Ali M. Fard

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.

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.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

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.

Digital broadband linearization of optical links

We present a digital postprocessing linearization technique to efficiently suppress dynamic distortions added to a wideband signal in an analog optical link. Our technique achieves up to 35 dB suppression of intermodulation distortions over multiple octaves of signal bandwidth. In contrast to conventional linearization methods, it does not require excessive analog bandwidth for performing digital correction. This is made possible by regenerating undesired distortions from the captured output, and subtracting it from the distorted digitized signal. Moreover, we experimentally demonstrate a record spurious-free dynamic range of 120 dB·Hz(2/3) over a 6 GHz electrical signal bandwidth. While our digital broadband linearization technique advances state-of-the-art optical links, it can also be applied to other nonlinear dynamic systems.

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.

Optical coherence tomography – near infrared spectroscopy system and catheter for intravascular imaging

Owing to its superior resolution, intravascular optical coherence tomography (IVOCT) is a promising tool for imaging the microstructure of coronary artery walls. However, IVOCT does not identify chemicals and molecules in the tissue, which is required for a more complete understanding and accurate diagnosis of coronary disease. Here we present a dual-modality imaging system and catheter that uniquely combines IVOCT with diffuse near-infrared spectroscopy (NIRS) in a single dual-modality imaging device for simultaneous acquisition of microstructural and compositional information. As a proof-of-concept demonstration, the device has been used to visualize co-incident microstructural and spectroscopic information obtained from a diseased cadaver human coronary artery.

Digital broadband linearization technique and its application to photonic time-stretch analog-to-digital converter

Suppression of distortion induced by nonlinearity in a dynamical system (such as an analog optical link) is very challenging, particularly for a wide-bandwidth signal. Conventional compensation techniques are computationally intensive, significantly limiting their realization in real-time applications. Here, we propose and demonstrate an efficient digital postprocessing technique to suppress distortions added to a wideband signal by a nonlinear system with memory effect. Experimentally, digital broadband linearization of the photonic time-stretch analog-to-digital converter (TSADC) is demonstrated. In case of TSADC, a dynamic range improvement of >15 dB compared to conventional memory-less correction method is achieved.

Nomarski serial time-encoded amplified microscopy for high-speed contrast-enhanced imaging of transparent media

High-speed high-contrast imaging modalities that enable image acquisition of transparent media without the need for chemical staining are essential tools for a broad range of applications; from semiconductor process monitoring to blood screening. Here we introduce a method for contrast-enhanced imaging of unstained transparent objects that is capable of high-throughput imaging. This method combines the Nomarski phase contrast capability with the ultrahigh frame rate and shutter speed of serial time-encoded amplified microscopy. As a proof of concept, we show imaging of a transparent test structure and white blood cells in flow at a shutter speed of 33 ps and a frame rate of 36.1 MHz using a single-pixel photo-detector. This method is expected to be a valuable tool for high-throughput screening of unstained cells.

Optical time-domain analog pattern correlator for high-speed real-time image recognition

The speed of image processing is limited by image acquisition circuitry. While optical pattern recognition techniques can reduce the computational burden on digital image processing, their image correlation rates are typically low due to the use of spatial optical elements. Here we report a method that overcomes this limitation and enables fast real-time analog image recognition at a record correlation rate of 36.7 MHz--1000 times higher rates than conventional methods. This technique seamlessly performs image acquisition, correlation, and signal integration all optically in the time domain before analog-to-digital conversion by virtue of optical space-to-time mapping.