Phase Holographic Imaging

Tracking cell movement with the HoloMonitor time-lapse cytometer.

With traditional cytometry it is difficult to study cellular behavior over time. Time-lapse cytometry combines time-lapse microscopy and image cytometry to give biologists a new tool for studying and understanding cellular dynamics.

Due to the difficulties in keeping cells healthy while maintaining good image quality, time-lapse video microscopy of living cells has in the past been only for the most determined cell biologists. Modern computer technology is, however, about to revolutionize the way cells are imaged and quantified in vitro.

In fact, the device that lets you read this article probably contains all the essential low-cost components needed to effortlessly image and measure a large number of cells individually over long time periods.

The availability of light sensitive, high resolution, digital image sensors, light emitting diodes (LED) and high speed computers now allow microscopes to be adapted to an environment suited for cells (Liu & Nolan 2012 Er Liu and John P. Nolan, 2012, 'Light emitting diodes: Light engines to simplify and economize advanced micro­scopy', Cytometry Part A, vol. 81A, no. 3, pp. 185-187., Piston 2009 David W. Piston, 2009, 'The impact of technology on light micro­scopy', Nature Milestones — light microscopy.) — not the opposite, as is presently the case.

Tracking cell area with the HoloMonitor time-lapse cytometer.

Time-lapse cytometry

Modern static image cytometry/high content analysis is non-destructive in the sense that cells can be observed directly in a cell culture vessel, making cytometry easy and visual. However, the true power of image cytometry first emerges when several images of the same cells are recoded over time.

Time-lapse cytometry allows cultured cells to be continuously monitored before and after treatment, minute by minute. By, for example, measuring individual cell volume and cell morphology, the developing health status of a treated cell culture can be studied repeatedly without removing it from the cell culture vessel.

There is no longer a need for laborious assays which destroy the sample to only give dry and non-intuitive measurements. With time-lapse cytometry, cytometric data can be accompanied with supporting videos which visualize how cancer cells shrivel up and die after being treated with a cancer drug, for example.

The visual information can answer questions like — Did the cells really shrivel up or did they die in an apoptotic explosion?. Unlike flow cytometry, time-lapse cytometry will immediately give an answer to such questions by simply looking at the cells when they die. This is the true power of time-lapse cytometry — the combination of quantitative and visual data collected over time.