A process chain for integrating microfluidic interconnection elements by micro- overmoulding of thermoplastic elastomers

This paper presents a process chain for in-line integration of microfluidic interconnection elements by a variant of micro-injection moulding (mu IM). A SEBS-based thermoplastic elastomer (TPE) was moulded over polymethylmethacrylate (PMMA) to produce a hybrid microfluidic structure with an aspect ratio of 2. The process chain implemented micro-milling for fabricating micro-structured tool inserts, and mu IM and micro-overmoulding was used for replication. A two-plate mould was used for moulding the substrate, whilst a three-plate mould with a replaceable insert was used for TPE overmoulding. The presented application was an interconnect system for a microfluidic device, which enabled direct fitting of standard tubes into microfluidic substrates. A leakage test showed that the interconnection was leak-proof within a range of flow rates between 0.32 and 0.62 ml min(-1)

Design and fabrication of a three-dimensional microfluidic device for blood separation using micro-injection moulding

Micro-manufacturing is a fast developing area due to the increasing demand for components and systems of high precision and small dimensions. A number of challenges are yet to be overcome before the full potential of such techniques is realised. Examples of such challenges include limitations in component geometry, material selection and suitability for mass production. Some micro-manufacturing techniques are still at early development stages, while other techniques are at higher stage of manufacturing readiness level but require adaptation in part design or manufacturing procedure to overcome such limitations. This article presents a case study, where the design of a micro-scale, biomedical device is adapted for functionality and manufacturability by a high-volume micro-fabrication technique. Investigations are described towards a disposable three-dimensional, polymer-based device for the separation of blood cells and plasma. The importance of attempting a three-dimensional device design and fabrication route was to take advantage of the highthroughput per unit volume that such systems can, in principle, allow. The importance of a micro-moulding fabrication route was to allow such blood-containing devices to be cheaply manufactured for disposability. Initial device tests showed separation efficiency up to approximately 80% with diluted blood samples. The produced prototype indicated that the process flow was suitable for high-volume fabrication of three-dimensional microfluidics

Flatness optimization of micro-injection moulded parts: The case of a PMMA microfluidic component

Micro-injection moulding (µ-IM) has attracted a lot of interest because of its potential for the production of low-cost, miniaturized parts in high-volume. Applications of this technology are, amongst others, microfluidic components for lab-on-a-chip devices and micro-optical components. In both cases, the control of the part flatness is a key aspect to maintaining the component's functionality. The objective of this work is to determine the factors affecting the flatness of a polymer part manufactured by µ-IM and to control the manufacturing process with the aim of minimizing the in-process part deformation. As a case study, a PMMA microfluidic substrate with overall dimensions of 10 mm diameter and 1 mm thickness was investigated by designing a µ-IM experiment having flatness as the experimental response. The part flatness was measured using a micro-coordinate measuring machine. Finite elements analysis was also carried out to study the optimal ejection pin configuration. The results of this work show that the control of the µ-IM process conditions can improve the flatness of the polymer part up to about 15 µm. Part flatness as low as 4 µm can be achieved by modifying the design of the ejection system according to suggested guideline

Micro-injection moulding of three-dimensional integrated microfluidic devices

This thesis investigates the use of micro-injection moulding (μIM), as a high-volume process, for producing three-dimensional, integrated microfluidic devices. It started with literature reviews that covered three topics: μIM of thermoplastic microfluidics, designing for three-dimensional (3-D) microfluidics and functional integration in μIM. Research gaps were identified: Designing 3-D microfluidics within the limitations of μIM, process optimisation and the integration of functional elements. A process chain was presented to fabricate a three-dimensional microfluidic device for medical application by μIM. The thesis also investigated the effect of processing conditions on the quality of the replicated component. The design-of-experiments (DOE) approach is used to highlight the significant processing conditions that affect the part mass taking into consideration the change in part geometry. The approach was also used to evaluate the variability within the process and its effect on the replicability of the process. Part flatness was also evaluated with respect to post-filling process parameters. The thesis investigated the possibility of integrating functional elements within μIM to produce microfluidic devices with hybrid structures. The literature reviews highlighted the importance of quality control in high-volume micromoulding and in-line functional integration in microfluidics. A taxonomy of process integration was also developed based on transformation functions. The experimental results showed that μIM can be used to fabricate microfluidic devices that have true three-dimensional structures by subsequent lamination. The DOE results showed a significant effect of individual process variables on the filling quality of the produced components and their flatness. The geometry of the replicated component was shown to have effect on influential parameters. Other variables, on the other hand, were shown to have a possible effect on process variability. Optimization statistical tools were used to improve multiple quality criteria. Thermoplastic elastomers (TPE) were processed with μIM to produce hybrid structures with functional elements.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Fabrication of ceramic micro-scale hollow components by micro-powder injection moulding

Rapid developments in microsystem technologies demand ceramic microcomponents of increasing geometrical complexity. State-of-the-art microfabrication routes of ceramics are either limited in geometrical complexity and/or high volume capabilities. This paper presents a process route by which ceramic microcomponents with relatively complex three-dimensional architectures could be realised by a high-volume technique. The proposed strategy, in which yttria- stabilised zirconia was implemented, combines the capabilities of insert- micromoulding, powder micro-overmoulding, catalytic debinding and sintering. The produced architectures demonstrate the capability of the technique to combine the high performance of ceramic materials with the dimensional accuracy and mass manufacturability of powder micromoulding

Evaluating and controlling process variability in micro-injection moulding

Microsystem technologies require relatively strict quality requirements. This is because their functionalities are usually dependent on stringent requirements of dimensions, masses or tolerances. When mass-producing micro-components, e.g. replication of disposable microfluidic diagnostics devices, the consistency of the produced components could be significantly affected by process variability. The variability could be associated with a specific process parameter or could be a result of process noise. This paper presents a methodology to assess and minimise process variability in micro-injection moulding, an example of well- established mass-production techniques for micro-components. A design-of- experiments approach was implemented, where five process parameters were investigated for possible effects on the process variability of two components. The variability was represented by the standard deviation of the replicated part mass. It was found that melt temperature was a significant source of variability in part mass for one of the components, whilst the other was affected by unsystematic variability. Optimisations tools such as response surfaces and desirability functions were implemented to minimise mass variability by more than 40%