Abstract

The use of Labcyte ECHO acoustic compound dispensing is
increasingly employed in academic research institutes for a wide range of assay
types and at The Institute of Cancer Research this has been very successful for
the majority of our screening assays. During initial screening against complex
3-D spheroid cultures involving co-culture of pancreatic stellate cells and
pancreatic cancer cells lines to model pancreatic desmoplasia we observed both
media dropout & extensive loss of spheroid integrity (10-20%) after
compound dispensing. We discovered that this loss was due to the rapid movement
of the upside down destination plate. To overcome this issue we developed
mirror image dispensing pattern protocols for primary screening assays and
concentration response experiments to reduce the destination plate movement.
Using these protocols the resulting media dropout rate was less than 1% across
the runs and the loss of 3-D spheroid integrity was eliminated. This has
increased our success rate across all our cell based assays & screens.
These protocols were a key enabler for screening of the AZ annotated library of
12500 compounds against our pancreatic desmoplasia 3-D spheroid model systems.
Our mirror image dispensing protocols will be invaluable for ensuring the
success of our increasingly complex drug screens involving 3-D spheroid and
organotypic cultures.