3D printing techniques allow for the precise placement of living cells, biological substances, and biochemical components, establishing themselves as a promising approach in bioengineering. Recently, 3D printing has been applied to develop human-relevant in vitro cancer models with highly controlled complexity and as a potential method for drug screening and disease modeling. Compared to 2D culture, 3D-printed in vitro cancer models more closely replicate the in vivo microenvironment. Additionally, they offer a reduction in the complexity and ethical issues associated with using in vivo animal models. This focused review discusses the relevance of 3D printing technologies and the applied cells and materials used in cutting-edge in vitro cancer models and microfluidic device systems. Future prospective solutions were discussed to establish 3D-printed in vitro models as reliable tools for drug screening and understanding cancer disease mechanisms.

In recent years the interest in synthetic scaffolds has increased significantly as an alternative to animal-derived materials, as well as the advancement of material and manufacturing engineering, has resulted in improved standardisation and reproducibility within the field. Despite these advancements, a significant amount of research on animal-derived scaffolds, whilst research on synthetic materials is lacking for the growth of non-tumourgenic breast cell lines. The main objective of this work is to manufacture biodegradable scaffolds using biocompatible materials such as PVA (Polyvinyl Alcohol), PU (Polyurethane), Ge (Gelatin) and PCL (Poly-(-caprolactone) to test human cell adhesion and investigate the optimal system that supports representative tissue organisation and that could be used as an alternative to Matrigel™. Here, human mammary fibroblasts (HMF) were used as proof of concept. The membranes were manufactured using the process of electrospinning and characterised by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (ATR-FTIR), contact angle, tensile strength, and degradation studies. The assessment of the membranes as a viable biomaterial for the growth and development of cells was studied by MTT proliferation assay, fluorescence microscopy and SEM imaging. Results demonstrate that all materials are suitable for HMF proliferation. However, from microscopy analysis, only PU and PVA membranes induced morphological organisation of HMF similar to those results obtained in the Matrigel™ control conditions. This feasibility study reveals that HMF organisation, and proliferation are affected by the properties of the scaffold. Consequently, scaffolds parameters should be adjusted and manipulated to impact cell behaviour and emulate in vivo conditions.

Assessment of coupling between transtibial sockets and users is historically based on clinicians' observations and experience, but can be inaccurate and unreliable. Therefore, we present a proof of concept, for five out of six possible degrees of freedom coupling metric system for a socket, using motion analysis calibrated on a 3D printed limb substitute. The method is compatible with any socket suspension method and does not require prior modifications to the socket. Calibration trials were used to locate the axis of rotation of the knee joint referenced against a marker cluster on the thigh; this allowed for the identification of the limb during test trials despite the entire residuum being obscured from view by the socket. The error in the technique was found to be within 0.7 mm in displacement and 0.7 degrees in rotation, based on the control data. Dynamic testing showed the Inter Quartile Range (IQR) of inter time step variance was <0.5 mm/deg for all metrics. The method can form a basis for objective socket evaluation, improve clinical practice and the quality of life for amputees.

Digitising prosthetic sockets and moulds is critical for advanced fabrication techniques enabling reduced lead times, advanced computer modelling, and personalised design history. Current 3D scanners are expensive (>GBP 5000) and difficult to use, restricting their use by prosthetists. In this paper, we explore the use and accuracy of smartphone photogrammetry (<GBP 1000) as an accessible means of digitising rectified socket moulds. A reversed digital twin method was used for evaluating accuracy, in addition to simplified genetic algorithms to identify an optimal technique. The identified method achieved an accuracy of 99.65% and 99.13% for surface area and volume, respectively, with an interclass coefficient of 0.81. The method presented is simple, requiring less than ten minutes to capture using twenty-six photos. However, image processing time can take hours, depending on the software used. This method falls within clinical limits for accuracy, requires minimal training, and is non-destructive; thus, it can be integrated into existing workflows. This technique could bridge the gap between digital and physical workflows, helping to revolutionise the prosthetics fitting process and supporting the inclusion of additive manufactured sockets.

This paper investigates the efficacy of silicone moulding methods using casting and injection moulding in a laboratory environment. The production of soft material components involves a variety of techniques, including both low-cost, in-house practices and high-level methods that require specialized training and expensive equipment. This paper focuses on two in-lab low-cost techniques: the casting method, which is commonly employed for shaping simple geometries, and the injection moulding process that produces highly intricate parts easily. To carry out the comparison study, a special shape was designed and three silicon materials (i.e., Ecoflex 00–50, Ecoflex 00–30 and DragonSkin-10) were selected first. Secondly, a mould was created using low-cost standard SLA and poly jet 3D printers. Thirdly, an effective in-lab fabrication process was proposed. Finally, a series of silicon parts were fabricated and compared.

The fit of a lower limb prosthetic socket is critical for user comfort and the quality of life of lower limb amputees. Sockets are conventionally produced using hand-crafted patient-based casting techniques. Modern digital techniques offer a host of advantages to the process and ultimately lead to improving the lives of amputees. However, commercially available scanning equipment required is often expensive and proprietary. Smartphone photogrammetry could offer a low cost alternative, but there is no widely accepted imaging technique for prosthetic socket digitisation. Therefore, this paper aims to determine an optimal imaging technique for whole socket photogrammetry and evaluate the resultant scan measurement accuracy. A 3D printed transtibial socket was produced to create digital and physical twins, as reference models. The printed socket was photographed from 360 positions and simplified genetic algorithms were used to design a series of experiments, whereby a collection of photos were processed using Autodesk ReCap. The most fit technique was used to assess accuracy. The accuracy of the socket wall volume, surface area and height were 61.63%, 99.61% and 99.90%, respectively, when compared to the digital reference model. The scanned model had a wall thickness ranging from 2.075 mm at the top to 7.758 mm towards the base of the socket, compared to a consistent thickness of 2.025 mm in the control model. The technique selected did not show sufficient accuracy for clinical application due to the degradation of accuracy nearer to the base of the socket interior. However, using an internal wall thickness estimation, scans may be of sufficient accuracy for clinical use; assuming a uniform wall thickness.

Bacterial vaginosis (BV) is an under-reported, underdiscussed and under-researched condition despite its high prevalence of 12%–50% worldwide.1 BV is characterised by an overgrowth of anaerobic bacteria, originally attributed to Gardnerella vaginalis (GV), disrupting the typically dominant lactobacilli vaginal ecosystem, resulting in discomfort and vaginal discharge with fishy odour. Women with BV have higher risk of transmission of STI and poor perinatal outcome.1 The aetiology of BV remains unknown, with a large number of bacteria associated to the condition and GV presence …

Modeling the physiology of the human placenta is still a challenge, despite the great number of scientific advancements made in the field. Animal models cannot fully replicate the structure and function of the human placenta and pose ethical and financial hurdles. In addition, increasingly stricter animal welfare legislation worldwide is incentivizing the use of 3R (reduction, refinement, replacement) practices. What efforts have been made to develop alternative models for the placenta so far? How effective are they? How can we improve them to make them more predictive of human pathophysiology? To address these questions, this review aims at presenting and discussing the current models used to study phenomena at the placenta level: in vivo, ex vivo, in vitro and in silico. We describe the main achievements and opportunities for improvement of each type of model and critically assess their individual and collective impact on the pursuit of predictive studies of the placenta in line with the 3Rs and European legislation.

Drug and chemical development along with safety tests rely on the use of numerous clinical models. This is a lengthy process where animal testing is used as a standard for pre-clinical trials. However, these models often fail to represent human physiopathology. This may lead to poor correlation with results from later human clinical trials. Organ-on-a-Chip (OOAC) systems are engineered microfluidic systems, which recapitulate the physiochemical environment of a specific organ by emulating the perfusion and shear stress cellular tissue undergoes in vivo and could replace current animal models. The success of culturing cells and cell-derived tissues within these systems is dependent on the scaffold chosen; hence, scaffolds are critical for the success of OOACs in research. A literature review was conducted looking at current OOAC systems to assess the advantages and disadvantages of different materials and manufacturing techniques used for scaffold production; and the alternatives that could be tailored from the macro tissue engineering research field.

A point of care device utilising Lab-on-a-Chip technologies that is applicable for biological pathogens was designed, fabricated and tested showing sample in to answer out capabilities. The purpose of the design was to develop a cartridge with the capability to perform nucleic acid extraction and purification from a sample using a chitosan membrane at an acidic pH. Waste was stored within the cartridge with the use of sodium polyacrylate to solidify or gelate the sample in a single chamber. Nucleic acid elution was conducted using the RPA amplification reagents (alkaline pH). Passive valves were used to regulate the fluid flow and a multiplexer was designed to distribute the fluid into six microchambers for amplification reactions. Cartridges were produced using soft lithography of silicone from 3D printed moulds, bonded to glass substrates. The isothermal technique, RPA is employed for amplification. This paper shows the results from two separate experiments: the first using the RPA control nucleic acid, the second showing successful amplification from Chlamydia Trachomatis. Endpoint analysis conducted for the RPA analysis was gel electrophoresis that showed 143 base pair DNA was amplified successfully for positive samples whilst negative samples did not show amplification. End point analysis for Chlamydia Trachomatis samples was fluorescence detection that showed successful detection of 1 copy/μL and 10 copies/μL spiked in a MES buffer.

Point of Care (PoC) devices and systems can be categorized into three broad classes (CAT 1, CAT 2, and CAT 3) based on the context of operation and usage. In this paper, the categories are defined to address certain usage models of the PoC device. PoC devices that are used for PoC testing and diagnostic applications are defined CAT 1 devices; PoC devices that are used for patient monitoring are defined as CAT 2 devices (PoCM); PoC devices that are used for as interfacing with other devices are defined as CAT 3 devices (PoCI). The PoCI devices provide an interface gateway for collecting and aggregating data from other medical devices. In all categories, data security is an important aspect. This paper presents a security framework concept, which is applicable for all of the classes of PoC operation. It outlines the concepts and security framework for preventing security challenges in unauthorized access to data, unintended data flow, and data tampering during communication between system entities, the user, and the PoC system. The security framework includes secure layering of basic PoC system architecture, protection of PoC devices in the context of application and network. Developing the security framework is taken into account of a thread model of the PoC system. A proposal for a low-level protocol is discussed. This protocol is independent of communications technologies, and it is elaborated in relation to providing security. An algorithm that can be used to overcome the threat challenges has been shown using the elements in the protocol. The paper further discusses the vulnerability scanning process for the PoC system interconnected network. The paper also presents a four-step process of authentication and authorization framework for providing the security for the PoC system. Finally, the paper concludes with the machine to machine (M2M) security viewpoint and discusses the key stakeholders within an actual deployment of the PoC system and its security challenges.

This paper presents the design of a modular point of care test platform that integrates a proprietary sample collection device directly with a microfluidic cartridge. Cell lysis, within the cartridge, is conducted using a chemical method and nucleic acid purification is done on an activated cellulose membrane. The microfluidic device incorporates passive mixing of the lysis-binding buffers and sample using a serpentine channel. Results have shown extraction efficiencies for this new membrane of 69% and 57% compared to the commercial Qiagen extraction method of 85% and 59.4% for 0.1ng/µL and 100ng/µL salmon sperm DNA respectively spiked in phosphate buffered solution. Extraction experiments using the serpentine passive mixer cartridges incorporating lysis and nucleic acid purification showed extraction efficiency around 80% of the commercial Qiagen kit. Isothermal amplification was conducted using thermophillic helicase dependant amplification and recombinase polymerase amplification. A low cost benchtop real-time isothermal amplification platform has been developed capable of running six amplifications simultaneously. Results show that the platform is capable of detecting 1.32×10(6) of sample DNA through thermophillic helicase dependant amplification and 1×10(5) copy numbers Chlamydia trachomatis genomic DNA within 10min through recombinase polymerase nucleic acid amplification tests.

During the last two decades silicon and MEMs technology had been the mainstay of early microfluidic devices. However, recent times have brought into focus the need for low cost and readily available materials capable of achieving the expected microfluidics physical and chemical requirements. Also what mentioning is the rapid improvement in microfabrication technology over the years, which has significantly aided new and cheaper ways to produce microfluidic Point-Of-Care-Testing devices commercially or for research purposes. This review article discusses the usefulness of a wide range of available materials and their unique properties suitability in microfluidic applications. Likewise, advantages and drawbacks of manufacturing procedures and outputs of different fabrication methods are also brought into focus.

Surface-enhanced Raman spectroscopy (SERS) substrates manufactured using complex nano-patterning techniques have become the norm. However, their cost of manufacture makes them unaffordable to incorporate into most biosensors. The technique shown in this paper is low-cost, reliable and highly sensitive. Chemical etching of solid Ag metal was used to produce simple, yet robust SERS substrates with broadband characteristics. Etching with ammonium hydroxide (NH4OH) and nitric acid (HNO3) helped obtain roughened Ag SERS substrates. Scanning electron microscopy (SEM) and interferometry were used to visualize and quantify surface roughness. Flattened Ag wires had inherent, but non-uniform roughness having peaks and valleys in the microscale. NH4OH treatment removed dirt and smoothened the surface, while HNO3 treatment produced a flake-like morphology with visibly more surface roughness features on Ag metal. SERS efficacy was tested using 4-methylbenzenethiol (MBT). The best SERS enhancement for 1 mM MBT was observed for Ag metal etched for 30 s in NH4OH followed by 10 s in HNO3. Further, MBT could be quantified with detection limits of 1 pM and 100 µM, respectively, using 514 nm and 1064 nm Raman spectrometers. Thus, a rapid and less energy intensive method for producing solid Ag SERS substrate and its efficacy in analyte sensing was demonstrated.

This research presents a comparative study of some EMAT configuration for generating ultrasonic bulk wave. The configurations studied are Spiral (SP) EMAT, and the proposed KeyType (KT) EMAT. A 2D Finite Element Model was developed to study and compare the density of the Induced Current (IC) and Lorentz Force (LF) generated at the skin depth, by individual EMAT coil configurations on four grades of commonly used pipe steel materials (CS70, TN80Cr3, L80SS and L80a). The results obtained showed that there is a significant improvement in the IC density and the strength of LF generated by the KT-EMAT especially when the coils are stacked. Hence a new coil configuration is proposed to enhance the performance of EMATs.

Advances in microfluidics and the introduction of isothermal nucleic acid amplification assays have resulted in a range of solutions for nucleic acid amplification tests suited for point of care and field use. However, miniaturisation of instrumentation for such assays has not seen such rapid advances and fluorescence based assays still depend on complex, bulky and expensive optics such as fluorescence microscopes, photomultiplier tubes and sensitive lens assemblies. In this work we demonstrate a robust, low cost platform for isothermal nucleic acid amplification on a microfluidic device. Using easily obtainable materials and commercial off-the-shelf components, we show real time fluorescence detection using a low cost photodiode and operational amplifier without need for lenses. Temperature regulation on the device is achieved using a heater fabricated with standard printed circuit board fabrication methods. These facile construction methods allow fabrications at a cost compatible with widespread deployment to resource poor settings.

Background/introduction Brunel DoCLab is part of the eSTI2 Consortium which is developing electronic self-testing and portable instruments for sexually transmitted infections using nucleic acid amplification test technologies. We have designed a point of care test platform that integrates a proprietary sample collection device directly with a microfluidic cartridge. A low cost benchtop real-time isothermal amplification platform has been developed capable of running six amplifications simultaneously. Aim(s)/objectives To evaluate the sample preparation and isothermal amplification within the low cost diagnostic platform. Methods The microfluidic device incorporates passive mixing of the lysis-binding buffers and sample. Cell lysis, within the cartridge, is conducted using a chemical method and nucleic acid purification is done on an activated cellulose membrane. Isothermal amplification was conducted using recombinase polymerase amplification (RPA). Results Preliminary results have shown extraction efficiencies for this new membrane of 69% and 57% compared to the commercial Qiagen extraction method of 85% and 59.4% for 0.1 ng/µL and 100 ng/µL salmon sperm DNA respectively spiked in phosphate buffered solution. Extraction experiments in the passive mixer cartridges with lysis and nucleic acid purification showed extraction efficiency around 80% of the commercial Qiagen kit. The platform is capable of detecting Chlamydia trachomatis genomic DNA within 10 min using RPA for 100,000 copies/µL. Discussion/conclusion The work presented here shows a low cost, rapid nucleic acid extraction, isothermal amplification and detection platform for diagnosing C. trachomatis. Work is on-going to fully integrate the sample-in to result platform for rapid diagnosis of STIs using genital samples.

This research paper presents in detail a novel modeling strategy to decouple and quantify the various transduction forces in operation when EMAT (Normally Biased and magnetostrictive configurations) are used on various grades of pipe steel materials. The strategy established the value of the critical excitation current (CEC) of the EMAT configurations studied. The CEC, when magnetostrictive EMAT configurations (MS-EMAT) are used to generate acoustic waves, was found to be: 260A, 268A, 270A, 274A, 279A, 280A, 286A, 289A, 294A and 305A for EN16, CS70, EN24, L80SS, L80A, TN80Cr3, EN8, EN36, EN3 and J55, respectively, while for Normally Biased EMAT configurations (NB EMAT), the critical excitation currents was found to be 181A, 190A, 197A, 205A, 240A, 122A, 203A, 160A, 231A and 200A for EN16, CS70, EN24, L80SS, L80A, TN80Cr3, EN8, EN36, EN3 and J55 respectively. This implies that beyond the CEC, where the dynamic Lorentz force mechanism dominates, it is possible to develop a coil only EMAT, thereby eliminating the undesirable effect of using a permanent magnet or electromagnet and also reducing the overall size of the EMAT. Furthermore, the research gave an insight into the relationship between the CEC and the electrical and magnetic properties of the steel materials used in this study and also compared the CEC for both the NB and MS-EMAT configurations. A conclusion drawn is that NB-EMATs are more efficient in the generation of acoustic waves as they have a lower CEC than their MS EMAT counterpart. (C) 2015 Elsevier B.V. All rights reserved.

Introduction Rapid and accurate field diagnostics have potential to impact on the burden of STIs in resource poor settings. Microfluidic and nano technologies offer opportunities to create molecular detection platforms but costs may be prohibitive. We present a low cost isothermal amplification, point of care test for rapid identification of sexually transmitted infections. Sample collection integrates directly with a microfluidic device for automated sample preparation, isothermal amplification and optical detection. Methods Cell lysis, within the microfluidic cartridge, is conducted using a chemical method and nucleic acid purification is achieved on activated cellulose membrane. The microfluidic device incorporates passive mixing of lysis-binding buffers and sample using a serpentine channel. Isothermal amplification is conducted using thermophillic helicase dependent amplification (tHDA) and recombinase polymerase amplification (RPA). A low cost real-time isothermal amplification platform has been developed capable of running six amplifications simultaneously. Results Results have shown extraction efficiencies for the new membrane of 69% and 57% compared to commercial Qiagen extraction of 85% and 59.4% for 0.1 ng/µL and 100 ng/µL salmon sperm DNA respectively spiked in phosphate buffered solution. Extraction experiments using the serpentine passive mixer cartridges incorporating lysis and nucleic acid purification showed extraction efficiency around 80% of the commercial Qiagen kit. The platform is capable of detecting 1.32 × 106 copies of target DNA through thermophillic helicase dependent amplification and 1 × 105 copies of Chlamydia trachomatis genomic DNA within 10 min through RPA. Conclusion We have produced a low cost, rapid nucleic acid extraction, isothermal amplification and detection platform consistent with use remote resource poor settings. The simple optics setup demonstrated high sensitivity and rapid detection of the tHDA and RPA reactions removing the requirement for expensive dichroic filters and lenses. Diagnostic performance of the device is currently being undertaken. Disclosure of interest statement No Disclosure of interest.