ABSTRACT
This article is intended to give an overview of applications in medical diagnostics that take advantage of biofunctional surfaces and thereby focuses on microarray technology. Following a general introduction to microarrays and the concept behind them, the potential and challenges of microarray technology are shown, thereby particularly emphasizing the application fields of cancer-and infectious disease diagnostics-and introducing some examples of our own microarray research in these areas. Last but not least special manifestations of the primary concept of microarrays are presented, such as lab-on-a-chip systems. 29.1 Introduction
In biology one can find a lot of specific interactions between certain types of biomolecules. Examples here are the binding of
complementary DNA strands, the interaction of a certain antigen (peptide or protein) with its corresponding antibody, and the specific binding of a ligand (sugar, fatty acid derivative, peptide, or protein) to its appropriate receptor. All biomolecules mentioned above can be used in principle for establishing a biofunctional surface. In microarray technology the most prominent molecule used for creating a biofunctional surface is DNA. Soon after the description of the double helix by Watson and Crick [31], it was shown that the two strands can be separated by heat or treatment with alkali. The reverse process, which underlies all the methods based on DNA renaturation or molecular hybridization, was first described by Marmur and Doty [16] and represents the basic concept of DNA microarrays, the most common type of arrays. The basics of microarray technology, its potential, and its various application fields are presented in the following section. 29.2 Basics and Potential of Microarray
Microarray technology has emerged in the past 15 years as a method for analyzing large numbers of biomolecules in parallel. It evolved from a number of different disciplines and techniques and can be seen as the continued development of molecular hybridization methods, the extended use of fluorescence microscopy, and a diagnostic assay using capture to a solid surface in a way to reduce the amount of analytes needed. Analysis of nucleic acids by hybridization has been a key method since the early 1960s. By reversing the Northern blotting principle so that the labeled moiety is derived from the messenger RNA sample and the immobilized fractions are the known sequences traditionally used as probes, the principle of parallel processing was already implemented in the 1970s by dot blots [13]. Dot blots are typically done in an ordered format corresponding to the layout of a 96-well microtiter plate and allow expression-or homology analysis on series of samples, with radioactive labeling in most cases. A major change in the field was the development of robotic devices (“gridding robots”) in the late 1980s, which allowed for the generation of higher-density membranes (“macroarrays”), thereby enabling for the first time simultaneous determination of expression levels of several hundred genes in one experiment.
