2. The Initial History of Microarrays The original DNA array was created with the colony hybridization method of Grunstein and Hogness [1]. In this method, the DNA of interest is cloned into Escherichia coli plasmids, and E. coli colonies with different hybrid plasmids can be screened to determine a specified DNA sequence or gene. DNA prints of the colonies are then hybridized to radioactive RNA, and are analyzed by autoradiography. This method can be used to isolate any gene. Using this approach, Gergen et al. [2] reported a method for making paper filter replicas of such an ordered collection and developed a strategy for creating a high-density (10,000 colonies/petri) unordered collection. These different mixtures of probes could be used for nucleic acid hybridization screens of recombinant DNA colonies. In 1980, Crampton et al. [3] compared RNA populations derived from normal human lymphocytes and fibroblasts by hybridizing each RNA to cDNA derived from the other RNA population. The isolation of cloned cDNA sequences revealed the differentially expression between two samples. Schena et al. [4] published a high-capacity system that was developed to analyze the gene expression in parallel. Microarray technologies which were prepared by high-speed robotic printing of complementary DNAs on glass were useful for quantitative expression analysis of the corresponding genes. Differential gene expression measurements were obtained using simultaneous, two-color fluorescence hybridization. In 1996, DeRisi et al. [5] published a method describing very high density cDNA microarrays on glass substrates using fluorescent probes, and these arrays were used to search for differences in gene expression associated with tumor suppression. Since these initial studies, DNA microarray technologies have developed rapidly in a variety of fields. 2.1. Microarray Devices (DNA Chip Synthesis) 2.1.1. In Situ Synthesized Type The methods for preparing DNA chips combine photochemistry and photolithography with solid-phase DNA synthesis chemistry to generate a high-density oligonucleotide probe array in situ [6,7,8]. These two-dimensional arrays containing hundreds or thousands of oligonucleotide probes provide a powerful DNA sequence analysis tool [6]. For example, this method is now used to produce the high-density gene chip probe arrays, which are used for the detection and analysis of point mutations and SNPs and for gene expression studies [9]. The change of the carried probe number in expression array by Affymetrix shows Table 1. microarrays-04-00454-t001_Table 1 Table 1 The change Probe/GeneChip number in expression arrays by Affymetrix. 2.1.2. Spotting Type Many microarray spotting technologies and techniques have been successfully developed. DNA chips can be produced using the spot method, in which cDNAs are selectively deposited on specific positions on a glass slide using a spotter. Two of the more important spotting techniques used are the pin-based fluid transfer systems [10,11,12,13] and the piezo-based inkjet dispenser systems [14]. Table 2 shows the change of the coverage of genes and transcripts in expression array by Agilent. The microarray devices have rapidly developed. microarrays-04-00454-t002_Table 2 Table 2 The change of the coverage of the genes and transcripts in expression array by Agilent. 3.