Micro- and nano-electromechanical systems (M/NEMS) have demonstrated outstanding sensing capabilities down to the yoctogram () scale in vacuum environment and cryogenic temperatures. In order to bring such extraordinary resolution levels into the study of biological processes, suspended microchannel resonators (SMRs) have been developed. SMRs are hollow devices allowing for fluidic confinement inside the body of the resonator, which can thus be kept in dry environment or encapsulated in vacuum. Analyte binding and flow-through experiments can be performed, these latter enabling single-cell analysis. In this paper, we survey the progress of over the past 20 years in the field of SMRs. We review the main fabrication, transduction and packaging strategies. We also provide an insight into the working principle of the sensors and their applications to microfluidics and biology.

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Oscillating micro-cantilever array enables immunoassay for single-step label-free analysis of candidate malaria vaccines. Differential read-out reveals epitope-specific timeline of malaria infection in complex serum samples.

We present a nanomechanical platform for real-time quantitative label-free detection of target biomolecules in a liquid environment with mass sensitivity down to few pg. Newly fabricated arrays of up to 18 cantilevers are integrated in a micromachined fluidic chamber, connected to software-controlled fluidic pumps for automated sample injections. We discuss two functionalization approaches to independently sensitize the interface of different cantilevers. A custom piezo-stack actuator and optical readout system enable the measurement of resonance frequencies up to 2 MHz. We implement a new measurement strategy based on a phase-locked loop (PLL), built via in-house developed software. The PLL allows us to track, within the same experiment, the evolution of resonance frequency over time of up to four modes for all the cantilevers in the array. With respect to the previous measurement technique, based on standard frequency sweep, the PLL enhances the estimated detection limit of the device by a factor of 7 (down to 2 pg in 5 min integration time) and the time resolution by more than threefold (below 15 s), being on par with commercial gold-standard techniques. The detection limit and noise of the new setup are investigated via Allan deviation and standard deviation analysis, considering different resonance modes and interface chemistries. As a proof-of-concept, we show the immobilization and label-free in situ detection of live bacterial cells (E. coli), demonstrating qualitative and quantitative agreement in the mechanical response of three different resonance modes.