Improved resolution in the detection of oligonucleotides up to 60-mers in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using pulsed-delayed extraction with a simple high voltage transistor switch.

Pulsed-delayed extraction using a simple high voltage transistor switch together with various sample purification approaches were used to enhance the resolution in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) of oligonucleotides up to 60 bases long. This switch can provide a 0-3 kV voltage pulse with a 75 ns fall time. A resolution of 500-900 was typically observed for samples from 5-mers to 60-mers using pulsed-delayed extraction (PDE) with the switch described herein. The resolution deteriorated to < 100 for oligonucleotides of > or = 65-mers. With the TOF acceleration region configuration used in this work, the resolution was found not to vary significantly over a delay range of 2-5 mus. As the DNA size increased to over 35-mer, HPLC purification was required to retain the enhancement in resolution provided by PDE MALDI-MS.