DOE:Layout 1 14/1/10 19:54 Page 46
Assays
Figure 13 picolitre-to-microlitre dispense technology (Figure
Hewlett Packard’s High-
1). HP’s dispense solution addresses a significant
Performance Dispense
product gap in high-performance titration of
Solution
DMSO-based small-molecule concentrate.
Biologists are currently taking advantage of the HP
technology’s dynamic range to titrate compounds
directly to assay plates, thus eliminating serial-dilu-
tion and other painful intermediate steps. End-
users are also enjoying results within minutes for
small-batch biochemical and cell-based assays.
Inhibitors with different potencies can each be
evaluated against bio-assay input variables for out-
puts such as IC
50
, Hill slope, signal strength, noise
and DMSO content. The HP dispense solution
enables non-contact dispensing of any compound
at any dose into any well in 96 and 384-well plate
micro-diaphragm allows any volume down to formats making creative layouts in any
200nL to be dispensed with a resolution of 200nL. row/column direction easy to implement. This new
The Formulator’s positive displacement micro- capability enables end-users to overcome previous
diaphragms handle viscous and non-viscous liquids barriers to conducting complex assays. For exam-
with ease and precision. The Formulator was ple, elaborate synergy or allosteric modulation
recently used by scientists at Novartis to investigate experiments are easy to plan, programme and
the DOE of kinase and protease assays
4
. achieve. The technology also enables very fine
Formulatrix hopes to launch the Tempest for DOE titration spacing which facilitates better data in
later in 2010 (Figure 12). general and easier enzyme binding titrations to
quantify the active fraction. Assay developers will
Hewlett-Packard Specialty Printing Systems also appreciate the exceptional flexibility of HP’s
(www.hp.com) is developing a high-performance dispense technology, which can rapidly enable
dispense solution for dose-response analysis. The multi-factorial experimental design. Preliminary
new dispense technology, which is leveraged from results suggest HP’s dispense solution could be
HP’s established printing franchise, is currently promising a new tool for DOE (Figure 13).
undergoing pre-commercial field testing at
BioPharma sites. Lab Scientists in assay develop- DOE software
ment, lead optimisation, ADMET and other simi- The following vendor snapshots provide details
lar groups are key end-users targeted to use HP’s some standalone software packages available to
support DOE in AD:
Clinical and pharmaceutical assay development is
a complex process. Minitab® statistical software
(www.minitab.co.uk) can help the assay developer
take advantage of statistical design of experiments
by selecting the best matrix of experimental condi-
tions to gain knowledge about the system being
studied with a minimum number of experiments
and a maximum degree of accuracy in the esti-
mates. A wide variety of design models such as
two-level factorials, D-optimal, robust designs and
others are available to check for interactions
between reagents and ensure that the full parame-
ter space is covered. Some designs such as Plackett-
Burman designs are used to screen multiple factors
while others, such as Response Surface Designs,
enable researchers to study the significant factors
in more detail, including their non-linear effects.
Figure 14: Contour Plot produced using Minitab® Statistical Software Minitab software can assist in determining the
46 Drug Discovery World Winter 2009/10
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