DOE:Layout 1 14/1/10 19:54 Page 41
Assays
DESIGN OF
EXPERIMENTS
useful statistical tool in assay
development or vendor disconnect!
The use of design of experiments (DOE) in assay development (AD) has the
potential to speed up assay optimisation (ie reduce assay development
bottlenecks) and to facilitate a more thorough evaluation of assay variables.
Only one liquid handling vendor currently offers application specific software
and support for investigating DOE in biological assays. Although standalone
DOE software packages are available, these were not written specifically for
biological applications and they vary in their suitability for AD. DOE needs to
be simpler to implement to make a major impact on AD. A market opportunity
exists for a turnkey solution that directly links statistical design with automated
liquid handler programming and also feeds the assay readout directly into the
statistical analysis, to suggest and facilitate further iterative retesting. Until new
tools or more encompassing solutions emerge, the full impact of DOE on AD
is unlikely to be realised.
D
esign of experiments (DOE) is a well estab- using a traditional approach (ie changing one setting at
By Dr John Comley
lished and proven statistical method which a time or sequential design). A typical AD lab may be
has broad application across many disci- expected to develop in excess of five assays per year,
plines and industries. Typically there are levels of with around one in 10 assays never achieving the
design which can be applied: these range from the sim- desired assay quality parameters/signal window (the
plest fractional factorial (which includes experiments main criteria of development success). Using the tradi-
to identify which factors are most critical), followed by tional approach up to around 10 different combina-
full factorial (which enables identification of signifi- tions of assay conditions (factors) may be explored
cant interactions between factors), and the more com- using either manual liquid handling or a basic auto-
plex surface area design (which facilitates finer opti- mated liquid handler set up. One of the methods com-
misation of factors). Assay development (AD) has panies are increasingly exploring to compress AD
become a bottleneck in many pharmaceutical organi- times without compromising on quality is DOE.
sation’s lead discovery operations, with assays typi- However, there is paucity of factual information
cally taking in excess of a month or more to develop around the application of DOE in AD, although many
Drug Discovery World Winter 2009/10 41
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