DOE:Layout 1 14/1/10 19:54 Page 45
Assays
Figure 10 (left): Screenshot of AAO for BioRAPTR™ software showing a randomised 1536-well plate map from a designed experiment that will translate
into reagent dispensing operations on the BioRAPTR Microfluidic Dispenser
Figure 11 (right): Beckman Coulter BioRAPTR™ is now available with automated assay optimisation software. This dispenser can be equipped with up to
eight different reagent bottles. Each well can be addressed individually for each reagent, allowing all possible combinations to be generated in one run. A
fully randomised 1536-plate with up to eight reagents per well in multiple concentrations can be generated within just a few minutes
into Biomek or BioRAPTR methods. The experi- inputs. This high-throughput device’s independent
mental design can be enhanced within AAO by channel control over all 96 channels enables it to
adding specific background wells for every set of dispense any volume of any input into any well of
experimental conditions. The software can also 96-, 384-, 1536-, or 3456-well plates. CVs below
create quality control wells such as positive or neg- 10%, a typical dead volume of 400µL, and a mini-
ative controls. Running the Biomek or BioRAPTR mum dispense volume of 200nL with no upper
methods and collecting data on a plate reader can limit make this an ideal instrument for high-
be interleaved with other operations necessary for throughput screening and precious sample dispens-
the assay such as shaking or incubation. This func- ing. The Tempest uses positive displacement instead
tionality allows inclusion of non-reagent experi- of pressurised bottles. The Formulator is a high-vis-
mental factors into the experimental design with cosity reagent dispenser with up to 34 different
no limitation to pipetting factors. Examples of reagent inputs, from either 50mL Falcon tubes or
non-reagent factors include incubation time and 125mL and 250mL Nalgene bottles. At the core of
temperature, plate shaking and wash protocols. the Formulator is a patent-pending microfluidic
AAO has been reported to significantly decrease chip that can measure and dispense discrete vol-
the time and cost of assay development as well as umes of liquid. The chip has 96 outputs each with
increase the robustness and sensitivity of high its own microfluidic valve cluster. Each valve clus-
throughput screens
2
. Biomek FX AAO has also ter has two micro-diaphragms (200nL and 2.5µL)
been successfully utilised in media optimisation for that can fill and dispense as fast as three times per
production cell lines of biopharmaceuticals
3
second. Combining multiple dispenses of each
(Figures 10 and 11).
Figure 12
Formulatrix (www.formulatrix.com) offers two liq-
Formulatrix Tempest liquid
uid handlers (the Tempest and the Formulator) that
handler
have potential utility for DOE. Both use microflu-
idic dispensing technology which provides these liq-
uid handlers with faster dispenses and a compact
design as compared to their traditional counter-
parts. The Tempest is a flexible reagent dispenser
that can dispense dilutions and factorial DOEs and
highly complex plate patterns from 12 reagent
Drug Discovery World Winter 2009/10 45
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