Biomedical Engineering Reference
In-Depth Information
3.2.2 Cardiac Biomarkers in Serum
Troponin and Myoglobin
Cardiac troponins occur in human blood only when the myocardium is directly
damaged. Although increased levels are not observable before 3-4 h after the
myocardial infarction, because of the lack of other markers, cardiac troponin I
(cTnI) and cardiac troponin T (cTnT) are currently considered as the ''gold stan-
dard'' in myocardial infarction diagnosis. The cutoff levels are in the ranges
0.01-0.1 ng/ml (cTnI) and 0.05-0.1 ng/ml (cTnT), respectively. In contrast to the
cardiac troponins, increased levels of myoglobin can be detected 1-3 h after the
myocardial infarction; the cutoff levels were specified in the range 70-200 ng/ml.
However, increased levels of myoglobin are not specific for myocardium damage.
Therefore, in the case of a suspected myocardial infarction, it would be beneficial
to monitor the concentrations of both troponin and myoglobin during the first few
hours for early and efficient diagnosis [
103
].
Commercially available POCT devices using electrochemical biosensors are
provided by Abbott Point of Care (i-STAT series), including a test cartridge for cTnI.
This amperometric biosensor setup allows the determination of cTnI in the range
0-50 ng/ml. In contrast to the POCT devices mentioned in
Sect. 3.2.1
, this biosensor
setup detects only a single biomarker [
104
]. Direct detection of cTnT in human serum
samples obtained from cardiac patients could also be performed with a label-free
capacitive immunosensor [
105
] and an SPR immunosensor [
106
]. In both cases, the
concentrations were determined prior to the biosensor measurements by means of
commercially available electroluminescence immunoassays. cTnT in serum could
be detected with the capacitive biosensor in the concentration range 0.07-6.83 ng/ml
[
105
], and with the SPR biosensor in the range 0.83-3.16 ng/ml [
106
].
An interesting approach was reported for direct detection of myoglobin with an
impedimetric biosensor. The sensing layer was based on half-antibody fragments
which could be immobilized in a well-defined orientation, resulting in very dense
layers on the biosensor surface. Serum was spiked with myoglobin over the
concentration range 10
-14
-10
-7
M, corresponding to 0.178 pg/ml to 1.78 lg/ml
(M
r
myoglobin 17,800) and could be detected with the biosensors in this wide
concentration range [
107
]. Finally, an SPR immunosensor using a SAM based on
16-mercaptohexadecanoic acid was successfully used to detect myoglobin and
cTnI in undiluted serum. (Actually, bovine serum was used for the measurements;
nevertheless a complex serum sample matrix was represented.) The limit of
detection of myoglobin was reported to be 0.9 ng/ml, and that of cTnI was 0.7 ng/
ml; in both cases linearity was reported to be up to 50 ng/ml [
78
].
C-reactive protein
CRP is a classic acute phase protein; however, it is a nonspecific biomarker
which indicates all kinds of tissue damage, bacterial infections, and other acute
