Biomedical Engineering Reference
In-Depth Information
reduced. Similar mechanisms can also be used to detect affinity binding systems
such as antigen-antibody reactions [
91
] or protein binding to a (small) recognition
element [
92
], both cases using deformation of an aptamer carrying a redox label in
a way that the measurable current will be changed (Fig.
2
c).
The strength of this approach is in the fact that the actual binding itself
triggers the signal, thus the reference to a molecular switch: if no binding
occurs, the switch will not be triggered. This principle is robust even in very
complex backgrounds (cell culture medium, serum, etc.) as it is not affected by
nonspecific adsorption on the transducer surface. As will be shown in the next
part of this chapter, applications of biosensors in real (serum) samples are
comparatively rare, despite the need for easy-to-use protein detection systems
and despite the potential of biosensors in this field. This new biosensor type
relying on a new test format has already been used for antibody detection and
for protein detection in serum samples [
91
,
92
]. Vascular endothelial growth
factor is a regulator of both physiologic and pathologic angiogenesis. With a
folding-based biosensor, a detection limit of 5 pM (190 pg/ml) in 50% blood
serum could be achieved, which is in the clinically relevant concentration range
[
92
].
2.4 Biosensor System Setup and Microfluidic Integration
The biosensor is the heart of every biosensor system. Without this component
no signal can be generated. However, in most cases this is not sufficient. To be
suitable for handling by the user, the biosensor needs to be provided in a way
that ensures the device's integrity during handling and prevents damage to the
device during operation. This is usually guaranteed by means of embedding the
device into a biosensor housing. The combination of a biosensor in its housing
is typically referred to as ''biosensor chip''. The physical embedding comes
with the disadvantage that the biosensor may no longer be directly accessible
for sample delivery or signal readout. This is why the biosensor housing
usually has to be supplied with features other than mere physical protection
[
15
].
There are several aspects to keep in mind when developing a housing
strategy for a biosensor. Foremost, ease of handling the component has to be
ensured. However, it may be equally important to keep in mind the additional
costs caused by the biosensor housing and the processes required for the
embedding. If the biosensor system is to be commercialized for the mass
market, compatible manufacturing techniques have to be chosen. In such a
scenario, the biosensor housing would usually be designed as a low-cost
component created in an industrially available polymer such as poly(methyl
methacrylate) or polystyrene. Furthermore, polydimethylsiloxane has become
popular in recent years, especially if active microfluidic structures (such as
