Optical Time Stretch for High-Speed and High-Throughput Imaging—From Single-Cell to Tissue-Wide Scales

Lau, Andy K. S.; Tang, Anson H. L.; Xu, Jianbin; Wei, Xiaoming; Wong, Kenneth K. Y.; Tsia, Kevin K.

doi:10.1109/jstqe.2015.2512978

Cited by 14 publications

(10 citation statements)

References 118 publications

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“…An all‐optical wavelength‐swept source is used for multi‐ATOM. This is based on a home‐built, and cost‐effective all‐normal dispersion (ANDi) laser [center wavelength = 1,064 nm, bandwidth = 15 nm, and repetition rate = 11.8 MHz] generates the pulse train (pulse width = ~12 ps), which is then stretched in time by a 10‐km single‐mode fiber (a total GVD = 0.38 ns/nm [Nufern, East Granby, CT]) and optically amplified by a ytterbium‐doped fiber amplifier module (output power = 36 dBm, on–off power gain = 36 dB). A diffraction grating (groove density = 1,200/mm, Littrow angle = 42.3°) spatially disperses the time‐stretched pulses to generate a one‐dimensional (1D) spectral shower.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Phase Imaging Flow Cytometry for Ultra‐Large‐Scale Single‐Cell Biophysical Phenotyping

et al. 2019

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Cellular biophysical properties are the effective label‐free phenotypes indicative of differences in cell types, states, and functions. However, current biophysical phenotyping methods largely lack the throughput and specificity required in the majority of cell‐based assays that involve large‐scale single‐cell characterization for inquiring the inherently complex heterogeneity in many biological systems. Further confounded by the lack of reported robust reproducibility and quality control, widespread adoption of single‐cell biophysical phenotyping in mainstream cytometry remains elusive. To address this challenge, here we present a label‐free imaging flow cytometer built upon a recently developed ultrafast quantitative phase imaging (QPI) technique, coined multi‐ATOM, that enables label‐free single‐cell QPI, from which a multitude of subcellularly resolvable biophysical phenotypes can be parametrized, at an experimentally recorded throughput of >10,000 cells/s—a capability that is otherwise inaccessible in current QPI. With the aim to translate multi‐ATOM into mainstream cytometry, we report robust system calibration and validation (from image acquisition to phenotyping reproducibility) and thus demonstrate its ability to establish high‐dimensional single‐cell biophysical phenotypic profiles at ultra‐large‐scale (>1,000,000 cells). Such a combination of throughput and content offers sufficiently high label‐free statistical power to classify multiple human leukemic cell types at high accuracy (~92–97%). This system could substantiate the significance of high‐throughput QPI flow cytometry in enabling next frontier in large‐scale image‐derived single‐cell analysis applied in biological discovery and cost‐effective clinical diagnostics. © 2019 International Society for Advancement of Cytometry

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Section: Methodsmentioning

confidence: 99%

Quantitative Phase Imaging Flow Cytometry for Ultra‐Large‐Scale Single‐Cell Biophysical Phenotyping

et al. 2019

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“…Note that we concern ourselves with ultrafast imaging techniques focusing on timeresolved light transport, recording either a single bounce (e.g., for LIDAR applications), or multiple scattering. Other impulse-based ultrafast imaging techniques, e.g., based on pulse stretching [Nakagawa et al 2014;Lau et al 2016], are not discussed in this work.…”

Section: Straight Temporal Recordingmentioning

confidence: 99%

Recent advances in transient imaging: A computer graphics and vision perspective

et al. 2017

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Figure 1: Left: In 1964, Harold Edgerton captured the iconic Bullet Through Apple image ( c MIT Museum). The bullet traveled at about 850 m/s, which translated into an exposure of approximately 4-10 millionth of a second. Right: Almost 50 years later, the femto-photography technique was introduced [Velten et al. 2013], capable of capturing light in motion, with an effective exposure time of one trillionth of a second. The large split image is a composite of the three complete frames shown in the insets. The complete videos of this and other scenes can be downloaded from AbstractTransient imaging has recently made a huge impact in the computer graphics and computer vision fields. By capturing, reconstructing, or simulating light transport at extreme temporal resolutions, researchers have proposed novel techniques to show movies of light in motion, see around corners, detect objects in highly-scattering media, or infer material properties from a distance, to name a few. The key idea is to leverage the wealth of information in the temporal domain at the pico or nanosecond resolution, information usually lost during the capture-time temporal integration. This paper presents recent advances in this field of transient imaging from a graphics and vision perspective, including capture techniques, analysis, applications and simulation.

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“…In this way, the imaging scan-rate is determined by the laser repetition rate, which can typically be MHz or even GHz [18]. The light source was a home-built broadband (~10 nm) mode-locked fiber laser centered at the wavelength of 1060 nm.…”

Section: Time-stretch Imaging Systemmentioning

confidence: 99%

“…The light source was a home-built broadband (~10 nm) mode-locked fiber laser centered at the wavelength of 1060 nm. The laser repetition rate, or equivalently the line-scan rate, is 11MHz with a high pulseto-pulse stability (~1% fluctuation in pulse intensity) [18]. The laser pulses from the modelocked laser were amplified by a custom ytterbium-doped fiber amplifier module and then time-stretched by a 20-km long single-mode fiber (with an average GVD of 0.54 ns/nm).…”

Section: Time-stretch Imaging Systemmentioning

confidence: 99%

Time-stretch microscopy on a DVD for high-throughput imaging cell-based assay

Tang¹,

Yeung²,

Chan³

et al. 2017

Biomed. Opt. Express

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Cell-based assay based on time-stretch imaging is recognized to be well-suited for high-throughput phenotypic screening. However, this ultrafast imaging technique has primarily been limited to suspension-cell assay, leaving a wide range of solid-substrate assay formats uncharted. Moreover, time-stretch imaging is generally restricted to intrinsic biophysical phenotyping, but lacks the biomolecular signatures of the cells. To address these challenges, we develop a spinning time-stretch imaging assay platform based on the functionalized digital versatile disc (DVD). We demonstrate that adherent cell culture and biochemically-specific cell-capture can now be assayed with time-stretch microscopy, thanks to the high-speed DVD spinning motion that naturally enables on-the-fly cellular imaging at an ultrafast line-scan rate of >10MHz. As scanning the whole DVD at such a high speed enables ultra-large field-of-view imaging, it could be favorable for scaling both the assay throughput and content as demanded in many applications, e.g. drug discovery, and rare cancer cell screening. Balakrishnan, C.-Y. Wang, P. Yaswen, A. Goga, and Z. Werb, "Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells," Nature 526(7571), 131-135 (2015).

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Optical Time Stretch for High-Speed and High-Throughput Imaging—From Single-Cell to Tissue-Wide Scales

Cited by 14 publications

References 118 publications

Quantitative Phase Imaging Flow Cytometry for Ultra‐Large‐Scale Single‐Cell Biophysical Phenotyping

Quantitative Phase Imaging Flow Cytometry for Ultra‐Large‐Scale Single‐Cell Biophysical Phenotyping

Recent advances in transient imaging: A computer graphics and vision perspective

Time-stretch microscopy on a DVD for high-throughput imaging cell-based assay

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