Journal of Laboratory Automation

Automation of large-scale compound storage, biological and chemical assays, and many other biopharmaceutical R&D processes have prompted the need for immediate and regular determination of equipment performance levels. The Automatic Metric Monitoring Program (AMMP) in Amgen Research is designed to fill this need. Standardized tests are performed at regular intervals with results instantaneously retrieved, analyzed, and stored in a database. Critical information is automatically tracked using control charts allowing immediate notification via e-mail alerts when problems or nonconforming performance is discovered. System usage and errors are automatically compiled with tabulated results provided at regular intervals and e-mail alarms issued for nonconforming operation. AMMP now provides researchers with needed real-time feedback on the performance of their automation systems.

Automating electrophoresis significantly reduces the time required for loading a large number of samples, increases the speed of electrophoresis analysis, and maximizes the resolution power (clear separation of fragments) of this technique. In addition, automation increases the precision of electrophoresis analysis. Here we demonstrate an automated, high-throughput method of loading 96 samples simultaneously onto an electrophoresis gel, using the Apogent Discoveries Tango™ system and the Invitrogen™ E-Gel® 96 system.

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.

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.

An enzyme-linked immunosorbent assay (ELISA) for Neospora caninum antibodies was automated with a robotic workstation, the Beckman Coulter Biomek 2000, to screen 200 bovine sera. Comparing these results with manually run ELISA data, a 95.92% agreement (K = 0.9592) between the two assays was obtained. The automated assay was specific and sensitive with excellent positive and negative predictive values. The results were repeatable and reproducible. The automation flexibility was high and the operation complexity was minimal. High-throughput screening (HTS) for bovine antibodies to Neospora caninum was achieved. The assay was developed according to the internationally recognized ISO17025 standard requirements.

We describe a new technology (patent pending) for high-throughput selection of poly(A)⁺ RNA from total RNA. A novel binding solution is used to ensure the efficient and specific binding of mRNA to oligo(dT) magnetic beads with high stringency, virtually eliminating the non-specific binding of ribosomal RNA (rRNA) either to oligo(dT) beads or to the poly(A)⁺ RNA bound to the beads. As quantified by real-time RT-PCR, more than 99% of the rRNA is removed in a single round selection and mRNAs are fully recovered for both highly-expressed (GAPDH) and poorly-expressed (DDPK) genes from a few μg total RNA. The protocol is adaptable to any generic robotic workstation and takes ∼30 minutes to process 96 samples.

Combinatorial chemistry is now widely used to synthesize large numbers of new chemical entities. New methods have been developed for early-stage pharma-cokinetic tests, to help decide which molecules have the properties required to make them efficacious and successful in the marketplace. Of the various physicochemical tests that are used to assess ADME, pK_a (aqueous ionization constant) is the key to understanding how other properties will be affected by pH. A new method is described for rapid measurement of pK_a of samples drawn from 96 well DMSO stock solutions.