The vibrational frequency of a NEMS resonator is an exquisitely sensitive function of its total mass. Any small variation in mass, e.g. from adsorbed addenda, will measurably alter its resonant frequency. Hence, nanomechanical resonators can be used as sensitive mass analyzers. Based on theoretical calculations (1) for physically realizable devices, it has been shown that a mass sensitivity below a single Dalton is realizable. These calculations correctly predict the performance of existing state-of-the-art NEMS resonators. Furthermore, this technique for mass sensing has some significant advantages such as straightforward integration with microfluidic preprocessors, extremely large mass dynamic range, and simpler forms of spectrometry since it is mass itself, and not m/z, that is detected. (Multiply-charged species “weigh” the same.) Our attainment of zeptogram mass sensitivity is described in two papers that first showed 7 zg, then 1zg mass sensitivity (2, 3).

NEMS-MS, if successful, will provide a new paradigm for high-throughput biological mass spectrometry with single-molecule resolution. Our initial NEMS-MS prototypes comprise single injectors delivering analytes to solitary NEMS mass sensors. However, the intrinsic power of this new technique is not solely in raw sensitivity. Instead, the significant opportunity of NEMS-MS originates from its combined attributes of sensitivity, compactness, and, especially, scalability. NEMS-MS systems are created by micro- and nanofabrication methods that are readily scalable up to highly-multiplexed instruments that can be produced en masse.

As a first step towards building a compact microfluidics compatible mass spectrometer, we are performing a proof of principle experiment of the protein mass detection using a single NEMS device. The schematics of the experiment, the simplified circuit for the measurement and the device micrograph are shown in the figure. We use a commercial electrospray ionization system to produce the ionized protein in the gas phase.