High-content screening (HCS) and high-throughput screening (HTS) were introduced more than a decade ago and are both analytical techniques used to study biological systems in parallel for various applications such as cell biology and drug discovery.
High content screening
Within the pharmaceutical industry, novel drugs require extensive research and development to find effective active drug compounds that are then screened for biological and pharmacological activity and the value of their use within medicine. With the development of technology, acquiring target compounds has become a more rapid and effective process, which is significant for creating successful drugs that gain approval from the Food and Drug Administration (FDA) for treating various diseases and disorders.
Compound library ranges can consist of hundreds to millions of compounds, and screening out pharmacologically active compounds from a large library is currently of high interest to researchers.
High-Throughput Screening
HTS technology consists of an analytical technique used mainly for molecular or cellular levels and depends on optical detection, including but not limited to fluorescence and spectrophotometric detection. This technology's versatility, including trace quantity, sensitivity, and accuracy, has made it perfect for drug discovery applications.
With increasing volumes of target molecules for drug discovery and development for various diseases, conventional screening methods cannot handle the high target numbers, which can be solved with the use of high-throughput screening technologies.
HTS uses experimental methods at the molecular and cellular level, including using microplates that can simultaneously identify a significant number of samples via an automated approach, which corresponds with a database that is produced. This technology screens targets such as receptors and enzymes, which can be assessed by their biological activity, even within a large sample number, using a single screening model that investigates which samples are active against specific targets.
The significance of this technology within drug discovery and development is remarkable, as this technology is more scalable compared to traditional screening methods due to HTS being able to screen thousands of samples daily.
High-Content Screening
HCS technology involves taking cells as the detection object and recording cells within a multi-well plate via the use of microscopic imaging, and this aids in analyzing the activity of substances and compounds within cells.
The aim to reduce the screening cost of HTS and accelerate the screening process has resulted in scientists decreasing the size of screening samples, such as from using a 96-well plate to high-density microplate screening using 384-well or 1,536-well plates.
Additionally, novel development for researchers includes increasing the level of information in every single screening as well as increasing the discovery of new information. This may be solved with the emergence of HTS, which can gather drug action signals with different interpretations using the same screening model.
HCS integrates different technologies including sample preparation, automated analysis equipment, supporting detection reagents, data processing software, and bioinformatics. The main elements of HCS consist of fluorescence microscopy, automated fluorescence image acquisition, detection tools, image processing, analysis software, result analysis, and data management.
This technology is established mainly at the cellular level, including targets such as membrane receptors and organelles. HCS can be seen as being more comprehensive than HTS technology due to its ability to simultaneously detect sample effects on various cell characteristics such as cell morphology, growth, migration, differentiation, apoptosis, as well as metabolic pathways and signal transduction, without losing the structural integrity of cells and their function.
A single HCS experiment can lead to a significant level of information on genes, proteins, and other cellular components to determine its biological activity and any potential toxicities of compounds.
This is critical as enhancing the amount of information on novel drug compounds can ensure they are comprehensively assessed on their efficacy, increasing their probability of being FDA-approved and becoming available in clinical practice. The simultaneous detection of multiple targets and assessing multiple compounds can aid in comprehensive evaluation which can determine its probability of becoming potentially novel drugs. HCS technology can accelerate the drug discovery process with novel targets and compounds being detected and assessed, reducing the overall cost and length of time for drugs to be developed by the pharmaceutical industry.
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Future Outlook
The continuous development of technologies means that novel technologies such as high-throughput and high-content screening can aid in analyzing drug compounds at a mass scale to assess efficacy. This is significant for the pharmaceutical industry and the development of drugs because this process is associated with high expenditure, time length, and high failure rate before receiving FDA approval.
However, technical challenges that can be optimized include optimizing imaging time, exposure time, and magnification and increasing the number of images per well of a microplate.
Overall, the use of HTS, as well as the more evolved HCS, may be revolutionary for drug discovery and development as it can lead to more drugs being developed and approved for a range of diseases experienced by global populations.
Read Next: What is High Throughput Screening?
Sources:
- Attene-Ramos, M.S., Austin, C.P. and Xia, M. (2014) "High throughput screening," Encyclopedia of Toxicology, pp. 916–917. Available at: https://doi.org/10.1016/b978-0-12-386454-3.00209-8.
- Blay, V. et al. (2020) "High-throughput screening: Today's biochemical and cell-based approaches," Drug Discovery Today, 25(10), pp. 1807–1821. Available at: https://doi.org/10.1016/j.drudis.2020.07.024.
- High-throughput screening and high-content screening (no date) High-throughput Screening and High-content Screening - Solutions / BOC Sciences. Available at: https://www.solutions.bocsci.com/resources/high-throughput-screening-and-high-content-screening.html (Accessed: January 12, 2023).
- Singh, S., Carpenter, A.E. and Genovesio, A. (2014) "Increasing the content of high-content screening: An overview," SLAS Discovery, 19(5), pp. 640–650. Available at: https://doi.org/10.1177/1087057114528537.
- Team, D.D.W. (2020) When high content screening meets high throughput, Drug Discovery World (DDW). Available at: https://www.ddw-online.com/when-high-content-screening-meets-high-throughput-1151-201112/ (Accessed: January 12, 2023).
Further Reading