The first transcriptome studies were based on microarray techniques (also known as DNA chips). Microarrays consist of thin glass layers with spots on which oligonucleotides, known as "probes" are arrayed; each spot contains a known DNA sequence.
When performing microarray analyses, mRNA is collected from a control and an experimental sample, the latter usually representative of a disease. The RNA of interest is converted to cDNA to increase its stability and marked with fluorophores of two colors, usually green and red, for the two groups. The cDNA is spread onto the surface of the microarray where it hybridizes with oligonucleotides on the chip and a laser is used to scan. The fluorescence intensity on each spot of the microarray corresponds to the level of gene expression and based on the color of the fluorophores selected, it can be determined which of the samples exhibits higher levels of the mRNA of interest.
One microarray usually contains enough oligonucleotides to represent all known genes; however, data obtained using microarrays does not provide information about unknown genes. During the 2010s, microarrays were almost completely replaced by next-generation techniques that are based on DNA sequencing.