Applications of biochip and microarray systems in pharmacogenomics.

Abstract

A DNA microarray system is usually comprised of DNA probes formatted on a microscale on a glass surface (chip), plus the instruments needed to handle samples (automated robotics), to read the reporter molecules (scanners) and analyse the data (bioinformatic tools). Biochips are formed by in situ (on chip) synthesis of oligonucleotides or peptide nucleic acids (PNAs) or spotting of DNA fragments. Hybridisation of RNA- or DNA-derived samples on chips allows the monitoring of expression of mRNAs or the occurrence of polymorphisms in genomic DNA. Basic types of DNA chips are the sequencing chip, the expression chip and chips for comparative genomic hybridisation. Advanced technologies used in automated microarray production are photolithography, mechanical microspotting and ink jets. Bioelectronic microchips contain numerous electronically active microelectrodes with specific DNA capture probes linked to the electrodes through molecular wires. Several biosensors have been used in combination with biochips. PNA biosensors commonly rely on the immobilisation of a single-stranded DNA sequence (the 'probe') onto a transducer surface for hybridisation with the complementary ('target') strand to give a suitable electrical signal. Other sensors are cell-based immunobiosensors with engineered molecular recognition, integrated biosensors based on phototransistor integrated circuits and sensors based on surface plasmon resonance. Microarray technologies offer enormous savings in time and labour as compared to standard gel-based microsatellite methods. Reading of the information and its management by bioinformatics is necessary because of the enormous amount of data generated by the various technologies using microarrays. Standardised procedures are essential for compatible data production, quality control and analysis. Expression monitoring is the most biologically informative application of this technology at present. Microarray technology has important applications in pharmacogenomics: drug discovery and development, drug safety and molecular diagnostics. DNA chips will facilitate the integration of diagnosis and therapeutics, as well as the introduction of personalised medicines.