Geometrical Considerations for the Design of Liquid-phase Biochemical Sensors Using a Cantilever\u27s Fundamental In-plane Mode

The influence of the beam geometry on the quality factor and resonance frequency of resonant silicon cantilever beams vibrating in their fundamental in-plane flexural mode in water has been investigated. Compared to cantilevers vibrating in their first out-of-plane flexural mode, utilizing the in-plane mode results in reduced damping and reduced mass loading by the surrounding fluid. Quality factors as high as 86 have been measured in water for cantilevers with a 20 μm thick silicon layer. Based on the experimental data, design guidelines are established for beam dimensions that ensure maximal Q-factors and minimal mass loading by the surrounding fluid, thus improving the limit-of-detection of mass-sensitive biochemical sensors. Elementary theory is also presented to help explain the observed trends. Additional discussion focuses on the tradeoffs that exist in designing liquid-phase biochemical sensors using in-plane cantilevers

Unconventional Uses of Microcantilevers as Chemical Sensors in Gas and Liquid Media

The use of microcantilevers as (bio)chemical sensors usually involves the application of a chemically sensitive layer. The coated device operates either in a static bending regime or in a dynamic flexural mode. While some of these coated devices may be operated successfully in both the static and the dynamic modes, others may suffer from certain shortcomings depending on the type of coating, the medium of operation and the sensing application. Such shortcomings include lack of selectivity and reversibility of the sensitive coating and a reduced quality factor due to the surrounding medium. In particular, the performance of microcantilevers excited in their standard out-of-plane dynamic mode drastically decreases in viscous liquid media. Moreover, the responses of coated cantilevers operating in the static bending mode are often difficult to interpret. To resolve these performance issues, the following emerging unconventional uses of microcantilevers are reviewed in this paper: (1) dynamic-mode operation without using a sensitive coating, (2) the use of in-plane vibration modes (both flexural and longitudinal) in liquid media, and (3) incorporation of viscoelastic effects in the coatings in the static mode of operation. The advantages and drawbacks of these atypical uses of microcantilevers for chemical sensing in gas and liquid environments are discussed

On the Relative Sensitivity of Mass-sensitive Chemical Microsensors

In this work, the chemical sensitivity of mass-sensitive chemical microsensors with a uniform layer sandwich structure vibrating in their lateral or in-plane flexural modes is investigated. It is experimentally verified that the relative chemical sensitivity of such resonant microsensors is -to a first order- independent of the microstructure\u27s in-plane dimensions and the flexural eigenmode used, and only depends on the layer thicknesses and densities as well as the sorption properties of the sensing film. Important implications for the design of mass-sensitive chemical microsensors are discussed, whereby the designer can focus on the layer stack to optimize the chemical sensitivity and on the in-plane dimensions and mode shape to optimize the resonator\u27s frequency stability

Effect of Hydrodynamic Force on Microcantilever Vibrations: Applications to Liquid-Phase Chemical Sensing

At the microscale, cantilever vibrations depend not only on the microstructure’s properties and geometry but also on the properties of the surrounding medium. In fact, when a microcantilever vibrates in a fluid, the fluid offers resistance to the motion of the beam. The study of the influence of the hydrodynamic force on the microcantilever’s vibrational spectrum can be used to either (1) optimize the use of microcantilevers for chemical detection in liquid media or (2) extract the mechanical properties of the fluid. The classical method for application (1) in gas is to operate the microcantilever in the dynamic transverse bending mode for chemical detection. However, the performance of microcantilevers excited in this standard out-of-plane dynamic mode drastically decreases in viscous liquid media. When immersed in liquids, in order to limit the decrease of both the resonant frequency and the quality factor, and improve sensitivity in sensing applications, alternative vibration modes that primarily shear the fluid (rather than involving motion normal to the fluid/beam interface) have been studied and tested: these include in-plane vibration modes (lateral bending mode and elongation mode). For application (2), the classical method to measure the rheological properties of fluids is to use a rheometer. However, such systems require sampling (no in-situ measurements) and a relatively large sample volume (a few milliliters). Moreover, the frequency range is limited to low frequencies (less than 200Hz). To overcome the limitations of this classical method, an alternative method based on the use of silicon microcantilevers is presented. The method, which is based on the use of analytical equations for the hydrodynamic force, permits the measurement of the complex shear modulus of viscoelastic fluids over a wide frequency range

Entanglement and squeezing in a two-mode system: theory and experiment

We report on the generation of non separable beams produced via the interaction of a linearly polarized beam with a cloud of cold cesium atoms placed in an optical cavity. We convert the squeezing of the two linear polarization modes into quadrature entanglement and show how to find out the best entanglement generated in a two-mode system using the inseparability criterion for continuous variable [Duan et al., Phys. Rev. Lett. 84, 2722 (2000)]. We verify this method experimentally with a direct measurement of the inseparability using two homodyne detections. We then map this entanglement into a polarization basis and achieve polarization entanglement.Comment: submitted to J. Opt. B for a Special Issue on Foundations of Quantum Optic

Leptogenesis beyond the limit of hierarchical heavy neutrino masses

We calculate the baryon asymmetry of the Universe in thermal leptogenesis beyond the usual lightest right-handed (RH) neutrino dominated scenario (N_1DS) and in particular beyond the hierarchical limit (HL), M_1 << M_2 << M_3, for the RH neutrino mass spectrum. After providing some orientation among the large variety of models, we first revisit the central role of the N_1DS, with new insights on the dynamics of the asymmetry generation and then discuss the main routes departing from it, focusing on models beyond the HL. We study in detail two examples of `strong-strong' wash-out scenarios: one with `maximal phase' and the limit of very large M_3, studying the effects arising when delta_2=(M_2-M_1)/M_1 is small. We extend analytical methods already applied to the N_1DS showing, for example, that, in the degenerate limit (DL), the efficiency factors of the RH neutrinos become equal with the single decay parameter replaced by the sum. Both cases disprove the misconception that close RH neutrino masses necessarily lead to a final asymmetry enhancement and to a relaxation of the lower bounds on M_1 and on the initial temperature of the radiation-dominated expansion. We also explain why leptogenesis tends to favor normal hierarchy compared to inverted hierarchy for the left-handed neutrino masses.Comment: 30 pages, 8 figures; corrected typo in Eq. (67); shortened Introduction, Section 3 and Conclusions; one figure removed; added 2 references; to appear in JCA

Flavour Issues in Leptogenesis

We study the impact of flavour in thermal leptogenesis, including the quantum oscillations of the asymmetries in lepton flavour space. In the Boltzmann equations we find different numerical factors and additional terms which can affect the results significantly. The upper bound on the CP asymmetry in a specific flavour is weaker than the bound on the sum. This suggests that -- when flavour dynamics is included -- there is no model-independent limit on the light neutrino mass scale,and that the lower bound on the reheat temperature is relaxed by a factor ~ (3 - 10).Comment: 19 pages, corrected equations for flavour oscillation

Metabolic effects of diets differing in glycaemic index depend on age and endogenous GIP

Aims/hypothesis High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. Methods Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr −/− ) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20–26 weeks of intervention, n = 8–10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. Results Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr −/− vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. Conclusions/interpretation The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial

A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease

Genome-wide association studies (GWAS), relying on hundreds of thousands of individuals, have revealed > 200 genomic loci linked to metabolic disease (MD). Loss of insulin sensitivity (IS) is a key component of MD and we hypothesized that discovery of a robust IS transcriptome would help reveal the underlying genomic structure of MD. Using 1,012 human skeletal muscle samples, detailed physiology and a tissue-optimized approach for the quantification of coding (> 18,000) and non-coding (> 15,000) RNA (ncRNA), we identified 332 fasting IS-related genes (CORE-IS). Over 200 had a proven role in the biochemistry of insulin and/or metabolism or were located at GWAS MD loci. Over 50% of the CORE-IS genes responded to clinical treatment; 16 quantitatively tracking changes in IS across four independent studies (P = 0.0000053: negatively: AGL, G0S2, KPNA2, PGM2, RND3 and TSPAN9 and positively: ALDH6A1, DHTKD1, ECHDC3, MCCC1, OARD1, PCYT2, PRRX1, SGCG, SLC43A1 and SMIM8). A network of ncRNA positively related to IS and interacted with RNA coding for viral response proteins (P < 1 × 10−48), while reduced amino acid catabolic gene expression occurred without a change in expression of oxidative-phosphorylation genes. We illustrate that combining in-depth physiological phenotyping with robust RNA profiling methods, identifies molecular networks which are highly consistent with the genetics and biochemistry of human metabolic disease