The Second Generation of the Laboratory Information System and the Laboratory Automation System in Osaka City University Hospital

The first total clinical laboratory system (TCLA) in the Osaka City University Hospital was introduced in 1993. After six years of operation, it was recently replaced by a new system. The goals of this replacement were as follows: 1. Improve the analytical performance. 2. Make the system operate more efficiently. 3. Improve the quality of laboratory analyses. We successfully reduced the labor required to operate the laboratory; made the laboratory reports quicker; reduced the number of retraction and revalidation of the results; and minimized the system downtime.     

Transferring Industrial Automation Technology to the Laboratory

Over the past few years, there has been much discussion about transferring industrial technology to laboratories. While it is easy to look at the superficial similarities, it is more important to examine the different requirements of different industries. In this way, it is possible to identify the technologies and techniques that can be successfully transferred to the laboratory to improve performance.This paper takes three very different industries - the bakery, High Throughput Screening (HTS) and mobile phone assembly and examines their different requirements. These industries have been selected from among the many sectors where the RTS Group operates - thus allowing real data from a number of situations to be used.One of the most important areas in automation design is the relationship between flexibility and throughput. This paper focuses on this relationship and its influence over machine configuration when comparing the requirements of the different industries.     

HTS Automation Study: Results from a 2001 Survey of the Current vs. Desired State of HTS Automation

A survey of directors of screening organizations was conducted in 2001 to evaluate their perceptions of the current vs. desired state of high-throughput screening (HTS) automation. The survey encompassed attributes such as automation flexibility, throughput and operation. These and other automation attributes were ranked based on importance to the respondent and/or the limitations these attributes imposed on the screening organization.     

Automation of Chemical Reaction Kinetics and Product Distribution Studies in Pharmaceutical Development

An automated instrument was designed and constructed to facilitate the performance of pharmaceutical degradation studies. A brief theoretical background on degradation kinetics is given to rationalize the design of the instrument and representative data are provided to illustrate its successful application. This system was found to be capable of conducting multiple simultaneous isothermal and nonisothermal kinetic studies with user-defined temperature profiles, sampling periods, and data logging.     

Optimizing Reaction Conditions of the NanoOrange® Protein Quantitation Method for Use With Microplate-based Automation

Because of the rapidly expanding need for higher sample throughput in drug discovery, automation of corresponding biochemical analyses is desirable. In particular, automation of protein quantitation is crucial since its results are used extensively. Recently, a single-reagent fluorescent protein quantitation method (NanoOrange®) with attractive performance attributes has become available. While it can potentially be automated with liquid handling workstations, several of this method's reaction parameters need to be optimized.

We studied the time and a temperature dependence of the NanoOrange protein quantitation reaction in ninety-six well black microplates using either a temperature-regulated hot block or a microwave oven as heat sources. Fluorescence of the NanoOrange reaction was quantified with a multimode microplate spectral scanner.

Time-dependent heating profiles of filled microplates placed on hot blocks at fixed temperatures (45, 55, 65, 75, and 95°C) revealed temperature differences of 4–7°C cooler for the outside wells compared to the inner wells, however the maximum well temperature did not exceed 65°C. Similar time-temperature studies of microwave-heated microplates revealed an equilibrium temperature of 45–49°C that was 10–16°C lower than microplates that were block heated.

The bovine serum albumin (BSA): NanoOrange standard curves created using a hot block increased in slope from 45°C to 55°C, but then remained constant from 65 to 85°C.

Fluorescence of the BSA: NanoOrange standard curve created using a microwave oven was about half the magnitude of the hot block-derived curves, possible reflecting a lower energy transfer rate of the microwave oven. We conclude that the NanoOrange protein quantitation method can be automated if a microplatecompatible hot block with a 65-85°C surface can heat the microplate for minimum of 15 min prior to quantifying the reaction's fluorescence.     

A Flexible and Robust Peer-to-Peer Architecture with XML-Based Open Communication for Laboratory Automation

Traditional lab automation systems are highly centralized: dispatch and coordination of activities are mediated by a system controller, usually via a single, monolithic control procedure. This approach, while conceptually simple, makes changes to the system difficult; adding or removing instruments and functionality can be a daunting task. In addition, most automated systems are tied to particular development languages and protocols, making operation in heterogeneous environments (i.e., the real world) problematic, since instrument software comes in many different implementations.We present a peer-to-peer architecture for lab automation, using an XML-based communication protocol. The architecture consists of peer instrument servers, an XML communication layer, and an open control center. Each instrument peer can control, be controlled by, and communicate information to other instrument peers to fulfill the automation task. Our protocol is based on XML-RPC, a lightweight communication standard built atop HTTP.This provides an open and flexible means of peer-to-peer interfacing. The control center serves as a convenient, Web-based interface to manage the instruments. The automated procedure can be distributed across all available instrument peers (each instrument assigned a set of responsibilities); the controller implements a limited set of high-level instructions. The software components included in our prototype system are implemented in various programming languages, including Java, C/C++, Visual Basic, and LabVIEW. Our approach facilitates rapid development of laboratory automation systems.     

Dynamic Formulation and Performance Evaluation of the 6-d.o.f. Parallel Structure Seismic Simulator

This paper presents the dynamic formulation and performance evaluation of the 6-d.o.f. parallel structure seismic simulator. By means of the principle of virtual work and the concept of link Jacobian matrices, the inverse dynamic model of the seismic simulator is set up. Then, a series of new dynamic performance indices with obvious physical meanings have been proposed. The dynamic performance index combining the acceleration, velocity and gravity terms of the dynamic equations has been achieved by decoupling the inverse dynamics in an exhaustive way. By using the index, it is possible for us to evaluate the performance in different directions. The index has been applied to the dynamic characteristic evaluation of the 6-d.o.f. parallel structure seismic simulator in the numerical simulation. Conclusions and results are provided at the end of the paper.     

Assay on FAQ''s on Total Lab Automation

The purpose of the introduction of an automated laboratory system in one format or another is reducing the costs of the laboratory by cutting staff. Also speeding up the performance often is a goal. At the same time it is planned to increase the quality of the work done by using automated labelling and reading of documents. The use of vacuum tubes and the handling of these by the apparatus are raising the safety of the labwork.

In this paper many aspects of the daily routines when using a TLA system are discussed. The aspects are collected during the discussions before and after the implementation of the Roche CLAS system in our laboratory. Some consequences were foreseen, and others came unexpectedly. But still the subjects form a point of discussion around the TLA systems. The most important message to be picked up is that one really has to consider all possible problems that could arise from the implementation of TLA.     

Automated Purification of DNA from Large Samples: A Study of Effectiveness and Labor Efficiency

Investigations into the underlying genetic contributions to human disease are transitioning from small family-based traditional linkage analyses to large population-based studies designed to identify genetic factors in more complex and common diseases that have the greatest impact on human health. These types of studies have driven the need for larger numbers of samples for analysis and more efficient and effective methods for DNA purification, especially for large samples that provide sufficient quantities of DNA for extensive analysis. The AUTOPURE LS™ Nucleic Acid Purification Instrument, by Gentra Systems, Inc., a platform capable of high-throughput sample purification from large samples, was developed to meet the demands of these large studies. This article presents data demonstrating the equivalency of DNA purified using the AUTOPURE LS automated instrument and the manual method based on the same purification process. In addition, we present data demonstrating the in-lab time savings realized by automating the purification process.     

Project Control for Laboratory Automation Outsourced to Consultants A 10-Step Process to Optimize the Effectiveness of Custom Information Technology Development

This article outlines a 10-step process for business leaders in the pharmaceutical, biotech, health sciences, and clinical fields, who hire information technology (IT) applications consultants to design, develop, implement, and integrate custom laboratory automation systems. The goal of this model is to identify steps to dramatically improve the effectiveness of the consultant and to reduce implementation risk factors. The probability of project success can be increased significantly when the basics of IT systems development is understood by those internal to the organization and management guides the consultant to the finish line using a defined project control process.     

A Fully Automated Process Using a Magnetic Particle Based Kit for Removal of Dye Terminators from Sequencing Reactions

Prolinx,® Inc. of Bothell, WA has developed the RapXtract™ 384 Dye Terminator Removal Kit for full automation of DNA sequencing reaction purification. The RapXtract product line is based upon proprietary superparamagnetic particle technology that eliminates the need for centrifugation, vacuum filtration, or modified primers to achieve purification of sequencing reactions. The kit described here is pre-dispensed in a 384-well microtiter plate and run on the TECAN GENESIS Workstation 150 (Tecan U.S. Inc., Research Triangle Park, NC). This system enables rapid purification of up to 384 sequencing reactions in a single run.As the completion of the Human Genome Project nears, it is imperative for biotechnology and pharmaceutical companies to increase throughput of DNA sequencing in order to be competitive in the drug discovery and validation process. The “race to market” requires a shift from standard DNA sequencing processes-including DNA sequencing reaction purification-towards complete walk-away automation for all steps.Existing sequencing reaction purification methods (Table 1) require considerable resources including: plastic and other laboratory consumables; specialized equipment, such as high-speed centrifuges or vacuum filtration apparatus; and labor-intensive protocols requiring large amounts of technician time. As a result, walk-away automation of standard purification methods is difficult and expensive.     

Automation of Serological Diagnosis for Herpes B Virus Infections Using Robot-Assisted Integrated Workstations

A robot-assisted automated facility was established within a biosafety level 3 laboratory located on a university campus. A unique integration of a Genesis (TECAN) liquid handler into the SAGIAN Core System (Beckman-Coulter) enabled tube liquid handling and transfer of reagents from tubes to microplates. An automated enzyme immunoassay (ELISA) for detecting herpes B virus antibodies was developed. Repetition experiments of the automated ELISA and comparison to the manual ELISA demonstrated the efficacy and high reproducibility of the automated method. It is anticipated that research and education activities will benefit from the establishment of the automated diagnostic laboratory in an academic environment.     

A simulation model for eliciting scheduling knowledge: an application to the precast manufacturing process

This paper discusses the process of eliciting scheduling knowledge from a simulation model and the development of a dynamic modelling approach to the scheduling process in the precast concrete industry. Due to the problems associated with eliciting scheduling knowledge from an ‘expert’ in the precast industry or perhaps in most of the manufacturing industries, simulation is used to complement human knowledge in this paper. Such knowledge will be used for online support to advise production schedulers and for further development of the simulation model by incorporating the knowledge in the model and making it more dynamic. The paper suggests that dynamic selection of scheduling rules during real-time operation has been recognised as a promising approach to the scheduling process in the precast industry. For this strategy to work effectively, sufficient knowledge is required to enable the model to predict the most effective scheduling rule to meet current factory status. The paper concludes that if the knowledge rules are used effectively, they could be a considerable managerial tool for exploring and improving managerial practices. Recommendations have been made regarding the development of a more realistic and practical scheduling system.     

Automated High Throughput Screening of Fluorescent Imaging Plate Reader (FLIPR) Assays Using Assay Platform™ Integrated with Activity Base for ‘on the fly’ Compound Reconfirmation

Advances in the field of automation have meant hitherto complex manual cell-based assays can now be automated. These improvements have brought significant enhancements in throughput, data fidelity and consistency, and allowed a reallocation of constrained resources.Building upon these improvements, we have linked our automated cell-based screening system, Assay Platform™, to Activity Base (IDBS), a software package designed to automate the analysis of HTS data. Customisation of this package has resulted in software that can identify ‘active’ compounds and re-pick them ‘on the fly’ from the original compound plates for triplicate re-testing without operator intervention.Based on an operator initially defining ‘normal’ parameters for assay activity in Activity Base, combined with an automated quality control software module that checks data fidelity, wells containing ‘active’ compounds can be re-picked and re-tested at the end of an automated screening run. Automating cell-based assays has significantly improved productivity, and, with the synergism of Activity Base, has given us greater power to complete each screening run and report ‘active’ compounds to Chemistry more rapidly. This article presents our approach to the automation of cell-based Fluorescent Imaging Plate Reader (FLIPR) screening together with automated active re-test confirmation using Activity Base.     

High Throughput Mapping of Protein-Protein Interactions: Automation of the Yeast Two-Hybrid System

Protein-protein interactions are a vital component in both the function and regulation of virtually all biological processes. In the yeast two-hybrid system, one of the most commonly-used methods for studying protein-protein interactions, protein-protein interactions are detected by expression of a reporter gene driven by the interaction between bait and prey proteins. We report here the development of an automated system, the MegaMate, for carrying out high throughput (over 100,000 clones per day) yeast two-hybrid screens with full data tracking.     

Global controllability of linear autonomous systems: A geometric consideration

The global controllability in finite time of a linear autonomous system with restrained controls is investigated. Necessary and sufficient conditions are obtained by an approach based on the consideration of geometric properties of the system.     

Object-Z: A specification language advocated for the description of standards

The importance of formalising the specification of standards has been recognised for a number of years. This paper advocates the use of the formal specification language Object-Z in the definition of standards. Object-Z is an extension to the Z language specifically to facilitate specification in an object-oriented style. First, the syntax and semantics of Object-Z are described informally. Then the use of Object-Z in formalising standards is demonstrated by presenting a case study based on the ODP Trader. Finally, a formal semantics is introduced that suggests an approach to the standardisation of Object-Z itself. Because standards are typically large complex systems, the extra structuring afforded by the Object-Z class construct and operation expressions enables the various hierarchical relationships and the communication between objects in a system to be succinctly specified.