Biomedical Engineering Reference
In-Depth Information
their approach and lithographic techniques to generate surface structures. This
groundbreaking work proved the principal feasibility of microorganism imprinting.
The first actual sensor measurements, however, were obtained with stamp surface-
imprinting strategies of yeast cells into both polyurethane [ 33 ] and sol-gel material
[ 53 ]. By applying SAW devices with a fundamental frequency of 433 MHz it is
even possible to sense a recognition event between the MIP and a single yeast cell.
Additionally, these MIPs show appreciable selectivity, not only against different
microorganisms, such as bacteria, but also between different types of yeast,
indicating that during “bioimprinting” not only the morphology of the respective
species plays an important role, but also its surface chemistry. This observation is
further corroborated by the design of sensor systems for biospecies that share
common geometrical features, but differ in surface chemistry. One example for
this is erythrocytes (i.e., red blood cells), which hold glycosidic moieties on their
respective cell surfaces, which determines blood group. When applied as a template
they lead to surface MIP in copolymer systems of acrylic/acrylamide monomers
and N -vinyl pyrrolidone [ 54 ]. Admittedly, the monomer composition in this case is
rather complex. However, this allows for tailoring the surface properties of the final
polymer to optimally match the template cell. The sensitivity of the red blood cells
does not allow a stamping protocol to be used, but sedimentation of erythrocytes in
a solution deposited on top of a spin-coated pre-polymer leads to surface cavities
having the original “donut” shape of the template cell (see Fig. 9 ).
Somewhat astonishingly, these cavities proved highly selective: on 10 MHz
QCM the MIPs not only allow to distinguish between different blood groups, but
even between subgroups that only differ by the amount of glycolipids on the cell
surface. It is also worth mentioning that measurements can take place in a diluted
whole blood matrix.
From the application point of view, however, viruses are among the most
interesting biospecies for chemical sensing, because currently no analysis
techniques exist for their rapid detection. The reason for this is their size: it is
usually between 10 and 100 nm. Hence virions are not accessible via light scattering
or other straightforward optical strategies that dominate in the field of automated
bioanalyte detection. Knez et al. published rather early work on the selective
nucleation of inorganic matrices on the tobacco mosaic virus (TMV) [ 27 ]. TMV
is not only a plant pathogen that is very harmful to different crops (obviously
tobacco, but also cucumber and pumpkin), but it also provides researchers with a
robust template for imprinting. The first actual sensors achieved with TMV-
imprinted polyurethanes were reported by Dickert et al. [ 55 ]. QCM coated with
such MIP can detect TMV highly selectively, even in complex media—namely
plant sap—without sample preparation, reaching a limit of detection of 1 mg L 1 .
Experiments with different serotypes of the human rhinovirus (HRV) show that in
this case differences in the surface protein structure also led to selectivity of the
respective bio-MIP [ 56 ].
Finally, an MIP sensor for the detection of homocysteine in blood [ 57 ] highlights
a further interesting approach for sensing as well as strategies to utilize molecular
imprinting to find novel catalysts. This fluorescent sensor made use of an MIP
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