Discussion

The High Throughput Biomedicine (HTB) unit at Institute for Molecular Medicine Finland (FIMM) is housing three Labcyte Echo liquid handlers, two 550s and one 525. Over the almost five years of operation we have successfully utilized acoustic dispensing in various projects covering several topics from genome wide RNA interference to viral targets. The substances commonly transferred with the instruments are siRNAs in solution and small molecule compound collections in DMSO.
One of the success stories is a screening platform for direct ex vivo drug sensitivity and resistance testing (DSRT) developed together with research groups at FIMM. The platform allows testing the functional and phenotypic response of primary cancer cells to a broad range of anti-cancer compounds and therefore identifies an individualized cancer therapy profile. This has been done for more than 100 primary patient samples from patients with leukemia, myeloma, ovarian cancer and glioma. The DSRT screening panel (seven 384-plates) contains 462 approved and investigational oncology compounds representing the active substances of almost all approved small molecule oncology drugs covering major investigational oncology drug classes.
All compounds are tested over a 10,000-fold concentration range to generate quantitative and reliable dose-response data. Utilization of acoustic dispensing technology allows us to reliably provide these compound plates to researchers in an assay-ready format. The assay has also successfully been adapted to a 1536-well plate format and we are actively developing informatics solutions to set up strategic drug combination testing and to analyse the results. Furthermore, to gain maximal understanding of the cellular responses, the cell lysates from the DSRT assays are followed up in ultra-miniaturized homogenous and reverse phase microarray assays following protein markers using Echo dispensers.