Cornell researchers describe faster imaging method for tracking cell metabolism

Cornell University researchers described a faster way to track metabolism in living cells on October 9, 2026, reporting in Ithaca, New York, on a microscopy study published the previous month. The laboratory method could help researchers follow changing cancer-cell behavior, although its proposed use in screening treatments has yet to be demonstrated.

The study, published in Science Advances on September 4, introduces two-photon fluorescence polarization ratiometric microscopy, or FPRM. The authors report that it measures a signal associated with cellular metabolic status more than an order of magnitude faster than fluorescence lifetime imaging microscopy, a commonly used comparison method. That speed comparison concerns the measurement method; it does not establish faster drug development or better patient outcomes.

How the new method reads cell metabolism

The method focuses on NADH, a molecule involved in transferring energy within cells. Researchers can learn about a cell’s metabolic state by examining how much NADH is bound to proteins and how much is unbound. Cornell’s account says fluorescence lifetime imaging microscopy, or FLIM, makes that distinction by measuring the delay between exciting molecules with light and detecting their fluorescence.

FPRM takes a different measurement. A laser-scanning microscope directs polarized, focused light across cells. A beam splitter sends the resulting fluorescence to two detectors at the same time. The balance between their readings indicates how the fluorescent molecules rotate, according to Cornell’s explanation of the technique.

Co-lead author Jack Crowley told Cornell the approach can provide information similar to FLIM with less light and in less time. The difference matters for experiments that repeatedly image the same cells: Cornell says prolonged light exposure can stress cells, making it harder to relate their movement to changes in metabolism.

What the laboratory experiments showed

The study reports that FPRM measurements followed expected metabolic changes after pharmaceutical and environmental perturbations. Its authors also correlated the measurements with cell shape and movement in both two-dimensional and three-dimensional collagen matrices. These are research models used to examine cell behavior, including questions about cancer metabolism.

The paper describes its ratiometric parameters as instrument-independent. That is a claim about how its measurements can be expressed across equipment, not evidence that every laboratory could immediately adopt the technique. Cornell reports that the team needed new analysis and calibration methods, as well as numerous control experiments, because the resulting data were difficult to interpret.

Lu Ling and Crowley are identified as co-lead authors. Ling began the project while working in Claudia Fischbach’s Cornell laboratory and later continued postdoctoral research at the University of California, Berkeley. Cornell says the team wanted a way to follow cancer-cell metabolism as it changes over minutes or hours, alongside observations of how individual cells move.

Potential uses and unresolved questions

The distinction between a faster measurement and a faster treatment screen is significant. The published work demonstrates the imaging approach in cells and engineered tissue models. Neither the study nor Cornell’s account establishes that FPRM has already accelerated a therapeutic screening programme, guided a clinical decision or improved outcomes for patients.

Cornell says two-photon imaging may also be useful in complex three-dimensional research systems, including organoids and model organisms. Crowley suggested that simpler measurement strategies could give more researchers ways to observe dynamic responses in such systems. Those possibilities remain proposed uses; the reported experiments do not measure how widely laboratories will adopt the method or what it would cost them.

For now, the result gives researchers another way to examine a question that conventional snapshots can miss: how metabolism changes while a living cell moves through its surroundings. Whether that added view improves drug testing will require evidence beyond the laboratory demonstrations reported in the September paper.