30 years of microfluidics

Microfluidics provides a great opportunity to create devices capable of outperforming classical techniques in biomedical and chemical research. In this review, the origins of this emerging field in the microelectronics industry are detailed. We also appraise how factors such as government funding influenced the development of new materials and fabrication techniques. Current applications of microfluidics are also examined and we highlight areas where work should be focussed in the future to ensure that the technology realises its full potential

Fabrication of mesoscale topographical gradients in bulk titanium and their use in injection moulding

Fabrication methods for titanium substrates exhibiting continuous micro and nano scale arrays, with increasing feature heights over the length of the array are reported. The resultant feature heights spanned 0–2 μm. Patterned gradient arrays of circular features with diameters of: 500 nm, 1 μm and 2 μm, spaced by twice the diameter were manufactured by the process using specially prepared titanium substrates. Patterns were exposed by electron beam lithography and the length of the patterned arrays was 15 mm or 20 mm. This work presents two selectivity amplification processes to achieve a gradient of feature heights ranging over the titanium array after consecutive reactive ion etching processes. The first, route A: a HSQ on Ti, gradient amplification process. The second, route B, a SiO2 layer amplification transfer into Ti. The crucial initial gradient component deposited for the amplification process for both routes was a diffusion limited plasma polymerised hexane gradient. Etching using respective reactive ion etch chemistries for each gradient transfer through the various selectivity amplification layers (employing consecutive etch steps, in this way) enables a dual amplification for each route to manufacture. The original gradient is transferred into titanium as a function of the sum of the respective selectivities between the materials, using the appropriate dry etch plasma conditions. The substrates henceforth are referred to as inlays, and were tested for use as a high throughput platform for polymer replication by injection moulding. It is envisaged that the fabrication methodology and resultant topographies have use in a range of engineering applications. The overall selectivity to Ti for polymerised hexane is increased by more than 20 times using each dual amplification process

Mechanical compatibility of sol–gel annealing with titanium for orthopaedic prostheses

Sol–gel processing is an attractive method for large-scale surface coating due to its facile and inexpensive preparation, even with the inclusion of precision nanotopographies. These are desirable traits for metal orthopaedic prostheses where ceramic coatings are known to be osteoinductive and the effects may be amplified through nanotexturing. However there are a few concerns associated with the application of sol–gel technology to orthopaedics. Primarily, the annealing stage required to transform the sol–gel into a ceramic may compromise the physical integrity of the underlying metal. Secondly, loose particles on medical implants can be carcinogenic and cause inflammation so the coating needs to be strongly bonded to the implant. These concerns are addressed in this paper. Titanium, the dominant material for orthopaedics at present, is examined before and after sol–gel processing for changes in hardness and flexural modulus. Wear resistance, bending and pull tests are also performed to evaluate the ceramic coating. The findings suggest that sol–gel coatings will be compatible with titanium implants for an optimum temperature of 500 °C

Chapter Nanopatterned Surfaces for Biomedical Applications

Optical physic

Sol-gel coatings for subaquatic self-cleaning windows

Self-cleaning windows are well known for their ability to function with airborne pollutants, but there is a growing industry for semi-permanent subaquatic optical devices, where the performance of such windows should be considered. Here sol-gel technology is explored as a means of producing self-cleaning, subaquatic, sapphire windows. We demonstrate removal of marine bacteria and, in the worst-case contamination scenario, dead North Sea crude oil (API 35). This greasy contaminant was smeared across the windows to effectively reduce optical transmission strength to just 54%. The titania-based sol-gel-coated windows can restore transmission to within 10% of the clean value in less than one day, unlike standard sapphire windows, which lose 68% transmission following contamination and aquatic submergence over the same duration. A range of theories to enhance the self-cleaning performance of the sol-gel coating were explored, but none of the tested variables were able to provide any enhancement for subaquatic performance

Interactive machine learning for fast and robust cell profiling

Automated profiling of cell morphology is a powerful tool for inferring cell function. However, this technique retains a high barrier to entry. In particular, configuring image processing parameters for optimal cell profiling is susceptible to cognitive biases and dependent on user experience. Here, we use interactive machine learning to identify the optimum cell profiling configuration that maximises quality of the cell profiling outcome. The process is guided by the user, from whom a rating of the quality of a cell profiling configuration is obtained. We use Bayesian optimisation, an established machine learning algorithm, to learn from this information and automatically recommend the next configuration to examine with the aim of maximising the quality of the processing or analysis. Compared to existing interactive machine learning tools that require domain expertise for per-class or per-pixel annotations, we rely on users’ explicit assessment of output quality of the cell profiling task at hand. We validated our interactive approach against the standard human trial-and-error scheme to optimise an object segmentation task using the standard software CellProfiler. Our toolkit enabled rapid optimisation of an object segmentation pipeline, increasing the quality of object segmentation over a pipeline optimised through trial-and-error. Users also attested to the ease of use and reduced cognitive load enabled by our machine learning strategy over the standard approach. We envision that our interactive machine learning approach can enhance the quality and efficiency of pipeline optimisation to democratise image-based cell profiling

Enhanced differentiation of human embryonic stem cells towards definitive endoderm on ultrahigh aspect ratio nanopillars

Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have highlighted that the properties of the physical environment, such as substrate stiffness, affect cellular behavior. Here, mass-produced, injection molded polycarbonate nanopillars are presented, where the surface mechanical properties, i.e., stiffness, can be controlled by the geometric design of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.0003). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of definitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure population compared to planar control. By contrast, further differentiation toward the pancreatic ­endoderm is less successful on “soft” pillars when compared to “stiff” pillars or control, indicating differential cues during the different stages of differentiation. To accompany the mechanical properties of the nanopillars, the concept of surface shear modulus is introduced to describe the characteristics of engineered elastic surfaces through micro or nanopatterning. This provides a framework whereby comparisons can be drawn between such materials and bulk elastomeric materials

Enhancing strength and toughness of adhesive joints via micro-structured mechanical interlocking

Acknowledgements: The authors would like to acknowledge the support of the Leverhulme Trust for supporting the work under project grant “Fundamental Mechanical Behaviour of Nano and Micro Structured Interfaces” (RPG-2017-353) and the EPSRC for providing an EPSRC-DTG PhD studentship (EP/N509668/1) for the first author. Personnel at the James Watt Nanofabrication Centre (JWNC) at the University of Glasgow are also thanked for their invaluable technical support.Peer reviewedPostprin