Biomedical Engineering Reference
In-Depth Information
Osmolarity
pH
1.0
0.8
7 154
408
508
pH 5
pH 6
pH 8
pH 9
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
0.0
-0.2
-0.2
-0.4
-0.4
0.01
0.1
Frequency (Hz)
1
0.01
0.1
Frequency (Hz)
1
Figure 11.9
(A) Difference in spectral power density for postdose relative to predose spectra for a range of
osmolarities. (B) Difference in spectral power density for postdose relative to predose spectra for
a range of pH.
elicit a volume-regulatory response. On the other hand, for 428 Osm and pH 8, both
spectrograms show a minor regulatory response.
One of the most important potential applications of TDS is for drug screening. TDS is
label-free and captures the physiological changes induced by applied drugs. An example of
two differential response spectrograms for colchicine and cytochalasin D is shown in
Figure 11.11 . Colchicine is an antimicrotubule drug that inhibits the polymerization of
microtubules [22] . Microtubules are required for cellular mitosis, but they also play
important roles in the cytoskeleton, in distributing stresses and in supporting organelle
transport. When colchicine is applied, there is a rapid enhancement of low frequencies,
followed by an enhancement of high frequencies approximately 3 h later. Cytochalasin D is
an antiactin drug [23] . Actin is also a part of the cellular cytoskeleton and plays an
important role in the stiffness of the cell membrane. Actin forms a cortex of interlinked
filaments inside the cell membrane that helps give it rigidity. Cytochalasin D inhibits the
polymerization of the actin filaments, and the cortex is degraded, leading to a more floppy
cell membrane. The enhancement in midfrequencies for cytochalasin is likely due to
enhanced membrane fluctuations and is shown in Figure 11.11 . After approximately 3 h,
the tissue undergoes a fast change to a new state with enhanced low and higher frequencies
similar to the enhancements at long times observed for colchicine. These signatures may be
related to cellular death under these high doses.
The time-frequency spectrograms in Figure 11.11 show distinctly different behaviors at
different times and act like unique fingerprints of the drug effect on the tissue. By using
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