The present invention relates to a method and device for detecting and/or quantifying one or multiple target molecules present in a solution by quantifying online their binding on specific capture molecules immobilized at different locations (spots) of a surface of an optically transparent solid support without substantial detection of target molecules present in solution. The present invention allows multiple target assays to be performed in a simultaneous detection. More particularly, the invention comprises detecting in real-time the hybridization between capture DNA molecules present on a micro-array and target polynucleotides present in solution. The invention is also related to real-time PCR of multiple targets on a micro-array.