A Dual-Mode 303-Megaframes-per-Second Charge-Domain Time-Compressive Computational CMOS Image Sensor.

An ultra-high-speed computational CMOS image sensor with a burst frame rate of 303 megaframes per second, which is the fastest among the solid-state image sensors, to our knowledge, is demonstrated. This image sensor is compatible with ordinary single-aperture lenses and can operate in dual modes, such as single-event filming mode or multi-exposure imaging mode, by reconfiguring the number of exposure cycles. To realize this frame rate, the charge modulator drivers were adequately designed to suppress the peak driving current taking advantage of the operational constraint of the multi-tap charge modulator. The pixel array is composed of macropixels with 2 × 2 4-tap subpixels. Because temporal compressive sensing is performed in the charge domain without any analog circuit, ultrafast frame rates, small pixel size, low noise, and low power consumption are achieved. In the experiments, single-event imaging of plasma emission in laser processing and multi-exposure transient imaging of light reflections to extend the depth range and to decompose multiple reflections for time-of-flight (TOF) depth imaging with a compression ratio of 8× were demonstrated. Time-resolved images similar to those obtained by the direct-type TOF were reproduced in a single shot, while the charge modulator for the indirect TOF was utilized.

Analysis and Design of a CMOS Ultra-High-Speed Burst Mode Imager with In-Situ Storage Topology Featuring In-Pixel CDS Amplification.

This paper presents an in-situ storage topology for ultra-high-speed burst mode imagers, enabling low noise operation while keeping a high frame depth. The proposed pixel architecture contains a 4T pinned photodiode, a correlated double sampling (CDS) amplification stage, and an in-situ memory bank. Focusing on the sampling noise, the system level trade-off of the proposed pixel architecture is discussed, showing its advantages on the noise, power, and scaling capability. Integrated with an AC coupling CDS stage, the amplification is obtained by exploiting the strong capacitance to the voltage relation of a single NMOS transistor. A comprehensive noise model is developed for optimizing the trade-off between the area and noise. As a proof-of-concept, a prototype imager with a 30 µm pixel pitch was fabricated in a CMOS 130 nm technology. A 108-cell memory bank is implemented allowing dense layout and parallel readout. Two types of CDS amplification stages were investigated. Despite the limited memory capacitance of 10 fF/cell, the photon transfer curves of both pixel types were measured over different operation speeds up to 20 Mfps showing a noise performance of 8.4 e-.

Ultra-high-speed dynamics of acoustic droplet vaporization in soft biomaterials: Effects of viscoelasticity, frequency, and bulk boiling point.

Phase-shift droplets are a highly adaptable platform for biomedical applications of ultrasound. The spatiotemporal response of phase-shift droplets to focused ultrasound above a certain pressure threshold, termed acoustic droplet vaporization (ADV), is influenced by intrinsic features (e.g., bulk boiling point) and extrinsic factors (e.g., driving frequency and surrounding media). A deep understanding of ADV dynamics is critical to ensure the robustness and repeatability of an ADV-assisted application. Here, we integrated ultra-high-speed imaging, at 10 million frames per second, and confocal microscopy for a full-scale (i.e., from nanoseconds to seconds) characterization of ADV. Experiments were conducted in fibrin-based hydrogels to mimic soft tissue environments. Effects of fibrin concentration (0.2 to 8 % (w/v)), excitation frequency (1, 2.5, and 9.4 MHz), and perfluorocarbon core (perfluoropentane, perfluorohexane, and perfluorooctane) on ADV dynamics were studied. Several fundamental parameters related to ADV dynamics, such as expansion ratio, expansion velocity, collapse radius, collapse time, radius of secondary rebound, resting radius, and equilibrium radius of the generated bubbles were extracted from the radius vs time curves. Diffusion-driven ADV-bubble growth was fit to a modified Epstein-Plesset equation, adding a material stress term, to estimate the growth rate. Our results indicated that ADV dynamics were significantly impacted by fibrin concentration, frequency, and perfluorocarbon liquid core. This is the first study to combine ultra-high-speed and confocal microscopy techniques to provide insights into ADV bubble dynamics in tissue-mimicking hydrogels.

Coupling Two Ultra-high-Speed Cameras to Elucidate Ultrasound Contrast-Mediated Imaging and Therapy.

Ultrasound contrast-mediated medical imaging and therapy both rely on the dynamics of micron- and nanometer-sized ultrasound cavitation nuclei, such as phospholipid-coated microbubbles and phase-change droplets. Ultrasound cavitation nuclei respond non-linearly to ultrasound on a nanosecond time scale that necessitates the use of ultra-high-speed imaging to fully visualize these dynamics in detail. In this study, we developed an ultra-high-speed optical imaging system that can record up to 20 million frames per second (Mfps) by coupling two small-sized, commercially available, 10-Mfps cameras. The timing and reliability of the interleaved cameras needed to achieve 20 Mfps was validated using two synchronized light-emitting diode strobe lights. Once verified, ultrasound-activated microbubble responses were recorded and analyzed. A unique characteristic of this coupled system is its ability to be reconfigured to provide orthogonal observations at 10 Mfps. Acoustic droplet vaporization was imaged from two orthogonal views, by which the 3-D dynamics of the phase transition could be visualized. This optical imaging system provides the temporal resolution and experimental flexibility needed to further elucidate the dynamics of ultrasound cavitation nuclei to potentiate the clinical translation of ultrasound-mediated imaging and therapy developments.

An Acoustic Device for Ultra High-Speed Quantification of Cell Strain During Cell-Microbubble Interaction.

Microbubbles utilize high-frequency oscillations under ultrasound stimulation to induce a range of therapeutic effects in cells, often through mechanical stimulation and permeabilization of cells. One of the largest challenges remaining in the field is the characterization of interactions between cells and microbubbles at therapeutically relevant frequencies. Technical limitations, such as employing sufficient frame rates and obtaining sufficient image resolution, restrict the quantification of the cell's mechanical response to oscillating microbubbles. Here, a novel methodology was developed to address many of these limitations and improve the image resolution of cell-microbubble interactions at high frame rates. A compact acoustic device was designed to house cells and microbubbles as well as a therapeutically relevant acoustic field while being compatible with a Shimadzu HPV-X camera. Cell viability tests confirmed the successful culture and proliferation of cells, and the attachment of DSPC- and cationic DSEPC-microbubbles to osteosarcoma cells was quantified. Microbubble oscillation was observed within the device at a frame rate of 5 million FPS, confirming suitable acoustic field generation and ultra high-speed image capture. High spatial resolution in these images revealed observable deformation in cells following microbubble oscillation and supported the first use of digital image correlation for strain quantification in a single cell. The novel acoustic device provided a simple, effective method for improving the spatial resolution of cell-microbubble interaction images, presenting the opportunity to develop an understanding of the mechanisms driving the therapeutic effects of oscillating microbubbles upon ultrasound exposure.