Frequency fluctuations in silicon nanoresonators

Frequency stability is key to performance of nanoresonators. This stability is thought to reach a limit with the resonator's ability to resolve thermally-induced vibrations. Although measurements and predictions of resonator stability usually disregard fluctuations in the mechanical frequency response, these fluctuations have recently attracted considerable theoretical interest. However, their existence is very difficult to demonstrate experimentally. Here, through a literature review, we show that all studies of frequency stability report values several orders of magnitude larger than the limit imposed by thermomechanical noise. We studied a monocrystalline silicon nanoresonator at room temperature, and found a similar discrepancy. We propose a new method to show this was due to the presence of frequency fluctuations, of unexpected level. The fluctuations were not due to the instrumentation system, or to any other of the known sources investigated. These results challenge our current understanding of frequency fluctuations and call for a change in practices

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Nanomechanical spectroscopy of ultrathin silicon nitride suspended membranes

Mechanical properties of a nanomechanical resonator significantly impact the performance of a resonant Nano-electromechanical system (NEMS) device. We study the mechanical properties of suspended membranes fabricated out of low-pressure chemical vapor deposited silicon nitride thin films. We fabricated doubly-clamped membranes of silicon nitride with thickness less than 50 nm and length varying from 5 to 60 μm. The elastic modulus and stress in the suspended membranes were measured using Atomic Force Microscope (AFM)-based nanomechanical spectroscopy. The elastic moduli of the suspended membranes are significantly higher than those of corresponding on-substrate thin films. We observed a reduction in net stress after the fabrication of suspended membrane, which is explained by estimating the thermal stress and intrinsic stress. We also use a mathematical model to study the stress and thickness-dependent elastic modulus of the ultrathin membranes. Lastly, we study the capillary force-gradient between the SiNx suspended membrane-Si substrate that could collapse the suspended membrane

DNA Detection Using Programmed Bilayer Nanopores

Pore-functionalization has been explored by several groups as a strategy to control DNA translocation through solid-state nanopores. Here we present a hybrid nanopore system consisting of single-layer graphene and a DNA origami layer to achieve base-selective control of DNA translocation rate through aligned nanopores of the two layers. This is achieved by incorporating unpaired dangling bases called overhangs to the origami near the pore region. Molecular dynamics simulations were used to optimize the design of the origami nanopore and the overhangs. Specifically, we considered the influence of the number and spatial distribution of overhangs on translocation times. The simulations revealed that specific interactions between the overhangs and the translocating single stranded DNA resulted in base-specific residence times. </p

DNA Translocation Through Vertically Stacked 2D Layers of Graphene & Hexagonal Boron Nitride Heterostructure Nanopore

Cost effective, fast and reliable DNA sequencing can be enabled by advances in nanopore based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal Boron Nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10x lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications

DNA Translocation through Hybrid Bilayer Nanopores

Pore functionalization has been explored by several groups as a strategy to control DNA translocation through solid-state nanopores. Here we present a hybrid nanopore system consisting of single-layer graphene and a DNA origami layer to achieve base-selective control of DNA translocation rate through aligned nanopores of the two layers. This is achieved by incorporating unpaired dangling bases called overhangs to the origami near the pore region. Molecular dynamics simulations were used to optimize the design of the origami nanopore and the overhangs. Specifically, we considered the influence of the number and spatial distribution of overhangs on translocation times. The simulations revealed that specific interactions between the overhangs and the translocating single-stranded DNA resulted in base-specific residence times

DNA Detection Using Programmed Bilayer Nanopores

<p>Pore-functionalization has been explored by several groups as a strategy to control DNA translocation through solid-state nanopores. Here we present a hybrid nanopore system consisting of single-layer graphene and a DNA origami layer to achieve base-selective control of DNA translocation rate through aligned nanopores of the two layers. This is achieved by incorporating unpaired dangling bases called overhangs to the origami near the pore region. Molecular dynamics simulations were used to optimize the design of the origami nanopore and the overhangs. Specifically, we considered the influence of the number and spatial distribution of overhangs on translocation times. The simulations revealed that specific interactions between the overhangs and the translocating single stranded DNA resulted in base-specific residence times. <b></b></p

Single-particle Mass Spectrometry with arrays of frequency-addressed nanomechanical resonators

International audienceOne of the main challenges to overcome to perform nanomechanical mass spectrometry analysis in a practical time frame stems from the size mismatch between the analyte beam and the small nanomechanical detector area. We report here the demonstration of mass spectrometry with arrays of 20 multiplexed nanomechanical resonators, each resonator is designed with a distinct resonance frequency which becomes its individual address. Mass spectra of metallic aggregates in the MDa range are acquired with more than one order of magnitude improvement in analysis time compared to individual resonators. A 20 NEMS array is probed in 150 ms with the same mass limit of detection as a single resonator. Spectra acquired with a conventional time-of-flight mass spectrometer in the same system show excellent agreement. We also demonstrate how mass spectrometry imaging at the single-particle level becomes possible by mapping a 4-cm-particle beam in the MDa range and above