High-Content Screening (HCS) is a drug development technique that consists of analyzing the effect of large libraries of pharmaceutical compounds on cell samples using automated microscopy. The microscopy modules used in HCS rely on certain electro-mechanical elements that make them rigid and overspecialized. However, HCS requires flexible imaging technologies due to the variety of samples involved in these studies.
- To develop a programmable microscope capable of encapsulating the functionality of multiple imaging modalities into a single instrument, potentially satisfying this need. The team hopes to build a prototype of this “swiss knife microscope” specifically oriented to HCS applications.
Problem to Solve
High-Content Screening (HCS) is an important method in drug discovery and development. The variety and complexity of the HCS assays impose considerable demands on instrument platforms, which are required to provide maximum flexibility. For example, very high frame rates are needed for monitoring fast transient phenomena such as calcium dynamics in cardiotoxicity assays. On the other hand, for dealing with autofluorescence samples or thick 3D cultures the capacity to reject out-of-focus light becomes crucial. Finally, for analyzing small organelles or fine structural elements, resolution is king. These are mutually exclusive goals that current technology cannot meet simultaneously.
Microscopes are limited because resolution, speed and sensitivity are mutually incompatible features. Any improvement in one magnitude is obtained to the detriment of the other two, so current microscope designs remain poor in several of these important metrics.
This new module for High-Content Screening (HCS) Microscopy is very flexible and allows users to reproduce the functionality of multiple confocal modalities in a single instrument, tuning its speed, resolution, and sensitivity at will.
This concept has been pursued for a long time under the name of "programmable array microscope" but this technology will be the first commercial implementation of a working microscope with this capacity.