Abstract We have developed a novel gene expression microarray system, 3D-Gene™, featuring micro-columnar structure on the platform made of black resin and micro-bead agitation for efficient hybridization. With these technological characteristics, 3D-Gene™ achieves dramatic reduction of background noise, exceptionally high sensitivity and reproducibility, and high correlation with qRT-PCR methodology particularly for genes with low expression. In addition to the general high performance, however, the medical devices in clinical settings must be versatile for a variety of biomarker types as well as sample types. Employing this microarray, we further developed a highly sensitive system to detect attomole-level miRNA which is reported to be a novel biomarker for some cancers. Moreover, we were able to detect gene profiles reproducibly and accurately from formalin-fixed paraffin-embedded (FFPE) tissue which is known to be stored worldwide in a large number for retrospective studies. Finally, we developed a RNA sample preparation protocol with no amplification process, resulting in a quick and cost-effective protocol with high accuracy. Taken together, we developed systems for gene expression detection using a high performance microarray suitable for a wide range of clinical applications. 3D-Gene™ could be a powerful tool for drug target discovery and clinical diagnostic for various diseases. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C143.