Charge Detection Mass Spectrometry for Single Ions

Authors: Elizabeth E Pierson Nathan C Contino David Z Keifer Martin F Jarrold

Publish Date: 2015/04/14

Volume: 26, Issue: 7, Pages: 1213-1220

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Abstract

Charge detection mass spectrometry CDMS provides a direct measure of the mass of individual ions through nondestructive simultaneous measurements of the mass to charge ratio and the charge To improve the accuracy of the charge measurement ions are trapped and recirculated through the charge detector By substantially extending the trapping time the uncertainty in the charge determination has been reduced by a factor of two from 13 elementary charges e to 065 e The limit of detection the smallest charge that can be reliably measured has been reduced by about the same proportion from 13 to 7 e The more precise charge measurements enable a substantial improvement in the mass resolution which is critical for applications of CDMS to mixtures of high mass ionsCharge detection mass spectrometry CDMS is a technique in which simultaneous measurement of the masstocharge ratio m/z and the charge z of individual ions yields the mass of each ion This approach circumvents the need to resolve charge states in a traditional m/z spectrum from an electrospray source which can become convoluted for ions above several hundred kDa 1 2 To measure m/z and z an ion with a known kinetic energy is passed through a conducting cylinder and the charge induced on the cylinder is detected The length of the signal the timeofflight through the tube is related to the ion’s m/z The amplitude of the signal is proportional to z Multiplying m/z and z for each ion yields m the m values are then binned to generate a mass spectrumSimultaneous detection of m/z and z was first used by Shelton and coworkers more than 50 years ago to determine the mass of highlycharged micronsized particles 3 The smallest particle detected was 02 μm in diameter with nearly 20000 elementary charges e Hendricks later published a study using a similar detector to size oil droplets generated by electrohydrodynamic spraying 4 He found that the charged oil droplets were near the Rayleigh limit 5 In 1990 Keaton et al and Stradling et al developed a more sensitive apparatus of the Shelton design with a limit of detection of ~1500 charges 6 7The growing interest in mass spectrometry of noncovalent protein complexes and nucleic acids in the early 1990s prompted the Smith group to develop a Fourier transform ion cyclotron resonance FTICR approach that was able to trap single MDasize DNA ions and simultaneously measure their m/z and z 8 In this approach charges states as low as +30 were detected with a precision of ±10 Despite this success the expensive instrumentation and the low accuracy associated with the charge measurement has limited its useAs an alternative to FTICR for measuring the mass of MDasize particles Fuerstenau and Benner and coworkers coupled an electrospray source with CDMS to measure the mass of DNA and polystyrene microspheres 9 10 11 The detector used in these studies was modeled after the original Shelton design The energy distribution of electrospray ions in this experiment was broad and precluded proper m/z determination Instead Benner measured the velocity of particles from the expansion into vacuum with all electrodes grounded and the velocity of particles after acceleration across a known potential The velocity difference allowed m/z determination The precision of the charge measurement was ±75 e and the limit of detection was ~330 e A few years later Fuerstenau and Benner’s singlepass method 12 13 was used to measure the masses of whole viruses although the mass resolution achieved in these early experiments was limited by the precision of the charge measurementRecently some groups have used CDMS in a variety of highmass applications that have not required precise charge measurements Antoine Dugourd and collaborators studied the charging capacity of polyethylene oxide PEO ions with masses of up to 7 MDa 14 Based on the lowerthanexpected charging they concluded that PEO was not fully extended in the gas phase The same group used CDMS to study the photodissociation of single PEO ions 15 and the size distribution of selfassembled amphiphilic block copolymers 16 In related work Chang and collaborators used the basic principle of concurrent z and m/z determination to measure the mass of red blood cells 17One way to improve the precision of the charge measurement is to signal average To this end Benner situated his charge detector within an electrostatic ion trap to perform multiple m/z and z measurements for each ion 18 The error in the charge measurement is expected to decrease by a factor of n 1/2 where n is the number of cycles an ion is trapped In that work ions were trapped for up to 450 cycles With a root mean square RMS noise of 50 e the charge measurements could theoretically be as precise as ±24 e However the limit of detection was still high ~250 e An alternative approach to multiple charge measurements first implemented by GameroCastaño is the use of a linear array of charge detectors 19 20 21 22 However although offering the advantage of higher throughput it has not been possible to achieve the charge accuracy obtained with a recirculating trap

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