Journal of Laboratory Automation

An evolving union of high throughput screening (HTS) and absorption, distribution, metabolism, excretion, and toxicology (ADMET) technologies have transformed drug discovery. Human tissue-based, in vitro ADMET assays can efficiently generate reliable profiles for structure-activity or structure-property relationships of compounds from screening “hit sets” or libraries. The process of identifying discovery compounds with desirable “druglike” properties has consequently become increasingly data-driven. Chemists and biologists initiate the process by submitting requests to our laboratory through an intranet database. A Caco-2 cell model, automated on a Tecan Genesis workstation, evaluates the intestinal absorption of drug candidates. Distribution properties are determined with a high-throughput equilibrium dialysis technique for measuring plasma protein binding. Drug metabolism can be evaluated on a Genesis workstation via measurements of metabolic stability in liver microsomes. Drug-drug interactions can be predicted with HTS techniques using human recombinant hepatic CYP450 isoforms. A Genesis workstation, integrated with a fluorescence plate reader, executes CYP450 inhibition assays. Cell toxicity assays using human hepatocytes can serve as early, high-throughput indicators of potential systemic drug toxicity. The early availability of ADMET profiling data can now enable discovery scientists to quickly evaluate the factors that influence the pharmacodynamic and pharmacokinetic properties of compounds in lead optimization.

Development of a flexible, open-architecture modular robotic workstation consisting of a Calipers' Twister II robotic arm, several Labsystems Multidrop dispensers, a Kendro Cytomat incubator, and a multimode BMG Polarstar Optima reader has been reported. Our new, fully functional scheduling software developed under LabWindows allows the integration of an unlimited number of devices from diverse suppliers using native communication protocols.

We describe automated methods for purifying genomic DNA from plant tissue. The Wizard Magnetic 96 Plant System uses MagneSil paramagnetic particles (PMPs) in a 96-well format to purify sufficient DNA for polymerase chain reaction (PCR)-based plant genotyping. The system can be scaled up for high yield to provide genomic DNA for large numbers of PCR-based tests or archiving. In contrast, the MagneSil ONE Fixed Yield System uses MagneSil ONE PMPs to purify a fixed amount of ultraclean DNA for high sensitivity in Third Wave Technology Invader single nucleotide polymorphism (SNP) Genotyping assays. These methods may be implemented on Beckman Coulter Biomek automated workstations.

In Germany, all slaughtered cattle and fallen stock above the age of 24 months are required to be tested for bovine spongiform encephalopathy (BSE). Due to short turnaround times and urgent economic demand for fast results in the slaughterhouses, a highly reliable and fast-running system is needed. Using the Prionics (Prionics AG, Schlieren, Switzerland) CheckLIA Rapidtest, a modular system was installed that has processed over 245,000 samples since February 2004. Test runs averaged 340 min per batch of 240 samples. The rate of initial reactive results was 1.95 in 1000 samples.

The advancement of technology in life science has created a need for improved accuracy and precision in pipetting small volumes¹ from 50 nL up to and above 10 μL. Tomtec has adapted ink-jet technology²⁻⁶ to meet this need in their Nano pipettor heads. A coefficient of variation (CV) of 5% is achievable at 50-nL volumes, improving to 1-2% at 1 μL and above. A pipettor must aspirate from a source and dispense to a destination, then repeat the process without detectable carryover. The Nano head 8 and Nano head 16 achieve this utilizing a novel standpipe design that permits a fast wash through of the liquid handling channels. Each pipettor may be individually controlled, creating another dimension in pipetting flexibility.

A move from fixed, statically scheduled laboratory automation systems to more dynamic and adaptive behavior introduces complexities and challenges that have not been thoroughly explored in the field of laboratory automation. Powerful tools are required for the systematic modeling, analysis, simulation, and control of such systems. In this first part of a tutorial series, we introduce and explore Petri nets as a tool that can be used to model dynamically controlled laboratory automation systems. Subsequent contributions to this series will look at formal mathematical techniques for analyzing Petri net models, and methods for simulating and controlling laboratory automation systems using Petri nets.

In the increasingly scrutinized pharmaceutical industry, regulatory agencies are demanding validation of any and all analytical instrumentation, including documentation associated with its implementation, qualification, and ability to report accurate and reliable results. Herein, we discuss the qualification and validation of an automated liquid handling system and an automated dissolution method. We describe the comparison of automated experiments versus manual experiments while addressing the pertinent validation and qualification considerations for each. Discussion of documentation and validation required for various regulated laboratories (good clinical practices (GCP), good laboratory practices (GLP), and good manufacturing practices (GMP)) is also reviewed.