Economic and strategic perspectives on investing in RMS and FMS

The evolution of manufacturing systems, according to changing internal and external conditions, requires design and assessment techniques that consider both strategic and financial criteria to evaluate the suitability of the Flexible and Reconfigurable system solutions in addressing these variations. In this paper, a fuzzy multi-objective mixed integer optimization model to evaluate RMS investments used in a multiple product demand environment is presented. The model incorporates in-house production and outsourcing options, machine acquisition and disposal costs, operational costs, and re-configuration cost and duration for the utilized modular machines. The resulting system configurations are optimized for lifecycle costs, responsiveness performance, and system structural complexity simultaneously. A complexity metric that incorporates the quantity of information using an entropy approach is used to represent the inherent structural complexity of the considered system configurations. It accounts for the complexity of the machine modules in a manufacturing system through the use of an index derived from a newly developed manufacturing systems classification code, which captures the effect machine types and technologies on the system’s structural complexity. A metric is proposed to measure the responsiveness ability and efficiency as well as the overall capability of each machine and effectiveness of machines changeover. The application of the developed planning and assessment model that incorporates these three criteria is illustrated with a case study where FMS and RMS alternatives were compared. The suitable conditions for investing in RMS are also discussed.     

Maintenance Integration in Manufacturing Systems: From the Modeling Tool to Evaluation

In manufacturing systems, wear-out and eventual failure are unavoidable. However, to reduce the rate of their occurrence and to prolong the life of equipment or the capacity for extended productive use of the equipment under the necessary technological functioning and servicing, maintenance can be performed. For large manufacturing systems, maintenance integration involves a particular development concerned with both complexity models and computing time. This paper presents an effective way of modeling complex manufacturing systems through hierarchical and modular analysis by using stochastic Petri nets and Markov chains. In the proposed approach, the integration of maintenance policies in a manufacturing system is facilitated by the development of a generic model. With this generic modeling, the user doesn't need to code the strategies but only to instantiate the generic model with the structure of the manufacturing system. This method allows various maintenance strategies to be coded in the generic model with the aim of studying their influence on system dependability and performance.     

Developing manufacturing control software: A survey and critique

The complexity and diversity of manufacturing software and the need to adapt this software to the frequent changes in the production requirements necessitate the use of a systematic approach to developing this software. The software life-cycle model (Royce, 1970) that consists of specifying the requirements of a software system, designing, implementing, testing, and evolving this software can be followed when developing large portions of manufacturing software. However, the presence of hardware devices in these systems and the high costs of acquiring and operating hardware devices further complicate the manufacturing software development process and require that the functionality of this software be extended to incorporate simulation and prototyping. This paper reviews recent methods for planning, scheduling, simulating, and monitoring the operation of manufacturing systems. A synopsis of the approaches to designing and implementing the real-time control software of these systems is presented. It is concluded that current methodologies support, in a very restricted sense, these planning, scheduling, and monitoring activities, and that enhanced performance can be achieved via an integrated approach.     

Fermentative biohydrogen production systems integration

Acidogenic fermentation can be used to produce hydrogen from a range of biomass sources. The effluent from this process can be utilised in a number of biological processes enabling further recovery of energy from the biomass. In this review a number of candidate technologies are assessed including conventional methanogenic anaerobic digestion, dark fermentative hydrogen production, photo-fermentation, and bioelectrochemical systems. The principles, benefits and challenges associated with integrating these technologies are discussed, with particular emphasis on integration with fermentative hydrogen production, and the current state of integrative development is presented. The various system configurations for potential integrations presented here may simultaneously permit an increase in the conversion efficiency of biomass to energy, improved adaptability to varying operating conditions, and improved stability. Such integration, while increasing system complexity, may mean that these bioprocesses could be deployed in a wider range of scenarios and be used with a greater range of substrates.     

A specification language for planning and fault recovery in manufacturing systems

This paper presents the syntax and semantics of a component-oriented rule-based language for specifying the formal models of manufacturing systems. A model captures the state of a component of the system in a set of first-order logic predicates, and it captures the semantics of the operations performed by this component in a set of rules that determine the preconditions and postconditions of an operation. The models are then used to plan the sequence of operations of each class of jobs to be manufactured by these systems. A plan-oriented fault detection and correction strategy is proposed. This strategy can automatically handle any combination of faults that may occur when monitoring the operations of manufacturing systems. A fault-tree is consulted prior to executing the scheduled operations of a plan, and the faults that affect the execution of these operations are handled subsequently. Resuming the original cyclic schedule is attempted, whenever feasible. As a proof of concept, a prototype implementation of both the main constructs of the component-oriented rule-based language and the planning and fault-recovery algorithms presented in this paper have been completed. This prototype is implemented on a Unix-based system in the Ada programming language. The specification of a manufacturing system is first expressed in the proposed language. These statements are then translated into Ada code. This code is next compiled by a Verdix Ada compiler and is executed in order to create and populate the model data structure of the system. A detailed plan of execution and a set of fault-recovery plans may then be derived for a job to be manufactured on this system.     

Reliability analysis of flexible manufacturing systems

High productivity is the primary goal of flexible manufacturing systems (FMSs) in which semi-independent workstations are integrated using automated material-transport systems and hierarchical local networks. Availability of various subsystems and of the system as a whole is a prerequisite for achieving functional integration as well as high throughput. An FMS also has inherent routing and operation flexibilities that provide it with a certain degree of fault tolerance. A certain volume of production can thus be maintained in the face of subsystem (i.e., machines, robots, material handling system, etc.) failures. In this article, we propose two reliability measures, namely, part reliability (PR) and FMS reliability (FMSR) for manufacturing systems and present algorithms to evaluate them. We also consider the dynamic or time-dependent reliability analysis as a natural generalization of the static analysis. The methods outlined use an algorithm that generates process-spanning graphs (PSGs), which are used to evaluate the reliability measures.     

Product Hardware Complexity and Its Impact on Inventory and Customer On-Time Delivery

This paper studies the impact of a reduction in hardware complexity on the supply-chain inventory against various customer on-time delivery alternatives and manufacturing environments. Different methods of reducing hardware complexity are proposed, and their impact on total supply-chain inventory and customer serviceability quantified. An analytical inventory optimization scheme taking into account multistage supply networks, product structure, forecast accuracy, lead-time variability, and supplier reliability is used to determine optimal inventory levels in a stochastic modeling environment. The analysis is based on a business case for an IBM midrange computer family consisting of more than 200 models and upgrades with hundreds of features. We investigate different hardware complexity reduction strategies, including low-usage feature reduction, low-volume feature reduction, and feature substitution, as well as quick response and postponement mechanisms. Our computational results show that, in a fabrication-fulfillment center environment, reducing hardware complexity results in significantly higher inventory savings than in an integrated manufacturing environment. The results presented in this paper were used to reduce hardware complexity in IBM's midrange computer division.     

Flexible and reconfigurable manufacturing systems paradigms

Reconfigurable Manufacturing System (RMS) is a new manufacturing systems paradigm that aims at achieving cost-effective and rapid system changes, as needed and when needed, by incorporating principles of modularity, integrability, flexibility, scalability, convertibility, and diagnosability. RMS promises customized flexibility on demand in a short time, while Flexible Manufacturing Systems (FMSs) provides generalized flexibility designed for the anticipated variations and built-in a priori. The characteristics of the two paradigms are outlined and compared. The concept of manufacturing system life cycle is presented. The main types of flexibility in manufacturing systems are discussed and contrasted with the various reconfiguration aspects including hard (physical) and soft (logical) reconfiguration. The types of changeability and transformability of manufacturing systems, their components as well as factories, are presented along with their enablers and compared with flexibility and reconfigurability. The importance of having harmonized human-machine manufacturing systems is highlighted and the role of people in the various manufacturing paradigms and how this varies in pursuit of productivity are illustrated. Finally, the industrial and research challenges presented by these manufacturing paradigms are discussed.     

Dimensionality Reduction of Bistable Biological Systems

Time hierarchies, arising as a result of interactions between system’s components, represent a ubiquitous property of dynamical biological systems. In addition, biological systems have been attributed switch-like properties modulating the response to various stimuli across different organisms and environmental conditions. Therefore, establishing the interplay between these features of system dynamics renders itself a challenging question of practical interest in biology. Existing methods are suitable for systems with one stable steady state employed as a well-defined reference. In such systems, the characterization of the time hierarchies has already been used for determining the components that contribute to the dynamics of biological systems. However, the application of these methods to bistable nonlinear systems is impeded due to their inherent dependence on the reference state, which in this case is no longer unique. Here, we extend the applicability of the reference-state analysis by proposing, analyzing, and applying a novel method, which allows investigation of the time hierarchies in systems exhibiting bistability. The proposed method is in turn used in identifying the components, other than reactions, which determine the systemic dynamical properties. We demonstrate that in biological systems of varying levels of complexity and spanning different biological levels, the method can be effectively employed for model simplification while ensuring preservation of qualitative dynamical properties (i.e., bistability). Finally, by establishing a connection between techniques from nonlinear dynamics and multivariate statistics, the proposed approach provides the basis for extending reference-based analysis to bistable systems.     

Economics and success factors of flexible manufacturing systems: The conventional explanation revisited

This article analyzes costs and relative benefits of several hundred flexible manufacturing systems (FMSs) in the world. The analyses are based on the computerized data bases, which make it easy to correlate different cost and benefit indicators with each other and to look for regular patterns and tendencies in the applications. Both investment cost distributions and the system complexity distributions are analyzed. The relative benefits and advantages and their relationships are shown. Finally, technical and economic explanations for successful implementation strategies are given. The results show that there are two classes of economically successful systems. The small-scale and technically compact systems are usually used in small-batch production for the replacement of semimanual production. The main benefits are increased capacity and productivity as well as quality improvements. The large-scale and technically complex systems are used in large-volume production for the replacement of fixed automation and transfer lines. The benefits are mainly due to the increased potential for flexibility and capital savings.     

A Classification for Hoist Scheduling Problems

Electroplating lines are totally automated manufacturing systems that are used to cover parts with a coat of metal. They consist of a set of tanks between which the parts to be treated are transported by one or several hoists. Scheduling the movements of these hoists is commonly called a hoist scheduling problem (HSP) in the literature. But the assumptions and constraints that must be taken into account greatly depend on the production environment (physical system, manufacturing specifications, and management policies). Consequently, there exist several classes of HSPs. The systematic frameworks usually used to classify deterministic scheduling problems do not allow distinguishing between these various kinds of HSPs. Therefore, identifying the scope of each published work and comparing the various proposed scheduling methods turn out to be difficult. Thus, this article presents notation for scheduling problems in electroplating systems, to make the specification of problem types and the identification of studied problem instances easier. An associated typology gives a survey of the literature and demonstrates the usefulness of the proposed classification scheme.     

An integrated cell‐free metabolic platform for protein production and synthetic biology

Cell‐free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell‐free systems, however, have been limited by their inability to co‐activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell‐free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co‐activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell‐free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements.     

Real-time software methodologies: Are they suitable for developing Manufacturing control software?

Computer-Integrated Manufacturing (CIM) systems may be classified as real-time systems. Hence, the applicability of methodologies that are developed for specifying, designing, implementing, testing, and evolving real-time software is investigated in this article. The paper highlights the activities of the software development process. Among these activities, a great emphasis is placed on automating the software requirements specification activity, and a set of formal models and languages for specifying these requirements is presented. Moreover, a synopsis of the real-time software methodologies that have been implemented by the academic and industrial communities is presented together with a critique of the strengths and weaknesses of these methodologies. The possible use of the real-time methodologies in developing the control software of efficient and dependable manufacturing systems is explored. In these systems, efficiency is achieved by increasing the level of concurrency of the operations of a plan, and by scheduling the execution of these operations with the intent of maximizing the utilization of the devices of their systems. On the other hand, dependability requires monitoring the operations of these systems. This monitoring activity facilitates the detection of faults that may occur when executing the scheduled operations of a plan, recovering from these faults, and, whenever feasible, resuming the original schedule of the system. The paper concludes that the set of surveyed methodologies may be used to develop the real-time control software of efficient and dependable manufacturing systems. However, an integrated approach to planning, scheduling, and monitoring the operations of these systems will significantly enhance their utility, and no such approach is supported by any of these methodologies.     

Availability Analysis for Multitask Production Systems

A multitask production system is one in which different subsets of the components can be used to perform distinct functions or tasks. For such a system, some of the components are used intermittently and some may be used continuously. This type of operational protocol is often applied to flexible manufacturing systems. In this paper, we develop models of the operational reliability and of the availability of multitask systems. We construct models for both the case in which preventive maintenance is used and the case in which preventive maintenance is not used. The models presented here constitute an extension to existing models to allow the study of the behavior of modern manufacturing equipment.     

The possible role of assignment catalysts in the origin of the genetic code

A model is presented for the emergence of a primitive genetic code through the selection of a family of proteins capable of executing the code and catalyzing their own formation from polynucleotide templates. These proteins are assignment catalysts capable of modulating the rate of incorporation of different amino acids at the position of different codons. The starting point of the model is a polynucleotide based polypeptide construction process which maintains colinearity between template and product, but may not maintain a coded relationship between amino acids and codons. Among the primitive proteins made are assumed to be assignment catalysts characterized by structural and functional parameters which are used to formulate the production kinetics of these catalysts from available templates. Application of the model to the simple case of two letter codon and amino acid alphabets has been analyzed in detail. As the structural, functional, and kinetic parameters are varied, the dynamics undergoes many bifurcations, allowing an initially ambiguous system of catalysts to evolve to a coded, self-reproductive system. The proposed selective pressure of this evolution is the efficiency of utilization of monomers and energy. The model also simulates the qualitative features of suppression, in which a deleterious mutation is partly corrected by the introduction of translational error.     

Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing

Background aimsRegulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities.MethodsTo support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood-donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products.ResultsThe system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products.ConclusionsOverall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories.     

Performance management of manufacturing system networks

Performance management of communication networks is critical for speed, reliability, and flexibility of information exchange between different components, subsystems, and sectors (e.g., factory, engineering design, and administration) of production process organizations in the environment of computer integrated manufacturing (CIM). Essential to this distributed total manufacturing system is the integrated communications network over which the information leading to process interactions and plant management and control is exchanged. Such a network must be capable of handling heterogeneous traffic resulting from intermachine communications at the factory floor, CAD drawings, design specifications, and administrative information. The objective is to improve the efficiency in handling various types of messages, e.g., control signals, sensor data, and production orders, by on-line adjustment of the parameters of the network protocol. This paper presents a conceptual design, development, and implementation of a network performance management scheme for CIM applications including flexible manufacturing. The performance management algorithm is formulated using the concepts of: (1) Perturbation analysis of discrete event dynamic systems; (2) stochastic approximation; and (3) learning automata. The proposed concept for performance management can also serve as a general framework to assist design, operation, and management of flexible manufacturing systems. The performance management procedure has been tested via emulation on a network test bed that is based on the manufacturing automation protocol (MAP) which has been widely used for CIM networking. The conceptual design presented in this paper offers a step forward to bridging the gap between management standards and users' demands for efficient network operations since most standards such as ISO and IEEE address only the architecture, services, and interfaces for network management.     

Suitability and perspectives on using recombinant insect cells for the production of virus-like particles

Virus-like particles (VLPs) can be produced in recombinant protein production systems by expressing viral surface proteins that spontaneously assemble into particulate structures similar to authentic viral or subviral particles. VLPs serve as excellent platforms for the development of safe and effective vaccines and diagnostic antigens. Among various recombinant protein production systems, the baculovirus–insect cell system has been used extensively for the production of a wide variety of VLPs. This system is already employed for the manufacture of a licensed human papillomavirus-like particle vaccine. However, the baculovirus–insect cell system has several inherent limitations including contamination of VLPs with progeny baculovirus particles. Stably transformed insect cells have emerged as attractive alternatives to the baculovirus–insect cell system. Different types of VLPs, with or without an envelope and composed of either single or multiple structural proteins, have been produced in stably transformed insect cells. VLPs produced by stably transformed insect cells have successfully elicited immune responses in vivo. In some cases, the yield of VLPs attained with recombinant insect cells was comparable to, or higher than, that obtained by baculovirus-infected insect cells. Recombinant insect cells offer a promising approach to the development and production of VLPs.     

Information Content,Complexity, and Uncertainty in Material Flow Analysis

Material Flow Analysis (MFA) is a useful method for modeling, understanding, and optimizing sociometabolic systems. Among others, MFAs can be distinguished by two general system properties: First, they differ in their complexity, which depends on system structure and size. Second, they differ in their inherent uncertainty, which arises from limited data quality. In this article, uncertainty and complexity in MFA are approached from a systems perspective and expressed as formally linked phenomena. MFAs are, in a graph‐theoretical sense, understood as networks. The uncertainty and complexity of these networks are computed by use of information measures from the field of theoretical ecology. The size of a system is formalized as a function of its number of flows. It defines the potential information content of an MFA system and holds as a reference against which complexity and uncertainty are gauged. Integrating data quality measures, the uncertainty of an MFA before and after balancing is determined. The actual information content of an MFA is measured by relating its uncertainty to its potential information content. The complexity of a system is expressed based on the configuration of each individual flow in relation to its neighboring flows. The proposed metrics enable different material flow systems to be compared to one another and the role of individual flows within a system to be assessed. They provide information useful for the design of MFAs and for the communication of MFA results. For exemplification, the regional MFAs of aluminum and plastics in Austria are analyzed in this article.     

Functional monolithic platforms: Chromatographic tools for antibody purification

Polymer monoliths are an efficient platform for antibody purification. The use of monoclonal antibodies (mAbs) and engineered antibody structures as therapeutics has increased exponentially over the past few decades. Several approaches use polymer monoliths to purify large quantities of antibody with defined clinical and performance requirements. Functional monolithic supports have attracted a great deal of attention as they offer practical advantages for antibody purification, such as more rapid analysis, smaller sample volume requirements and the opportunity for a greater target molecule enrichment. This review focuses on the development of synthetic and natural polymer-based monoliths for antibody purification. The materials and methods employed in monolith production are discussed, highlighting the properties of each system. We also review the structural characterization techniques available using monolithic systems and their performance under different chromatographic approaches to antibody capture and release. Finally, a summary of monolithic platforms developed for antibody separation is presented, as well as expected trends in research to solve current and future challenges in this field. This review comprises a comprehensive analysis of proposed solutions highlighting the remarkable potential of monolithic platforms.