Enabling next-generation cell line development using continuous perfusion and nanofluidic technologies

The manufacturing process for a biologic begins with establishing a clonally derived, stable production cell line. Generating a highly productive cell line is time and resource intensive and involves screening of a large number of candidates. While miniaturization and automation strategies can reduce resources and increase throughput, they have matured and recent advances have been incremental. With increasing pressure on time to commercialization and the increasing diversity and complexity of therapies in discovery research, there is a need to transform cell line development to accelerate patient access to novel therapies and nanofluidic technology are on potential solution. In this study, we present cell line development data on the Berkeley Lights integrated platform. Cells are manipulated at a single cell level though use of OptoElectronic Positioning (OEP) technology which utilizes projected light patterns to activate photoconductors that gently moves cells. Common cell culture tasks can be programmed though software allowing thousands of cell lines to cultured simultaneously. Cultures can be interrogated for productivity and growth characteristics while on the chip at ~100-fold miniaturization and continuous perfusion of cell culture medium enables effective and robust cell growth and product concentration despite starting from a single cell. Concepts from perfusion culture are also applied to measure productivity and product quality. We demonstrate that commercial production CHO cell lines can be cultured in this nanofluidic environment and show that sub clone isolation, recovery, and selection are achieved with high efficiency. Overall, this technology has the potential to transform cell line development workflows through the replacement of laborious manual processes with nanofluidics and automation, and can ultimately enable the rapid selection of high performing cell lines

Enabling agile web development through in-browser code generation and evaluation

Rapid evolution and flexibility are the key of modern web application development. Rapid Prototyping approaches try to facilitate evolution by reducing the time between the elicitation of a new requirement and the evaluation of a prototype by both developers and customers. Software generation, with disciplines such as Software Product Lines Engineering or Model Driven Engineering, favours the required flexibility for the development process. Nevertheless, each small change in the design of an application requires a full redeployment of complex environments in order to allow customers to test and evaluate the new configuration. In this work we present an approach that improves the development process reducing the complexity of deploying evaluation prototypes and enabling an agile development cycle. The approach can be applied using software generation and it is based on in-browser generation and evaluation. We also describe two real world tools that have integrated the proposed approach in their development cycle

Using ERP as a basis for Enterprise application integration

Architecting and implementing e-Business supply chain solutions across and within the modern day enterprise, is now becoming a necessity in order to maintain competitive and be adaptable to market needs. As such, the integration of information and processes is a vital step, using technologies such as using Enterprise Resource Planning (ERP), Supply Chain Management (SCM) and enterprise portal platforms. The effective sharing of resource planning and other enterprise related data across and within the enterprise is typically seen as a facet of a business to business (B2B) platform. However, such infrastructures typically involve a tight integration across intra and inter-organisational systems. This paper examines an Enterprise Application Integration (EAI) initiative taken by a global manufacturer of industrial automation products, which attempted to utilise ERP as an integration tool across its internal B2B infrastructure, to achieve such an aim. This paper discusses those integration considerations and complexities, experienced by the case company upon embarking on an EAI integration programme through the adoption of a core ERP as a catalyst for organizational change. In doing so the authors present an analysis of the inherent risks and limitations of this approach in terms of previously published literature in the field, relating to technology-driven organizational change and EAI impact and adoption frameworks

PuLSE-I: Deriving instances from a product line infrastructure

Reusing assets during application engineering promises to improve the efficiency of systems development. However, in order to benefit from reusable assets, application engineering processes must incorporate when and how to use the reusable assets during single system development. However, when and how to use a reusable asset depends on what types of reusable assets have been created.Product line engineering approaches produce a reusable infrastructure for a set of products. In this paper, we present the application engineering process associated with the PuLSE product line software engineering method - PuLSE-I. PuLSE-I details how single systems can be built efficiently from the reusable product line infrastructure built during the other PuLSE activities

Ontological approach to derive product configurations from a Software Product Line Reference Architecture

Software Product Lines (SPL) based on reuse, claim to improve evolution, time to market and decrease software development costs. Concrete software products or systems, members of the SPL family, are derived by instantiating a generic Reference Architecture (RA), holding common and variant components. The construction of RA is a complex and costly task, as well as its usage for product derivation, due to the huge number of variants, essentially caused by non functional requirements variability. In consequence, the selection of an RA instance or Feasible Solution (FS), meeting RA constraints and customer requirements, is not straightforward. In this work RA is built by a bottom-up process from existing products; RA and its instances are represented by a non-directed connected graph. The HIS-RA Ontology also represents RA and captures Healthcare Integrated Information Systems (HIS) domain knowledge. Moreover, FS must be connected (the induced graph by FS in RA has no isolated components), consistent (it verifies consistency rules among FS components), and working (it meets domain functional (FR) and non functional (NFR) requirements). The main goal of this paper is to define a semiautomatic process (FFSP), to derive consistency rules using the HIS-RA Ontology built-in reasoning capabilities, to construct consistent, connected and working FS. Software quality is considered by FFSP  in the traceability between FR and NFR, and it is specified by ISO/IEC 25010, to guarantee RA evolution and the overall concrete product configuration quality. FFSP is validated on a HIS domain a case study

Ontological approach to derive product configurations from a Software Product Line Reference Architecture

Abstract Software Product Lines (SPL) based on reuse, claim to improve evolution, time to market and decrease software development costs. Concrete software products or systems, members of the SPL family, are derived by instantiating a generic Reference Architecture (RA), holding common and variant components. The construction of RA is a complex and costly task, as well as its usage for product derivation, due to the huge number of variants, essentially caused by non functional requirements variability. In consequence, the selection of an RA instance or Feasible Solution (FS), meeting RA constraints and customer requirements, is not straightforward. In this work RA is built by a bottom-up process from existing products; RA and its instances are represented by a non-directed connected graph. The HIS-RA Ontology also represents RA and captures Healthcare Integrated Information Systems (HIS) domain knowledge. Moreover, FS must be connected (the induced graph by FS in RA has no isolated components), consistent (it verifies consistency rules among FS components), and working (it meets domain functional (FR) and non functional (NFR) requirements). The main goal of this paper is to define a semiautomatic process (FFSP), to derive consistency rules using the HIS-RA Ontology built-in reasoning capabilities, to construct consistent, connected and working FS. Software quality is considered by FFSP in the traceability between FR and NFR, and it is specified by ISO/IEC 25010, to guarantee RA evolution and the overall concrete product configuration quality. FFSP is validated on a HIS domain a case study

A review of information flow diagrammatic models for product-service systems

A product-service system (PSS) is a combination of products and services to create value for both customers and manufacturers. Modelling a PSS based on function orientation offers a useful way to distinguish system inputs and outputs with regards to how data are consumed and information is used, i.e. information flow. This article presents a review of diagrammatic information flow tools, which are designed to describe a system through its functions. The origin, concept and applications of these tools are investigated, followed by an analysis of information flow modelling with regards to key PSS properties. A case study of selection laser melting technology implemented as PSS will then be used to show the application of information flow modelling for PSS design. A discussion based on the usefulness of the tools in modelling the key elements of PSS and possible future research directions are also presented