Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint

The signal-to-noise ratio of planar ISFET pH sensors deteriorates when reducing the area occupied by the device, thus hampering the scalability of on-chip analytical systems which detect the DNA polymerase through pH measurements. Top-down nano-sized tri-gate transistors, such as silicon nanowires, are designed for high performance solid-state circuits thanks to their superior properties of voltage-to-current transduction, which can be advantageously exploited for pH sensing. A systematic study is carried out on rectangular-shaped nanowires developed in a complementary metal-oxide-semiconductor (CMOS)-compatible technology, showing that reducing the width of the devices below a few hundreds of nanometers leads to higher charge sensitivity. Moreover, devices composed of several wires in parallel further increase the exposed surface per unit footprint area, thus maximizing the signal-to-noise ratio. This technology allows a sub milli-pH unit resolution with a sensor footprint of about 1 \ub5m2, exceeding the performance of previously reported studies on silicon nanowires by two orders of magnitude

More DNA–Aptamers for Small Drugs: A Capture–SELEX Coupled with Surface Plasmon Resonance and High-Throughput Sequencing

To address limitations in the production of DNA aptamers against small molecules, we introduce a DNA-based capture-SELEX (systematic evolution of ligands by exponential enrichment) protocol with long and continuous randomized library for more flexibility, coupled with in-stream direct-specificity monitoring via SPR and high throughput sequencing (HTS). Applying this capture-SELEX on tobramycin shows that target-specificity arises at cycle number 8, which is confirmed by sequence convergence in HTS analysis. Interestingly, HTS also shows that the most enriched sequences are already visible after only two capture-SELEX cycles. The best aptamers displayed KD of approximately 200 nM, similar to RNA and DNA-based aptamers previously selected for tobramycin. The lowest concentration of tobramycin detected on label-free SPR experiments with the selected aptamers is 20-fold smaller than the clinical range limit, demonstrating suitability for small-drug biosensing

Digital approaches in Electronic biochips

Download Citation Email Print Request Permissions Save to Project Electronic biochips are defined by the merge of integrated electronics, containing diverse sensors, with reaction solution and sample hold in reaction chamber(s). Based on their overall structure, electronic biochips can work in either well-confined or in area-confined configurations. Extreme parceling of the sample (digital approach), coupled with electronic biochips, can radically enhance the throughput performance of the assay, especially in an area-defined configuration. This takes advantage of the increased sensitivity that follows device miniaturization, as illustrated in our experiments on Silicon Nano Ribbons

Isothermal multiple displacement amplification of DNA templates in minimally buffered conditions using phi29 polymerase

The isothermal amplification of DNA in minimally buffered conditions allows to perform and monitor nucleic acid amplification with minimal technological and operative requirements. We show in this work how phi29 can operate multiple displacement amplification in minimally buffered conditions producing, as a readout, pH shifts attaining subunits of pH

Comparison between front- and back-gating of Silicon Nanoribbons in real-time sensing experiments

Field-effect transistors (FETs) with open gate structures such as Silicon Nanoribbons (SiNRs) are promising candidates to become general platforms for ultrasensitive, label-free and real-time detection of biochemical interactions on surface. This work proposes and demonstrates the viability of a solution for integrating Ag/AgCl reference electrodes with the microfluidics. A comparison between different polarization schemes is carried out with an analysis of the respective advantages and disadvantages

Detecting particles flowing through interdigitated 3D microelectrodes

Counting cells in a large microchannel remains challenging and is particularly critical for in vitro assays, such as cell adhesion assays. This paper addresses this issue, by presenting the development of interdigitated three-dimensional electrodes, which are fabricated around passivated pillarshaped silicon microstructures, to detect particles in a flow. The arrays of micropillars occupy the entire channel height and detect the passage of the particle through their gaps by monitoring changes in the electrical resistance. Impedance measurements were employed in order to characterize the electrical equivalent model of the system and to detect the passage of particles in real-time. Three different geometrical micropillar configurations were evaluated and numerical simulations that supported the experimental activity were used to characterize the sensitive volume in the channel. Moreover, the signal-to-noise-ratio related to the passage of a single particle through an array was plotted as a function of the dimension and num ber of micropillars

Real-time high-sensitivity impedance measurement interface for tethered BLM biosensor arrays

This paper presents a switched-capacitor (SC) current integrator circuit for impedance measurement of tethered bilayer lipid membrane (tBLM) biosensors. The circuit comprises a small number of high performance components enabling enhanced experimental flexibility and reliability. The sensitivity is improved significantly by suppressing the output offset through pseudo-differential operation, using R-C components for the reference impedance. The sensing and reference electrodes are excited with low-amplitude differential voltage pulses and the current response to membrane resistance (RM) change of the tBLM biosensor is converted to voltage by a precision, low-noise SC integrator available as a single-package IC. Tests with both electrical models and actual biosensors demonstrated that the proposed circuit operates with high sensitivity and can be used in single chip versions for low-cost and high-sensitive tBLM biosensor arrays, featuring multiple electrode sites

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio