Alexandre Serov

First fully integrated 2-D array of single-photon detectors in standard CMOS technology

A two-dimensional (2-D) array (4 by 8) of single-photon avalanche diodes integrated in an industrial complementary metal-oxide-semiconductor (CMOS) process is presented. Each pixel combines a photodiode biased above its breakdown voltage in the so-called Geiger mode, a quenching resistor, and a simple comparator. The pitch between the pixels is 75 /spl mu/m and the diameter of each pixel is 6.4 /spl mu/m. The full integration allows reducing the number of charge carriers in a Geiger pulse. The electroluminescence responsible for optical crosstalks between pixels is then reduced leading to a negligible optical crosstalk probability. Thanks to the cleanness of the fabrication process, no afterpulsing effects are noticed. At room temperature, most of the pixels exhibit a dark-count rate of about 50 Hz. The detection probability is almost identical for all 32 pixels of the array with relative variation in the range of a few percents. This letter demonstrates the feasibility of an array of single-photon detectors sensitive in the visible part of the spectrum. Besides low production costs and compactness, an undeniable benefit lies in the potential to easily modify the design to fit a specific application. Furthermore, the CMOS integration opens the way to on-chip data processing.

Full-field laser Doppler perfusion imaging and monitoring with an intelligent CMOS camera

A system for full-field laser Doppler blood flow imaging has been developed and tested on biomedical samples. The new imaging system allows 2D flow maps or monitoring flux signals to be obtained from a plurality of measured points simultaneously by using a 2D array of photodetectors. The detection part of the system is based on an intelligent CMOS camera with a built-in digital signal processor and memory. The imaging time of the system is as much as to 4 times faster than for the conventional scanning laser Doppler imager. The performance of the system was evaluated in vitro and in vivo. The first measurement results with this new system on human skin are reported.

High-speed laser Doppler perfusion imaging using an integrating CMOS image sensor

This paper describes the design and the performance of a new high-speed laser Doppler imaging system for monitoring blood flow over an area of tissue. The new imager delivers high-resolution flow images (256x256 pixels) every 2 to 10 seconds, depending on the number of points in the acquired time-domain signal (32-512 points). This new imaging modality utilizes a digital integrating CMOS image sensor to detect Doppler signals in a plurality of points over the area illuminated by a divergent laser beam of a uniform intensity profile. The integrating property of the detector improves the signal-to-noise ratio of the measurements, which results in high-quality flow images. We made a series of measurements in vitro to test the performance of the system in terms of bandwidth, SNR, etc. Subsequently we give some examples of flow-related images measured on human skin, thus demonstrating the performance of the imager in vivo. The perspectives for future implementations of the imager for clinical and physiological applications are discussed.

Parallel single molecule detection with a fully integrated single-photon 2X2 CMOS detector array

We present parallel single molecule detection (SMD) and fluorescence correlation spectroscopy (FCS) experiments with a fully integrated complementary metal oxide semiconductor (CMOS) single-photon 2x2 detector array. Multifocal excitation is achieved with a diffractive optical element (DOE). Special emphasis is placed on parallelization of the total system. The performance of the novel single-photon CMOS detector is investigated and compared to a state-of-the-art single-photon detecting module [having an actively quenched avalanche photodiode (APD)] by measurements on free diffusing molecules at different concentrations. Despite the order of magnitude lower detection efficiency of the CMOS detector compared to the state-of-the-art single-photon detecting module, we achieve single molecule sensitivity and reliably determine molecule concentrations. In addition, the CMOS detector performance for the determination of the fraction of slowly diffusing molecules in a primer solution (two-component analysis) is demonstrated. The potential of this new technique for high-throughput confocal-detection-based systems is discussed.

Full-field high-speed laser Doppler imaging system for blood-flow measurements

We describe the design and performance of a new full-field high-speed laser Doppler imaging system developed for mapping and monitoring of blood flow in biological tissue. The total imaging time for 256x256 pixels region of interest is 1.2 seconds. An integrating CMOS image sensor is utilized to detect Doppler signal in a plurality of points simultaneously on the sample illuminated by a divergent laser beam of a uniform intensity profile. The integrating property of the detector improves the signal-to-noise ratio of the measurement, which results in high-quality flow-images provided by the system. The new technique is real-time, non-invasive and the instrument is easy to use. The wide range of applications is one of the major challenges for a future application of the imager. High-resolution high-speed laser Doppler perfusion imaging is a promising optical technique for diagnostic and assessing the treatment effect of the diseases such as e.g. atherosclerosis, psoriasis, diabetes, skin cancer, allergies, peripheral vascular diseases, skin irritancy and wound healing. We present some biological applications of the new imager and discuss the perspectives for the future implementations of the imager for clinical and physiological applications.

Combined laser Doppler and laser speckle imaging for real- time blood blow measurements

Laser Doppler (LDI) and laser speckle imaging (LSI) are two optical non-invasive techniques that are used to obtain 2D maps of blood flow in biological tissues. Each of these techniques has some benefits and drawbacks for measuring the blood flow. LSI is a true real-time imaging technique, but less sensitive to changes of flow parameters such as speed and concentration. In contrast, LDI has superior measurement accuracy but it is not a real-time technique. Recently we have developed a blood-flow imaging system that combines both imaging modalities with a gain in speed and accuracy. Using a single integrating CMOS image sensor for measuring both the Doppler signal spectrum and the image speckle contrast flow-map images are produced. In LDI mode, the flow map refresh rate is 1.2 seconds per 256x256 pixels image. In LSI mode the frame rate is 10 flow-map images per second. We present the basic design and in-vivo performance of this new hybrid imaging system. Subsequently, we discuss the potential of the new instrument for future implementations into clinical research.

Real-time optically sectioned wide-field microscopy employing structured light illumination and a CMOS detector

Real-time optically sectioned microscopy is demonstrated using an AC-sensitive detection concept realized with smart CMOS image sensor and structured light illumination by a continuously moving periodic pattern. We describe two different detection systems based on CMOS image sensors for the detection and on-chip processing of the sectioned images in real time. A region-of-interest is sampled at high frame rate. The demodulated signal delivered by the detector corresponds to the depth discriminated image of the sample. The measured FWHM of the axial response depends on the spatial frequency of the projected grid illumination and is in the μm-range. The effect of using broadband incoherent illumination is discussed. The performance of these systems is demonstrated by imaging technical as well as biological samples.

Laser Doppler blood-flow imaging combined with topographical imaging of the sample

We present a combination of topography measurements based on digital fringe projection and blood flow imaging based on Laser Doppler Imaging (LDI). Both techniques are optical, non-contact and high-speed whole-field methods well suited for in-vivo measurements on the skin. Laser Doppler perfusion imaging is an interferometric technique used for visualization of two-dimensional (2D) maps of blood flow. Typically the measured sample has a surface with a specific 3D relief. In many cases the sample relief can be of importance for correct interpretation of the obtained perfusion data. We combined the topography and the blood flow data obtained from the same object. The structural information provided by the topography is completed by the functional images provided by LDI.

Subwavelength-resolution fluorescent correlation spectroscopy using a solid immersion lens

In this paper we present recent spectroscopic studies using a Solid Immersion Lens for Fluorescent Correlation Spectroscopy measurements. We compare the performance of the Solid Immersion Lens confocal microscope built-up in our group to the performance of a conventional confocal microscope used for FCS. The novelty of the new SIL-FCS microscope is a system containing a conventional objective (NA = 0.6) combined with a Solid Immersion Lens used for single molecule experiment. Important parameters for single molecule experiments such as collection efficiency and excitation field confinement are investigated for different modes of the SIL objective system.

Mitochondrial toxins are detected in the spermatozoa motility assay

Reference EPFL-CONF-180020doi:10.1016/j.toxlet.2012.03.416View record in Web of Science Record created on 2012-07-13, modified on 2017-05-10