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Multiplexed Micro-Lithography - Strategies and Applications

Multiplexed Micro-Lithography - Strategies and Applications

Falko Brinkmann 


Dissertation, Westfälische Wilhelms-Universität (WWU) (2014) 

Date: 2014

This thesis focusses on the fabrication of complex microstructures by multiplexed polymer pen lithography (PPL). The advancement of the technology presented here leads to applications in various fields of research. Examples in biology, medicine, diagnostics and printable electronics underline the relevance of PPL in nanotechnology.

Chapter 3 introduces the type of lithography development that is applied in the scope of this work. In brief, the 2×2cm2 PPL stamp, that consists of some 10,000 polymer-pyramids, is coated with various inks in different sections (image on the right). The strategy of PPL is based on the motorized movement of the whole stamp onto a surface. Thereby complex lines, dot- and mosaic-structures can be generated by each pen. The micrometer-precise navigation in the range of centimeters allows interdigitating patterns of various materials (multiplexing). Phospholipids, proteins, biotin as well as photonic quantum dots and conductive nanoparticles are shown to be feasible inks. Extensive microstructures in the scale of square centimeters play an important role in biology. Cells colocalize on features of extracellular matrix proteins. Cell-adhesion experiments can be performed by multiplexed protein arrays when the cells get exposed to different substances. The latter is of importance in the field of neuron research. Chapter 4 shows axons whose outgrowth is guided by a protein pattern, however, only if an interdigitated repulsive-acting structure is provided (image on the left).

The metastasis of cancer patients is caused by circulating tumor cells (CTCs). Upon leaving the primary tumor, CTCs circulate in the blood system and have the ability to settle in distant organs and perform mitosis. Chapter 5 introduces a novel approach that isolates cancer cells on micro-structured surfaces. Sensitized tumor cells from a culture are spiked into a blood sample of a healthy donor. A custom-made microfluidic chip ensures that the cells come sufficiently into contact with the microstructure located at the bottom of the device by an integrated micro-vortex system (image on the right). Only sensitized cells are immobilized on the microstructure through the process of antibody binding. Healthy blood cells pass by the chip. This approach recovers almost 50% of the tumor cells at a specificity of 85%.

Chapter 6 describes the fabrication of optical biosensors by a technique based on PPL. Custom-made multiplexed stamp pads are utilized to specifically coat polymer-goblets with functional phospholipids (image on the left). These microscopic goblets act as resonators during the exposure of light as they are able to emit discrete wavelengths. In the case of a specific binding event to a functionalized microgoblet, a redshift in the resonance frequency can be detected by spectrometry. Using the multiplexed stamp pads, arrays of up to 100 goblet-sensors can be functionalized.

PPL can also be applied in the field of printable electronics. Here, electronic devices are generated in a direct way, without the need of clean-rooms, photolithography or wet-etching techniques. Liquid polymers and metallic nanoparticles are used as conductive, semi-conductive or dielectric inks. Chapter 7 demonstrates the method to write 2,500 transistor-like structures consisting of silver and indium-oxide inks on one square centimeter (image on the right). Using PPL, the precise deposition of electrodes with a proximity as low as 2µm can be realized. I-V-measurements show the electrical properties of these devices.