Optimization and Efficiency Improvements in Charge Detection Mass Spectrometry Charge Measurement

As molecules of 1MDa and greater in size garner interest in the scientific community, new analysis techniques have emerged to provide the means to analyze them. Charge detection mass spectrometry (CDMS) is one of these. By directly measuring the charge and m/z of an ion the mass can be directly calculated. The charge measurements are made via a charge-sensitive amplifier, which historically have been operated with a feedback resistor to stabilize the operating point and discharge the feedback capacitor. However, the feedback resistor becomes the primary source of noise even when cryogenically cooled. Recent work has been done to remove the feedback resistor from the circuit and discharge the feedback capacitor using the detector leakage current. This design has minimized noise for the charge measurement allowing integer state charge resolution to be reached, but only after a 1500ms measurement time.
To decrease the total measurement time to reach integer state resolution, the charge root mean square deviation (RMSD) can be minimized. By improving the charge-sensitive amplifier, the noise will be reduced and by extension the charge RMSD. Since the resistor-less amplifier has a positive gate voltage it limits the selection of the input for a junction field effect transistor (JFET). To avoid this problem the gate voltage was negatively biased via photoelectrons. Reducing the gate voltage opens the specific constraints on JFET selection allowing the use of low noise JFETs. A low noise JFET on the resistor-less amplifier will further decrease the RMSD and then make it possible to reach charge state resolution with a reduced measurement time at a rate squared to that of the decrease in charge RMSD.