Effect of microneedles on transdermal permeation enhancement of amlodipine

The present study aimed to investigate the effect of microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of amlodipine (AMLO). Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses were done using dimensionless parameters like concentration of AMLO (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Microinjection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 6.84- and 6.11-fold increase in the cumulative amount (48 h) of AMLO permeated was observed with 1.5 mm ADM and PM-3 treatments respectively, when compared to passive permeation amounts. Good correlations (R2 > 0.89) were observed between different dimensionless parameters with scaling analyses. The enhancement in AMLO permeation was found to be in the order of 1.5 mm ADM ≥ PM-3 > 1.2 mm ADM > 0.6 mm ADM ≥PM-1 > passive. The study suggests that MN application enhances the AMLO transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

Comparison of crystallization characteristics and mechanical properties of polypropylene processed by ultrasound and conventional micro injection molding

YesUltrasound injection molding has emerged as an alternative production route for the manufacturing of micro-scale polymeric components, where it offers significant benefits over the conventional micro-injection molding process. In this work, the effects of ultrasound melting on the mechanical and morphological properties of micro-polypropylene parts were characterized. The ultrasound injection molding process was experimentally compared to the conventional micro-injection molding process using a novel mold, which allows mounting on both machines and visualization of the melt flow for both molding processes. Direct measurements of the flow front speed and temperature distributions were performed using both conventional and thermal high-speed imaging techniques. The manufacturing of micro-tensile specimens allowed the comparison of the mechanical properties of the parts obtained with the different processes. The results indicated that the ultrasound injection molding process could be an efficient alternative to the conventional process

Optimising process conditions for multiple quality criteria in micro-injection moulding

This paper presents a statistical technique to optimise process conditions for multiple quality criteria in micro-injection moulding. A sample hierarchical component with micro-features was replicated where it was required to improve the process conditions for both complete mould filling and variability in mass. A design-of-experiments approach was used to investigate the effect of five processing parameters on both criteria. It was found that holding pressure, melt temperature and injection velocity were statistically significant for part mass, whereas injection velocity alone was significant for mass variation. Desirability functions were used to predict processing conditions that improved both requirements within pre-set conditions. The technique was validated by experiment and it was shown to be applicable for process parameters for multiple criteria

Biofluid behaviour in 3D microchannel systems: Numerical analysis and design development of 3D microchannel biochip separators

This paper describes the design and development cycle of a 3D biochip separator and the modelling analysis of flow behaviour in the biochip microchannel features. The focus is on identifying the difference between 2D and 3D implementations as well as developing basic forms of 3D microfluidic separators. Five variants, based around the device are proposed and analysed. These include three variations of the branch channels (circular, rectangular, disc) and two variations of the main channel (solid and concentric). Ignoring the initial transient behaviour and assuming steady state flow has been established, the efficiencies of the flow between the main and side channels for the different designs are analysed and compared with regard to relevant biomicrofluidic laws or effects (bifurcation law, Fahraeus effect, cell-free phenomenon, bending channel effect and laminar flow behaviour). The modelling results identify flow features in microchannels, a constriction and bifurcations and show detailed differences in flow fields between the various designs. The manufacturing process using injection moulding for the initial base case design is also presented and discussed. The work reported here is supported as part of the UK funded 3D-MINTEGRATION project

Study of blood flow behaviour in microchannels

Microfluidic (also known as lab-on-a-chip) devices offer the capability of manipulating very low volumes of fluids (of the order of micro litres) for several applications including medical diagnostics. This property makes microfluidic devices very attractive when the fluid, such as blood, has a limited supply because the patients cannot easily and frequently provide a large sample. This is typically the case for aged, diseased patients that do require frequent sampling during acute care or of older people that have the option of being treated and cared for at home [1]. Prototype lab-on-a-chip devices for medical diagnostics comprise a number of elements which separately perform different functions within the system. Activity within the research community is focusing on the better integration of device functionalities with the long term goal of creating fully integrated, portable, affordable clinical devices. However, engineering these solutions for the large volume production of lab-on-a-chip devices requires design rules which are not yet entirely available. This paper describes the results obtained from a set of experiments run to draw generic design rules for the manufacture of a cells/plasma micro separator [2]. The cells/plasma micro separator was selected for investigation because it is a strategic element required in the preparation of blood samples for many different analytical devices. The experiments focused on the study of the behaviour of whole blood passing through micro constrictions which are required for enhancing the separation effect [3]. The test microfluidic device was an aluminium specimen designed and manufactured to incorporate micro constrictions of different width and length. The metallic aluminium test device was designed for manufacturing by micromilling and diamond cutting processes in view of applying these techniques to the manufacture of micro-moulds for the high-volume production of plastic microfluidic devices via micro-injection moulding. The widths of the constrictions were 23, 53 and 93um and the lengths were 300 and 700um. The blood flow pattern and the level of haemolysis generated in the whole blood were determined for flow rates between 0.2 and 1 ml/min. Initial results suggested that the above conditions generate a stable flow and do not cause blood haemolysis following passage through the narrow constrictions. This result implies that constrictions as narrow as 23 um and as long as 700um can be safely used in blood microfluidic devices under appropriate flow conditions without the risk of damaging the blood components

Evaluation of manufacturing techniques for a minifluidics demonstrator system

A multi-disciplinary team based at Heriot-Watt University and other Universities has been set up to tackle the design and manufacturing of lab-on-a-chip for industries as one of the demonstrators of the EPSRC Grand Challenge project "3D-Mintegration". The team focuses on the analysis of foetal genetic material extracted from maternal blood as a smart alternative to invasive prenatal testing such as amniocentesis. The first module of the microsystem envisaged achieves a separation of blood cells from plasma. This system permits the testing of different manufacturing techniques