QCM-D in Applications

Technology Background in Applications

Coagulation

Coagulation of blood involves different processes, which can have different physical effects. In the primary hemostasis, platelets adhere to the damaged endothelium, to form a platelet plug. In secondary hemostasis, fibrinogen is polymerised to fibrin to reinforce the plug, which also converts the surrounding blood from a liquid to a gel like substance, i.e. the viscosity of the blood changes. Both processes, the adsorption of cells to a surface, as well as the change of the viscosity of a liquid, can be detected with QCM by measuring the change of frequency together with damping. Being a real time method, QCM is perfectly applicable for coagulation measurements. Different parts of the hemostatic process can be triggered by adding different coagulants to the blood sample.

Cell Analysis

In the past decade, the QCM has emerged as a powerful analytical tool, that is capable of detecting the response of living cells that adhere to the crystal surface. The amplitude of the acoustic shear wave drops exponentially with distance from the sensor surface. This is important for cell analysis with QCM, as the sensor will only be sensitive to the portion of the cell in the vicinity of the surface. The penetration depths δ of the acoustic wave is given by

δ=√(η_l/(ϱ_l πf_0 ))

where  ϱ_l is the density of the liquid and η_l is its dynamic viscosity. If one assumes the cell to have properties like water and the resonance frequency being f_0= 10MHz, the resulting penetration depth is δ= 179nm. The QCM sensor is thus sensitive to the interactions of the cell with the sensor surface and insensitive to changes in the inner portion of cells. The process of adhesion of cells to the substrate is vital for survival, differentiation and migration of many types of cells. By providing information about cell adhesion, QCM is a unique tool to obtain insight into the behavior of both healthy and infected cells. Mammalian cells will not be damaged during the measurement process, because the amplitude of the acoustic wave is too small to cause any damage.  The second strength of QCM in cell analysis is the possibility to monitor the impact of environmental stimuli to the behavior of cells in real-time. Environmental stimuli range from cytotoxins, coagulants, growth factors, etc. to the presence of bacteria. Reactions of cells range from changes of adhesion, division, migration, to death and removal of cells. All of these reactions lead to changes in frequency and/or damping.