High Content Screening (HCS)
High Content Screening is a microplate-based assay methodology using automated imaging and microscopy to observe and record cellular-level biological activities in intact, living cells responding to an applied stimulus, such as a potential drug compound. The assays are built around a series of fluorescent probes for specific proteins, cell bodies or structures. The ability to run parallel assays per cell by visualizing multiple fluorescent probes simultaneously and to monitor in real-time complex cellular responses is a distinct advantage of the technology. The morphology and subpopulations of individual cells and sub-cellular components, and the relationships between various measured parameters can be observed, analyzed and interpreted on an individual cell or population average basis. A typical HCS system includes equipment for automated liquid and cell handling, and a digital imaging device plus software for acquiring, processing, storing and analyzing large amounts of data.
The goal of high content screening is to provide deep, detailed, functional information to facilitate quality decisions about the progression of drug candidate compounds or to discover and better understand potential drug targets. HCS can provide such data as quantifying the activation of multiple receptors, identifying differentiated cell states, monitoring cell signaling pathways and analysis of gene expression. These can be used to screen potentially bioactive entities to gain insights into a compounds bioavailability, potency, specificity and toxicity, often via a single carefully multiplexed assay. Cellular activity represents the first level of complexity in a biological system, consisting of many interacting, regulated pathways involving hundreds of proteins in a complex network of activity. Cell-based assays are more meaningful than those involving isolated proteins, but are far less complex and expensive than whole organism studies.
Sophisticated high content screening image acquisition instruments and data analysis software are available from a number of vendors such as:
• ThermoFisher Cellomics® Arrayscan®
• Perkin Elmer® Opera®
• BD Biosciences Pathway™
• TTP LabTech Acumen®
• MDS Analytical Technologies ImageXpress®
• GE- IN Cell Analyzer
Each instrument is designed to automatically acquire and store fluorescent images of cells in microtiter plate wells. Digital imaging is done using confocal or bright field microscopes or laser scanners. Each detection method has advantages for specific applications, and many research programs employ several types. Most instruments will come with software for analyzing the digital images for a range of biological parameters.
Caliper Integrated Systems for HCS
Cell based assays can be highly technique-dependent and often greatly benefit from the consistent and precisely controllable liquid handling and reproducible event timing of automated sample preparation. Caliper Integrated Systems for HCS are a line of systems designed to provide fast and reliable automated solutions to specific applications such as High Content Screening. Utilizing proven and robust "automation-friendly" building blocks, Caliper has created compact, reliable solutions that cost less than conventional approaches, take up little lab space and and require less than a day of installation. A typical Staccato HCS system would include an imaging instrument, a Caliper Twister™ II robot for microplate transport and storage, allowing scientists to “walk away” from lengthy image acquisition sessions and a Sciclone ALH 3000 liquid handler to perform the technique-sensitive sample preparation prior to imaging. Dispensing speed and mixing methods can be precisely controlled so as not to disrupt cells in microwells and to insure fast and uniform dilutions. Caliper's industry leading iLinkPro® software is used to create sample preparation methods with tight control over plate-to-plate event scheduling. Other peripheral devices, such as incubators and bar code readers can be included as needed.
Sciclone ALH 3000 Advanced Liquid Handler
Sciclone ALH 3000 is the most flexible liquid handler available with a twenty position deck and a variety of on-deck options such as shaking and temperature controlled locators. Sciclone is able to swap arrays 'on the fly' and can support any one of three interchangeable heads (nL, Low Volume or High Volume) and also supports a bulk reagent dispenser as well as the eight channel 'Z8.' Sciclone also offers an optional servo gripper for on-deck automation.
Twister II Advance Capability Microplate Handler
Twister II was designed to address the need for a microplate handler with multiple instrument capability, increased speed and capacity, serving as the hub for a new breed of automated systems. This proven, low-cost microplate handler provides a time saving alternative to stackers and a money saving alternative to larger, more complex transport systems. A capacity of up to 400 plates allows significant walk-away time from lengthy HCS scanning. 5 axes of motion make it compatible with virtually any device.
