insight - Matrox

The drug discovery process not only develops new drugs that cure,
control, or prevent disease . This process must also include rigorous
testing for severe side effects . This is particularly true for drugs that
are intended for long-term or even lifetime use, such as anti-rejection
drugs for transplant patients .
Long before human trials can proceed, drugs must be tested for their
efficacy and safety . The Preclinical Safety unit at Novartis (Basel,
Switzerland) has the responsibility of determining adverse side effects
of all new molecular entities (drugs) in vitro (i .e ., in cultured cells)
and in vivo (animal testing) . Besides other toxicological studies, the
researchers perform genetic toxicology assays (tests) to assess the
genotoxic potential of new drug candidates . Drug effects on mammalian
cells are studied, using chromosomal abnormalities (besides other
cellular and nuclear endpoints) to assess the compound’s potential
hazards . When such abnormalities occur, it means that the drug in
question has interacted with the cell’s genome . Dr . Wilfried Frieauff,
Laboratory Manager of the Preclinical Safety unit says that when a
statistically and biologically significant increase in these events are
observed, there’s a potential for the drug candidate to induce cancer .
Frieauff manages the labs, and he is responsible for the image analysis
platform – its development, system maintenance, and support . The
Preclinical Safety unit runs hundreds of tests annually on literally
millions of cells . Given the numbers, it’s no surprise that the analysis
process is one that benefits from automation .
At the end of the 1980s, Frieauff’s lab began to use Leitz MIAS image
analyzers for that purpose . But by the late 1990s, Dr . Frieauff realized
that the systems were seriously outdated . “It was a stand-alone system
that could not be part of a network . Replacement parts were no longer
available,” he explains . These early image analysis systems had a
maximum capacity of processing only 16 slides in a row . “Sometimes we
would load the slides on Friday, and the system would finish and sit idling
until Monday morning .” More importantly, Frieauff expected the future
would bring more image analysis development projects and he “realized
that it was time to totally re-engineer and modernize our image analysis .”
Case Study: Novartis
After extensive research of the market, Frieauff selected several
components that would comprise the new ROBIAS, the Robotic Image
Analysis System . ROBIAS is built from an electronically-driven Leica DM
RXA/2 microscope mounted with a SONY DXC-390 color CCD camera
that is connected to host PC with a Matrox Meteor-II/Multi-Channel
frame grabber . An optional robotic slide feeder can automatically
place up to 130 slides on the microscope’s stage for processing, which
is performed by using custom-developed image analysis algorithms
based on the Matrox Imaging Library .
Automated microscopy
Due to the subjective nature of manual microscopy and the increasing
need for accurate, standardized results, image processing techniques
have been used in microscopy for some time . Indeed, medical
diagnostic and pharmaceutical applications need precise results
– lives are at stake – and automated microscopy offers complete
objectivity (thanks to image processing algorithms) and relieves the
human eye of difficult and fatiguing tasks .
The ROBIAS system performs specific cytogenetics assays (cell-genetic
tests) that examine both in vitro and in vivo samples:
• micronucleus test (MNT) in vivo (regulatory test to be conducted for
drug registration)
• comet assay in vivo
• metaphase finding for chromosome aberration analysis (regulatory
test to be conducted for drug registration )
• MNT in vitro (for early genotoxicity screening)
• comet assay in vitro (for early genotoxicity screening)
• MNT in primary human lymphocytes (currently under development)
By studying the cells’ DNA, the researchers can add evidence to a drug’s
relative safety, or identify potential hazards . For the micronucleus
test or the chromosome aberration analysis, the researchers look
for chromosomal abnormalities which become visible when the cell
passes through mitosis .
The Robotic Image Analysis System (ROBIAS) is built from a electricpowered
microscope and an optional robotic slide feeder .
IMAGING INSIGHT Vol. 10 No. 1
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