High-throughput screening
[2][3] Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests.
A screening facility typically holds a library of stock plates, whose contents are carefully catalogued, and each of which may have been created by the lab or obtained from a commercial source.
To prepare for an assay, the researcher fills each well of the plate with some biological entity that they wish to conduct the experiment upon, such as a protein, cells, or an animal embryo.
Manual measurements are often necessary when the researcher is using microscopy to (for example) seek changes or defects in embryonic development caused by the wells' compounds, looking for effects that a computer could not easily determine by itself.
Otherwise, a specialized automated analysis machine can run a number of experiments on the wells (such as shining polarized light on them and measuring reflectivity, which can be an indication of protein binding).
A high-capacity analysis machine can measure dozens of plates in the space of a few minutes like this, generating thousands of experimental datapoints very quickly.
[8] Consequently, one of the most fundamental challenges in HTS experiments is to glean biochemical significance from mounds of data, which relies on the development and adoption of appropriate experimental designs and analytic methods for both quality control and hit selection .
[9] HTS research is one of the fields that have a feature described by John Blume, Chief Science Officer for Applied Proteomics, Inc., as follows: Soon, if a scientist does not understand some statistics or rudimentary data-handling technologies, he or she may not be considered to be a true molecular biologist and, thus, will simply become "a dinosaur.
[23] Drops of fluid separated by oil replace microplate wells and allow analysis and hit sorting while reagents are flowing through channels.
In 2010, researchers developed a silicon sheet of lenses that can be placed over microfluidic arrays to allow the fluorescence measurement of 64 different output channels simultaneously with a single camera.
Here technologies that enable the identification of potent, selective, and bioavailable chemical probes are of crucial interest, even if the resulting compounds require further optimization for development into a pharmaceutical product.
[27] In 2016-2018 plate manufacturers began producing specialized chemistry to allow for mass production of ultra-low adherent cell repellent surfaces which facilitated the rapid development of HTS amenable assays to address cancer drug discovery in 3D tissues such as organoids and spheroids; a more physiologically relevant format.
[28][29][30] HTS is a relatively recent innovation, made feasible largely through modern advances in robotics and high-speed computer technology.
The open access policy ensures that researchers from all over the world can take advantage of this facility without lengthy intellectual property negotiations.
Functional genomics is typically paired with high content screening using e.g. epifluorescent microscopy or laser scanning cytometry.
Columbia University has an HTS shared resource facility with ~300,000 diverse small molecules and ~10,000 known bioactive compounds available for biochemical, cell-based and NGS-based screening.
Northwestern University's High Throughput Analysis Laboratory supports target identification, validation, assay development, and compound screening.
The non-profit Scripps Research Molecular Screening Center (SRMSC)[32] continues to serve academia across institutes post-MLPCN era.
In the United States, the National Institutes of Health or NIH has created a nationwide consortium of small-molecule screening centers to produce innovative chemical tools for use in biological research.
In addition, the NIH created the National Center for Advancing Translational Sciences or NCATS, housed in Shady Grove Maryland, that carries out small molecule and RNAi screens in collaboration with academic laboratories.
