Bio-Microarrays Based on Functional Nanoparticles


Achim Weber Fraunhofer Institute for Interfacial Engineering und Biotechnology, University of Stuttgart

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Microarray technology is a key factor in today's biotechnology research. There already exists a variety of chip-based polynucleic acids analysis systems. DNA microchips are already commercially available and are widely used in laboratories worldwide. In contrast, new methods are needed for the starting era of proteomics—the investigation of function, structure, and molecular interaction among proteins. Protein microarrays are widely expected to play an outstanding role in this new field of research.

The change of scope from nucleic acids to proteins needs, by far, more than a little change in the technology to be applied. Especially, there is a tremendous need to develop new microarrays with a flexible surface chemistry. Proteins are, by far, more complex in their material properties than polynucleic acids. Whereas DNA is composed of only four different nucleotides, which are chemically quite closely related to one another, proteins consist of 21 different amino acids that can differ drastically in their chemical functionality. Additionally, posttranslational modifications on proteins within organisms create an even larger variety in the chemical properties of naturally occurring proteins and polypeptides. Therefore, intending to establish a protein-oriented microarray technology, there is an immense need for a large variety of different tailor-made surface chemistries.

In our approach described here, we provide a prestructured microarray for the immobilization of proteins. By adsorbing a patterned layer of nanoparticles with various surface modifications to a substrate, we separate the two steps of chemical tailoring of the surface on a molecular level and the subsequent microstructuring of the chip in two fundamentally independent processes. Thereby, an extremely efficient microarray preparation is realized while providing notably high flexibility in chemical surface structures. In the first step, by means of chemical nanotechnology, tailor-made nanoparticles are prepared. The particle's surface is customized to match the specific demands for the immobilization of a certain kind or class of proteins. In a second step, the nanoparticles are deposited on a chip to render a microstructured monolayer array of nanoparticles. This microstructure can be achieved by a choice of different lithographic processes. Either photolithography, microcontact printing, or microspotting is applied for nanoparticle deposition only at well-defined areas of the substrate. The resulting system is a nanoparticle-based microarray ready for the selective binding of protein ligands.