Silicon-based single-photon avalanche diodes (SPADs) implemented in front-side illuminated arrays and imagers have often suffered from fill factor limitations. The corresponding reduced sensitivity can be sometimes traded off with longer acquisition times thanks to SPAD’s noiseless read-out. The use of SPADs can however be critically affected in many applications, especially when photon-starved, or when several photons need to be detected in coincidence. The fill factor loss can be recovered by employing microlens arrays, which are difficult to build with relatively large pitch (> 10 μm) and low native SPAD fill factor (as low as 10%). To address these challenges, we have developed several generations of refractive microlenses by photoresist reflow used to fabricate molds. These structures were used to imprint UV-curable hybrid polymer microlenses on SPAD arrays. Replications were successfully carried out on large SPAD arrays with very thin residual layers (~10 μm), as required for higher numerical aperture (NA > 0.25). Replications were also carried out for the first time in a multi-chip operation regime at the wafer reticle level. By optimizing the lens sag and residual layer thickness, concentration factors (CFs) within 15-20% of the theoretical maxima were obtained for the smaller arrays (32×32 and 512×1). The spectral response was flat above 400 nm. CF values up to 4.2 with good uniformity were measured on large 512×512 arrays with 16 μm pixel pitch and a native fill factor of 10.5%. This result was confirmed by simulations when using the actual measured lens shape. We thus demonstrated good spectral and spatial uniformity and high CF, while moving to higher NAs and larger sensor sizes with respect to previous work.
Significance: Multi-laboratory initiatives are essential in performance assessment and standardization—crucial for bringing biophotonics to mature clinical use—to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison.
Aim: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew.
Approach: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging).
Results: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5 % over 1 h, and day-to-day reproducibility of <3 % . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities.
Conclusions: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset—available soon in an open data repository—can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
Diffraction phase microscopy (DPM) provides the possibility of high-resolution quantitative phase imaging, based on equipment of an optical microscope with a special module working in a common-path off-axis configuration. As an optical microscopy technique, DPM has a limited focus depth, which is the smaller the higher is the objective's numerical aperture. In this paper we present the results of experimental investigation of numerical focusing with the angular spectrum method in DPM.
Nowadays is developed a lot of techniques for the refractive index measurements. One of them describe in this article. We are used method of optical microscopy, there is diffraction phase microscopy with transmissionreflection illumination for measurements of red blood cells (RBCs) refractive index. Theory of measurements refractive index and results of experiments also are presented in the article.
Fourier optics approach is employed in the work do describe formal theory of diffraction phase microscope (DPM). Final expression for optical field in registration plain is given. Optimal spatial filter diameter and numerical aperture is calculated theoretically. DPM is used in the work for reconstruction of phase map of red blood cells in blood slide. The filter windows diameter influence on phase map reconstruction is shown experimentally.
Experimental setup of diffraction phase microscope (DPM) with double low-coherence lighting system is presented in the paper. Algorithm of interference picture processing and optical thickness, height, volume and mean cells volume (MCV) of RBC calculating is shown. We demonstrate results of experiments with blood smears and ability of the method to calculate 3D model of the biological cells shape. Investigation change dynamics of RBC morphology after injection glucose for diabetes by DPM is shown in the paper.
The burning issue in modern medicine is the diagnosis and treatment of various life-threatening diseases, in particular the diseases of brain. One of them is intracranial hemorrhage (ICH). It occurs especially among newborn babies and is hard-diagnosed. In order to understand the nature of the ICH, the microcirculation of blood, which serves key functions within the body, is analyzed. On this basis a series of experiments was done, in the results of which it was showed, that latent stage of ICH is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor effect of adrenaline. So, stress-related changes of the cerebral venous blood flow (CVBF) can be the source of this disease. In this paper registration CVBF was made with the help of commercially available Thorlabs Swept Source OCT System, using the correlation mapping method. In this method values of correlation coefficient of several images are analyzed. In the result of the algorithm the correlation map was obtained. By the resulting map the diameter of vessels was calculated, which is necessary for examination of effects of adrenalin to the vessels and identification symptoms of ICH.
The method of autocorrelation low coherence interferometry is proposed for diagnostics of layered media inner structure.
The possible applications of this method in technology and biomedicine are presented. In this method the low coherence
optical field is reflected from the object's structure and then analyzed using the Michelson interferometer. Since the
object is outside of the Michelson interferometer the axial position of the object is not important and thus the object can
move during the measurements. The theoretical background of this autocorrelation method for a media with discrete and
continuous optical structure modification is presented.
It is well known that the spectral properties of the light source relate explicitly to the correlation properties of the source field. Thus it is possible to have an action on the correlation function of the source affecting on emission spectrum. It is shown in this paper that correlation analysis of the light source field allows to perform control of the spectral properties of the source. Availability of Michelson interferometer for investigation of the thin structure of emission spectrum of superluminescent diodes (SLD) and appreciation of the use of its in low coherence interference schemes are discussed in this work.
Effects of spatial coherence of optical field with wide frequency and angular spectra in the Michelson interferometer are studied. Manly effects of longitudinal spatial coherence are considered. It is shown that in classical configuration of the Michelson interferometer the effects of not temporal, but spatial coherence are taken place. Experimental data of observation of spatial and temporal coherence effects in image domain behind a lens at the output of the Michelson interferometer are shown.
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