A multi-scale approach to shaping carbon nanotube structures for hollow microneedles

The concept of a carbon nanotube microneedle array is explored in this thesis from multiple perspectives including microneedle fabrication, physical aspects of transdermal delivery, and in vivo transdermal drug delivery experiments. Starting with standard techniques in carbon nanotube (CNT) fabrication, including catalyst patterning and chemical vapor deposition, vertically-aligned carbon nanotubes are utilized as a scaffold to define the shape of the hollow microneedle. Passive, scalable techniques based on capillary action and unique photolithographic methods are utilized to produce a CNT-polymer composite microneedle. Specific examples of CNT-polyimide and CNT-epoxy microneedles are investigated. Further analysis of the transport properties of polymer resins reveals general requirements for applying arbitrary polymers to the fabrication process.

The bottom-up fabrication approach embodied by vertically-aligned carbon nanotubes allows for more direct construction of complex high-aspect ratio features than standard top-down fabrication approaches, making microneedles an ideal application for CNTs. However, current vertically-aligned CNT fabrication techniques only allow for the production of extruded geometries with a constant cross-sectional area, such as cylinders. To rectify this limitation, isotropic oxygen etching is introduced as a novel fabrication technique to create true 3D CNT geometry. Oxygen etching is utilized to create a conical geometry from a cylindrical CNT structure as well as create complex shape transformations in other CNT geometries.

CNT-polymer composite microneedles are anchored onto a common polymer base less than 50 µm thick, which allows for the microneedles to be incorporated into multiple drug delivery platforms, including modified hypodermic syringes and silicone skin patches. Cylindrical microneedles are fabricated with 100 µm outer diameter and height of 200-250 µm with a central cavity, or lumen, diameter of 30 µm to facilitate liquid drug flow. In vitro delivery experiments in swine skin demonstrate the ability of the microneedles to successfully penetrate the skin and deliver aqueous solutions.

An in vivo study was performed to assess the ability of the CNT-polymer microneedles to deliver drugs transdermally. CNT-polymer microneedles are attached to a hand actuated silicone skin patch that holds a liquid reservoir of drugs. Fentanyl, a potent analgesic, was administered to New Zealand White Rabbits through 3 routes of delivery: topical patch, CNT-polymer microneedles, and subcutaneous hypodermic injection. Results demonstrate that the CNT-polymer microneedles have a similar onset of action as the topical patch. CNT-polymer microneedles were also vetted as a painless delivery approach compared to hypodermic injection. Comparative analysis with contemporary microneedle designs demonstrates that the delivery achieved through CNT-polymer microneedles is akin to current hollow microneedle architectures. The inherent advantage of applying a bottom-up fabrication approach alongside similar delivery performance to contemporary microneedle designs demonstrates that the CNT-polymer composite microneedle is a viable architecture in the emerging field of painless transdermal delivery.

Feasibility study of carbon nanotube microneedles for rapid transdermal drug delivery

We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polymer. Flow through the microneedles as well as in vitro penetration of the microneedles into swine skin is demonstrated. Furthermore, we present a trade study comparing the difficulty and complexity of the fabrication process of our CNT-polymer microneedles with other standard microneedle fabrication approaches. Copyright © Materials Research Society 2013.

Microneedles for intradermal and transdermal drug delivery

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum, impose significant limitations for successful systemic delivery of broad range of therapeutic molecules particularly macromolecules and genetic material. Microneedle (MN) has been proposed as a strategy to breach the stratum corneum barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves use of micron sized needles fabricated of different materials and geometries to create transient aqueous conduits across the skin. MN, alone or with other enhancing strategies, has been demonstrated to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo experiments. This suggested the promising use of MN technology for various possible clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. MN has been proved as minimally invasive and painless in human subjects. This review article focuses on recent and future developments for MN technology including the latest type of MN design, challenges and strategies in MNs development as well as potential safety aspects based on comprehensive literature review pertaining to MN studies to date. (C) 2013 Elsevier B.V. All rights reserved.

Fabrication and characterization of gold coated hollow silicon microneedle array for drug delivery

In this paper, we present the fabrication and characterization of Ti and Au coated hollow silicon microneedles for transdermal drug delivery applications. The hollow silicon microneedles are fabricated using isotropic etching followed by anisotropic etching to obtain a tapered tip. Silicon microneedle of 300 mu m in height, with 130 mu m outer diameter and 110 mu m inner diameter at the tip followed by 80 mu m inner diameter and 160 mu m outer diameter at the base have been fabricated. In order to improve the biocompatibility of microneedles, the fabricated microneedles were coated with Ti (500 nm) by sputtering technique followed by gold coating using electroplating. A breaking force of 225 N was obtained for the fabricated microneedles, which is 10 times higher than the skin resistive force. Hence, fabricated microneedles can easily be inserted inside the skin without breakage. The fluid flow through the microneedles was studied for different inlet pressures. A minimum inlet pressure of 0.66 kPa was required to achieve a flow rate of 50 mu l in 2 s with de-ionized water as a fluid medium. (C) 2014 Elsevier B.V. All rights reserved.

Flexural behaviour and design of cold-formed steel beams with rectangular hollow flanges

Until recently, the hot-rolled steel members have been recognized as the most popular and widely used steel group, but in recent times, the use of cold-formed high strength steel members has rapidly increased. However, the structural behavior of light gauge high strength cold-formed steel members characterized by various buckling modes is not yet fully understood. The current cold-formed steel sections such as C- and Z-sections are commonly used because of their simple forming procedures and easy connections, but they suffer from certain buckling modes. It is therefore important that these buckling modes are either delayed or eliminated to increase the ultimate capacity of these members. This research is therefore aimed at developing a new cold-formed steel beam with two torsionally rigid rectangular hollow flanges and a slender web formed using intermittent screw fastening to enhance the flexural capacity while maintaining a minimum fabrication cost. This thesis describes a detailed investigation into the structural behavior of this new Rectangular Hollow Flange Beam (RHFB), subjected to flexural action The first phase of this research included experimental investigations using thirty full scale lateral buckling tests and twenty two section moment capacity tests using specially designed test rigs to simulate the required loading and support conditions. A detailed description of the experimental methods, RHFB failure modes including local, lateral distortional and lateral torsional buckling modes, and moment capacity results is presented. A comparison of experimental results with the predictions from the current design rules and other design methods is also given. The second phase of this research involved a methodical and comprehensive investigation aimed at widening the scope of finite element analysis to investigate the buckling and ultimate failure behaviours of RHFBs subjected to flexural actions. Accurate finite element models simulating the physical conditions of both lateral buckling and section moment capacity tests were developed. Comparison of experimental and finite element analysis results showed that the buckling and ultimate failure behaviour of RHFBs can be simulated well using appropriate finite element models. Finite element models simulating ideal simply supported boundary conditions and a uniform moment loading were also developed in order to use in a detailed parametric study. The parametric study results were used to review the current design rules and to develop new design formulae for RHFBs subjected to local, lateral distortional and lateral torsional buckling effects. Finite element analysis results indicate that the discontinuity due to screw fastening has a noticeable influence only for members in the intermediate slenderness region. Investigations into different combinations of thicknesses in the flange and web indicate that increasing the flange thickness is more effective than web thickness in enhancing the flexural capacity of RHFBs. The current steel design standards, AS 4100 (1998) and AS/NZS 4600 (1996) are found sufficient to predict the section moment capacity of RHFBs. However, the results indicate that the AS/NZS 4600 is more accurate for slender sections whereas AS 4100 is more accurate for compact sections. The finite element analysis results further indicate that the current design rules given in AS/NZS 4600 is adequate in predicting the member moment capacity of RHFBs subject to lateral torsional buckling effects. However, they were inadequate in predicting the capacities of RHFBs subject to lateral distortional buckling effects. This thesis has therefore developed a new design formula to predict the lateral distortional buckling strength of RHFBs. Overall, this thesis has demonstrated that the innovative RHFB sections can perform well as economically and structurally efficient flexural members. Structural engineers and designers should make use of the new design rules and the validated existing design rules to design the most optimum RHFB sections depending on the type of applications. Intermittent screw fastening method has also been shown to be structurally adequate that also minimises the fabrication cost. Product manufacturers and builders should be able to make use of this in their applications.

Flexural behaviour and design of hollow flange steel beams

The LiteSteel Beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using a patented Dual Electric Resistance Welding technique. The LSB has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. It is commonly used as rafters, floor joists and bearers and roof beams in residential, industrial and commercial buildings. It is on average 40% lighter than traditional hot-rolled steel beams of equivalent performance. The LSB flexural members are subjected to a relatively new Lateral Distortional Buckling mode, which reduces the member moment capacity. Unlike the commonly observed lateral torsional buckling of steel beams, lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist and web distortion. Current member moment capacity design rules for lateral distortional buckling in AS/NZS 4600 (SA, 2005) do not include the effect of section geometry of hollow flange beams although its effect is considered to be important. Therefore detailed experimental and finite element analyses (FEA) were carried out to investigate the lateral distortional buckling behaviour of LSBs including the effect of section geometry. The results showed that the current design rules in AS/NZS 4600 (SA, 2005) are over-conservative in the inelastic lateral buckling region. New improved design rules were therefore developed for LSBs based on both FEA and experimental results. A geometrical parameter (K) defined as the ratio of the flange torsional rigidity to the major axis flexural rigidity of the web (GJf/EIxweb) was identified as the critical parameter affecting the lateral distortional buckling of hollow flange beams. The effect of section geometry was then included in the new design rules using the new parameter (K). The new design rule developed by including this parameter was found to be accurate in calculating the member moment capacities of not only LSBs, but also other types of hollow flange steel beams such as Hollow Flange Beams (HFBs), Monosymmetric Hollow Flange Beams (MHFBs) and Rectangular Hollow Flange Beams (RHFBs). The inelastic reserve bending capacity of LSBs has not been investigated yet although the section moment capacity tests of LSBs in the past revealed that inelastic reserve bending capacity is present in LSBs. However, the Australian and American cold-formed steel design codes limit them to the first yield moment. Therefore both experimental and FEA were carried out to investigate the section moment capacity behaviour of LSBs. A comparison of the section moment capacity results from FEA, experiments and current cold-formed steel design codes showed that compact and non-compact LSB sections classified based on AS 4100 (SA, 1998) have some inelastic reserve capacity while slender LSBs do not have any inelastic reserve capacity beyond their first yield moment. It was found that Shifferaw and Schafer’s (2008) proposed equations and Eurocode 3 Part 1.3 (ECS, 2006) design equations can be used to include the inelastic bending capacities of compact and non-compact LSBs in design. As a simple design approach, the section moment capacity of compact LSB sections can be taken as 1.10 times their first yield moment while it is the first yield moment for non-compact sections. For slender LSB sections, current cold-formed steel codes can be used to predict their section moment capacities. It was believed that the use of transverse web stiffeners could improve the lateral distortional buckling moment capacities of LSBs. However, currently there are no design equations to predict the elastic lateral distortional buckling and member moment capacities of LSBs with web stiffeners under uniform moment conditions. Therefore, a detailed study was conducted using FEA to simulate both experimental and ideal conditions of LSB flexural members. It was shown that the use of 3 to 5 mm steel plate stiffeners welded or screwed to the inner faces of the top and bottom flanges of LSBs at third span points and supports provided an optimum web stiffener arrangement. Suitable design rules were developed to calculate the improved elastic buckling and ultimate moment capacities of LSBs with these optimum web stiffeners. A design rule using the geometrical parameter K was also developed to improve the accuracy of ultimate moment capacity predictions. This thesis presents the details and results of the experimental and numerical studies of the section and member moment capacities of LSBs conducted in this research. It includes the recommendations made regarding the accuracy of current design rules as well as the new design rules for lateral distortional buckling. The new design rules include the effects of section geometry of hollow flange steel beams. This thesis also developed a method of using web stiffeners to reduce the lateral distortional buckling effects, and associated design rules to calculate the improved moment capacities.

Strengthening of circular hollow steel tubular sections using high modulus CFRP sheets

This paper describes the behaviour of very high strength (VHS) circular steel tubes strengthened by carbon fibre reinforced polymer (CFRP) and subjected to axial tension. A series of tests were conducted with different bond lengths and number of layers. The distribution of strain through the thickness of CFRP layers and along CFRP bond length was studied. The strain was found to generally decrease along the CFRP bond length far from the joint. The strain through the thickness of the CFRP layers was also found to decrease from bottom to top layer. The effective bond length for high modulus CFRP was established. Finally empirical models were developed to estimate the maximum load for a given CFRP arrangement.

Large-scale fabrication of H2(H2O)Nb2O6 and Nb2O5 hollow microspheres

Hollow micro-sized H2(H2O)Nb2O6 spheres constructed by nanocrystallites have been successfully synthesized via a bubble-template assisted hydrothermal process. In the reaction process, H2O2 acts as a bubble generator and plays a key role in the formation of the hollow structure. An in situ bubble-template mechanism has been proposed for the possible formation of the hollow structure. The spherelike assemblies of these H2(H2O)Nb2O6 nanoparticles have been transformed into their corresponding pseudohexagonal phase Nb2O5 through a moderate annealing dehydration process without destroying the hierarchical structure. Optical properties of the as-prepared hollow spheres were investigated. It is exciting that the absorption edge of the hollow Nb2O5 microspheres shifts about 18 nm to the violet compared with bulk powders in the UV/vis spectra, indicating its superior optical properties.

Lateral distortional buckling tests of a new hollow flange channel beam

The LiteSteel beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using their patented dual electric resistance welding and automated continuous roll-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. The LSBs are commonly used as flexural members in buildings. However, the LSB flexural members are subjected to lateral distortional buckling, which reduces their member moment capacities. Unlike the commonly observed lateral torsional buckling of steel beams, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist, and cross sectional change due to web distortion. An experimental study including more than 50 lateral buckling tests was therefore conducted to investigate the behaviour and strength of LSB flexural members. It included the available 13 LSB sections with spans ranging from 1200 to 4000 mm. Lateral buckling tests based on a quarter point loading were conducted using a special test rig designed to simulate the required simply supported and loading conditions accurately. Experimental moment capacities were compared with the predictions from the design rules in the Australian cold-formed steel structures standard. The new design rules in the standard were able to predict the moment capacities more accurately than previous design rules. This paper presents the details of lateral distortional buckling tests, in particular the features of the lateral buckling test rig, the results and the comparisons. It also includes the results of detailed studies into the mechanical properties and residual stresses of LSBs.