text: Automation and low volume assay formats were leveraged by scientists at the NIH Chemical Genomics Center (NCGC) to develop quantitative HTS (qHTS), a paradigm to pharmacologically profile large chemical libraries through the generation of full concentration-response relationships for each compound.  With accompanying curve fitting and cheminformatics software qHTS data yields half maximal effective concentration (EC50), maximal response, Hill coefficient (nH) for the entire library enabling the assessment of nascent structure activity relationships (SAR).
  In March 2010, research was published demonstrating an HTS process allowing 1,000 times faster screening (100 million reactions in 10 hours) at 1-millionth the cost (using 10 times the reagent volume) than conventional techniques using drop-based microfluidics. 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.  This process can analyze 200,000 drops per second.
  In 2013, researchers have disclosed an approach with small molecules from plants. In general, it is essential to provide high-quality proof-of-concept validations early in the drug discovery process. 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. Nuclear receptor RORα, a protein that has been targeted for more than a decade to identify potent and bioavailable agonists, was used as an example of a very challenging drug target. Hits are confirmed at the screening step due to the bell-shaped curve. This method is very similar to the quantitative HTS method (screening and hit confirmation at the same time), except that using this approach greatly decreases the data point number and can screen easily more than 100.000 biological relevant compounds.
  Whereby traditional HTS drug discovery uses purified proteins or intact cells, recent development of the technology is associated with the use of intact living organisms, like the nematode Caenorhabditis elegans and zebrafish (Danio rerio).
  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.