Journal of Laboratory Automation

Quantification of hemodynamics may be invaluable in a drug development setting. However, one of the challenges in the application of imaging technologies for compound screening purposes is the large volume of data in a short amount of time. This article focuses on methods developed for large-scale hemodynamic quantification, as measured from high-frequency Doppler ultrasound in rodents. An integrative semiautomated method for processing Doppler ultrasound images is described and validated. In the context of experimental biology, this toolbox allows for a comprehensive hemodynamic evaluation of in vivo physiology as the result of medical intervention, thus enabling rapid compound screening in preclinical drug development.

A totally integrated serial dilution assay plate preparation system that fully uses the high precision nanoliter dispensing capabilities of acoustic liquid handlers has been developed and implemented. The application uses a hybrid of a serial dilution method and a direct dilution method, achieving a wide concentration range for the dilution series, while avoiding additive errors inherent to traditional serial dilution methods. The method allows assay miniaturization, which greatly reduces reagent and consumable costs to the customers. The system is in production at AstraZeneca and has generated high-quality assay ready plates for high-throughput screening and secondary screening since 2005. Further development in recent years has expanded the flexibility of the assay ready plate creation process to meet varied screening requirements.

We will discuss the requirements for assay ready plates for concentration response testing and describe the novel plate creation method in detail with the rigorous validation procedures. Along with method validation data, some real-life screening results will be presented to compare an experiment conducted on compounds prepared using the novel hybrid method and those prepared using a more traditional serial dilution method, which endorses the application of the novel method.

Drug candidates with poor physicochemical properties (such as solubility) tend to have low bioavailability. For example, basic compounds might dissolve under acidic stomach conditions but then precipitate because of a change in pH under the neutral conditions found in the intestines. Therefore, it is essential to prevent precipitation and maintain high drug concentrations in the intestines to improve in vivo plasma exposure. Substances that act as antiprecipitants have been reported as well as bio-relevant media that mimic conditions in the stomach and small intestine. This report describes the development of an antiprecipitant screening system for basic model compounds using 96-well plates and bio-relevant media. Fourteen potential antiprecipitants were screened on one plate, which resulted in the identification of four substances that maintained a supersaturation state. To confirm these results, supersaturation studies were conducted according to the United States Pharmacopeia (USP) II dissolution method, and the results of the newly developed system correlated well with those of the USP II method. This novel system is useful for small-scale formulation screening during early preclinical development. This 96-well plate system will be available for the easily automated system in comparison with the conventional USP II system.

Polymer latexes are essential components in a wide range of commercial products and formulations such as, paints, cosmetics, coatings, biotechnology, and functionalized supports. Many difficulties are intrinsic to the implementation of polymer latex research, particularly in the purification of the final latex dispersions and the control and reproducibility of particle size, therefore making high-throughput research in this area especially challenging. In this article, we demonstrate how the investigation of the influential synthesis factors on polymer latex materials properties can be swiftly and reproducibly achieved by the combinational use of experimental design, automated synthesis, and a newly developed high-throughput purification process. Through the implementation of flexible automated platforms, a significant increase in the throughput of this previously manual process was achieved. Reaction models were used to examine the synergistic and antagonistic effects of the latex synthesis parameters, thereby allowing the controlled synthesis of fully characterized libraries of surface–functional polymer latexes to be rapidly produced and screened for a wide range of applications.

The complete blood count (CBC) has by and large remained confined to the traditional laboratory setting since its inception. Used in a variety of diagnostic assessments, the CBC has essentially become limited to clinical laboratories because of reliance on large automated hematology devices. With many potential uses at the point of care and clinical settings, as well as the research laboratory, a portable low-cost hematology analyzer could aid in earlier detection of a wide variety of medical conditions. Using smaller sample volumes, inexpensive polymers, and low power consumption, microfluidic devices present one such route toward miniaturization of the traditional flow cytometer-based hematology analyzers. This review focuses on challenges for development of cost-effective portable analyzers, potential areas for point-of-care clinical usage, current commercial systems with increasing portability, and recent research in improved miniaturization and automation, including developments in acoustic and inertial focusing techniques and novel detection methodologies.

We have designed and implemented a framework for creating a fully automated high-throughput phototransfection system. Integrated image processing, laser target position calculation, and stage movements show a throughput increase of >23x over the current manual phototransfection method although the potential for even greater throughput improvements (>110x) is described. A software tool for automated off-line single-cell morphological measurements, as well as real-time image segmentation analysis, has also been constructed and shown to be able to quantify changes in the cell before and after the process, successfully characterizing them, using metrics such as cell perimeter, area, major and minor axis length, and eccentricity values.

This article details recent efforts where student innovation has been harnessed to address international needs for accessible healthcare technology, with a specific focus on global regions where the availability of needed instrumentation is rare. This article sheds insight into the history of the organization, its objectives, as well as its current progress and future roadmap.