Lensfree Optical Tomographic Microscope with a Large Imaging Volume on a Chip published in PNAS (2011)

By S.O Isikman , W. Bishara , S. Mavandadi , F. Yu , S. Feng , R. Lau and A. Ozcan (2011)

We present a lens-free optical tomographic microscope, which enables imaging a large volume of approximately 15 mm3 on a chip, with a spatial resolution of < 1 ?m × < 1 ?m × < 3 ?m in x, y and zdimensions, respectively. In this lens-free tomography modality, the sample is placed directly on a digital sensor array with, e.g., ? 4 mm distance to its active area. A partially coherent light source placed approximately 70 mm away from the sensor is employed to record lens-free in-line holograms of the sample from different viewing angles. At each illumination angle, multiple subpixel shifted holograms are also recorded, which are digitally processed using a pixel superresolution technique to create a single high-resolution hologram of each angular projection of the object. These superresolved holograms are digitally reconstructed for an angular range of ± 50°, which are then back-projected to compute tomograms of the sample. In order to minimize the artifacts due to limited angular range of tilted illumination, a dual-axistomography scheme is adopted, where the light source is rotated along two orthogonal axes. Tomographic imaging performance is quantified using microbeads of different dimensions, as well as by imaging wild-type Caenorhabditis elegans. Probing a large volume with a decent 3D spatialresolution, this lens-free optical tomography platform on a chip could provide a powerful tool for high-throughput imaging applications in, e.g., cell and developmental biology.