Optical imaging reads individual immune-cell metabolism in a lab study

A microscope looks at immune cells drawn from blood, without staining them or taking them apart. In Madison, the Skala Lab at the Morgridge Institute used optical metabolic imaging to distinguish activated from quiescent individual immune cells in complex blood-cell samples—a result the team reports with 93% accuracy two hours after stimulation.

The cells were peripheral blood mononuclear cells, or PBMCs, a group made up predominantly of immune cells and already isolated in standard clinical workflows. Earlier metabolic measurements generally required researchers to separate cell types or add chemical labels. OMI instead directs two long-wavelength photons at the sample, exciting the natural fluorescence of products created by cell metabolism; the microscope can then read whether a cell is active or quiescent while leaving it intact.

The study, led by biomedical engineer Melissa Skala with Ph.D. student Jeremiah Riendeau, also reported 96% accuracy for quiescent monocytes, 88% for activated monocytes and 74% for natural killer cells in both states. The samples came from three human volunteers. Label-based methods can reach up to 100% accuracy, but they may harm the cells, while OMI allows the same sample to be monitored over time or used in later experiments.

In practical terms, that preserved sample could help researchers and, eventually, clinical teams assess the fitness of immune cells before they are processed for treatments such as CAR T therapy, which engineers a patient’s own cells to fight certain cancers. It could also add functional information to the cell counts used in work on blood cancers, lupus, sepsis and cognitive decline. Those applications are prospective, not current clinical services.

The remaining obstacle is access. Two-photon microscopes are not available in every laboratory, Riendeau says, so the Skala Lab and its collaborators are working to make the measurement more widely available and are pursuing commercialization. The team hopes to work with hospital collaborators to develop clinical applications; for now, the evidence comes from a laboratory study on donated human samples.