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REVIEWSDespite the remarkable scientific advances over the past
few decades, little positive effect has been seen on the
drug discovery industry. The increased investment in
R&D has not yet paid off: there has been a steady decline
in the number of drugs against new targets reaching the
marketplace1. Analysts point to various reasons for this
decrease in productivity. One surprising observation
is that this decline coincides with the advent of combinatorial chemistry and high-throughput screening
(HTS)2. The target-based approach which is based
on the assumption that disruption of a single gene or
molecular mechanism is a key event in disease ontogeny
promised increased screening capacities and rational
drug discovery, and has replaced the more traditional
physiology-based approach that emerged more than two
decades ago.The perceived failure of this model for drug discovery has sparked many debates about how to improve it.
A common view is that disease or biology-relevant
screens and models should be brought into the drug
discovery process much earlier in an attempt to decrease
the current drug attrition rate. Within this context,
modern cell biology provides a means through which we
can model different aspects of disease biology. Primary
human cells can be used as in vitro systems in various
therapeutic areas, and such biologically relevant cell
assays are becoming increasingly recognized as screening
tools that are robust and amenable to automation/HTS3.
However, the realization of such a strategy requires
practical tools that enable the implementation of a more
biology-driven approach to drug discovery.Cellular imaging is emerging as a crucial tool that
would enable the integration of biological complexity into drug discovery. However, cellular imaging has
always been a largely descriptive science, and in its early
days such techniques were solely amenable to smallscale experimental samples, typically gathering data
from 101,000 cells at a time. In addition, such systems
required constant monitoring by highly skilled personnel, particularly when handling data extracted from
digital images, limiting the use of imaging technologies
to target identification or mechanism of action studies.We define cellular imaging as the use of a system/technology capable of visualizing a cell population, single cell
or subcellular structures, applied in combination with
image-analysis tools. Such detection systems include (but
are not limited to) microscopes, fluorescence macroconfocal detectors and fluorometric imaging plate...