Microscopy of cells for examining changes in their internal structure is at the heart of diagnostics for many diseases. The holy grail of diagnosis—early detection of onset of pathologies—is, however, almost entirely dependent on chemical detection of biomarkers. Disease diagnosis is essentially an inverse problem that inherently suffers from non-uniqueness. To increase the probability of uniqueness, one necessarily needs to examine orthogonal sets of evidences or effects of the disease. Cells as micro-scale structures undergo considerable internal physical change due to onset of pathologies. These structural changes affect the mechanical response of cells that can be measured and used as probes for internal changes. One such mechanical response is the natural vibration of a cell. Natural frequencies are so unique to every structure that any change in the structure is quite faithfully reflected in the measured frequency. The resolution of changes in the natural frequency depends on the measurement technique.
Laser Doppler vibrometry is a powerful technique for recording vibration data from structures. We have developed a method that uses this vibrometry to probe changes in the internal structure of cells due to onset of pathologies. We use cells as mechanical structures, excite them using base excitation, and record their oscillations non-invasively using a laser beam. We have carried out experiments on muscle cells of lab-raised drosophila with controlled mutations in order to introduce certain myopathies, and shown that the change in the very first natural frequency is extremely well correlated with different myopathies. This correlation provides a tool for internal structural changes as an indirect microscopy of the cell. We have been able to identify myopathies unambiguously in several blind tests. Our results are also corroborated with independent confocal microscopy. This technique promises to be a powerful tool for disease diagnostics based on this mechano-microscopy of cells.