Biomedical Engineering Reference
In-Depth Information
physico-chemical properties that may affect T
2
, such as hemoglobin content and
viscosity. Sample-to-sample variations could be controlled by splitting the sample
between two nanoparticle reagent chambers, such that the detection chamber
contained nanoparticles sensitized to the target analyte, while the reference
chamber contained identical nanoparticles that were not sensitized to the target
analyte. The addition of a sample would then lead to a difference in T
2
between
the two chambers only when the analyte was present (Figure 1.11). Accordingly,
the calibration curve would be determined from the difference in T
2
between the
sample and control chambers [49] .
Splitting the sample between multiple chambers can also be used to expand the
dynamic range by preloading chambers with different concentrations of nanopar-
ticles. This would allow for higher sensitivity measurements at low target concen-
trations, and simultaneous lower sensitivity measurements over a much wider
dynamic range. In time, this approach will most likely diminish the proportion of
inaccurate readings due to biosensor prozoning, and also avoid the user having to
prepare sequential dilutions of the sample [49].
These approaches for validating acquired T
2
values can be applied by measuring
multiple samples sequentially with a single detector [61], or by acquiring T
2
mea-
surements from two samples simultaneously with a single detector [49]. The T2
Biosystems team demonstrated that a single detection coil could be used to
measure the T
2
of two samples at the same time by means of a tailored bi-expo-
nential fi t method. This method was shown to accurately measure two T
2
values
as long as they were at least 21% different. This approach can also expand the
number of simultaneous measurements from a single detection coil, thus increas-
ing the number of possible tests on a given hardware system [49]. However, the
Figure 1.11
Background variations in T
2
can
be controlled by splitting the sample between
two chambers: one chamber that contains
particles sensitized to the target analyte (solid
line), and one that contains particles
not
sensitized to the target analyte (dashed line).
(a) In the absence of analyte, the two
chambers will have identical relaxation curves
and no change in T
2
will be reported; (b) In
the presence of analyte, the chamber with
sensitized nanoparticles will have a different
T
2
from that of the reference chamber (shaded
area). The quantitative change in T
2
can be
obtained by curve fi tting [49].
