Microfluidically fabricated pH-responsive anionic amphiphilic microgels for drug release

© 2016 The Royal Society of Chemistry. Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic acid (AA) and the hydrophobic, non-ionic n-butyl acrylate (BuA) were synthesised using a lab-on-a-chip device. Hydrophobic droplets were generated via a microfluidic platform that contained a protected form of AA, BuA, the hydrophobic crosslinker, ethylene glycol dimethacrylate (EGDMA), and a free radical initiator in an organic solvent. These hydrophobic droplets were photopolymerised within the microfluidic channels and subsequently hydrolysed, enabling an integrated platform for the rapid, automated, and in situ production of anionic amphiphilic microgels. The amphiphilic microgels did not feature the conventional core-shell structure but were instead based on random amphiphilic copolymers of AA and BuA and hydrophobic crosslinks. Due to their amphiphilic nature they were able to encapsulate and deliver both hydrophobic and hydrophilic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the surrounding aqueous solution and the hydrophobic content of the microgels

Tailoring pH-responsive acrylic acid microgels with hydrophobic crosslinks for drug release

Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of different compositions were synthesised using a lab-on-a-chip device. The microgels were formed by polymerising hydrophobic droplets. The droplets were generated via a microfluidic platform and contained a protected form of AA, a hydrophobic crosslinker (ethylene glycol dimethacrylate, EGDMA) and a free radical initiator in an organic solvent. Following photopolymerisation and subsequent hydrolysis, AA based microgels of amphiphilic nature were produced and it was demonstrated that they can successfully deliver both hydrophilic as well as hydrophobic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the aqueous solution as well as the crosslinking density and hydrophobic content of the microgels

Implementation of Physician Orders for Life Sustaining Treatment in nursing homes in California: evaluation of a novel statewide dissemination mechanism.

BackgroundImplementing Physician Orders for Life Sustaining Treatment (POLST) forms aims to improve communication of life-sustaining treatment preferences across care venues. California enabled this clinical tool in 2009, and a novel intervention of community coalitions was undertaken to advance POLST in localities around the state. Coalitions engaged facilities, including nursing homes (NHs), to foster POLST adoption. Eighteen months after introduction of POLST, we studied POLST implementation in California NHs.MethodsNHs randomly selected in coalition and non-coalition areas were mailed surveys about POLST preparation and use in 2010. Coalitions identified which NHs they worked with.ResultsOf 546 NHs surveyed, 143 (52 %) in coalition areas and 141 (52 %) in non-coalition areas responded. In 82 % of responding NHs, staff received POLST education and 59 % of NHs reported having a formal policy on handling POLST. Two-thirds of NHs had admitted a resident with a POLST, and 15 % of newly admitted residents over the past month had a POLST (range 0-100 %). Eighty-one percent of NHs had completed a POLST with a resident. Fifty-four percent of residents were estimated to have a POLST (range 0-100 %) (coalition area NHs 60 % vs. non- coalition area NHs 48 %, p = 0.02). Within coalition areas, NHs that had worked with coalitions were more likely to have completed a POLST with a resident after admission than NHs that had not worked with coalitions. Few NHs (7 %) reported difficulty following POLST orders, but 38 % noted difficulty involving physicians in POLST completion.ConclusionLess than 2 years after introduction, many California nursing homes report using POLST, although some NHs reported no experience. A novel community coalition intervention facilitated POLST implementation

The generation of multi-laminar reagent streams for rapid, sequential (bio)chemical reactions on magnetic particles in a continuous flow microreactor

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.We demonstrate a versatile microfluidic system for performing rapid, consecutive (bio)chemical reactions in continuous flow. Surface-functionalised magnetic microparticles are introduced into a chamber and pulled, via a magnet, across a series of laminar flow streams containing different reagents, thus performing multiple sequential reactions on the particles’ surface. Such a continuous flow method eliminates many of the inefficiencies associated with batch techniques, such as the time-consuming, laborious sequential reaction and washing steps, to yield a system that can perform analyses far more rapidly and with less reagent volume than conventional methods. This innovative device has been applied to a two-reaction step mouse IgG sandwich immunoassay and one- and two-reaction step DNA hybridisation assays, all of which were completed within one minute. These results pave the way for a multi-purpose microreactor that can perform a variety of analytical and synthetic processes.This study is funded by the Engineering and Physical Sciences Research Council (EPSRC)

Quasi multipartite entanglement measure based on quadratic functions

We develop a new entanglement measure by extending Jaeger's Minkowskian norm entanglement measure. This measure can be applied to a much wider class of multipartite mixed states, although still "quasi" in the sense that it is still incapable of dividing precisely the sets of all separable and entangled states. As a quadratic scalar function of the system density matrix, the quasi measure can be easily expressed in terms of the so-called coherence vector of the system density matrix, by which we show the basic properties of the quasi measure including (1) zero-entanglement for all separable states, (2) invariance under local unitary operations, and (3) non-increasing under local POVM (positive operator-valued measure) measurements. These results open up perspectives in further studies of dynamical problems in open systems, especially the dynamic evolution of entanglement, and the entanglement preservation against the environment-induced decoherence effects.Comment: 10pages,1 figur

Inverse Problems in a Bayesian Setting

In a Bayesian setting, inverse problems and uncertainty quantification (UQ) --- the propagation of uncertainty through a computational (forward) model --- are strongly connected. In the form of conditional expectation the Bayesian update becomes computationally attractive. We give a detailed account of this approach via conditional approximation, various approximations, and the construction of filters. Together with a functional or spectral approach for the forward UQ there is no need for time-consuming and slowly convergent Monte Carlo sampling. The developed sampling-free non-linear Bayesian update in form of a filter is derived from the variational problem associated with conditional expectation. This formulation in general calls for further discretisation to make the computation possible, and we choose a polynomial approximation. After giving details on the actual computation in the framework of functional or spectral approximations, we demonstrate the workings of the algorithm on a number of examples of increasing complexity. At last, we compare the linear and nonlinear Bayesian update in form of a filter on some examples.Comment: arXiv admin note: substantial text overlap with arXiv:1312.504

Suppressing nano-scale stick-slip motion by feedback

When a micro cantilever with a nano-scale tip is manipulated on a substrate with atomic-scale roughness, the periodic lateral frictional force and stochastic fluctuations may induce stick-slip motion of the cantilever tip, which greatly decreases the precision of the nano manipulation. This unwanted motion cannot be reduced by open-loop control especially when there exist parameter uncertainties in the system model, and thus needs to introduce feedback control. However, real-time feedback cannot be realized by the existing virtual reality virtual feedback techniques based on the position sensing capacity of the atomic force microscopy (AFM). To solve this problem, we propose a new method to design real-time feedback control based on the force sensing approach to compensate for the disturbances and thus reduce the stick-slip motion of the cantilever tip. Theoretical analysis and numerical simulations show that the controlled motion of the cantilever tip tracks the desired trajectory with much higher precision. Further investigation shows that our proposal is robust under various parameter uncertainties. Our study opens up new perspectives of real-time nano manipulation.Comment: 8 pages, 10 figure

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

Decoherence Control in Open Quantum System via Classical Feedback

In this work we propose a novel strategy using techniques from systems theory to completely eliminate decoherence and also provide conditions under which it can be done so. A novel construction employing an auxiliary system, the bait, which is instrumental to decoupling the system from the environment is presented. Our approach to decoherence control in contrast to other approaches in the literature involves the bilinear input affine model of quantum control system which lends itself to various techniques from classical control theory, but with non-trivial modifications to the quantum regime. The elegance of this approach yields interesting results on open loop decouplability and Decoherence Free Subspaces(DFS). Additionally, the feedback control of decoherence may be related to disturbance decoupling for classical input affine systems, which entails careful application of the methods by avoiding all the quantum mechanical pitfalls. In the process of calculating a suitable feedback the system has to be restructured due to its tensorial nature of interaction with the environment, which is unique to quantum systems. The results are qualitatively different and superior to the ones obtained via master equations. Finally, a methodology to synthesize feedback parameters itself is given, that technology permitting, could be implemented for practical 2-qubit systems to perform decoherence free Quantum Computing.Comment: 17 pages, 4 Fig