The present invention relates to methods and systems for single molecule based nucleic acid amplification and subsequent detection of nucleic acid molecules, and particularly to the determination of SNPs, mutations, and to the diagnosis of diseases associated with the changes of these nucleic acid molecules.

Provided herein are methods of determining the size and purify of nucleic acids (e.g., mRNAs) by using hydrophilic interaction chromatography (HILIC)-based methods to separate the nucleic acids from a mixture, followed by mass spectrometry to determine the size of the nucleic acids.

Provided herein are methods of determining the size and purify of nucleic acids (e.g., mRNAs) by using hydrophilic interaction chromatography (HILIC)-based methods to separate the nucleic acids from a mixture, followed by mass spectrometry to determine the size of the nucleic acids.