MIP Sensors on the Way to Real-World Applications - Designing Receptors for the Next Generation of Biosensors - page 177

antibodies”—because the latter are usually governed by hydrophobic interactions
despite the fact that most of the analytes are water soluble, at least to some extent.
4.3 MIP Sensors Applications in Biosensing
Right from the birth of molecular imprinting, the resulting receptor materials have
frequently been referred to as “artificial antibodies” [ 13 , 50 , 51 ]. Of course there is
substantial interest in MIPs on account of the hope that they can be used as a
replacement for biological antibodies [ 52 ]. The reasons are twofold: first,
antibodies for specific applications can come at a rather high price, and second,
replacing biological materials by comparably low cost and mass-producible
polymers is tempting, both economically and in terms of manufacturing technol-
ogy. This “logical” proximity to antibodies led to the development of the so-called
“MIA” or molecularly imprinted sorbent assays that have been reviewed by Ansell
[ 51 ]. One of the earliest approaches was reported in 1993 by Vlatakis et al. [ 13 ]
already aiming at two compounds that are of clinical interest. The first MIA focused
on the detection of diazepam, a sedative, the other on theophylline, which is used as
a bronchodilator. Both systems relied on acrylate-based polymers, once more
making use of their ability to undergo hydrogen bonding and the facile polymeri-
zation properties of (meth)acrylate monomers (which has made acrylic polymers
some of the most widely researched matrices in molecular imprinting). Comparing
the results of the MIP immunoassays with enzyme-multiplied immunoassays
(EMIT) showed that both methods gave the same results when used to determine
the serum concentrations of theophylline in 32 patient samples. Similar results were
observed in the case of diazepam.
Especially for smaller molecules such as the two above-mentioned ones, MIPs
show some advantageous features when compared to their natural counterparts [ 3 ]:
• It is easier to produce an MIP against a small molecule, than an antibody.
• Antibodies are only functional in aqueous environments, but MIPs are inherently
equally active in aqueous and nonaqueous conditions.
• Antibodies are sensitive and stable only within a specific range of temperature
and pH, whereas MIPs are more rugged.
A further strong point of the imprinting technique is the fact that it is not
restricted to molecular analytes, but can also be extended to larger structures.
This opens up the possibility to address even entire microorganisms. However,
for that purpose bulk imprinting is not feasible, because this would on one hand lead
to layer heights in the range of some ten of micrometers and on the other hand make
diffusion of the prospective analyte to the interaction centers almost impossible.
Vulfson et al. [ 31 , 32 ] were the first to overcome these problems by generating
bacteria MIP on a polymer surface via emulsion polymerization. The outcome is
MIP “latex” particles comprising surface cavities that reproduce the geometrical
features of the template bacteria. The authors also pointed out the parallels between