Neutral particle mass spectrometry with nanomechanical systems

Abstract

Current approaches to mass spectrometry (MS) require ionization of the analytes of interest. For high-mass species, the resulting charge state distribution can be complex and difficult to interpret correctly. Here, using a setup comprising both conventional time-of-flight MS (TOF-MS) and nano-electromechanical systems-based MS (NEMS-MS) in situ, we show directly that NEMS-MS analysis is insensitive to charge state: the spectrum consists of a single peak whatever the species' charge state, making it significantly clearer than existing MS analysis. In subsequent tests, all the charged particles are electrostatically removed from the beam, and unlike TOF-MS, NEMS-MS can still measure masses. This demonstrates the possibility to measure mass spectra for neutral particles. Thus, it is possible to envisage MS-based studies of analytes that are incompatible with current ionization techniques and the way is now open for the development of cutting-edge system architectures with unique analytical capability.

Figure 1. Hybrid setup for TOF-MS and NEMS-MS of nanoparticles.

(a) Diagram showing the full setup from left to right: the cluster source, an intermediate chamber comprising deflection plates, the deposition chamber and an in-line TOF mass spectrometer. Both NEMS holder and QCM are retractable, making sequential NEMS-MS, TOF-MS and QCM measurements possible in identical operating conditions. (b) Colourized scanning electron microscope image of a typical doubly clamped in-plane resonator used in this study. The beams were designed to resonate around 25 MHz for mode 1 and 65 MHz for mode 2. Typical dimensions for the resonant beam were: 160 nm (thickness), 300 nm (width) and 5–10 μm (length). Electrostatic actuation was used, and in-plane motion transduction was performed using piezoresistive nanogauges in a bridge configuration to allow background cancellation. Gate electrodes were specifically patterned for mode 1 and mode 2 actuation. A bias voltage at ω−▵ω was applied at the centre of the nanogauge bridge and the tension/compression in the nanogauges at ω was used to mix the differential output down at ▵ω, a few 10 s of kHz (see also Supplementary Methods). Manufacturing details and electrical operation are described elsewhere.

Figure 2. NEMS-MS greatly clarifies the spectrum.

Spectra for a nanocluster population with a mean mass of around 2,420 kDa acquired by both TOF and NEMS-MS. The TOF data was smoothed by applying a Savitsky–Golay filter. While multiply charged particles generate several peaks in the TOF-MS spectrum, the NEMS directly weighs the particle masses, yielding a single peak.

Figure 3. Demonstration of neutral-particle MS.

Results of TOF-MS and NEMS-MS analysis of populations with and without charged particles. Charged particles can be removed by tuning the voltage on the deflection plates in the intermediate chamber: when this potential is set to 0 V (upper graphs), both ionized and neutral particles flow towards the deposition chamber, while with a voltage of 40 V (lower graphs) only neutral particles enter the deposition chamber. Three different nanoparticle populations were produced and measured using different experimental settings. These populations had mean masses of around 1,300, 2,300 and 3,400 kDa. The TOF displays singly, doubly and even triply charged particles when ions are not deflected. However, just like any ion-based MS instrument, the TOF is unable to produce spectra for the populations composed solely of neutral particles. NEMS-MS successfully detects the particles regardless of their charge states and delivers identical spectra for all configurations.