Metabolomics on integrated circuit

We have demonstrated a chip-based diagnostics tool for the quantification of metabolites, using specific enzymes, to study enzyme kinetics and calculate the Michaelis-Menten constant. An array of 256×256 ion-sensitive field effect transistors (ISFETs) fabricated in a complementary metal oxide semiconductor (CMOS) process is used for this prototype. We have used hexokinase enzyme reaction on the ISFET CMOS chip with glucose concentration in the physiological range of 0.05 mM – 231 mM and successfully studied the enzyme kinetics of hexokinase in detail. This will promote future research towards multiplexing enzyme-based metabolite quantification on a single chip, ultimately opening a pathway towards a personal metabolome machine

Light Sheet Tomography (LST) for <i>in situ</i> imaging of plant roots

The production of crops capable of efficient nutrient use is essential for addressing the problem of global food security. The ability of a plant's root system to interact with the soil micro-environment determines how effectively it can extract water and nutrients. In order to assess this ability and develop the fast and cost effective phenotyping techniques which are needed to establish efficient root systems, in situ imaging in soil is required. To date this has not been possible due to the high density of scatterers and absorbers in soil or because other growth substrates do not sufficiently model the heterogeneity of a soil's microenvironment. We present here a new form of light sheet imaging with novel transparent soil containing refractive index matched particles. This imaging method does not rely on fluorescence, but relies solely on scattering from root material. We term this form of imaging Light Sheet Tomography (LST). We have tested LST on a range of materials and plant roots in transparent soil and gel. Due to the low density of root structures, i.e. relatively large spaces between adjacent roots, long-term monitoring of lettuce root development in situ with subsequent quantitative analysis was achieved

An Expanded Range of Catalysts for Synthesizing Biodegradable Polyphosphonates

In this paper we expand the scope of catalysts able to mediate the ring opening polymerisation of the phosphonate monomer 2-methyl-1,3,2-dioxaphosphalone-2-oxide. A range of nitrogen bases efficiently catalyse the reaction, each with pK as of 19 or above; lower pK a bases do not ring open the monomer. Aluminium based catalysts supported by salen and salan ligand frameworks also afford exceptional control, with conversions in excess of 99% and dispersities under 1.1. Together, these studies significantly expand the scope of catalysts to prepare this biodegradable, non-toxic, water soluble polymer. Additionally, we report efforts to expand the monomer scope for these catalysts, showing that altering ring structure and substitution can strongly inhibit productive ring opening. </jats:p

Suitability of hybrid gravitational waveforms for unequal-mass binaries

This article studies sufficient accuracy criteria of hybrid post-Newtonian (PN) and numerical relativity (NR) waveforms for parameter estimation of strong binary black-hole sources in second- generation ground-based gravitational-wave detectors. We investigate equal-mass non-spinning binaries with a new 33-orbit NR waveform, as well as unequal-mass binaries with mass ratios 2, 3, 4 and 6. For equal masses, the 33-orbit NR waveform allows us to recover previous results and to extend the analysis toward matching at lower frequencies. For unequal masses, the errors between different PN approximants increase with mass ratio. Thus, at 3.5PN, hybrids for higher-mass-ratio systems would require NR waveforms with many more gravitational-wave (GW) cycles to guarantee no adverse impact on parameter estimation. Furthermore, we investigate the potential improvement in hybrid waveforms that can be expected from 4th order post-Newtonian waveforms, and find that knowledge of this 4th post-Newtonian order would significantly improve the accuracy of hybrid waveforms.Comment: 11 pages, 14 figure

Post-polymerization functionalization of poly(ethylene oxide)–poly(β-6-heptenolactone) diblock copolymers to tune properties and self-assembly

Copolymers were synthesized and functionalized with a variety of moieties to tune self-assembly and install drugs or fluorescent dyes. , Polyester-based amphiphilic block copolymers and their nanoassemblies are of significant interest for a wide range of applications due to the degradability of the polyester block. However, the commonly used polyesters lack functional groups on their backbones, limiting the possibilities to chemically modify these polymers. Described here are new poly(ethylene oxide) (PEO)–poly(β-6-heptenolactone) (PHEL) block copolymers having pendant alkenes at each repeat unit on the PHEL block. First, the self-assembly of these block copolymers in aqueous solution was studied and it was found that they formed solid nanoparticles and vesicles depending on the relative block lengths. Next the alkene moieties of the block copolymer were modified with either hydrophilic or hydrophobic pendant groups using thiol–ene reactions, allowing the hydrophilic mass fractions and consequently the self-assembled morphologies to be tuned, accessing both smaller nanoparticles and cylindrical assemblies. It was also demonstrated that the anti-cancer drug paclitaxel or a fluorescent rhodamine dye could be easily conjugated to the block copolymers and the self-assembly of these conjugates was explored. Overall, the results of this study demonstrate that PEO-PHEL block copolymers can serve as versatile backbones for the preparation of functional, polyester-based materials

Mechanical Evidence of the Orbital Angular Momentum to Energy Ratio of Vortex Beams

We measure, in a single experiment, both the radiation pressure and the torque due to a wide variety of propagating acoustic vortex beams. The results validate, for the first time directly, the theoretically predicted ratio of the orbital angular momentum to linear momentum in a propagating beam. We experimentally determine this ratio using simultaneous measurements of both the levitation force and the torque on an acoustic absorber exerted by a broad range of helical ultrasonic beams produced by a 1000-element matrix transducer array. In general, beams with helical phase fronts have been shown to contain orbital angular momentum as the result of the azimuthal component of the Poynting vector around the propagation axis. Theory predicts that for both optical and acoustic helical beams the ratio of the angular momentum current of the beam to the power should be given by the ratio of the beam’s topological charge to its angular frequency. This direct experimental observation that the ratio of the torque to power does convincingly match the expected value (given by the topological charge to angular frequency ratio of the beam) is a fundamental result

An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 216 sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2 – 12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM – 231 mM, encompassing glucose’s physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine

First direct comparison of non-disrupting neutron star-black hole and binary black hole merger simulations

We present the first direct comparison of numerical simulations of neutron star-black hole and black hole-black hole mergers in full general relativity. We focus on a configuration with non spinning objects and within the most likely range of mass ratio for neutron star-black hole systems (q=6). In this region of the parameter space, the neutron star is not tidally disrupted prior to merger, and we show that the two types of mergers appear remarkably similar. The effect of the presence of a neutron star on the gravitational wave signal is not only undetectable by the next generation of gravitational wave detectors, but also too small to be measured in the numerical simulations: even the plunge, merger and ringdown signals appear in perfect agreement for both types of binaries. The characteristics of the post-merger remnants are equally similar, with the masses of the final black holes agreeing within dM< 5 10^{-4}M_BH and their spins within da< 10^{-3}M_BH. The rate of periastron advance in the mixed binary agrees with previously published binary black hole results, and we use the inspiral waveforms to place constraints on the accuracy of our numerical simulations independent of algorithmic choices made for each type of binary. Overall, our results indicate that non-disrupting neutron star-black hole mergers are exceptionally well modeled by black hole-black hole mergers, and that given the absence of mass ejection, accretion disk formation, or differences in the gravitational wave signals, only electromagnetic precursors could prove the presence of a neutron star in low-spin systems of total mass ~10Msun, at least until the advent of gravitational wave detectors with a sensitivity comparable to that of the proposed Einstein Telescope.Comment: 13 pages, 9 figure