Microwire crossbar arrays for chemical, mechanical, and thermal stimulation of cells

Over the past two decades, miniaturized biophysical tools, referred to as lab-on-a-chip or micro-total-analysis-systems, have become a vivid field of interdisciplinary research. This development is owed to the fact that these tools promise lower sample and time consumption and higher parallelization than classical wet-lab experiments. At the same time, these tools can offer a resolution that is often impossible to achieve with classical probe-based techniques. In this context, the present thesis investigates the use of microwire crossbar arrays to deliver chemical, mechanical, and thermal stimuli to networks of biological cells. The first part of this work considers magnetic microparticles as transducers of chemical and mechanical stimuli. To this end, a chipbased approach to exert precise control over these particles is examined. Here, microwire crossbar arrays are used as miniaturized electromagnets to generate highly localized magnetic fields. These fields, in turn, are used to exert precise control over the particles at subcellular resolution. In order to ensure successful delivery of the particles, simple but efficient protocols for the transport of particles are investigated. In the application of these protocols, a new approach to deploy and control individual particles on-chip is introduced. This method effectively cancels the risk of undesired delivery to another than the target cell allowing reliable and controlled stimulation of single cells. In order to demonstrate the excellent control over the particle, an analytical simulation of the system is compared to experimental data. The latter is obtained using an image processing algorithm that allows for particle detection at submicron resolution. In the second part, the parallel generation of magnetic and dielectrophoretic forces is investigated as a means to avoid particle immobilization due to adhesive particle/surface interactions. Using finite elements simulations, the magnetic and electric fields generated by the arrays are analyzed. The theoretical results from these simulations are then compared to experimental data obtained from individual particles levitated on the chip. Finally, field configurations that allow full three-dimensional control over the particle are presented. These results demonstrate for the first time the precise three-dimensional actuation of a single particle using only in-plane actuators. As an on-chip version of magnetic tweezers, this method poses a versatile tool to a number of biophysical investigations. The last part of the thesis examines microwire crossbar arrays as a tool for the thermal stimulation of cells cultured on the chip. In particular, stimuli of high thermal energy are applied via resistive heating of the microwires. The technique is then examined as a possible chip-based method to generate highly resolved lesions in biological networks. As an exemplary functional cell network cardiomyocyte-like HL-1 cells are grown on the chips. The localization of the lesion is examined using fluorescent staining methods. The functionality of the network before and after the lesion is analyzed via Ca imaging. Here, correlation and frequency analyses are used to give an insight