Current developments in microarray technologies are dependent on efficient chemical means for the immobilization of biomolecules on solid substrates. Surface Chemistry is the key for successful preparation of microstructured surfaces functionalized with nucleic acids, proteins, or small-molecule probe compounds. We have developed the use of dendrimers, branched molecules containing a large number of functional groups in their outer sphere, as an intermediate layer in between the solid substrate and the biomolecular content. These Dendrimer Slides allow for a tremendous increase in signal intensity, and thus sensitivity in analytical assays. Dendrimer coating also yields highly homogeneous biochips with an outstanding physico-chemical stability, thus enabling consecutive chemical modification steps and also biochip regeneration. In a collaborative effort with collegues at the Max-Planck Institute for Molecular Physiology, Dortmund, the dendrimer surfaces are being used for the development of Bioorthogonal Coupling chemistries for generating protein microarrays.
Functional proteins conjugated with single-stranded nucleic acids can be immobilized on a DNA-Microarray. This method, termed DNA-Directed Immobilization (DDI), not only proceeds with greater immobilization efficiency than conventional adsorption techniques, it also allows for reversible and site-selective functionalization of inorganic substrates with enzymes, immunoglobulins and other (macro)molecules. Therefore, DDI enables the facile production of laterally microstructured arrays of proteins and even living cells. In addition to the generation of microarrays, reusable biosensor chips and lab-on-a-chip devices, the DDI method has also particularly strong implications on Materials Science and Nanobiotechnology.
Schroeder, H., Adler, M., Gerigk, K., Müller-Chorus, B., Götz, F., Niemeyer, C. M. (2009) A User Configurable Microfluidic Device for Multiplexed Immunoassays Based on DNA-Directed Assembly. Anal. Chem. 81, 1275.
Jonkheijm, P., Weinrich, D., Schroeder, H., Niemeyer, C. M., Waldmann, H. (2008) Chemical Strategies for Generating Protein Biochips. Angew. Chem. Int. Ed. 47, 9618.
Schroeder, H., Ellinger, B., Becker, C. F. W., Waldmann, H., Niemeyer, C. M. (2007) Generation of Live Cell Microarrays by Means of DNA-Directed Immobilization of Specific Cell Surface Ligands. Angew. Chem. Int. Ed. 46, 4180.
Wacker, R., Schroeder, H., Niemeyer, C. M. (2004) Performance of antibody microarrays fabricated by either DNA-directed immobilization, direct spotting, or streptavidin-biotin attachment: a comparative study. Anal. Biochem. 330, 281.
Benters, R., Niemeyer, C. M., Wöhrle, D. (2001) Dendrimer-Activated Solid Supports for Nucleic Acid- and Protein-Microarrays; ChemBioChem, 2, 686.