Tampere University achieves long-term imaging of living cells

A new lensless imaging method developed by Tampere University is intended to image living cells without additional staining, and do so over extended lengths of time while cell cultures grow.

Described in Applied Physics Letters the device is compact enough to be placed inside standard cell-culture incubators and then monitor the living cells continuously for hours or days. 

Data gathered this way is important because of the value in long-term, uninterrupted and label-free monitoring of large numbers of individual cells, commented the Tampere team. Doing so produces quantitative information about the behaviour of separate cells, rather than only capturing the average behaviour of a larger cell population.

Tampere based its technique on quantitative phase imaging (QPI), in which variations to the phase shift of light, rather than its conventional absorption or reflectance, are used to gather data suitable for conversion into contrast differences for imaging purposes.

Advances in QPI are closely connected to developments in computational methods and data processing, and hence to the application of AI models to the task. In 2025 a team at Germany's HZDR center exploited the usually undesirable chromatic aberrations in optical data as the basis for QPI, described at the time as "a clever combination of physics and generative AI."

Tampere set out to address two particular limitations of quantitative phase imaging. One is that conventional QPI methods typically rely on large and complex microscope systems that are not well suited for long-term monitoring inside a cell-culture incubator.

A second hurdle to recovering phase information in lensless systems is the challenging computational problem that this poses, one that has traditionally required multiple images or additional optical components.

The result is SF-PULSE, a lensless quantitative phase imaging method which combines an AI-based neural network with physics-informed image reconstruction.

Development of new biomedical instrumentation

"Our SF-PULSE method can reconstruct quantitative phase information from a single measurement image without the need for complex optical hardware," commented Igor Shevkunov from Tampere University. "The method reduced computational errors, improved reconstruction stability and enabled accurate long-term tracking of individual cells."

In trials SF-PULSE monitored cell cultures for 46 hours, using data derived from phase-shift to determine cell masses and correlating dynamic variations in the refractive index to changes in the cells. Individual cells could be tracked through the course of their development cycles, with SF-PULSE detecting when cell death was underway. 

Rather than simply providing another imaging modality, SF-PULSE has the potential to enable entirely new types of biological experiments, according to the Tampere project. The method could support applications such as drug-response studies, toxicity screening and investigations of cell-death mechanisms.

Because the system is compact, lensless and capable of monitoring hundreds or even thousands of cells simultaneously across a wide field of view, it could also be used for automated biological analytics and the development of new biomedical instrumentation in the future.

"Importantly, researchers can follow not only how a cell population changes, but also how individual cells grow, move, divide, and gain or lose biomass over time," noted Tampere's Meenakshisundaram Kandhavelu. "This is often more informative than examining the average behaviour of a cell population alone."