Protein Precipitation for the Purification of Therapeutic Protein

This thesis documents the application of precipitant scouting and analytical tools for the development of a precipitation process for the purification of therapeutic proteins in biopharmaceuticals. Precipitation has the potential to bypass the bottlenecks in productivity experienced with packed bed chromatographic separations, offering a fast, robust first purification step with volume reduction at low cost. In order to evaluate a large number of precipitation candidates, microscale investigations aided by automated liquid handling robotics were chosen, which conferred precision, speed, and complex experimental design with microliter material requirements and in-line analytics. A precipitation screening methodology was successfully built onto a Tecan liquid handling platform including product recovery and techniques for measuring soluble protein, liquid volumes, and recovered protein precipitate. The protocol was supplemented with a custombuild Excel VBA driven Tecan control tool. This accelerated progress by freeing up the potential of the liquid handling arm, which was curtailed by system software. These techniques were then used to characterise effective precipitants for the purification of monoclonal antibodies. Optimal conditions were identified on pure protein models, which were the bridged to process relevant cell culture fluid. Process performance, notably recovery yield and product quality were the investigated on the precipitant conditions brought forward. Process integration aspects were explored, by linking precipitation with an anion exchange chromatography step. This led to discussion on future work and process scale up considerations

A framework for smart production-logistics systems based on CPS and industrial IoT

Industrial Internet of Things (IIoT) has received increasing attention from both academia and industry. However, several challenges including excessively long waiting time and a serious waste of energy still exist in the IIoT-based integration between production and logistics in job shops. To address these challenges, a framework depicting the mechanism and methodology of smart production-logistics systems is proposed to implement intelligent modeling of key manufacturing resources and investigate self-organizing configuration mechanisms. A data-driven model based on analytical target cascading is developed to implement the self-organizing configuration. A case study based on a Chinese engine manufacturer is presented to validate the feasibility and evaluate the performance of the proposed framework and the developed method. The results show that the manufacturing time and the energy consumption are reduced and the computing time is reasonable. This paper potentially enables manufacturers to deploy IIoT-based applications and improve the efficiency of production-logistics systems

Logistics outsourcing and 3PL selection: A Case study in an automotive supply chain

Outsourcing logistics functions to third-party logistics (3PL) providers has been a source of competitive advantage for most companies. Companies cite greater flexibility, operational efficiency, improved customer service levels, and a better focus on their core businesses as part of the advantages of engaging the services of 3PL providers. There are few complete and structured methodologies for selecting a 3PL provider. This paper discusses how one such methodology, namely the Analytic Hierarchy Process (AHP), is used in an automotive supply chain for export parts to redesign the logistics operations and to select a global logistics service provider

The influencing mechanism of manufacturing scene change on process domain knowledge reuse

It is necessary for a enterprise to reuse outside process domain knowledge to develop intelligent manufacturing technology. The key factors influencing knowledge reuse in digital manufacturing scene are manufacturing activities and PPR (Products, Processes and Resources) related to knowledge modeling, enterprise and integrated systems related to knowledge utilizing. How these factors influence knowledge modeling and utilizing is analyzed. Process domain knowledge reuse across the enterprises consists of knowledge reconfiguration and integrated application with CAx systems. The module-based knowledge model and loosely-coupled integration application of process domain knowledge are proposed. The aircraft sheet metal process domain knowledge reuse is taken as an example, and it shows that the knowledge reuse process can be made flexible and rapid

Computerization of workflows, guidelines and care pathways: a review of implementation challenges for process-oriented health information systems

There is a need to integrate the various theoretical frameworks and formalisms for modeling clinical guidelines, workflows, and pathways, in order to move beyond providing support for individual clinical decisions and toward the provision of process-oriented, patient-centered, health information systems (HIS). In this review, we analyze the challenges in developing process-oriented HIS that formally model guidelines, workflows, and care pathways. A qualitative meta-synthesis was performed on studies published in English between 1995 and 2010 that addressed the modeling process and reported the exposition of a new methodology, model, system implementation, or system architecture. Thematic analysis, principal component analysis (PCA) and data visualisation techniques were used to identify and cluster the underlying implementation ‘challenge’ themes. One hundred and eight relevant studies were selected for review. Twenty-five underlying ‘challenge’ themes were identified. These were clustered into 10 distinct groups, from which a conceptual model of the implementation process was developed. We found that the development of systems supporting individual clinical decisions is evolving toward the implementation of adaptable care pathways on the semantic web, incorporating formal, clinical, and organizational ontologies, and the use of workflow management systems. These architectures now need to be implemented and evaluated on a wider scale within clinical settings

Generative feature-based design-by-constraints as a means of integration within the manufacturing industry

The article examines the development of computer aids within manufacturing industry and proposes an alternative approach to the way we design and the designer's role within manufacturing. A feature-based generative design-by-constraints approach is applied, which requires the designer to specify solutions in terms of manufacturing data, which is captured by means of an interactive simulation of machining processes, in which the constraints of equipment, materials and tools are displayed to the designer. The effect of this approach on the integration of all areas within a manufacturing environment is explored, as is the simultaneous design nature of this approach

Ship product modelling

This paper is a fundamental review of ship product modeling techniques with a focus on determining the state of the art, to identify any shortcomings and propose future directions. The review addresses ship product data representations, product modeling techniques and integration issues, and life phase issues. The most significant development has been the construction of the ship Standard for the Exchange of Product Data (STEP) application protocols. However, difficulty has been observed with respect to the general uptake of the standards, in particular with the application to legacy systems, often resulting in embellishments to the standards and limiting the ability to further exchange the product data. The EXPRESS modeling language is increasingly being superseded by the extensible mark-up language (XML) as a method to map the STEP data, due to its wider support throughout the information technology industry and its more obvious structure and hierarchy. The associated XML files are, however, larger than those produced using the EXPRESS language and make further demands on the already considerable storage required for the ship product model. Seamless integration between legacy applications appears to be difficult to achieve using the current technologies, which often rely on manual interaction for the translation of files. The paper concludes with a discussion of future directions that aim to either solve or alleviate these issues

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing