Biomedical Engineering Reference
In-Depth Information
1. Introduction
The selective recognition of biological molecules governs many essential biological
interactions, which has attracted much attention in recent years. Mimicking these processes
with synthetic receptors is still a major challenge in chemistry, physics and biology. Among
the variety of approaches for the preparation of tailor-made artificial receptors that can
selectively bind predetermined target molecules, molecular imprinting has been widely
recognized as the most promising technique, which offers a number of distinct advantages [1,
2]. Molecular imprinting technology allows the creation of synthetic receptors with binding
constants comparable to natural receptors, but capable of withstanding much harsher
conditions, such as acids, bases, metal ions, organic solvents, extreme pH, high pressure and
temperature. These artificial materials can be prepared in large quantities with good
reproducibility and low cost [3].
The principle of molecular imprinting has been widely illustrated in some reviews [4-7].
Generally, the imprinting relies on the formation of a host-guest complex between a template
molecule and one or more functional monomers in an appropriate solvent. After the addition
of a cross-linking agent and subsequent polymerization, a highly cross-linked polymer matrix
is formed which encapsulates the template molecule. Then, the template molecules are
extracted from the polymer, leaving cavities with suitable size, shape, and functional group
orientation which are complementary to the target molecule. From the 1990s, molecular
imprinting technology has been extensively exploited and many kinds of molecules have been
successfully imprinted for a variety of applications, including affinity chromatography
supports, solid phase extraction membranes, biomimetic sensors, environmental monitoring
and drug delivery [8-14].
However, despite significant growth within the field, the majority of template molecules
studied thus far have been characterized by their low molecular weight and insolubility in
aqueous systems. In this field, imprinting of biomacromolecules is one of the most
challenging tasks. More physical and chemical factors need to be considered on the
preparation of biomacromolecular receptors in comparison to the molecular receptors for
small targets. The first report on protein imprinting was proposed by Glad T. et al. in 1985
[15]. In the following years, many contributions in the molecular imprinting of peptides and
proteins were conducted by Mosbach K [16-19]. The molecular imprinted polymers
synthesized in these early studies were tested for their ability to selectively recognize their
respective target molecules in organic solvents. However, most molecules of biological
importance are water soluble, and many natural recognition events such as antigen-antibody
binding occur in aqueous media. Moreover, proteins have a flexible structure and
conformation, which can be easily affected by changes in temperature or in the environment.
According to the calculation reported by Nicholls [20], it is difficult, from thermodynamical
viewpoint, to develop successful imprints for such molecules. So, the main challenge during
the synthesis of molecular imprinted polymers selective to biomacromolecules is the fact that
they need to be imprinted at conditions close to their natural environment ensuring
conformational integrity. Furthermore, these materials need to provide access to the binding
pockets, which is different from conventional molecular imprinted polymers expecting
diffusion of the template molecules into the matrix during rebinding.
