Development and fabrication of optical biosensors based on biophotonic sensing cells (BICELLs)

El objetivo de esta tesis es el desarrollo y caracterización de biosensores ópticos sin marcado basados en celdas sensoras biofotónicas (BICELLs). Éstas son un nuevo concepto de biosensor desarrollado por el grupo de investigación y consiste en la combinación de técnicas de interrogación vertical, junto a estructuras fotónicas producidas usando métodos de micro- y nanofabricación. Varias conclusiones son extraídas de este trabajo. La primera, que se ha definido una BICELL estándar basada en interferómetros Fabry-Perot (FP). Se ha demostrado su capacidad para la comparación de rendimiento entre BICELLs estructuradas y para la realización de inmunoensayos de bajo coste. Se han estudiado diferentes técnicas de fabricación disponibles para la producción de BICELLs. Se determinó que la litografía de contacto a nivel de oblea produce estructuras de bajo coste, reproducibles y de alta calidad. La resolución alcanzada ha sido de 700 nm. El estudio de la respuesta a inmunoensayos de las BICELLs producidas se ha desarrollado en este trabajo. Se estudió la influencia de BICELLs basadas en diferentes geometrías y tamaños. De aquí resulta un nuevo enfoque para predecir el comportamiento de respuesta para la detección biológica de cualquier biosensor óptico estructurado, relacionando su superficie efectiva y su sensibilidad óptica. También se demostró una técnica novedosa y de bajo coste para la caracterización experimental de la sensibilidad óptica, basada en el depósito de películas ultradelgadas. Finalmente, se ha demostrado el uso de BICELLs desarrolladas en esta tesis, en la detección de aplicaciones reales, tales como hormonas, virus y proteínas. ABSTRACT The objective of this thesis is the development and characterization of optical label-free biosensors based on Bio-Photonic sensing Cells (BICELLs). BICELL is a novel biosensor concept developed by the research group, and it consists of a combination of vertical interrogation optical techniques and photonic structures produced by using micro- and nano-fabrication methods. Several main conclusions are extracted from this work. Firstly, a standard BICELL is defined based on FP interferometers, which demonstrated its capacity for accomplishing performance comparisons among different structured BICELLs, as well as to achieve low-cost immunoassays. Different available fabrication techniques were studied for BICELL manufacturing. It is found that contact lithography at wafer scale produce cost-effective, reproducible and high quality structures. The resolution achieved was 700 nm. Study on the response of developed BICELLs to immunoassays is performed within this work. It is therefore studied the influence of BICELLs based on different geometries and sizes in the immunoassay, which resulted in a new approach to predict the biosensing behaviour of any structured optical biosensor relating to its effective surface and optical sensitivity. Also, it is demonstrated a novel and low-cost characterization technique of the experimental optical sensitivity, based on ultrathin-film deposition. Finally, it is also demonstrated the capability of using the developed BICELLs in this thesis for real applications detection of hormones, virus and proteins.

Effects of high-color-discrimination capability spectra on color-deficient vision

Light sources with three spectral bands in specific spectral positions are known to have high-color-discrimination capability. W. A. Thornton hypothesized that they may also enhance color discrimination for color-deficient observers. This hypothesis was tested here by comparing the Rösch–MacAdam color volume for color-deficient observers rendered by three of these singular spectra, two reported previously and one derived in this paper by maximization of the Rösch–MacAdam color solid. It was found that all illuminants tested enhance discriminability for deuteranomalous observers, but their impact on other congenital deficiencies was variable. The best illuminant was the one derived here, as it was clearly advantageous for the two red–green anomalies and for tritanopes and almost neutral for red–green dichromats. We conclude that three-band spectra with high-color-discrimination capability for normal observers do not necessarily produce comparable enhancements for color-deficient observers, but suitable spectral optimization clearly enhances the vision of the color deficient.

Development of a Mechanism and Process to Continuously Produce Spherical, Torrefied Biomass

Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2016-06-17 02:15:25.215

Improved conventional force capability : raising the nuclear threshold : a staff study /

Mode of access: Internet.

Examining the role of networking capability in small and medium firm internationalization

While research on SME internationalization has increased, there remains a lack of relevant theory on the SME internationalization process. The literature reports that small firms overcome their resource poverty-based constraints to internationalization by developing network relationships. Networking enables SMEs to acquire much needed internationalization process knowledge, and knowledge for the development of innovative products and services for this internationalization. However, networking activity has not yet been conceptualized and measured as a competitive capability in internationalization research. Drawing on the capability-based theory of competitive strategy, this paper conjectures that internationally entrepreneurial SMEs build and nurture distinctive networking capabilities, enabling them to acquire new knowledge. These learning capabilities enable them to pursue innovation thereby facilitating nternationalization. Data from Australian firms largely supports the conceptual framework. Implications for theory and practice are presented.

Improving the economic decision making capability and viability of Chinese wool textile mills

The successful restructuring of Chinese industries is of immense importance not only for the continued development of China but also to the stability of the world economy. The transformation of the Chinese wool textile industry illustrates well the many problems and pressures currently facing most Chinese industries. The Chinese wool textile industry has undergone major upheaval and restructuring in its drive to modernize and take advantage of developments in world textile markets. Macro level ownership and administrative reforms are well advanced as is the uptake of new technology and equipment. However, the changing market and institutional environment also demands an increasing level of sophistication in mill management decisions including product selection, input procurement, product pricing, investment appraisal, cost analysis and proactive identification of new market and growth opportunities. This paper outlines a series of analyses that have been integrated into a decision-making model designed to assist mill managers with these decisions. Features of the model include a whole-of-mill approach, a design based on existing mill structures and information systems, and the capacity for the model to be tailored to individual mills. All of these features facilitate the adoption of the model by time and resource constrained managers seeking to maintain the viability of their enterprises in the face of extremely dynamic market conditions.

A study of business user based information systems development, and modelling success factors

This thesis describes research into business user involvement in the information systems application building process. The main interest of this research is in establishing and testing techniques to quantify the relationships between identified success factors and the outcome effectiveness of 'business user development' (BUD). The availability of a mechanism to measure the levels of the success factors, and quantifiably relate them to outcome effectiveness, is important in that it provides an organisation with the capability to predict and monitor effects on BUD outcome effectiveness. This is particularly important in an era where BUD levels have risen dramatically, user centred information systems development benefits are recognised as significant, and awareness of the risks of uncontrolled BUD activity is becoming more widespread. This research targets the measurement and prediction of BUD success factors and implementation effectiveness for particular business users. A questionnaire instrument and analysis technique has been tested and developed which constitutes a tool for predicting and monitoring BUD outcome effectiveness, and is based on the BUDES (Business User Development Effectiveness and Scope) research model - which is introduced and described in this thesis. The questionnaire instrument is designed for completion by 'business users' - the target community being more explicitly defined as 'people who primarily have a business role within an organisation'. The instrument, named BUD ESP (Business User Development Effectiveness and Scope Predictor), can readily be used with survey participants, and has been shown to give meaningful and representative results.

Design and development of a time of flight fast scattering spectrometer : a quantitative surface analysis technique and a new approach towards the experimental investigation of the surface particle interactions

A new surface analysis technique has been developed which has a number of benefits compared to conventional Low Energy Ion Scattering Spectrometry (LEISS). A major potential advantage arising from the absence of charge exchange complications is the possibility of quantification. The instrumentation that has been developed also offers the possibility of unique studies concerning the interaction between low energy ions and atoms and solid surfaces. From these studies it may also be possible, in principle, to generate sensitivity factors to quantify LEISS data. The instrumentation, which is referred to as a Time-of-Flight Fast Atom Scattering Spectrometer has been developed to investigate these conjecture in practice. The development, involved a number of modifications to an existing instrument, and allowed samples to be bombarded with a monoenergetic pulsed beam of either atoms or ions, and provided the capability to analyse the spectra of scattered atoms and ions separately. Further to this a system was designed and constructed to allow incident, exit and azimuthal angles of the particle beam to be varied independently. The key development was that of a pulsed, and mass filtered atom source; which was developed by a cyclic process of design, modelling and experimentation. Although it was possible to demonstrate the unique capabilities of the instrument, problems relating to surface contamination prevented the measurement of the neutralisation probabilities. However, these problems appear to be technical rather than scientific in nature, and could be readily resolved given the appropriate resources. Experimental spectra obtained from a number of samples demonstrate some fundamental differences between the scattered ion and neutral spectra. For practical non-ordered surfaces the ToF spectra are more complex than their LEISS counterparts. This is particularly true for helium scattering where it appears, in the absence of detailed computer simulation, that quantitative analysis is limited to ordered surfaces. Despite this limitation the ToFFASS instrument opens the way for quantitative analysis of the 'true' surface region to a wider range of surface materials.

Development of an on-demand beam pulsing system for Pixe-analysis of thick targets

This work concerns the developnent of a proton irduced X-ray emission (PIXE) analysis system and a multi-sample scattering chamber facility. The characteristics of the beam pulsing system and its counting rate capabilities were evaluated by observing the ion-induced X-ray emission from pure thick copper targets, with and without beam pulsing operation. The characteristic X-rays were detected with a high resolution Si(Li) detector coupled to a rrulti-channel analyser. The removal of the pile-up continuum by the use of the on-demand beam pulsing is clearly demonstrated in this work. This new on-demand pu1sirg system with its counting rate capability of 25, 18 and 10 kPPS corresponding to 2, 4 am 8 usec main amplifier time constant respectively enables thick targets to be analysed more readily. Reproducibility tests of the on-demard beam pulsing system operation were checked by repeated measurements of the system throughput curves, with and without beam pulsing. The reproducibility of the analysis performed using this system was also checked by repeated measurements of the intensity ratios from a number of standard binary alloys during the experimental work. A computer programme has been developed to evaluate the calculations of the X-ray yields from thick targets bornbarded by protons, taking into account the secondary X-ray yield production due to characteristic X-ray fluorescence from an element energetically higher than the absorption edge energy of the other element present in the target. This effect was studied on metallic binary alloys such as Fe/Ni and Cr/Fe. The quantitative analysis of Fe/Ni and Cr/Fe alloy samples to determine their elemental composition taking into account the enhancement has been demonstrated in this work. Furthermore, the usefulness of the Rutherford backscattering (R.B.S.) technique to obtain the depth profiles of the elements in the upper micron of the sample is discussed.

Development of plasmid dna formulations for application as microspheric dna vaccines

The advent of DNA vaccines has heralded a new technology allowing the design and elicitation of immune responses more adequate for a wider range of pathogens. The formulation of these vaccines into the desired dosage forms extends their capability in terms of stability, routes of administration and efficacy. This thesis describes an investigation into the fabrication of plasmid DNA, the active principle of DNA vaccines, into microspheres, based on the tenet of an increased cellular uptake of microparticulate matter by phagocytic cells. The formulation of plasmid DNA into microspheres using two methods, is presented. Formulation of microspheric plasmid DNA using the double emulsion solvent evaporation method and a spray-drying method was explored. The former approach involves formation of a double emulsion, by homogenisation. This method produced microspheres of uniform size and smooth morphology, but had a detrimental effect on the formulated DNA. The spray-drying method resulted in microspheres with an improved preservation of DNA stability. The use of polyethylenimine (PEI) and stearylamine (SA) as agents in the microspheric formulation of plasmid DNA is a novel approach to DNA vaccine design. Using these molecules as model positively-charged agents, their influence on the characteristics of the microspheric formulations was investigated. PEI improved the entrapment efficiency of the plasmid DNA in microspheres, and has minimal effect on either the surface charge, morphology or size distribution of the formulations. Stearylamine effected an increase in the entrapment efficiency and stability of the plasmid DNA and its effect on the micropshere morphology was dependent on the method of preparation. The differences in the effects of the two molecules on microsphere formulations may be attributable to their dissimilar physico-chemical properties. PEI is water-soluble and highly-branched, while SA is hydrophobic and amphipathic. The positive charge of both molecules is imparted by amine functional groups. Preliminary data on the in vivo application of formulated DNA vaccine, using hepatitis B plasmid, showed superior humoral responses to the formulated antigen, compared with free (unformulated) antigen.

Development and deployment of an autonomous micro-drilling system for cochleostomy

This thesis describes the design and development of an autonomous micro-drilling system capable of accurately controlling the penetration of complaint tissues and its application to the drilling of the cochleostomy; a key stage in the cochlea implant procedure. The drilling of the cochleostomy is a precision micro-surgical task in which the control of the burr penetration through the outer bone tissue of the cochlea is vital to prevent damage to the structures within and requires a high degree of skill to perform successfully. The micro-drilling system demonstrates that the penetration of the cochlea can be achieved consistently and accurately. Breakthrough can be detected and controlled to within 20µm of the distal surface and the hole completed without perforation of the underlying endosteal membrane, leaving the membranous cochlea intact. This device is the first autonomous surgical tool successfully deployed in the operating theatre. The system is unique due to the way in which it uses real-time data from the cutting tool to derive the state of the tool-tissue interaction. Being a smart tool it uses this state information to actively control the way in which the drilling process progresses. This sensor guided strategy enables the tool to self-reference to the deforming tissue and navigate without the need for pre-operative scan data. It is this capability that enables the system to operate in circumstances where the tissue properties and boundary conditions are unknown, without the need to restrain the patient.

Knowledge-based development in leading regions across the globe:an exploratory analysis of the co-evolution of resources, capabilities, and outputs

It is widely observed that the global geography of innovation is rapidly evolving. This paper presents evidence concerning the contemporary evolution of the globe's most productive regions. The paper uncovers the underlying structure and co-evolution of knowledge-based resources, capabilities and outputs across these regions. The analysis identifies two key trends by which the economic evolution and growth patterns of these regions are differentiated-namely, knowledge-based growth and labour market growth. The knowledge-based growth factor represents the underlying commonality found between the growth of economic output, earnings and a range of knowledge-based resources. The labour market growth factor represents the capability of regions to draw on their human capital. Overall, spectacular knowledge-based growth of leading Chinese regions is evident, highlighting a continued shift of knowledge-based resources to Asia. It is concluded that regional growth in knowledge production investment and the capacity to draw on regional human capital reserves are neither necessarily traded-off nor complementary to each other. © 2012 Urban Studies Journal Limited.

International technology transfer and development of capabilities in Chinese state-owned manufacturing enterprises:lessons from 20 years of case research

Technological capabilities in Chinese manufacturing have been transformed in the last three decades. However, the extent to which domestic market oriented state owned enterprises (SOEs) have developed their capabilities is not clear. Six SOEs in the automotive, steel and machine tools sectors in Beijing and Tianjin have been studied since the mid-1990s to assess the capability levels attained and the role of external sources and internal efforts in developing them. Aided by government policies, acquisition of technology and their own efforts, the case study companies appear to be broadly following the East Asian late industrialisation model. All six enterprises demonstrate competences in operating established technology, managing investment and making product and process improvements. The evidence suggests that companies without foreign joint venture (JV) collaborations have made more progress in this respect.

Ophthalmic engineering:the development of novel instrumentation to further research in the field

The principle theme of this thesis is the advancement and expansion of ophthalmic research via the collaboration between professional Engineers and professional Optometrists. The aim has been to develop new and novel approaches and solutions to contemporary problems in the field. The work is sub divided into three areas of investigation; 1) High technology systems, 2) Modification of current systems to increase functionality, and 3) Development of smaller more portable and cost effective systems. High Technology Systems: A novel high speed Optical Coherence Tomography (OCT) system with integrated simultaneous high speed photography was developed achieving better operational speed than is currently available commercially. The mechanical design of the system featured a novel 8 axis alignment system. A full set of capture, analysis, and post processing software was developed providing custom analysis systems for ophthalmic OCT imaging, expanding the current capabilities of the technology. A large clinical trial was undertaken to test the dynamics of contact lens edge interaction with the cornea in-vivo. The interaction between lens edge design, lens base curvature, post insertion times and edge positions was investigated. A novel method for correction of optical distortion when assessing lens indentation was also demonstrated. Modification of Current Systems: A commercial autorefractor, the WAM-5500, was modified with the addition of extra hardware and a custom software and firmware solution to produce a system that was capable of measuring dynamic accommodative response to various stimuli in real time. A novel software package to control the data capture process was developed allowing real time monitoring of data by the practitioner, adding considerable functionality of the instrument further to the standard system. The device was used to assess the accommodative response differences between subjects who had worn UV blocking contact lens for 5 years, verses a control group that had not worn UV blocking lenses. While the standard static measurement of accommodation showed no differences between the two groups, it was determined that the UV blocking group did show better accommodative rise and fall times (faster), thus demonstrating the benefits of the modification of this commercially available instrumentation. Portable and Cost effective Systems: A new instrument was developed to expand the capability of the now defunct Keeler Tearscope. A device was developed that provided a similar capability in allowing observation of the reflected mires from the tear film surface, but with the added advantage of being able to record the observations. The device was tested comparatively with the tearscope and other tear film break-up techniques, demonstrating its potential. In Conclusion: This work has successfully demonstrated the advantages of interdisciplinary research between engineering and ophthalmic research has provided new and novel instrumented solutions as well as having added to the sum of scientific understanding in the ophthalmic field.

Organisational receptivity for change:combining context and capability to explain competitive advantage

This thesis explores efforts to conjoin organisational contexts and capabilities in explaining sustainable competitive advantage. Oliver (1997) argued organisations need to balance the need to conform to industry’s requirements to attain legitimization (e.g. DiMaggio & Powell, 1983), and the need for resource optimization (e.g. Barney, 1991). The author hypothesized that such balance can be viewed as movements along the homogeneity-heterogeneity continuum. An organisation in a homogenous industry possesses similar characteristics as its competitors, as opposed to a heterogeneous industry in which organisations within are differentiated and competitively positioned (Oliver, 1997). The movement is influenced by the dynamic environmental conditions that an organisation is experiencing. The author extended Oliver’s (1997) propositions of combining RBV’s focus on capabilities with institutional theory’s focus on organisational context, as well as redefining organisational receptivity towards change (ORC) factors from Butler and Allen’s (2008) findings. The authors contributed to the theoretical development of ORC theory to explain the attainment of sustainable competitive advantage. ORC adopts the assumptions from both institutional and RBV theories, where the receptivity factors include both organisational contexts and capabilities. The thesis employed a mixed method approach in which sequential qualitative quantitative studies were deployed to establish a robust, reliable, and valid ORC scale. The adoption of Hinkin’s (1995) three-phase scale development process was updated, thus items generated from interviews and literature reviews went through numerous exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to achieve convergent, discriminant, and nomological validities. Samples in the first phase (semi structured interviews) were hotel owners and managers. In the second phase, samples were MBA students, and employees of private and public sectors. In the third phase, samples were hotel managers. The final ORC scale is a parsimonious second higher-order latent construct. The first-order constructs comprises four latent receptivity factors which are ideological vision (4 items), leading change (4 items), implementation capacity (4 items), and change orientation (7 items). Hypotheses testing revealed that high levels of perceived environmental uncertainty leads to high levels of receptivity factor. Furthermore, the study found a strong positive correlation between receptivity factors and competitive advantage, and between receptivity factors and organisation performance. Mediation analyses revealed that receptivity factors partially mediate the relationship between perceived environmental uncertainty, competitive advantage and organisational performance.