Nanoscopy on the Chea(i)p

Super-resolution microscopy allows for stunning images with a resolution well beyond the optical diffraction limit, but the imaging techniques are demanding in terms of instrumentation and software. Using scientific-grade cameras, solid-state lasers and top-shelf microscopy objective lenses drives the price and complexity of the system, limiting its use to well-funded institutions. However, by harnessing recent developments in CMOS image sensor technology and low-cost illumination strategies, super-resolution microscopy can be made available to the mass-markets for a fraction of the price. Here, we present a 3D printed, self-contained super-resolution microscope with a price tag below 1000 $ including the objective and a cellphone. The system relies on a cellphone to both acquire and process images as well as control the hardware, and a photonic-chip enabled illumination. The system exhibits 100nm optical resolution using single-molecule localization microscopy and can provide live super-resolution imaging using light intensity fluctuation methods. Furthermore, due to its compactness, we demonstrate its potential use inside bench-top incubators and high biological safety level environments imaging SARS-CoV-2 viroids. By the development of low-cost instrumentation and by sharing the designs and manuals, the stage for democratizing super-resolution imaging is set.B.S.A. acknowledges funding from European Commission ERC Starting Grant (336716) and ERC PoC 957464 and ), Research Council of Norway (Grant 288565). We acknowledge funding by the DFG Transregio Project TRR166, TP04 (PT) and the Leibniz ScienceCampus InfectoOptics SAS-2015-HKI-LWC (AJ). The authors further acknowledge the support of this work by a grant from the IZKF (ACSP02) (SDE). The study was further funded by the Deutsche Forschungsge-meinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2051, Project-ID 390713860). This work was financially supported by the Deutsche Forschungsge- 10 meinschaft through the Cluster of Excellence “Balance of the Microverse” under Germany’s Excellence Strategy – EXC 2051 – Project-ID 690 390713860. We thank Fatina Siwczak and Swen Carlstedt for fruitful discussions. We further thank Merete Storflor and S¨oren Abel (Infection Biology Research Group, UiT) for providing the Ecoli samples and Deanna Wolfson (Optics group, UiT) for help with preparation of the Ecoli samples. We would like to thank Sindy Burgold-Voigt and Ralf Ehricht from Leibniz IPHT Jena for their great methodical contribution and the fruitful discussions. We thank especially Ingo Fuchs who helped a lot in understanding the principles of the acquisition process of cellphone cameras as well as his support of the software design. Pablo Carravilla acknowledges the Basque Government postdoctoral program (POS 2019 2 0022) for funding his position. pMDLg/pRRE and pRSV-Rev were a gift from Didier Trono (Addgene plasmid #12251 and #12253; http://n2t.net/addgene:12251 and http://n2t.net/addgene:12253; RRID:Addgene 12251 and RRID:Addgene 12253). K.O.S is supported by a Career fellowship from the South-Eastern Norway Regional Health AuthorityN