Technology of the month
Category
Technology platforms / Core facilities
Main applications
The use of 3D cell culture models, such as spheroids and organoids, is currently seen as a research strategy to rapidly access more complex human biology, and also as a means to reduce and perhaps in the future replace, at least in some studies, laboratory animal models. An example of a potential successful application is early preclinical drug discovery, which is unfortunately doomed to fail in 90% of cases in the preclinical stages with current models. Such 3D models, combined with automated high-throughput screening of large drug libraries and high-content imaging, are expected to increase the quality of compounds entering preclinical stages. In addition, screening with already approved drugs (repurposing) could provide a timely solution for patients, so-called personalized medicine.
The technology
The BioSciences Screening Scientific Platform utilizes sample miniaturization and automation technologies to enable high throughput and high content screening (HTS/HCS) to identify new molecular probes/tools for the discovery of new chemical and biological entities with potential therapeutic application. HTS combines the use of robots, typically liquid handlers, to transfer thousands/millions of compounds to microplates carrying the cellular models, which are read in microplate readers after incubation; typical outputs are cell viability/cytotoxicity. HCS takes advantage of automated sample preparation and handling to feed automated microscopes that combine image acquisition with analysis and visualization tools to extract quantitative data from single cells, tissues or whole organisms.
Requirements
HTS/HCS requires expensive state-of-the-art equipment and specialized personnel. Our scientific platform provides open access (fee-based) to the scientific community and industry through project design, assay development, data analysis and reporting.
Required equipment includes: cell culture facilities, liquid handlers, plate handlers, incubators, multimode microplate readers, high content screening microscopes, high performance computers and servers.
Future perspectives
3D models are expected to mimic human disease. However, they still lack the complexity of the whole organism. Nevertheless, much research has been done to incorporate, for example, the vasculature and circulating immune cells. Much is also expected from 3D culture platforms such as (multi)organs-on-chip. In addition, these models must be amenable to HTS/HCS. Today, spheroids are the preferred model for screening, but soon we expect to be able to do drug discovery with organoids and chips. While today we use confocal microscopes for high content screening, in the future we expect to be able to do high throughput light sheet microscopy.
Contact person
André Maia
Head of BioSciences Screening Scientific Platform
i3S – Institute for Research and Innovation in Health
Porto, Portugal
Link to webpage
https://www.i3s.up.pt/scientific-platform.php?groupid=93