  We developed a method for measuring blood coagulation using superparamagnetic
iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF). The
3rd and 5th harmonic signals from SPIONs mixed with blood induced by AMF were
detected using a gradiometer coil. Blood coagulation was induced artificially
by adding CaCl2 solution to whole blood of sheep at various temperatures and
hematocrits. We calculated the coagulation rate (k) and normalized signal
intensity at infinite time (Sinf) by fitting the time course of the normalized
3rd harmonic signal to S(t)=(1-Sinf)exp(-kt)+Sinf. The k values increased
significantly with increasing temperature and decreased significantly with
increasing hematocrit. The Sinf values decreased significantly with increasing
temperature and tended to increase with increasing hematocrit. Blood
anticoagulation was induced by adding heparin to the whole blood sampled from
mice. There were significant differences in both the 3rd and 5th harmonic
signals between groups with and without heparin at 25 min or more after adding
heparin. We also calculated the 3rd and 5th harmonic signals for viscosities
ranging from 0.001 to 1 kg/m/s, with an assumption that the magnetization and
particle size distribution of SPIONs obey the Langevin theory of paramagnetism
and log-normal distribution, respectively. The 3rd and 5th harmonic signals
increased slowly with increasing viscosity and had peaks at approximately 0.015
and 0.025 kg/m/s, respectively. After these peaks, they decreased monotonically
with increasing viscosity. These results confirm the rationale of our method.
In conclusion, our method will be useful for measuring blood coagulation and
anticoagulation and for studying their processes.

Medical Physics