Label-free 3D Refractive Index Tomography of Live Cancer Cells by Digital Holographic Microscopy

Tomographic phase optical microscopy (TPM) is a well-known technique for imaging cells without staining and visualizing their inherent 3-D refractive index profile. Most TPM techniques are implemented by scanning the illumination of a cell adhered to a slide. This method incorporates inability to measure high spatial frequencies (missing apple-core). Common solution to this problem is sample rotating, mostly done with expensive equipment. Here we proposed a new, low-cost TPM approach that provides a full 3-D refractive-index distribution of single cells in suspension. The cells are inserted into a capillary and trapped in a low-density gel. Rotation is done mechanically. This system is plugged into an interferometer and projections are acquired and processed into the cellular 3-D refractive-index map. The novelty of this method is the full 360° coverage of the cell examined, and knowledge of the viewing angle at each time point, all in a simple low-cost assembly. This technique is expected to be useful for label-free cell sorting and a powerful tool for widening cell probing, since it can be incorporated in many types of optical systems and cell types.