Multi-component ion modifiers and arcing suppressants to enhance differential mobility spectrometry for separation of peptides and drug molecules.

The optimization of ion/molecule chemistry in a differential mobility spectrometer (DMS) is shown to result in improved peak capacity, separation, and sensitivity. We have experimented with a modifier composed of multiple components, where each component accomplishes a specific task on mixtures of peptides and small drug molecules. Use of a higher proton affinity modifier (hexanol) provides increased peak capacity and separation. Analyte ion/modifier proton transfer is suppressed by adding a large excess of low proton affinity modifier (water or methanol), significantly increasing signal intensity and sensitivity for low proton affinity analytes. Finally, addition of an electrical arcing suppressant (chloroform) allows the device to operate reliably at higher separation fields, improving peak capacity and separation. We demonstrate a 20% increase in the device peak capacity without any loss of sensitivity and estimate that further optimization of the modifier composition can increase this to 50%. Use of 3-, 4-, or even 5-component modifiers offers the opportunity for the user to fine-tune the modifier performance to maximize the device performance, something not possible with a single component modifier.