Biosensors for Diagnostic Applications - Molecular Diagnostics - page 116

1 Introduction
Diagnostic applications include the detection of disease-related biomarkers, e.g.,
metabolites or proteins, in human body fluids. Biomarker concentrations can be
used to define disease type, state, or progress as well as the patient's response to
therapy. Research on disease-related biomarkers is an ongoing process [ 1 ]. It is
undeniable that established biomarkers exist which are significant for certain dis-
eases, such as increased levels of blood glucose typically indicate diabetes [ 2 ].
However, other biomarkers reported to be disease-related are still under investi-
gation regarding their significance in clinical diagnostics [ 1 ]. This applies, for
instance, for biomarkers which are used to specify subtypes of diseases, such as
markers used for classification of a tumor into subsets, which could be a useful tool
in a more efficient medical treatment [ 1 , 3 ]. Furthermore, particularly in the latter
case, more than one biomarker has to be determined to allow efficient diagnosis,
leading to marker profiles or ''molecular signatures'' [ 3 , 4 ]. Although these markers
might not be fully established in clinical routine, owing to strict requirements
regarding human health, the number of clinical tests is still rising, resulting in an
increasing demand for suitable and effective analytical instruments [ 5 ].
Currently, testing for biomarkers is typically performed in centralized labora-
tories using large automated clinical analyzers based on DNA or protein micro-
arrays including immunoassay methods [ 6 , 7 ]. They usually allow multiplex
detection of several analytes, but also require trained staff and increased time and
effort [ 5 ]. On the other hand, portable analytical instruments for determining blood
glucose levels [ 8 , 9 ] or blood coagulation [ 10 ] for patient self-testing are available.
They provide results within minutes, enabling independent dosage of medication
in the patient's self-management. These devices usually determine only a single
analyte or a few analytes, but this is sufficient for the applications they are
designed for. However, between the multianalyte high-throughput arrays used in
centralized laboratories and the single-analyte devices used by the patients
themselves there is a huge gap. For detection of marker profiles, e.g., at a phy-
sician's office, user-friendly instruments are required. They should allow rapid
detection and quantification of several analytes without the need for specialized
staff. For this testing scheme outside the central laboratories, i.e., near the patient,
the term ''point-of-care testing'' (POCT) has been adopted. Although many dif-
ferent technologies and systems have been developed in this area, a clear leader
has not yet been established in clinical routine [ 5 , 11 ].
Biosensor setups have also been considered as POCT devices. According to the
definition by the International Union of Pure and Applied Chemistry (IUPAC),
a biosensor is an integrated receptor-transducer device, i.e., it combines a bio-
chemical recognition system (receptor) with a detector (transducer). A biosensor
transforms the biochemical (biological) response into a measurable output
signal [ 12 ]. Therefore, biosensors should not require additional processing steps
or reagents between sampling and signal output, and hence are most promising
when it comes to quantitative, fast, and economic measurements [ 3 - 5 , 11 , 13 ].