Weighing Molecular Heavyweights: Megadalton Mass Spectrometry
We are interested in developing methods to determine accurate masses for objects in the mega- to gigadalton size regime (106-109 amu) such as viruses, complexes, and nanoparticles. Nanomechanical oscillators only offer zeptogram sensitivity. Traditional mass spectrometry based methods which determine m/z (the mass to charge ratio) are able to “weigh” ions up to around 1 megadalton, at which point it becomes difficult to resolve the charge states (ions with a different number of charges). Large ions can have hundreds or even thousands of charges. One solution to this problem is to simultaneously measure m/z and z (the charge). A measurement of the average m/z and average z yields an average value for m. However, if m/z and z are measured for individual ions the mass distribution is obtained. The m/z and z can be measured by a technique called charge detection mass spectrometry.
Charge Detection Mass Spectrometry
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When a highly charged ion enters the charge detection cylinder it induces an image charge which is amplified pick-up by a sensitive amplifier. The ion in bounced back and forth between two ion mirrors (an approach first employed by Henry Benner). The frequency of the signal yields the time of flight and hence provides an accurate value for m/z. The amplitude yields z. If z can be determined with an uncertainty of less that one electron, an accurate value of the mass can be determined for each individual ion. Because the mass of each individual ion is measured it is possible to determine the mass distribution for a heterogeneous sample.
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Potential Applications include:
 Characterizing large complexes
Detection and identification of viruses
Determining size distributions for nanoparticles
The photograph on the right shows the charge detection mass spectrometer that we are building.
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