Pursuing the Diffraction Limit with Nano-LED Scanning Transmission Optical Microscopy

Recent research into miniaturized illumination sources has prompted the development of alternative microscopy techniques. Although they are still being explored, emerging nano-light-emitting-diode (nano-LED) technologies show promise in approaching the optical resolution limit in a more feasible manner. This work presents the exploration of their capabilities with two different prototypes. In the first version, a resolution of less than 1 µm was shown thanks to a prototype based on an optically downscaled LED using an LED scanning transmission optical microscopy (STOM) technique. This research demonstrates how this technique can be used to improve STOM images by oversampling the acquisition. The second STOM-based microscope was fabricated with a 200 nm GaN LED. This demonstrates the possibilities for the miniaturization of on-chip-based microscopes.

[1]  He Zhang,et al.  Pixel super-resolved lens-free on-chip microscopy based on dual laterally shifting modulation. , 2020, Applied optics.

[2]  Qian Chen,et al.  Computational microscopy with programmable illumination and coded aperture , 2017, Other Conferences.

[3]  Dongmin Seo,et al.  A review of recent progress in lens-free imaging and sensing. , 2017, Biosensors & bioelectronics.

[4]  A. Tonomura,et al.  Principle and application of phase-shifting electron holography , 1994 .

[5]  Keng C Chou,et al.  Review of Super-Resolution Fluorescence Microscopy for Biology , 2011, Applied spectroscopy.

[6]  Aydogan Ozcan,et al.  Lensless digital holographic microscopy and its applications in biomedicine and environmental monitoring. , 2017, Methods.

[7]  Ningmei Yu,et al.  An on-chip instrument for white blood cells classification based on a lens-less shadow imaging technique , 2017, PloS one.

[8]  Fabien Momey,et al.  3D lens-free time-lapse microscopy for 3D cell culture , 2017, European Conference on Biomedical Optics.

[9]  J. Garcia-Sucerquia.  Color lensless digital holographic microscopy with micrometer resolution. , 2012, Optics letters.

[10]  Jerker Widengren,et al.  Stimulated Emission Depletion Microscopy. , 2017, Chemical reviews.

[11]  Aydogan Ozcan,et al.  Lensless Imaging and Sensing. , 2016, Annual review of biomedical engineering.

[12]  G. Cox.  Biological confocal microscopy , 2002 .

[13]  S. Hell,et al.  Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. , 1994, Optics letters.

[14]  José-Angel Conchello,et al.  Fluorescence microscopy , 2005, Nature Methods.

[15]  I. Underwood,et al.  Active-Matrix GaN Micro Light-Emitting Diode Display With Unprecedented Brightness , 2015, IEEE Transactions on Electron Devices.

[16]  A. Waag,et al.  Nano illumination microscopy: a technique based on scanning with an array of individually addressable nanoLEDs. , 2020, Optics express.

[17]  C. Lin,et al.  High Performance Ultraviolet Micro-LED Arrays for Fine-Pitch Micro Displays , 2019, 2019 IEEE Photonics Conference (IPC).

[18]  A. Ozcan,et al.  Pixel super-resolution using wavelength scanning , 2015, Light: Science & Applications.

[19]  Rainer Heintzmann,et al.  Super-Resolution Structured Illumination Microscopy. , 2017, Chemical reviews.

[20]  Jie Chao,et al.  Dark-field microscopy in imaging of plasmon resonant nanoparticles. , 2014, Colloids and surfaces. B, Biointerfaces.

[21]  D. Vobornik,et al.  Scanning near-field optical microscopy. , 2008, Bosnian journal of basic medical sciences.

[22]  A. Waag,et al.  Directly addressable GaN-based nano-LED arrays: fabrication and electro-optical characterization , 2020, Microsystems & nanoengineering.

[23]  Aydogan Ozcan,et al.  Wide field-of-view lens-free fluorescent imaging on a chip. , 2010, Lab on a chip.

[24]  L. Novotný,et al.  Nonlinear Dark-field Microscopy , 2022 .

[25]  H. Ewers,et al.  Expansion stimulated emission depletion microscopy (ExSTED) , 2018, bioRxiv.

[26]  M. R. Young.  Principles and Technique of Fluorescence Microscopy , 1961 .

[27]  J. Bowers,et al.  GaN-Based Miniaturized Cyan Light-Emitting Diodes on a Patterned Sapphire Substrate With Improved Fiber Coupling for Very High-Speed Plastic Optical Fiber Communication , 2012, IEEE Photonics Journal.

[28]  Laurent Cognet,et al.  Super-resolution microscopy approaches for live cell imaging. , 2014, Biophysical journal.

[29]  A. Ozcan,et al.  Deep learning in holography and coherent imaging , 2019, Light: Science & Applications.

[30]  A. Waag,et al.  Optical design of InGaN/GaN nanoLED arrays on a chip: toward: highly resolved illumination , 2020, Nanotechnology.

[31]  S. van de Linde,et al.  Light-induced cell damage in live-cell super-resolution microscopy , 2015, Scientific Reports.

[32]  A lens-free single-shot fluorescent imaging system using CMOS image sensors with dielectric multi-layer filter , 2017, 2017 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS).

[33]  Yan Feng,et al.  Resolution-Enhanced Lensless Color Shadow Imaging Microscopy Based on Large Field-of-View Submicron-Pixel Imaging Sensors , 2018, CVPR 2018.

[34]  François Templier,et al.  Influence of size-reduction on the performances of GaN-based micro-LEDs for display application , 2017 .

[35]  Kei May Lau,et al.  GaN-based LED micro-displays for wearable applications , 2015 .

[36]  A. Waag,et al.  Beyond solid-state lighting: Miniaturization, hybrid integration, and applications of GaN nano- and micro-LEDs , 2019, Applied Physics Reviews.

[37]  Juan I. Larruquert,et al.  Self-consistent optical constants of SiO 2 and Ta 2 O 5 films , 2016 .

[38]  R. Heintzmann.  Handbook of biological confocal microscopy , 2006 .

[39]  Huaxia Shen,et al.  Portable deep learning singlet microscope , 2020, Journal of biophotonics.

[40]  Ricardo Henriques,et al.  PALM and STORM: Unlocking live‐cell super‐resolution , 2011, Biopolymers.

[41]  J. Garcia-Sucerquia,et al.  Automatic three-dimensional tracking of particles with high-numerical-aperture digital lensless holographic microscopy. , 2012, Optics letters.

[42]  Ashok Veeraraghavan,et al.  Single-frame 3D fluorescence microscopy with ultraminiature lensless FlatScope , 2017, Science Advances.

[43]  Qian Chen,et al.  Adaptive pixel-super-resolved lensfree in-line digital holography for wide-field on-chip microscopy , 2017, Scientific Reports.

[44]  Shunro Fuke,et al.  Optical properties of hexagonal GaN , 1997 .

[45]  X. Gidrol,et al.  3D LENSFREE MICROSCOPY FOR 3D CELL CULTURE , 2019 .

[46]  Jun Ohta,et al.  Highly sensitive lens-free fluorescence imaging device enabled by a complementary combination of interference and absorption filters , 2018, Biomedical optics express.

[47]  Giancarlo Pedrini,et al.  Short-coherence digital microscopy by use of a lensless holographic imaging system. , 2002, Applied optics.

[48]  G. Fogazzi,et al.  Microscopic examination of urine sediment: Phase contrast versus bright field. , 2018, Clinica chimica acta; international journal of clinical chemistry.

[49]  H. Morkoç,et al.  Micro-LEDs, a Manufacturability Perspective , 2019, Applied Sciences.

[50]  Chun-Min Lo,et al.  High-resolution quantitative phase-contrast microscopy by digital holography. , 2005, Optics express.

[51]  Stephen W. Paddock,et al.  Confocal Microscopy , 2019, Methods in Molecular Biology.

[52]  Yicong Wu,et al.  Faster, sharper, and deeper: structured illumination microscopy for biological imaging , 2018, Nature Methods.

[53]  R. Dobarzić,et al.  [Fluorescence microscopy]. , 1975, Plucne bolesti i tuberkuloza.