High-content screening technology is mainly based on automated digital microscopy and flow cytometry, in combination with IT-systems for the analysis and storage of the data.
“High-content” or visual biology technology has two purposes, first to acquire spatially or temporally resolved information on an event and second to automatically quantify it. Spatially resolved instruments are typically automated microscopes, and temporal resolution still requires some form of fluorescence measurement in most cases. This means that a lot of HCS instruments are (fluorescence) microscopes that are connected to some form of image analysis package. These take care of all the steps in taking fluorescent images of cells and provide rapid, automated and unbiased assessment of experiments.
HCS instruments on the market today can be separated based on an array of specifications that significantly influence the instruments versatility and overall cost.  These include speed, a live cell chamber that includes temperature and  control (some also have humidity control for longer term live cell imaging), a built in pipettor or injector for fast kinetic assays, and additional imaging modes such as confocal, bright field, phase contrast and FRET.  One of the most incisive difference is whether the instruments are optical confocal or not. Confocal microscopy summarizes as imaging/resolving a thin slice through an object and rejecting out of focus light that comes from outside this slice.  Confocal imaging enables higher image signal to noise and higher resolution than the more commonly applied epi-fluorescence microscopy.  Depending on the instrument confocality is achieved via laser scanning, a single spinning disk with pinholes or slits, a dual spinning disk, or a virtual slit.  There are trade offs of sensitivity, resolution, speed, photo-toxicity, photo-bleaching, instrument complexity, and price between these various confocal techniques.
What all instruments share is the ability to take, store and interpret images automatically and integrate into large robotic cell/medium handling platforms.