Journal of Laboratory Automation

A new system concept has been developed for microfluidic devices in which thermal actuation is used to achieve most or all fluid and reaction control functions (e.g., valves, pumps, mixers, separators, heaters, and coolers). Thermal actuation makes it possible to incorporate the fluid-containing components in a module that can be physically separated from the actuation elements, making the fluid-bearing module disposable. The actuation elements are embedded in a reusable module, reducing the complexity and cost of the disposable unit. The thermally-actuated valve is central to the system design, and has been well characterized. Thermal-actuation concepts for other fluid-handling functions have been developed and, in most cases, demonstrated. The approach is scalable from microchip to microtiter-plate formats. It can also be integrated into existing microchip technologies to expand functionality. Prototypes have been built and tested in combination with a DNA array for diagnostics of infectious diseases.

We have designed and implemented a computer application called CHECKIN to submit open-access NMR data to the Wyeth Research compound validation and registration workflow process. At Wyeth Research, all analytical data used for compound validation and subsequent registration must be examined by Discovery Analytical Chemistry (DAC) staff. The traditional process required the medicinal chemist to submit vials of a pure sample to DAC to perform assays to validate its structure. For NMR analysis, DAC used this material to prepare a sample in deuterated solvent, which is used to collect one-dimensional ¹H NMR data. DAC then reviews the spectra for consistency with the proposed chemical structure. This evaluation process was designed to reduce the number of misidentified compounds submitted to the corporate library by having a second set of eyes examine the data for each submission.

This new computer application allows the medicinal chemist to select previously acquired hands-on NMR data and enter it into the standard workflow for evaluation, bypassing the sample preparation and data acquisition steps. The CHECKIN application saves time for the medicinal chemist and DAC staff, as well as compound library material for Wyeth. An explanation of the workflow and implementation for Bruker and Varian NMR data will be described.

An efficient and versatile Compound Management operation is essential for the success of all downstream processes in high-throughput screening (HTS) and small molecule lead development. Staff, equipment, and processes need to be not only reliable, but remain flexible and prepared to incorporate paradigm changes. In the present report, we describe a system and associated processes that enable handling of compounds for both screening and follow-up purposes at the NIH Chemical Genomics Center (NCGC), a recently established HTS and probe development center within the Molecular Libraries Initiative of the NIH Roadmap. Our screening process, termed quantitative HTS (qHTS), involves assaying the complete compound library, currently containing > 200,000 members, at a series of dilutions to construct a full concentration—response profile. As such, Compound Management at the NCGC has been uniquely tasked to prepare, store, register, and track a vertically developed plate dilution series (i.e., inter-plate titrations) in the 384-well format. These are compressed into a series of 1536-well plates and are registered to track all subsequent plate storage. Here, we present details on the selection of equipment to enable automated, reliable, and parallel compound manipulation in 384- and 1536-well formats, protocols for preparation of inter-plate dilution series for qHTS, as well as qHTS-specific processes and issues.

Recently, robotic automation in clinical test has become a subject of keen interest because it is a fusion of biotechnology and robotic technology. In this article, we present a new robotic platform for clinical test suitable for small- or medium-sized laboratories. The platform is designed to minimize the consumption of reagents, and to easily integrate various testing equipments because it is functionally modularized. It is aimed to accommodate 70 kinds of clinical tests, which are the most frequently conducted in hospitals. The BioRobot platform is developed, and its feasibility is validated experimentally.

The utility of acoustic droplet ejection (ADE), originally used to transfer dimethyl sulfoxide (DMSO) solutions, is expanded beyond the transfer of DMSO to a wide variety of aqueous solutions common to biochemical experiments and assays. Aqueous-based liquids are transferred with high precision (coefficient of variation <5% for volume transfers of 5–50 nL) and accuracy (within 5% of expected volume), similar to that seen with DMSO transfers. The precision and accuracy of the technique are measured via fluorescence. ADE transfers of aqueous solutions may facilitate the miniaturization of assays leading to increased throughput and reduced reagent usage.

In this second part of the tutorial series, we continue the investigation of Petri net theory as it applies to laboratory automation systems. The focus of this tutorial is the application of theoretical results to the analysis of laboratory automation system models. The mathematical description of a Petri net is introduced. Several analytical methods are reviewed and applied to examples of laboratory automation systems. Analytical results include the identification of deadlock situations, computation of cycle times, optimization of design, and the automatic calculation of system-control schemes.