Current Mass Spec Instrumentation Interests

Charge Reduction Electrospray Mass Spectrometry (CREMS)

This project was originally undertaken in order to test whether or not electrospray instruments would exhibit the same fall off in signal intensity at large m/z as MALDI instruments. The charge state of ions produced by electrospray ionization can be reduced in a controlled manner using bipolar ions produced by a 210 Po a particle source. The bipolar ions are produced by reaction of the a particles with a bath gas of medical air. The electrospray produced ions pass through a neutralization chamber where the charge on the ions is altered by proton transfer reactions with the bipolar ions. The bipolar nature of the generated ions allows this method to be used in either positive or negative ion mode. The amount of charge reduction can be altered by controlling the a particle flux as well as the amount of time the ions spend in the neutralization chamber. The neutralization chamber is positioned in front of the mass spectrometer inlet and is adaptable to virtually any type of mass analyzer.

Charge reduction can also be carried out using a corona discharge eliminating the need for a radioactive source. In this approach, a corona discharge is used in place of a particles to create ions from the bath gas. This configuration can also be used in either positive of negative ion mode by simply changing the polarity of the corona discharge.

CREMS is effective at reducing the charge state of large ions to principally +1 (or -1) thus eliminating spectral congestion caused by the presence of a large number of different charge states for a given analyte . This affords ESI instruments one the principle advantages of MALDI instruments. In addition, CREMS sources are gentle, easily coupled to on-line purification steps such as HPLC, and suitable for mixture analysis.

Mass spectra of ubiquitin , mw = 8565 Da , obtained after varying degrees of charge reduction.

CREMS publications:

Ebeling , D.D., Westphall , M.S., Scalf , M. and Smith, L.M. 2001. A cylindrical capacitor ionization source: droplet generation and controlled charge reduction for mass spectrometry. Rapid Commun . Mass Spectrom . , 15 , 401-405.

Ebeling , D., Westphall , M.S., Scalf , M. and Smith, L.M. 2000. Corona discharge in charge reduction electrospray mass spectrometry. Analytical Chemistry , 72 (21), 5158-5161.

Scalf , M., Westphall , M.S. and Smith, L.M. 2000. Charge reduction electrospray mass spectrometry. Analytical Chemistry , 72 (1), 52-60.

Scalf , M., Westphall , M.S., Krause, J., Kaufman, S.L. and Smith, L.M. 1999. Controlling charge states of large ions. Science , 283 (5399) 194-197.

Piezoelectric “Droplet On Demand?Droplet Sources

Piezoelectric droplet sources were pursued out of a desire to increase sensitivity and decrease sample volume requirements when using electrospray ionization methods. In this technique, a piezoelectric droplet dispenser is used to create discrete packets of ions for analysis by mass spectrometry. This droplet source can simply be used in place of a traditional electrospray source in front of the mass spectrometer. This technique utilizes a glass capillary placed inside a piezoelectric element. The tip is placed in front of the mass spectrometer inlet and the solution inside is held at a potential just lower than that required to produce normal electrospray . Voltage pulses can then be applied to the piezoelectric element causing it to constrict radially thereby causing a droplet to be emitted from the capillary tip. Detection limits comparable to those obtained by conventional nanoelectrospray methods can be obtained using this technique. One advantage of the piezoelectric dispenser is that the larger tip diameter is less prone to clogging, a problem which plagues conventional nanoelectrospray tips.

Advantages of the piezoelectric droplet source include the ability to precisely control the frequency of ionization pulses thereby controlling the volume of sample consumed per mass spectrum. Additionally, the characteristics of the voltage pulse applied to the piezoelectric element can be tuned to affect the volume and form of the emitted droplets. The piezoelectric dispenser is also compatible with a range of organic/aqueous solvent compositions; pulse parameters can be optimized for a given composition.

This technique demonstrates attomolar detection limits allowing the dispenser to be used for single pulse experiments requiring as little as 10 picoliters of sample solution.

Piezoelectric droplet dispenser publications:

Berggren, W.T., Westphall , M.S. and Smith, L.M. 2002. Single pulse nanoelectrospray ionization. Analytical Chemistry , 74 (14), 3443-3448.

Acoustic Droplet Levitation

Another current research focus involves electrospray from acoustically levitated droplets. In this approach, charge is supplied to a levitated parent droplet and highly charged daughter droplets are ejected toward the mass spectrometer inlet. The focus of this work is to reduce or eliminate the problem of signal suppression by preferential ionization. The eventual goal is to facilitate the direct analysis of complex mixtures by mass spectrometry. This will be accomplished by the continuous recharging of the parent droplet which ensures that all of the daughter droplets entering the mass spectrometer possess sufficient charge to ionize all analyte molecules contained therein. Another interesting prospect for this type of ion source would be to carry out reactions within the levitated droplets by addition of reagents using piezoelectric droplet dispensers.

Inductive Ion Detectors

Work in our lab has focused on inductive detectors due to their reduced fall off in signal at high m/z. The principle of operation of inductive ion detectors is as follows: As the analyte ions pass between the conductive detector plates, a charge of opposite polarity is induced on the detector surface. The resulting current can be converted to a voltage and amplified yielding the signal. Inductive ion detectors possess some advantages over the microchannel plate detectors employed in most mass spectrometers. Inductive ion detectors do not exhibit saturation effects, a property which makes them useful for the analysis of high m/z ions. Work in our lab has focused on the use of inductive ion detectors in a MALDI instrument in order to extend the m/z range which can be analyzed from a single mixture.

Publications featuring inductive detectors:

Chen, X., Westphall , M.S. and Smith, L.M. 2003. Mass spectrometric analysis of DNA mixtures: instrumental effects responsible for decreased sensitivity with increasing mass. Analytical Chemistry. , 75 (21) 5944-5952.