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DOE:Layout 1 14/1/10 19:54 Page 44
Assays
factors considered in this analysis were greater
Figure 7: Most useful type of DOE training than three, ie all options were considered needed
(ie desirable) to drive greater uptake of DOE.
Fully integrated approach on-site 42%
Overall these findings suggest that the current
Biology application(s) specific 35%
DOE offerings and the way in which they are
Software package specific 12% offered to assay developers (eg mainly as stand-
Liquid handler specific 7% alone components) does not currently meet their
Fully integrated approach off-site 5%
needs and there is a significant vendor disconnect
in this respect.
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%
No. responding (all respondents)
Other applications of DOE
© HTStec 2009
In addition to AD, survey respondents were asked
to comment on other drug discovery-related areas
where DOE approaches might be usefully applied
Figure 8: What is most needed to drive wider uptake
(Figure 9). Optimising liquid handler dispensing
settings was the area where the majority (38%) of
and greater use of DOE
respondents plan to implement DOE. This was fol-
lowed by optimising reader settings and cell culture
Better understanding/greater knowledge of DOE 4.02
media optimisation (both equal at 31% respond-
Easier implementation 3.79
ing); then sample preparation (26% responding)
Easier interpretation of data 3.60
and protein expression (21% responding).
Software that directly links the statistical design and automated liquid
3.57
handler programming
DOE training courses that focus on screening and biology applications 3.53
Latest liquid handling tools for DOE
Biology specific versions of DOE software 3.53
The following vendor snapshots provide details of
some of the latest liquid handling tools that sup-
An integrated total solution 3.47
Better dispensing systems, suited to multiple reagents with minimal
port DOE in AD:
3.40
dead volume
Software that links assay readout with statistical analysis 3.39
Beckman Coulter (www.beckman.com) pioneered
Greater applicability to cell-based assays 3.35
assay optimisation using DOE on the Biomek®
1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00
2000 Liquid Handling Workstation with the intro-
Rating SCORE 1 to 5 (where 1 = least needed and 5 = most needed)
duction of SAGIAN™ Automated Assay
© HTStec 2009
Optimization (AAO) software, developed in col-
laboration with SmithKline Beecham in 1999. The
AAO software was later adapted to the Biomek FX
Figure 9: Areas other than assay development where
instrument to take advantage of the FX’s individual
eight-channel pipetting head to significantly
respondents plan to implement DOE
increase pipetting speed over the Biomek 2000
workstation. The latest adaptation of the AAO
Optimising liquid handler dispensing settings 38%
software is a version for Beckman Coulter’s
Optimising reader settings 31%
Cell culture media optimisation 31% BioRAPTR™ Microfluidic Dispenser. The
Sample preparation 26%
BioRAPTR can deliver up to eight different
Protein expression 21%
Protein crystallisation 14%
reagents simultaneously to the wells of high-densi-
Other 12% ty microplates. The system executes accurate, con-
Formulation development 10%
tact-free dispensing of the reagents for volumes
High throughput mutagenesis 5%
Mass spectrometry 5%
ranging between 100nL and 60µL into an entire
Metabolomics 2%
experiment plate in just a few minutes. The
0% 5% 10% 15% 20% 25% 30% 35% 40%
BioRAPTR AAO software supports both 384- and
% Responding
1536-well formats which enables assay developers
© HTStec 2009
to explore a wide range of assay factors allowing
thousands of experimental conditions to be tested
simultaneously, effectively enabling the use of com-
plex response surface designs for rapid assay opti-
misation. The AAO software provides a ‘Wizard-
Style’ interface to translate DOE design tables from
the most common statistical software packages
44 Drug Discovery World Winter 2009/10
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