Optical diffraction tomographic microscopy: a cutting-edge label-free three-dimensional bioimaging

Optical diffraction tomographic microscopy (ODTM) is an advanced label-free three-dimensional optical microscopic imaging technique. It measures the three-dimensional refractive index (RI) distributions of unstained, transparent biological specimens with high resolution from scattered fields based on the diffraction tomography theorem. Both the morphological and biophysical parameters, as well as the internal organelles of the specimen, can be further analyzed from the measured RI values. ODTM has been increasingly employed in the field of biology, yielding numerous promising results. In order to further promote the application and popularization of this technology in biological research, we provide a tutorial on the fundamental principles and instrumentation of ODTM. The distinct characteristics of ODTM using various illumination strategies and reconstruction algorithms are presented. Observation results from single cells, tissues, and small-scale biological objects are shown to demonstrate the superior performance of ODTM. Current trends and future perspectives of ODTM are discussed.