Biomedical Engineering Reference
In-Depth Information
The diagnosis of such a neurodegenerative disease is required in an early stage to
allow early treatment and thus delay of severe symptoms. Current research in this
field includes the investigation of disease-related biomarkers in CSF. Sampling of
CSF is less invasive than sampling of brain tissue, and owing to its proximity to the
brain, it should be better suited than serum to reflect processes in the brain [
101
].
SPR biosensors have been used to investigate biomarkers in CSF aiming at
diagnosis of Alzheimer's disease. Amyloid b peptides in CSF have been reported
as potential biomarkers for Alzheimer's disease. A sandwich assay based on an
SPR immunosensor was developed to determine the concentrations of two dif-
ferent amyloid b peptides in CSF. The secondary antibody was required as a
means of signal enhancement because of the low (subnanomolar) concentrations of
amyloid b peptides in CSF. CSF samples from patients diagnosed with
Alzheimer's disease could be distinguished from CSF samples from healthy
donors [
143
]. Furthermore, it was suggested that the mitochondrial enzyme
17b-hydroxysteroid dehydrogenase type 10 (17b-HSD10) binds to amyloid b
peptides. Therefore, the 17b-HSD10/amyloid b peptide complex could also serve
as an Alzheimer's disease biomarker. To detect concentrations of this complex,
antibody against amyloid b peptide was immobilized on SPR biosensors. After
patient CSF samples (dilution factor 1:2) had been applied, antibody against
17b-HSD10 was applied as a secondary antibody (sandwich assay). An increase in
signal response should only be obtained when the 17b-HSD10/amyloid b peptide
complex binds to the surface, and not when the pure amyloid b peptide binds. The
results were in good correlation with results obtained from ELISA tests performed
with the same samples. Samples from patients diagnosed with Alzheimer's disease
could be distinguished from control samples obtained from patients suffering from
noninflammatory neurological diseases [
144
].
4 Conclusion
Biosensor development started around 50 years ago with the development of an
''enzyme electrode'' for monitoring glucose in blood. Since then, biosensor
development has been ongoing, with clinical applications still being one of the
main driving forces. However, despite the fact that biosensors are promising
devices when it comes to fast and easy detection of analytes, their use has not yet
been established in clinical routine, in contrast, for instance, to immunoassay
techniques.
There is no doubt that numerous publications and patents dealing with bio-
sensors have been published. However, looking at the material published in the last
few years more closely, we realized that only a comparatively small part of the
work reported was performed using real samples. One reason for this discrepancy
might be that the problem of nonspecific binding arising from complex sample
matrices has not been completely solved. Strategies commonly used to deal with
nonspecific binding in a typical biosensor measurement usually have to be adapted
