Ultrafast laser-scanning time-stretch imaging at visible wavelengths

Optical time-stretch imaging enables the continuous capture of non-repetitive events in real time at a line-scan rate of tens of MHz—a distinct advantage for the ultrafast dynamics monitoring and high-throughput screening that are widely needed in biological microscopy. However, its potential is limited by the technical challenge of achieving significant pulse stretching (that is, high temporal dispersion) and low optical loss, which are the critical factors influencing imaging quality, in the visible spectrum demanded in many of these applications. We present a new pulse-stretching technique, termed free-space angular-chirp-enhanced delay (FACED), with three distinguishing features absent in the prevailing dispersive-fiber-based implementations: (1) it generates substantial, reconfigurable temporal dispersion in free space (>1 ns nm−1) with low intrinsic loss (<6 dB) at visible wavelengths; (2) its wavelength-invariant pulse-stretching operation introduces a new paradigm in time-stretch imaging, which can now be implemented both with and without spectral encoding; and (3) pulse stretching in FACED inherently provides an ultrafast all-optical laser-beam scanning mechanism at a line-scan rate of tens of MHz. Using FACED, we demonstrate not only ultrafast laser-scanning time-stretch imaging with superior bright-field image quality compared with previous work but also, for the first time, MHz fluorescence and colorized time-stretch microscopy. Our results show that this technique could enable a wider scope of applications in high-speed and high-throughput biological microscopy that were once out of reach.

[1]  M. Shirasaki Large angular dispersion by a virtually imaged phased array and its application to a wavelength demultiplexer. , 1996, Optics letters.

[2]  H. Haus,et al.  Design and fabrication of double-chirped mirrors. , 1997, Optics letters.

[3]  A. S. Bhushan,et al.  Photonic time stretch and its application to analog-to-digital conversion , 1999 .

[4]  B Golubovic,et al.  Double Gires-Tournois interferometer negative-dispersion mirrors for use in tunable mode-locked lasers. , 2000, Optics letters.

[5]  Gerald F. Marshall,et al.  Handbook of Optical and Laser Scanning , 2004 .

[6]  William E. Ortyn,et al.  Cellular image analysis and imaging by flow cytometry. , 2007, Clinics in laboratory medicine.

[7]  A. Taylor,et al.  Ultrafast optical wide field microscopy , 2009, 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum electronics and Laser Science Conference.

[8]  B. Jalali,et al.  Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena , 2009, Nature.

[9]  Bahram Jalali,et al.  Performance of serial time-encoded amplified microscopy , 2010, CLEO/QELS: 2010 Laser Science to Photonic Applications.

[10]  Bahram Jalali,et al.  Giant tunable optical dispersion using chromo-modal excitation of a multimode waveguide. , 2011, Optics express.

[11]  Tae-Jung Ahn,et al.  Ultrarapid Optical Frequency-Domain Reflectometry Based Upon Dispersion-Induced Time Stretching: Principle and Applications , 2012, IEEE Journal of Selected Topics in Quantum Electronics.

[12]  K. Goda,et al.  Hybrid Dispersion Laser Scanner , 2012, Scientific Reports.

[13]  A. Schmid,et al.  Single-cell analysis in biotechnology, systems biology, and biocatalysis. , 2012, Annual review of chemical and biomolecular engineering.

[14]  Kevin K Tsia,et al.  Exploiting few mode-fibers for optical time-stretch confocal microscopy in the short near-infrared window. , 2012, Optics express.

[15]  Bahram Jalali,et al.  High-throughput single-microparticle imaging flow analyzer , 2012, Proceedings of the National Academy of Sciences.

[16]  S Choi,et al.  Development of a high speed laser scanning confocal microscope with an acquisition rate up to 200 frames per second. , 2013, Optics express.

[17]  Andrew Evans,et al.  Digital imaging in pathology: whole-slide imaging and beyond. , 2013, Annual review of pathology.

[18]  K. Goda,et al.  Dispersive Fourier transformation for fast continuous single-shot measurements , 2013, Nature Photonics.

[19]  Diego Gutierrez,et al.  Femto-photography , 2013, ACM Trans. Graph..

[20]  Bahram Jalali,et al.  Digitally-synthesized beat frequency multiplexing for sub-millisecond fluorescence microscopy , 2013 .

[21]  Ata Mahjoubfar,et al.  Label-free high-throughput cell screening in flow. , 2013, Biomedical optics express.

[22]  Yu Oishi,et al.  Sequentially timed all-optical mapping photography (STAMP) , 2014, Nature Photonics.

[23]  Peter Bechtold,et al.  Electro-optic and Acousto-optic Laser Beam Scanners , 2014 .

[24]  Yibo Zhang,et al.  Wide-field computational imaging of pathology slides using lens-free on-chip microscopy , 2014, Science Translational Medicine.

[25]  Edmund Y Lam,et al.  Interferometric time-stretch microscopy for ultrafast quantitative cellular and tissue imaging at 1 μm , 2014, Journal of biomedical optics.

[26]  Shizhong Xie,et al.  Multiwavelength time-stretch imaging system. , 2014, Optics letters.

[27]  Philipp S. Hoppe,et al.  Single-cell technologies sharpen up mammalian stem cell research , 2014, Nature Cell Biology.

[28]  Chiye Li,et al.  Single-shot compressed ultrafast photography at one hundred billion frames per second , 2014, Nature.

[29]  E. Lam,et al.  Speed-dependent resolution analysis of ultrafast laser-scanning fluorescence microscopy , 2014 .

[30]  Ata Mahjoubfar,et al.  Ultrafast dark-field surface inspection with hybrid-dispersion laser scanning , 2014 .

[31]  Edmund Y. Lam,et al.  Asymmetric-detection time-stretch optical microscopy (ATOM) for ultrafast high-contrast cellular imaging in flow , 2013, Scientific Reports.

[32]  H. Amini,et al.  Inertial microfluidic physics. , 2014, Lab on a chip.

[33]  Kenneth K Y Wong,et al.  28 MHz swept source at 1.0 μm for ultrafast quantitative phase imaging. , 2015, Biomedical optics express.

[34]  Cheng Lei,et al.  High-throughput optofluidic particle profiling with morphological and chemical specificity. , 2015, Optics letters.

[35]  Haohua Tu,et al.  Enhancement of optical coherence microscopy in turbid media by an optical parametric amplifier , 2015, Journal of biophotonics.

[36]  Stephan J Sigrist,et al.  Ultrafast, temporally stochastic STED nanoscopy of millisecond dynamics , 2015, Nature Methods.

[37]  Cheng Lei,et al.  Optical time-stretch imaging: Principles and applications , 2016 .

[38]  Kenneth K. Y. Wong,et al.  Optical Time Stretch for High-Speed and High-Throughput Imaging—From Single-Cell to Tissue-Wide Scales , 2016, IEEE Journal of Selected Topics in Quantum Electronics.

[39]  Ho Cheung Shum,et al.  Ultrafast Microfluidic Cellular Imaging by Optical Time-Stretch. , 2016, Methods in molecular biology.