Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity. Previously, samples as light as 7 zeptograms (1 zg = 10(-21) g) have been weighed in vacuum, and proton-level resolution seems to be within reach. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum. Here we demonstrate that suspended microchannel resonators can weigh single nanoparticles, single bacterial cells and sub-monolayers of adsorbed proteins in water with sub-femtogram resolution (1 Hz bandwidth). Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles.

We used a suspended microchannel resonator (SMR) combined with picoliter-scale microfluidic control to measure buoyant mass and determine the ‘instantaneous’ growth rates of individual cells. The SMR measures mass with femtogram precision, allowing rapid determination of the growth rate in a fraction of a complete cell cycle. We found that for individual cells of Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae and mouse lymphoblasts, heavier cells grew faster than lighter cells.

The surface stress induced during the formation of alkanethiol self-assembled monolayers (SAMs) on gold from the vapor phase was measured using a micromechanical cantilever-based chemical sensor. Simultaneous in situ thickness measurements were carried out using ellipsometry. Ex situ scanning tunneling microscopy was performed in air to ascertain the final monolayer structure. The evolution of the surface stress induced during coverage-dependent structural phase transitions reveals features not apparent in average ellipsometric thickness measurements. These results show that both the kinetics of SAM formation and the resulting SAM structure are strongly influenced both by the surface structure of the underlying gold substrate and by the impingement rate of the alkanethiol onto the gold surface. In particular, the adsorption onto gold surfaces having large, flat grains produces high-quality self-assembled monolayers. An induced compressive surface stress of 15.9 ± 0.6 N/m results when a c(4×2) dodecanethiol SAM forms on gold. However, the SAMs formed on small-grained gold are incomplete and an induced surface stress of only 0.51 ± 0.02 N/m results. The progression to a fully formed SAM whose alkyl chains adopt a vertical (standing-up) orientation is clearly inhibited in the case of a small-grained gold substrate and is promoted in the case of a large-grained gold substrate.

Many interactions drive the adsorption of molecules on surfaces, all of which can result in a measurable change in surface stress. This article compares the contributions of various possible interactions to the overall induced surface stress for cantilever-based sensing applications. The surface stress resulting from adsorption-induced changes in the electronic density of the underlying surface is up to 2-4 orders of magnitude larger than that resulting from intermolecular electrostatic or Lennard-Jones interactions. We reveal that the surface stress associated with the formation of high quality alkanethiol self-assembled monolayers on gold surfaces is independent of the molecular chain length, supporting our theoretical findings. This provides a foundation for the development of new strategies for increasing the sensitivity of cantilever-based sensors for various applications.

We demonstrate the measurement of mass, density, and size of cells and nanoparticles using suspended microchannel resonators. The masses of individual particles are quantified as transient frequency shifts, while the particles transit a microfluidic channel embedded in the resonating cantilever. Mass histograms resulting from these data reveal the distribution of a population of heterogeneously sized particles. Particle density is inferred from measurements made in different carrier fluids since the frequency shift for a particle is proportional to the mass difference relative to the displaced solution. We have characterized the density of polystyrene particles, Escherichia coli, and human red blood cells with a resolution down to 10 −4 g/cm 3 .

We present a methodology for preparing silicon nitride nanopores that provides in situ control of size with sub-nanometer precision while simultaneously reducing electrical noise by up to three orders of magnitude through the cyclic application of high electric fields in an aqueous environment. Over 90% of nanopores treated with this technique display desirable noise characteristics and readily exhibit translocation of double-stranded DNA molecules. Furthermore, previously used nanopores with degraded electrical properties can be rejuvenated and used for further single-molecule experiments.

The surface stress response of micromechanical cantilever-based sensors was studied as a function of the morphology, adhesion, and cleanliness of the gold sensing surface. Two model systems were investigated: the adsorption of alkanethiol self-assembled monolayers at the gas-solid interface and the potential-controlled adsorption of anions at the liquid-solid interface. The potential-induced surface stress, on a smooth and continuous polycrystalline Au(111)-textured microcantilever in 0.1 M HClO4, is in excellent agreement with macroscopic Au(111) single-crystal electrode results. It is shown that ambient contaminants on the sensing surface dramatically alter the surface stress-potential response. This observation can be misinterpreted as evidence that for polycrystalline Au(111) microcantilever electrodes, surface stress is dominated by surface energy change. Results for anions adsorption on gold are in contrast to the gas-phase model system. We demonstrate that the average grain size of the gold sensing surface strongly influences the magnitude of the surface stress change induced by the adsorption of octanethiol. A 25-fold amplification of the change in surface stress is observed on increasing the average gold grain size of the sensing surface from 90 to 500 nm.

Nanopore arrays are fabricated by controlled dielectric breakdown (CBD) in solid-state membranes integrated within polydimethylsiloxane (PDMS) microfluidic devices. This technique enables the scalable production of independently addressable nanopores. By confining the electric field within the microfluidic architecture, nanopore fabrication is precisely localized and electrical noise is significantly reduced. Both DNA and protein molecules are detected to validate the performance of this sensing platform.