ReviewDevelopments in microarray technologies
Section snippets
Gene expression analysis
The first use of microarrays was in immunological assays 1., 2. but the advent of genome sequencing created a demand for simultaneous multi-gene analysis. The ‘DNA chip’ combined advances in high-throughput oligonucleotide synthesis with PCR amplification to generate arrays of probes that are capable of detecting changes in the transcriptome via hybridization. Advances in detection and computation, and an increasing recognition that the expression of a gene was as important as its presence or
DNA microarrays
Expression analysis for the quantitative gene expression of many genes can be performed using either one- or two-colour fluorescent schemes. One-colour analysis is primarily used for arrays prepared by photolithography. Affymetrix (http://www.affymetrix.com) patented this process under the trade name GeneChip™ [10]. In this method, expression profiles for each sample are generated on a different chip using a single fluorescent label, such as phycoerythin, and the different images are then
Protein and peptide microarrays
DNA arrays are limited to providing information on the identity or amount of RNA or DNA present in a sample, providing that suitable controls are available. Translational products of genes can not be analyzed on such arrays and, therefore, require the use of polypeptide-based arrays. Most drug targets are proteins, therefore, protein and peptide microarrays are set to have an important impact on drug discovery. To date, such microarrays have not been used to their full potential due to
Glycomics
Although peptide arrays are delivering increasing amounts of information, current arrays do not address the problem of post-translation modification. Many proteins and biomolecules are modified by the covalent attachment of sugar residues, known as glycans. Many biological processes involve sugar–receptor binding and microarrays will become an important tool for the study of such interactions in this rapidly expanding field.
Neoglycolipids, spotted onto nitrocellulose and PVD, provide an example
Tissue and cell microarrays
Analysis of gene or protein expression levels can only begin to provide us with relevant information about the biological function of the gene, its potential clinical impact or its suitability as a drug target. Functional genomics enables the validation of targets that have been identified by microarray screening.
Conventional histological analysis of tissue specimens is a slow and labour-intensive process: tissues are first preserved in formalin before being embedded in paraffin for sectioning,
The future of microarray technology
DNA-, protein-, glycomic- and cell-based microarrays continue to be developed to extract more data from smaller sample volumes. New technologies are now emerging to improve their overall design, to increase the speed of analysis and to reduce sample size even further. Box 2 indicates commercially available microarray technologies that use novel platform technologies.
In a drug development context, the analyst or laboratory requirement is to be able to undertake a fundamentally simple
Conclusions
Microarray technologies offer significant potential for advancements in both biochemical and pharmaceutical analysis. In principle, this is only bounded by the limits of ethics or human imagination. The real challenge in the future comes in the form of application engineering, methodology validation and technology transfer from innovation generation to generation with the end-user in mind. This can only be achieved by rapid acceptance of new technology and by wider recognition of the benefits
Acknowledgements
We would like to thank Ariel Louwrier for his continuous support and encouragement.
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