Living 3D in vitro tissue cultures, grown from immortalized cell lines, act as living sentinels as pathogenic bacteria invade the tissue. The infection is reported through changes in the intracellular dynamics of the sentinel cells caused by the disruption of normal cellular function by the infecting bacteria. Here, the Doppler imaging of infected sentinels shows the dynamic characteristics of infections. Invasive Salmonella enterica serovar Enteritidis and Listeria monocytogenes penetrate through multicellular tumor spheroids, while non-invasive strains of Escherichia coli and Listeria innocua remain isolated outside the cells, generating different Doppler signatures. Phase distributions caused by intracellular transport display Lévy statistics, introducing a Lévy-alpha spectroscopy of bacterial invasion. Antibiotic treatment of infected spheroids, monitored through time-dependent Doppler shifts, can distinguish drug-resistant relative to non-resistant strains. This use of intracellular Doppler spectroscopy of living tissue sentinels opens a new class of microbial assay with potential importance for studying the emergence of antibiotic resistance.

Tumor heterogeneity is one of the greatest obstacles standing in the way of successful cancer therapy. Cancer in a single patient is not a single disease, but is a host of related diseases, all of which need to respond to a single treatment regimen. We have completed the first human clinical trial in esophageal cancer using dynamic-contrast OCT (DC-OCT) based on full-frame digital holography to assess the spatial heterogeneity of biopsy response to platinum-based chemotherapy. A deep twin neural network successfully identified biopsy sub-phenotypes in the dynamic tissue response that enabled accurate prediction of patient treatment success.

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