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to obtain molecularly imprinted materials in the form of nanogels of defined structure and low PDI values (Wulff et al. 2006). Subrahmanyam et al. (2013) combined
the post-dilution method with controlled iniferter polymerization, thus extending
the applicability of this approach to UV initiated CRP. As a result, they obtained
imprinted soluble NPs with low PDI values and could increase the yield of NPs
from 5% to 14% (Subrahmanyam et al. 2013). CRP systems have been widely used
in combination with precipitation polymerization, as it allows the precise control
over the resulting particle sizes (Zhang 2013).
5.3.2.4 Solid-Phase Synthesis
MIP NPs synthesized by traditional methods, which have the template free in solution, present limited utility mainly due to the heterogeneity of the binding site and
the poor accessibility of the site, which makes them have a polyclonal nature. To
overcome these typical drawbacks, Poma et al. (2013) developed a method to synthesize nanoMIPs, namely the solid-phase approach, which is based on the covalent
immobilization of the template onto the surface of a solid support. By immobilizing
the template, the degrees of freedom of the template are reduced, and the formation
of the polymer at the interface with the support guarantees that the binding sites are
always accessible. In addition, the template coupling to the solid phase is oriented,
and therefore, imprinted sites are always created for the same part of the template,
which results in more ‘monoclonal’ MIPs. This fact constitutes an additional advantage to imprint proteins in an oriented manner, giving rise to NPs capable of recognizing that orientation of the template (Guerreiro et al. 2014; Xu et al. 2017b).
This approach is fully compatible with automation and allows the preparation of
MIP NPs in a controlled, reproducible and scalable manner (Poma et al. 2013). In
addition, this is the first MIP synthesis method that allows the reuse of templates,
which could be a great advantage when it comes to scarce or expensive templates.
In this approach, the template always remains attached to the solid phase, while the
MIP NPs are released by a simple temperature change. Furthermore, the composition of the polymerization mixture can be modified to confer ad-hoc functionalities
to the resulting NPs (Canfarotta et al. 2016a; Mazzotta et al. 2016).
NanoMIPs synthesized by this technique minimize diffusion effects and allow
faster kinetics, which may contribute to its use in chemical sensing (Wackerlig and
Lieberzeit 2015), electrochemical sensors (Basozabal et  al. 2014; Garcia-Mutio
et  al. 2016) and immunoassays (Chianella et  al. 2013; Smolinska-Kempisty
et al. 2016).
Ambrosini et al. (2013) proposed a solid-phase polymerization method to prepare soluble MIP NPs for proteins. To achieve the targeted protein immobilization,
an affinity ligand was attached to the solid support. MIP NPs were then synthesized
on this support, and thereafter, easily released, due to their thermosensitive properties (Ambrosini et al. 2013). On the other hand, Poma et al. (2014) developed an
automated chemical reactor under computer control for the solid-phase synthesis of
MIN for proteins such as trypsin and α-amylase.
5 Plastic Receptors Developed by Imprinting Technology as Smart Polymers Imitating…
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