Manipulation of magnetic microparticles in liquid phases for on-chip biomedical analysis methods

Magnetic microparticles and their application in bioanalytical microfluidic systems have been steadily gaining interest in recent years. This progress is fueled by the comparatively large and long range magnetic forces that can be obtained independently of the fluidic flow pattern. This thesis work presents new approaches for using magnetic microparticles in Lab-on-a-Chip systems. The first approach deals with the design of a magnetic droplet manipulation system and the second combines magnetic particle actuation with integrated optical detection. The applicability of both systems for miniaturized bioanalysis will be shown, demonstrating the potential of magnetic particle based Lab-on-a-Chip systems. The magnetic droplet manipulation system tackles the handling of small liquid volumes, which is an important task in miniaturized analytical systems. The careful adjustment of hydrophilic/hydrophobic surface properties and interfacial tensions leads to the design of a system, where small droplets are manipulated in a controllable fashion. The system's setup permits the direct implementation of bioanalytical protocols and two different procedures are in consequence examined. Based on a commercial laboratory kit, a platform for the on-chip extraction and purification of DNA will be designed. The miniaturized setup allows the user to capture and clean the DNA obtained from a raw cell sample containing as little as 10 cells, which is several orders of magnitude lower than known for macroscopic systems. A similar performance is observed for the colorimetric antibody detection further-on evaluated in the droplet manipulation system, where the small sample volumes permit a significant reduction of the reaction times. With the possibility of concentrating the biomolecules of interest on the particle surface, a sensitive and fast immunosorbent assay can be devised. A further miniaturization is examined in a CMOS system, which combines magnetic actuation and optical detection. The small dimensions of the actuation system allow the manipulation of single magnetic microparticles and the integration of Single Photon Avalanche Diodes (SPADs) enables their optical detection. An innovative detection algorithm permits hereby to distinguish the particles in size and, in combination with a velocity measurement, to evaluate the magnetic properties of the detected particles. In consequence, bioanalysis on a single magnetic particle using fluorescent measurements can be performed, as is shown by preliminary experiments.