Microarray chip-based technology is a promising and emerging technique that has great potential for rapid and high through-put genetic screening. Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is a detection method that offers speed, sensitivity, accuracy and automation. The objective of this study is to demonstrate the feasibility of solid phase Genetic Bit Analysis (GBA) for single nucleotide polymorphisms (SNPs) analysis using MALDI-TOF MS as the detection method. Our goals will be to: (1) demonstrate the feasibility of using mass labeled ddNTPs incorporated into GBA primers for subsequent detection in MALDI-TOF MS, (2) develop a solid phase chemistry that will allow GBA primers to be uncoupled from a solid surface for subsequent analysis by MALDI-TOF MS. (3) demonstrate SNP analysis by GBA using MALDI-TOF MS detection for genotype calling on a micro chip. The success of this Phase I study will allow the development of a microarray GBA diagnostic chip capable of analyzing SNPs by MALDI-TOF MS detection.
The direct application of MALDI-TOF MS detection to solid phase GBA will result in an advanced version of GBA, which provides a number of advantages over traditional fluorescence or ELASA based detection methods. Specifically, it permits rapid, one-step, accurate mass-based separation with the possibility of automation.
