Expert view: Addressing the big challenges in cell-based assays

As the drug discovery industry takes on the complex disease states that plague our world, the need for more relevant and timely answers from cell-based assays has become a major challenge.

Facets of this challenge include physiological relevance, data content per assay, and turning the resulting data content into actionable answers quickly, which ultimately leads to better iterative decisions in shorter timeframes.

To drive relevance and content, the use of primary cells, complex co-cultures, induced pluripotent stem cells, and specific microenvironments like 3D assays are being developed and used at an increased pace across the industry. One example is creating more comprehensive immune cell functional assays that combine cell immuno-phenotyping of critical subpopulations, functional assessment of those subpopulations (health, activation, killing potential), and simultaneous multiplexed cytokine profiling in every well.

Another example is the use of macro-cellular structures called spheroids to reproduce the spatial and temporal microenvironment of tumours or tissues, thus producing more physiologically relevant responses from the cells when exposed to potentially therapeutic molecules. Of course, any assay that cannot be reproducibly created and measured at moderate to high throughput has little value to drug discovery, so Sartorius addresses this need with the IntelliCyt iQue Screener PLUS for suspension cell and bead analysis.

Enabling the high-content assays above creates a significant challenge to rapidly turn all the data into straightforward, actionable answers. Plate-level analytics, like generating dose-response curves and standard curves, are needed to determine levels of compound potency, specificity and toxicity. Methods for combining multiplexed assay outputs into desired activity ‘profiles’ and the ability to visualise ‘hit wells’ across plates are required to compare, identify, and rank molecules that move forward. Sartorius platforms include these key features.

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