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.

What to measure? is a key question in nanoscience, and it is not straightforward to address as different physicochemical properties define a nanoparticle sample. Most prominent among these properties are size, shape, surface charge, and porosity. Today researchers have an unprecedented variety of measurement techniques at their disposal to assign precise numerical values to those parameters. However, methods based on different physical principles probe different aspects, not only of the particles themselves, but also of their preparation history and their environment at the time of measurement. Understanding these connections can be of great value for interpreting characterization results and ultimately controlling the nanoparticle structure–function relationship. Here, the current techniques that enable the precise measurement of these fundamental nanoparticle properties are presented and their practical advantages and disadvantages are discussed. Some recommendations of how the physicochemical parameters of nanoparticles should be investigated and how to fully characterize these properties in different environments according to the intended nanoparticle use are proposed. The intention is to improve comparability of nanoparticle properties and performance to ensure the successful transfer of scientific knowledge to industrial real‐world applications.

Using suspended nanochannel resonators (SNRs), we demonstrate measurements of mass in solution with a resolution of 27 ag in a 1 kHz bandwidth, which represents a 100-fold improvement over existing suspended microchannel resonators and, to our knowledge, is the most precise mass measurement in liquid today. The SNR consists of a cantilever that is 50 µm long, 10 µm wide, and 1.3 µm thick, with an embedded nanochannel that is 2 µm wide and 700 nm tall. The SNR has a resonance frequency near 630 kHz and exhibits a quality factor of approximately 8000 when dry and when filled with water. In addition, we introduce a new method that uses centrifugal force caused by vibration of the cantilever to trap particles at the free end. This approach eliminates the intrinsic position dependent error of the SNR and also improves the mass resolution by increasing the averaging time for each particle.

Microfabricated transducers enable the label-free detection of biological molecules in nanoliter sized samples. Integrating microfluidic detect ion and sample-preparat ion can greatly leverage experimental efforts in systems biology and pharmaceutical research by increasing analysis throughput while dramatically reducing reagent cost.Microfabricated resonant mass sensors are among the most sensitive devices for chemical detection, but degradation of the sensitivity in liquid has so far hindered their successful application in biology. This thesis introduces a type of resonant transducer that overcomes this limitation by a new device design: Adsorption of molecules to the inside walls of a suspended microfluidic channel is detected by measuring the change in mechanical resonance frequency of the channel. In contrast to resonant mass sensors submersed in water, the sensitivity and frequency resolution of the suspended microchannel resonator is not degraded by the presence of the fluid. Our device differs from a vibrating tube densitometer in that the channel is very thin, and only molecules that bind to the walls can build up enough mass to be detected; this provides a path to specificity via molecular recognition by immobilized receptors.Suspended silicon nitride channels have been fabricated through a sacrificial polysilicon process and bulk micromachining, and the packaging and microfluidic interfacing of the resonant sensors has been addressed. Device characterization at 30 mTorr ambient pressure reveals a quality factor of more than 10,000 for water filled resonators; this is two orders of magnitude higher than previously demonstrated Q-values of resonant mass sensors for biological measurements.Calculation of the noise and the sensitivity of suspended microchannel resonators indi-

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 .

Dissipation of mechanical energy underlies the sensitivity of many nanomechanical devices, with environmental effects often having a significant effect. One case of practical relevance is the interaction of elastic beam resonators with fluid, which is known to dramatically increase energy dissipation. Recently, we investigated energy dissipation in a different class of elastic beam resonator that embeds a microfluidic channel in its interior. In this paper, we examine the effect of the beam material Poisson ratio on these devices and discover that it can strongly affect energy dissipation--this is in direct contrast to conventional cantilever beams immersed in fluid. Increasing the Poisson ratio in these microfluidic devices is found to decrease energy dissipation, with the incompressible material limit providing minimum energy dissipation. Our paper establishes that, in this limit, placement of the fluid channel away from the beam neutral axis has negligible effect on energy dissipation in many cases of practical interest. The physical implications of these findings are discussed, and a detailed comparison with available experimental results is provided.

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IN MEMORIAM. This paper is dedicated to the memory of Dr. J. Bruce Wagner, Jr. (1926–2006), long time Professor of Materials Science and Engineering at the Northwestern University, Evanston, IL and Regents Professor of the Arizona State University, Tempe, AZ. Professor Wagner was prominent scientist in the area of solid‐state science, electrochemistry and high temperature chemistry. He served as Director of the Material Research Centre at the Technological Institute of Northwestern University, Director of the Centre for Solid State Science at the Arizona State University. He was also the President of the Electrochemical Society.The present work reports the electrical properties for high purity polycrystalline TiO2 using the measurements of electrical conductivity in the temperature range 1123–1323 K and in the gas phase of controlled oxygen activity (10–13 Pa < p (O2) < 105 Pa). The slope of the log σ vs. log p (O2) dependence is –1/5.4, which is considered in terms of mixed electronic and ionic compensation. The electrical conductivity data within the n –p transition were used for the determination of the conductivity components related to electrons, electron holes and ions. These data were used for the determination of the n –p transition point. The band gap determined from the conductivity components related to electronic charge carriers is equal to 2.8 eV. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)