Keisuke Goda

Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena

Ultrafast real-time optical imaging is an indispensable tool for studying dynamical events such as shock waves, chemical dynamics in living cells, neural activity, laser surgery and microfluidics. However, conventional CCDs (charge-coupled devices) and their complementary metal–oxide–semiconductor (CMOS) counterparts are incapable of capturing fast dynamical processes with high sensitivity and resolution. This is due in part to a technological limitation—it takes time to read out the data from sensor arrays. Also, there is the fundamental compromise between sensitivity and frame rate; at high frame rates, fewer photons are collected during each frame—a problem that affects nearly all optical imaging systems. Here we report an imaging method that overcomes these limitations and offers frame rates that are at least 1,000 times faster than those of conventional CCDs. Our technique maps a two-dimensional (2D) image into a serial time-domain data stream and simultaneously amplifies the image in the optical domain. We capture an entire 2D image using a single-pixel photodetector and achieve a net image amplification of 25 dB (a factor of 316). This overcomes the compromise between sensitivity and frame rate without resorting to cooling and high-intensity illumination. As a proof of concept, we perform continuous real-time imaging at a frame speed of 163 ns (a frame rate of 6.1 MHz) and a shutter speed of 440 ps. We also demonstrate real-time imaging of microfluidic flow and phase-explosion effects that occur during laser ablation.

High-throughput single-microparticle imaging flow analyzer

Optical microscopy is one of the most widely used diagnostic methods in scientific, industrial, and biomedical applications. However, while useful for detailed examination of a small number (< 10,000) of microscopic entities, conventional optical microscopy is incapable of statistically relevant screening of large populations (> 100,000,000) with high precision due to its low throughput and limited digital memory size. We present an automated flow-through single-particle optical microscope that overcomes this limitation by performing sensitive blur-free image acquisition and nonstop real-time image-recording and classification of microparticles during high-speed flow. This is made possible by integrating ultrafast optical imaging technology, self-focusing microfluidic technology, optoelectronic communication technology, and information technology. To show the system’s utility, we demonstrate high-throughput image-based screening of budding yeast and rare breast cancer cells in blood with an unprecedented throughput of 100,000 particles/s and a record false positive rate of one in a million.

A quantum-enhanced prototype gravitational-wave detector

The quantum nature of the electromagnetic field imposes a fundamental limit on the sensitivity of optical precision measurements such as spectroscopy, microscopy and interferometry. The so-called quantum limit is set by the zero-point fluctuations of the electromagnetic field, which constrain the precision with which optical signals can be measured. In the world of precision measurement, laser-interferometric gravitational-wave detectors, are the most sensitive position meters ever operated, capable of measuring distance changes of the order of 10- 18 m r.m.s. over kilometre separations caused by gravitational waves from astronomical sources. The sensitivity of currently operational and future gravitational-wave detectors is limited by quantum optical noise. Here, we demonstrate a 44% improvement in displacement sensitivity of a prototype gravitational-wave detector with suspended quasi-free mirrors at frequencies where the sensitivity is shot-noise-limited, by injecting a squeezed state of light. This demonstration is a critical step towards implementation of squeezing-enhancement in large-scale gravitational-wave detectors.

Inertial Manipulation and Transfer of Microparticles Across Laminar Fluid Streams

A general strategy for controlling particle movement across streams would enable new capabilities in single-cell analysis, solid-phase reaction control, and biophysics research. Transferring cells across streams is difficult to achieve in a well-controlled manner, since it requires precise control of fluid flow along with external force fields or precisely manufactured mechanical structures. Herein a strategy is introduced for particle transfer based on passive inertial lift forces and shifts in the distribution of these forces for channels with shifting aspect ratios. Uniquely, use of the dominant wall-effect lift parallel to the particle rotation direction is explored and utilized to achieve controllable cross-stream motion. In this way, particles are positioned to migrate across laminar streams and enter a new solution without significant disturbance of the interface at rates exceeding 1000 particles per second and sub-millisecond transfer times. The capabilities of rapid inertial solution exchange (RInSE) for preparation of hematological samples and other cellular assays are demonstrated. Lastly, improvements to inline flow cytometry after RInSE of excess fluorescent dye and focusing for downstream analysis are characterized. The described approach is simply applied to manipulating cells and particles and quickly exposing them to or removing them from a reacting solution, with broader applications in control and analysis of low affinity interactions on cells or particles.

Amplified dispersive Fourier-transform imaging for ultrafast displacement sensing and barcode reading

Dispersive Fourier transformation is a powerful technique in which the spectrum of an optical pulse is mapped into a time-domain waveform using chromatic dispersion. It replaces a diffraction grating and detector array with a dispersive fiber and single photodetector. This simplifies the system and, more importantly, enables fast real-time measurements. Here we describe a novel ultrafast barcode reader and displacement sensor that employs internally amplified dispersive Fourier transformation. This technique amplifies and simultaneously maps the spectrally encoded barcode into a temporal waveform. It achieves a record acquisition speed of 25MHz—four orders of magnitude faster than the current state of the art.Dispersive Fourier transformation is a powerful technique in which the spectrum of an optical pulse is mapped into a time-domain waveform using chromatic dispersion. It replaces a diffraction grating and detector array with a dispersive fiber and single photodetector. This simplifies the system and, more importantly, enables fast real-time measurements. Here we describe a novel ultrafast barcode reader and displacement sensor that employs internally amplified dispersive Fourier transformation. This technique amplifies and simultaneously maps the spectrally encoded barcode into a temporal waveform. It achieves a record acquisition speed of 25MHz—four orders of magnitude faster than the current state of the art.

Performance of serial time-encoded amplified microscope

Serial time-encoded amplified microscopy (STEAM) is a new high-sensitivity ultrafast real-time imaging modality. Here we describe an analysis of its spatial resolution, frame rate, and detection sensitivity.

Hybrid Dispersion Laser Scanner

Laser scanning technology is one of the most integral parts of todays scientific research, manufacturing, defense, and biomedicine. In many applications, high-speed scanning capability is essential for scanning a large area in a short time and multi-dimensional sensing of moving objects and dynamical processes with fine temporal resolution. Unfortunately, conventional laser scanners are often too slow, resulting in limited precision and utility. Here we present a new type of laser scanner that offers ∼1,000 times higher scan rates than conventional state-of-the-art scanners. This method employs spatial dispersion of temporally stretched broadband optical pulses onto the target, enabling inertia-free laser scans at unprecedented scan rates of nearly 100 MHz at 800 nm. To show our scanners broad utility, we use it to demonstrate unique and previously difficult-to-achieve capabilities in imaging, surface vibrometry, and flow cytometry at a record 2D raster scan rate of more than 100 kHz with 27,000 resolvable points.

High-speed nanometer-resolved imaging vibrometer and velocimeter

Conventional laser vibrometers are incapable of performing multidimensional vibrometry at high speeds because they build on single-point measurements and rely on beam scanning, significantly limiting their utility and precision. Here we introduce a laser vibrometer that performs high-speed multidimensional imaging-based vibration and velocity measurements with nanometer-scale axial resolution without the need for beam scanning. As a proof-of-concept, we demonstrate real-time microscopic imaging of acoustic vibrations with 1 nm axial resolution, 1200 image pixels, and 30 ps dwell time at 36.7 MHz scan rate.

High-throughput optical coherence tomography at 800 nm

We report high-throughput optical coherence tomography (OCT) that offers 1,000 times higher axial scan rate than conventional OCT in the 800 nm spectral range. This is made possible by employing photonic time-stretch for chirping a pulse train and transforming it into a passive swept source. We demonstrate a record high axial scan rate of 90.9 MHz. To show the utility of our method, we also demonstrate real-time observation of laser ablation dynamics. Our high-throughput OCT is expected to be useful for industrial applications where the speed of conventional OCT falls short.

Real-time optical reflectometry enabled by amplified dispersive Fourier transformation

The axial scan rate of optical frequency-domain reflectometry and optical coherence tomography can be increased to megahertz frequencies by dispersive Fourier transformation. However, the fundamental connection between dispersion and loss creates a trade-off between detection sensitivity and acquisition speed. Here we circumvent this predicament by using distributed Raman postamplification of the reflection from the sample. The Raman amplification enables measurement of weak signals, which are otherwise buried in detector noise. It extends the depth range without sacrificing the acquisition speed. Single-shot imaging with improved sensitivity at an axial scan rate of 36.6MHz is demonstrated.