Lensfree On-chip Tomographic Microscopy Employing Multi-angle Illumination and Pixel Super-resolution

Tomographic imaging has been a widely used tool in medicine as it can providethree-dimensional (3D) structural information regarding objects of different size scales.In micrometer and millimeter scales, optical microscopy modalities find increasing useowing to the non-ionizing nature of visible light, and the availability of a rich set ofillumination sources (such as lasers and light-emitting-diodes) and detection elements(such as large format CCD and CMOS detector-arrays). Among the recently developed opticaltomographic microscopy modalities, one can include optical coherence tomography, opticaldiffraction tomography, optical projection tomography and light-sheet microscopy.^1-6 These platforms provide sectional imaging of cells, microorganisms andmodel animals such as C. elegans, zebrafish and mouse embryos.Existing 3D optical imagers generally have relatively bulky and complex architectures,limiting the availability of these equipments to advanced laboratories, and impeding theirintegration with lab-on-a-chip platforms and microfluidic chips. To provide an alternativetomographic microscope, we recently developed lensfree optical tomography (LOT) as ahigh-throughput, compact and cost-effective optical tomography modality. ⁷ LOTdiscards the use of lenses and bulky optical components, and instead relies on multi-angleillumination and digital computation to achieve depth-resolved imaging of micro-objectsover a large imaging volume. LOT can image biological specimen at a spatial resolution of<1 μm x <1 μm x <3 μm in the x, y and z dimensions, respectively, over a largeimaging volume of 15-100 mm³, and can be particularly useful for lab-on-a-chipplatforms.