Automated Ultra-Fast High Content Imaging Enables High Throughput Live Cell Assays with Submicron Resolution
By Matthew Boisvert (PhD) and Martin Theiss (PhD), Araceli Biosciences
The advantage of live cell assays
Live cell assays provide kinetic insight into dynamic cellular processes, following the same cells over time. End-point assays might overlook robust effects or come to erroneous conclusions because cells were fixed too early or late. Further, fixation distorts cell morphology and induces artifacts. Therefore, a live cell assay should be the gold standard for looking at biological processes (e.g. protein translocation, cell killing, and drug responses).
The challenges of scaling up live cell assays
Live cell imaging with good sample coverage and resolution is limited by acquisition speed and instrument availability: With 1-2 hours to acquire a plate, is the first well imaged in the same state as the last? Time constraints mean compromises, limiting time points and number of plates acquired on traditional instruments.
Summary
Here we demonstrate how to achieve scale with high resolution live cell imaging: The speed of the Araceli Endeavor Pro allows timepoint-based high content imaging at scale, with hourly and daily data. These hourly-imaged cells look less perturbed than if they were imaged with traditional high content imaging (HCI). Expanding on these capabilities, we show that live cell assays are possible with pooled screens, repetitively imaging a one-well plate with 100% well coverage in <20 minutes with single cell analysis of pooled cells. Automation can expand these capabilities further, imaging nearly 500 million cells in 24 hours at submicron resolution.