Particle enhanced point of care diagnostics utilizing quartz crystal microbalances

The present thesis deals with the development and production of a microfluidic „lab on a chip“ analysis system for point of care diagnostics. It focuses on increasing the detection limit of a microfluidic quartz crystal microbalance (QCM). In addition to sample preparation with superparamagnetic micro- or nanoparticles, the measuring range extension by means of these particles is investigated.
In addition to the manufacturing and quality control of the QCM mass sensor, an oscillator circuit which allows to carry out measurements in liquids and thus at high damping of the QCM is presented. To quantify C-reactive protein (CRP), two multicomponent coatings are used on the QCM. One consists of an antibody fragment (scFv-Fc) sandwich which allows the measurement of different samples directly after another without the need for complex regeneration steps. The second consists of an adapted ELISA antibody sandwich pair which enables the attachment of superparamagnetic nanoparticles. Both allow amplification of the measurement signal at constant CRP concentrations.
Furthermore a magnetic manipulation system is developed. Specially designed pole pieces made from a galvanically deposited nickel-iron alloy or a metal foil are used. Their shape dictates the magnetic gradient along the microchannel and thus defines the moving path of the particles. Both, the fabrication of the system and the magnetic simulation of the pole piece are discussed in detail. Depending on the choice of the volume flow, the particle flow behavior within the microchannel can be controlled and various fluidic operations can be realized.
Finally, the integration of both subsystems into a lab on a chip system is investigated.