possess the most important feature of biological antibodies - specific molecular recognition. They can thus be used in applications where selective binding events are of importance, such as immunoassays, affinity separation, biosensors, and directed synthesis and catalysis. Since its beginnings in the 1970s, the technique of molecular imprinting has greatly diversified during the last decade both from a materials point of view and from an application point of view. Still, there is much room for further improvement. The key challenges, in particular the binding site homogeneity and water compatibility of MIPs, and the possibility of synthesizing MIPs specific for proteins, are actively addressed by research groups over the World. Other important points are the conception of composite materials based on MIPs, in order to include additional interesting properties into the material, and the synthesis of very small and quasi-soluble MIPs, close in size to proteins.

The current state of the art in the development of methodologies for the preparation of MIPs in predetermined physical forms is critically reviewed, with particular attention being paid to the forms most widely employed in practical applications, such as spherical beads in the micro- to nanometer range, microgels, monoliths, membranes. Although applications of the various MIP physical forms are mentioned, the focus of the paper is mainly on the description of the various preparative methods. The aim is to provide the reader with an overview of the latest achievements in the field, as well as with a mean for critically evaluating the various proposed methodologies towards an envisaged application. The review covers the literature up to early 2010, with special emphasis on the developments of the last 10years.

Molecularly imprinted polymers (MIPs) are tailor-made receptors that possess the most important feature of biological antibodies and receptors – specific molecular recognition. They can thus be used in applications where selective binding events are of importance, such as chemical sensors, biosensors and biochips. For the development of microsensors, sensor arrays and microchips based on molecularly imprinted polymers, micro and nanofabrication methods are of great importance since they allow the patterning and structuring of MIPs on transducer surfaces. It has been shown that because of their stability, MIPs can be easily integrated in a number of standard microfabrication processes. Thereby, the possibility of photopolymerizing MIPs is a particular advantage. In addition to specific molecular recognition properties, nanostructured MIPs and MIP nanocomposites allow for additional interesting properties in such sensing materials, for example, amplification of electromagnetic waves by metal nanoparticles, magnetic susceptibility, structural colors in photonic crystals, or others. These materials will therefore find applications in particular for chemical and biochemical detection, monitoring and screening.

Biomimetic assays with molecularly imprinted polymers (MIPs) are bound to be an alternative to the traditional immuno-analytical methods based on antibodies. This is due to the unique combination of advantages displayed by the artificial materials including the absence of animal inoculation and sacrifice, unnecessary hapten conjugation to a carrier protein for stimulated production, the possibility of manufacturing MIPs against toxic substances, excellent physicochemical stability, reusability, ease of storage, and recognition in organic media. If the selectivity and affinity of MIPs are increased, many more immuno-like assays will be developed using radioactive, enzymatic, colorimetric, fluorescent, chemiluminescent, or electrochemical interrogation methods. This chapter provides a comprehensive comparison between the bio- and biomimetic entities and their usage.

A sensor is a device, which responds to a physical or chemical stimulus in order to produce a measurable detection signal or to control another operation [1]. Sensors are encountered in innumerable applications and have become an integral part of our day-to-day life. Examples of everyday use of sensors include a thermocouple, which responds to the change in temperature by an output voltage, or a touch-sensitive sensor of an interactive monitor screen. Basically, a sensor can respond, that is change its signal, to a single factor being sensed, i.e. either to the change of temperature or pressure in the above examples.

Most analytical applications of molecularly imprinted polymers are based on their selective adsorption properties towards the template or its analogs. In chromatography, solid phase extraction and electrochromatography this adsorption is a dynamic process. The dynamic process combined with the nonlinear adsorption isotherm of the polymers and other factors results in complications which have limited the success of imprinted polymers. This chapter explains these problems and shows many examples of successful applications overcoming or avoiding the problems.

Molecular imprinting has grown considerably over the last decade with more and more applications being developed. The use of this approach for the generation of enzyme-mimics is here reviewed with a particular focus on the most recent achievements using different polymer formats such as microgels and nanogels, beads, membranes and also silica nanoparticles.