High Throughput Central: What are Screening Centers?
Learning Objectives
1. Describe screening centers.
2. List equipment and services commonly offered at screening centers.
3. Evaluate how screening centers are used in contemporary research.
Legend
Screening centers are facilities that implement multi-disciplinary equipment to perform high-throughput assays. Microplates with large number of wells are regularly used in screening centers. Original image by LJNovaScotia from Pixabay.
What are Screening Centers?
Screening centers are facilities that combine equipment and expertise from a number of scientific disciplines to enable a variety of high-throughput processes. The exact services and equipment offered depend on the particular screening center though most are focused on drug discovery. Historically, high-throughput screening was primarily used by the pharmaceutical industry until the founding of Harvard’s Institute of Chemistry and Cell Biology in 1997 (1). Today, screening centers are an essential component of the drug discovery pipeline and can be found globally (2). Screening centers are generally affiliated with academic institutions though there are a number of government screening centers like the National Center for Advancing Translational Sciences (NCATS) Early Translation Branch (ETB). The research triangle region alone features screening centers at North Carolina Central University’s BRITE Institute and Duke’s RNAi Facility. The specific services and equipment available at a particular screening center are facility-dependent but can be generally grouped into the following categories: Genetic and chemical Screening, library management, and project management. Screening centers combine miniaturization, robotics, replication, and validation to enable high-throughput discovery.
High-throughput Screening
Genetic and chemical screening is a type of high-throughput screening used to identify “Hit” or “Lead” compounds from biological or chemical libraries. High-throughput screening often involves the usage of equipment such as a liquid handling system, a plate handling system, and a barcode management system (3). The liquid handling system is responsible for the physical movement of liquids and administration of treatments based on the programmed script. The plate handling system works in conjunction with the liquid handling system to ensure microplates are in the correct position based on the same programmed script. Lastly, a barcode management system capable of both labeling and scanning ensures the large number of samples are documented properly. Depending on the type of assay performed, a visualization system such a microplate reader will also be used. Some of the most common assays include small molecule screening, siRNA screening, target-based screening, and phenotypic screening.
Library Management
Chemical and biological libraries are essential components of high-throughput screening and it is the responsibility of screening centers to maintain high-quality libraries. The compounds within a library are what ultimately become the “hits” or “leads” of a high-throughput screen. A screening center with a wider selection of libraries will be able to achieve a more diverse set of screens.
Project Support
Many screening centers offer services that broadly fall under the category of project support. Some screening centers like the Scripps High-Throughput Molecular Screening Center offer assay development services that help automate and scale-up a low-throughput assay (4). Others like UWCCC’s Small Molecule Screening Facility offer walk-up equipment usage, allowing labs to access specialized equipment without the large upfront cost.
Screening Centers in Contemporary Research
Screening centers are important facilities in the context of modern scientific research. They bring together specialist from a variety of fields and leverage their know-how to perform high throughput experiments. A 2019 showcase highlighted how academic screening centers are being used in contemporary environments across the globe (2). Researchers at the Helmholtz Centre for Infection Research in Germany use their “open-access” screening center to characterize new antibacterial and antiviral drugs. Researchers at the Stem Cell Hotel in the United Kingdom use their screening center to develop standardized characterization methods for induced pluripotent stem cells (IPSCs). Researchers at the Drug Discovery Initiative in Japan offer free access to their 280,000 sample chemical library in exchange for disclosure of one’s research goals. Screening centers continue to make high-throughput technologies more accessible to the scientific community at large.
Questions and Answers
1. What is a screening center?
A screening center is a facility that features equipment and staff from a variety of scientific disciplines and enable high-throughput discovery through the principles of miniaturization, robotics, replication, and validation.They are often affiliated with academic or research institutions.
2. Why are screening centers important?
Screening centers are important because they increase access to high-throughput technologies.Screening centers increase access to high-throughput technologies by removing the burden of purchasing specialized equipment on individual labs. This allows researchers to consider implementing high-throughput methods into their experimental design. Without screening centers some of this equipment would be cost prohibitive.
3. List the key component and services offered at screening centers.
High-throughput Screening, Library Management, and Project Support
4. How do screening centers promote social justice?
By reducing the barrier of entry, screening centers promote the usage of high-throughput technologies from a wider set of researchers. Researchers from institutions without access to high-throughput technologies can work external screening centers to advance their work.
Audio Recordings
References
1. The academic pursuit of screening. (2007). Nature Chemical Biology, 3(8), 433–433. https:// doi.org/10.1038/nchembio0807-433
2. Bickle, M. (2019). The Academic Pill: How Academia Contributes to Curing Diseases. SLAS DISCOVERY: Advancing the Science of Drug Discovery, 24(3), 203–212. https://doi.org/ 10.1177/2472555218824280
3. Douglas S. Auld, P. D., Peter A. Coassin, B. S., Nathan P. Coussens, P. D., Hensley, P., Klumpp-Thomas, C., Michael, S., G. Sitta Sittampalam, P. D., O. Joseph Trask, B. S., Bridget K. Wagner, P. D., Jeffrey R. Weidner, P. D., Mary Jo Wildey, P. D., & Jayme L. Dahlin, M. D. (2020). Microplate Selection and Recommended Practices in High-throughput Screening and Quantitative Biology. In www.ncbi.nlm.nih.gov. Eli Lilly & Company and the National Center for Advancing Translational Sciences. https://www.ncbi.nlm.nih.gov/sites/ books/NBK558077/
4. High-Throughput Molecular Screening Center | Scripps Research. (2019). Scripps.edu. https://www.scripps.edu/science-and-medicine/cores-and-services/high-throughput molecular-screening-center/