Structured illumination microscopy (SIM) enables live-cell super-resolution imaging of subcellular structures at high speeds. At present, linear SIM uses free-space optics to illuminate the sample with the desired light patterns; however, such arrangements are prone to misalignment and add cost and complexity to the microscope. Here, we present an alternative photonic chip-based two-dimensional SIM approach (cSIM) in which the conventional glass sample slide in a microscope is replaced by a planar photonic chip that importantly both holds and illuminates the specimen. The photonic chip reduces the footprint of the light illumination path of SIM to around 4 × 4 cm2. An array of optical waveguides on the chip creates standing wave interference patterns at different angles, which illuminate the sample via evanescent fields. High-refractive-index silicon nitride waveguides allow a 2.3 times enhancement in imaging spatial resolution, exceeding the usual 2 times limit of SIM. In summary, cSIM offers a simple, stable and affordable approach for performing two-dimensional super-resolution imaging over a large field of view.
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The data associated with the figures and Supplementary information can be obtained at https://github.com/UiTcSIM/cSIM.git.
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We thank R. Heintzmann and S. Das for help with the SIM reconstruction algorithms and design of the fibre-optical phase modulator, respectively. We also acknowledge C. I. Øie and D. Wolfson for help with biological specimens and T. Huser for fruitful conceptual discussions. This work was supported by the European Research Council (grant no. 336716 to B.S.A.).
B.SA. and O.G.H. have applied for patent GB1705660.7 on SIM-on-chip. B.S.A. and Ø.I.H. are founders of Chip NanoImaging (https://www.chipnano.com/) that is commercializing SIM-on-chip technology. The other authors declare no competing interests.
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Helle, Ø.I., Dullo, F.T., Lahrberg, M. et al. Structured illumination microscopy using a photonic chip. Nat. Photonics 14, 431–438 (2020). https://doi.org/10.1038/s41566-020-0620-2
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Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences (2021)