Journal of Laboratory Automation

The aqueous solubility of a drug candidate is a vital physicochemical property that stops a drug candidate from proceeding further in the drug development processes. Classical solubility determination methods, which are commonly used in pharmaceutical laboratories, are expensive and time-consuming. In this work, an automated determination method is proposed that is based on a laser monitoring technique, and the validity of the measured solubilities is checked by comparing the measured solubilities of acetaminophen at various temperatures as proposed in various literatures. An additional set of acetaminophen solubilities in various concentrations of a surface active agent is measured at various temperatures, which has been reported for the first time, and it could be applied in the pharmaceutical industry, where solubilization of acetaminophen in aqueous solutions is required.

In modern laboratories, software can drive the full experimental process from data acquisition to storage, processing, and analysis. The automation of laboratory data acquisition is an important consideration for every laboratory. When implementing a laboratory automation scheme, important parameters include its reliability, time to implement, adaptability, and compatibility with software used at other stages of experimentation. In this article, we present an open-source, flexible, and extensible Python package for Laboratory Automation, Control, and Experimentation (PLACE). The package uses modular organization and clear design principles; therefore, it can be easily customized or expanded to meet the needs of diverse laboratories. We discuss the organization of PLACE, data-handling considerations, and then present an example using PLACE for laser-ultrasound experiments. Finally, we demonstrate the seamless transition to post-processing and analysis with Python through the development of an analysis module for data produced by PLACE automation.

Label-free measurements of the reaction kinetics of a small sample volume are essential for efficient drug discovery, requiring methods and systems that are rapid, accurate, and cost-effective. Herein, we present an integrated optofluidic system for label-free characterization of reactions in a nanoliter reagent volume. This system contains a droplet-based microfluidic sampling section and an optical fiber–based spectroscopy detection section. By manipulating droplets containing reagents at certain concentrations at different times, quantifiable measurements via absorption spectroscopy can be made in a simple, sensitive, and high-throughput manner. We have demonstrated our system’s capability by performing potency (IC₅₀) assays of an inhibitor in a TEM-1 β-lactamase (enzyme) and nitrocefin (substrate) system. This integrated platform can potentially provide an automated, label-free, and low-cost method for many other assays of reaction kinetics.

In the modern molecular diagnostic laboratory, cost considerations are of paramount importance. Automation of complex molecular assays not only allows a laboratory to accommodate higher test volumes and throughput but also has a considerable impact on the cost of testing from the perspective of reagent costs, as well as hands-on time for skilled laboratory personnel. The following study tracked the cost of labor (hands-on time) and reagents for fluorescence in situ hybridization (FISH) testing in a routine, high-volume pathology and cytogenetics laboratory in Treviso, Italy, over a 2-y period (2011–2013). The laboratory automated FISH testing with the VP 2000 Processor, a deparaffinization, pretreatment, and special staining instrument produced by Abbott Molecular, and compared hands-on time and reagent costs to manual FISH testing. The results indicated significant cost and time saving when automating FISH with VP 2000 when more than six FISH tests were run per week. At 12 FISH assays per week, an approximate total cost reduction of 55% was observed. When running 46 FISH specimens per week, the cost saving increased to 89% versus manual testing. The results demonstrate that the VP 2000 processor can significantly reduce the cost of FISH testing in diagnostic laboratories.

Background: IC₅₀ and EC₅₀ values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC₅₀/EC₅₀ assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC₅₀/EC₅₀ assay throughput demand. Result: A general-purpose, automation-assisted IC₅₀/EC₅₀ assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC₅₀/EC₅₀ values, graphing, and reporting. Conclusion: The automation-assisted IC₅₀/EC₅₀ assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC₅₀/EC₅₀ assay experimental productivity and data processing efficiency.

Transcription activator–like effectors (TALEs) are becoming powerful DNA-targeting tools in a variety of mammalian cells and model organisms. However, generating a stable cell line with specific gene mutations in a simple and rapid manner remains a challenging task. Here, we report a new method to efficiently produce monoclonal cells using integrated TALE nuclease technology and a series of high-throughput cell cloning approaches. Following this method, we obtained three mTOR mutant 293T cell lines within 2 months, which included one homozygous mutant line.

We present a miniaturized plate reader for measuring optical density in 96-well plates. Our standalone reader fits in most incubators, environmental chambers, or biological containment suites, allowing users to leverage their existing laboratory infrastructure. The device contains no moving parts, allowing an entire 96-well plate to be read several times per second. We demonstrate how the fast sampling rate allows our reader to detect small changes in optical density, even when the device is placed in a shaking incubator. A wireless communication module allows remote monitoring of multiple devices in real time. These features allow easy assembly of multiple readers to create a scalable, accurate solution for high-throughput phenotypic screening.

High-throughput screening is an established technique in drug discovery and, as such, has also found its way into academia. High-throughput screening generates a considerable amount of data, which is why specific software is used for its analysis and management. The commercially available software packages are often beyond the financial limits of small-scale academic laboratories and, furthermore, lack the flexibility to fulfill certain user-specific requirements. We have developed a Python module, screening_mgmt, which is a lightweight tool for flexible data retrieval, analysis, and storage for different screening assays in one central database. The module reads custom-made analysis scripts and plotting instructions, and it offers a graphical user interface to import, modify, and display the data in a uniform manner. During the test phase, we used this module for the management of 10,000 data points of various origins. It has provided a practical, user-friendly tool for sharing and exchanging information between researchers.

We planned an original study to investigate the morphological changes caused by spurious hemolysis of whole-blood samples, analyzed using an automated image analysis system. Seven whole-blood specimens anticoagulated with EDTA were pooled and divided in two aliquots. The former was left untreated, whereas the latter was subjected to mechanical hemolysis by forced aspiration with an insulin syringe. The complete blood cell count was performed on a Sysmex XE-2100, and the aliquots were then processed with CellaVision DM96. In spuriously hemolyzed samples, the main findings included a rarefaction of erythrocytes, the presence of a remarkable number of cellular debris, a greater degree of microcytosis and anisocytosis, the appearance of band neutrophils, a shift of values between lymphocytes and monocytes, and an increase in smudge cells, artifacts, and large platelets. The results of this study demonstrate for the first time that blood cell morphology may be consistently biased in spuriously hemolyzed whole blood and that the use of an automated image analysis system such as the CellaVision DM96 may be a suitable approach to identify spurious hemolysis in whole-blood specimens.