MICROARRAY TECHNOLOGY

Microarray technology

Microarray technology

Introduction

The development of microarray technology is intimately connected with the transition of molecular biology from its classical phase into its post-genomic era. Microarray technology promises not only to dramatically speed up the experimental work of molecular biologists but also to make possible a whole new experimental approach in molecular biology. Instead of investigating the complexity of biological effects by analyzing single genes of putative importance one after the other, many or even all genes of an organism can now be tested at once. Although technically still in the early stages of development, microarrays are already indispensable for two new full-genomic approaches: large-scale genotyping and gene-expression profiling. In connection with genome sequencing projects, the former gives the microarray unprecedented potential as a DNA-analytical system and the latter takes the microarray from the basic research laboratory and establishes it as a key component of high-throughput screening systems in drug research.

The January 1999 supplement of Nature Genetics was devoted completely to this field. More recent information is available from reviews covering general aspects [1 and 2], technical details , experimental solutions or biological results [5 and 6] and specifically the field of cancer as well as from more than 200 companies worldwide engaged in the development and application of this technology. The scope of this review is therefore restricted to some examples of recent technical advances and research applications, and is focused on current trends in the movement of the microarray from being a purely research method to becoming an analytical instrument applicable in the clinic as well as in industry.

The present state of microarray technology

Working with microarrays requires the combination of at least five different components : the chip itself with its special surface; the device for producing microarrays by spotting the nucleic acids (probes) onto the chip or for their in situ synthesis; a fluidic system for hybridization to target DNA; a scanner to read the chips; and sophisticated software programs to quantify and interpret the results. Additional tools are required for extracting nucleic acids from biological material to prepare them for the analysis. For each of these components special equipment is now commercially available. In addition, microarray components or complete systems, ready-to-use gene collections and PCR product libraries of cDNA and even comprehensive microarray studies are commercially offered as services (for details see [3 and 9]). Usually, the different systems show very different levels of reliability and reproducibility, are not compatible with each other and require a skilled scientist to setup, commission and even to routinely run them. The value of microarray experiments still depends critically on the quality of arraying, recently made possible by bubble jet technology or maskless in situ synthesis of oligonucleotides . Microarray experiments also depend on probe and target preparation, experimental variations during hybridization and specifically on the selection of the nucleic acids affixed to the microarray surface. Further, microarray experiments depend on the homogeneity of the surface and linking chemistries on the chip as well as on background and overexposure problems during ...