Introducing NEOGLY™, a novel body-worn QCL-based non-invasive continuous glucose monitoring device (NI-CGM). Developed under ISO 13485 regulation, it shows relevant glycemia predictions based on mid-infrared photoacoustic spectroscopy as well as AI-based algorithms fed by a digital twin that covers the entire detection chain including device modeling and human skin properties.
Materials such as Si, SiGe, Ge, SiN and AlN can be used for Mid-IR (3 up to 8µm). For LWIR which ranges from 8µm to 13µm, absorption limitations define the materials which can be used, such as Ge, SiGe, chalcogenides, ZnS.... Array waveguide grating devices, with SiGe waveguides cladded by Si or Ge waveguides capped by thick SiGe layers, have been designed and fabricated. They target the simultaneous detection of several gas using arrays of QCL sources. The index difference between the core and the claddings is around 0.5 on the 3-13 µm spectral range. To increase the miniaturization, the index difference has to be increased. So by using cladding material with lower index, new platforms called “Ge on insulator” have been developed such as SiGe on SiN, Ge on SiN, Ge on AlN,
Photoacoustic (PA) spectroscopy is one of the most sensitive technique used to monitor chemical emission or detect gas traces. Coupled to quantum cascade lasers, this system is widely used in a large number of application fields from industrial control to health monitoring. Mass production for a large dissemination of such systems requires however further development for both decreasing their footprint and manufacturing cost. Since the last 6 years CEA-LETI has developed different versions of miniaturized photoacoustic cells. We have already demonstrated the detection of gas traces with a tiny silicon based-PA cell. Nevertheless, this first result was obtained with commercial MEMS microphones. Even if these components are reliable and enough performant they are not dedicated to photoacoustic gas detection and cannot be easily integrated into a fabrication process flow. To cope with these issues we suggest using both the M&NEMS technology and the MIR photonics. The new PAdetector termed microPA is built by stacking two 200 mm wafers: a sensor wafer, which includes the microphone (MEMS mechanical diaphragm and NEMS piezoresistive gauges), capillaries and fluidic ports, and a cap wafer, which includes the PA cell, the expansion volume, SiGe waveguides guiding the light into the PA cell, metal routing and electric contacts. Frequency response measurements as well as PA gas detection have been carried out. The system shows a mechanical resonance of the diaphragm at the frequency of 6500 Hz, in good agreement with the simulation. First CO2 and CH4 tests in laboratory condition demonstrates a limit of detection in the ppm range and a NNEA of 10-8 W.cm-1.Hz-1/2.
The costs of manufacturing QCL are still a major bottleneck for the adoption of this technology for chemical sensing. The integration of MIR sources on Si substrate based on CMOS technology paves the way for high-volume low-cost fabrication. Furthermore, the use of Si-based fabrication platform open the way to the co-integration of QCL MIR sources with Si-based waveguides, allowing realization optical sensors fully integrated on planar substrate. We report the fabrication of DFB QCL sources operating at 7.4μm on silicon substrate within 200 mm CMOS/MEMS pilot line. To do so, we have developed an appropriate fabrication process flow that fully respects the design and the process rules of a standard CMOS manufacturing line. Moreover, we have developed wafer level electro-optic characterization on prober station. The characterizations done at wafer level on thousands devices have demonstrated average threshold current densities close to between 3 kA/cm2 and 2.5 kA/cm2 with a relative dispersion around 5%. The optical power can reach 1 mW at ambient temperature, 1.5% duty cycle. This fabrication run achieves performance at the state of the art, that are comparable with those of QCL fabricated on InP substrate. With a yield of 98% on the wafer central fields, this work give perspectives to address application fields needing low cost MIR laser sources.
We present several integrated technologies on Silicon, from visible to mid-infrared, for particulate matter and gas detection. We present new concepts to detect in the visible particulate matter with a high sensitivity and a discrimination of both particle sizes and refractive indices. For gas detection, mid-infrared technologies developments include on one hand, microhotplate thermal emitters, as a cheap solution for gas sensing, eventually enhanced by plasmonics, and on the other hand quantum cascade lasers-based photoacoustic sensors, for high precision measurement, and for which the integration on Silicon is pushed forward for a reduction of costs.
Photoacoustic (PA) spectroscopy is among the most sensitive techniques used to monitor chemical emission or detect gas traces. In the mid-infrared, where most of gases of interest have their strongest absorption lines, this technique takes advantage of the high optical power and room temperature operation of quantum cascade lasers (QCL). We have recently demonstrated that centimeter-size PA cells can compete, with bulky commercial systems for gas sensing without any compromises on performances. We demonstrate a new step towards cost reduction, extreme integration, and mass deployment of such PA sensors with a miniaturized silicon PA-cell fabricated on standard CMOS tools. The design, fabrication and characterizations of this new sub-centimeter PA cell built on a silicon platform are presented. First, the component has been designed using a detailed physical model, accounting for viscous and thermal losses, and metamodel-based optimization techniques. Second, it has been fabricated on our 200 mm CMOS pilot line. Several wafers have been released and diced. Single chips have then been assembled with commercial capacitive microphones and finally characterized on our reference gas bench. The photoacoustic simulations and the acoustics experiments are in a good agreement. The tiny PA cell exhibits a sensitivity down to the ppm level for CO2 at 2300 cm-1, as well as for CH4 at 3057 cm-1 even in a gas flow. Taking advantage of the integration of QCLs on Si and photonic circuitry, the silicon PA cell concept is currently being extended towards a fully integrated multigas detector.
The Mid-IR spectral range (2.5 μm up to 12 μm) has been considered as the paradigm for innovative silicon photonic devices. In less than a decade, chemical sensing has become a key application for Mid-IR silicon photonic devices because of the growing potential in spectroscopy, materials processing, chemical and biomolecular sensing, security and industry applications. Measuring in this spectral range, usually called molecule fingerprint region, allows to address a unique combination of fundamental absorption bands orders of magnitude stronger than overtone and combination bands in the near IR. This feature provides highly selective, sensitive and unequivocal identification of the chemicals.
Progress in Cascade Laser technology (QCL and ICL) allows to select emission wavelengths suitable to target the detection of specific chemicals. With these sources, novel spectroscopic tools allowing real-time in-situ detection of gasses down to traces are nowadays commercially available.
Mid-IR Si photonics has developed a novel class of integrated components leading to the integration at chip level of the main building blocks required for chemical sensing, i.e. the source, the PICs and the detector. Three main directions of improvement can be drawn: i) extend the range of wavelengths available from a single source, ii) move beam handling and routing from discrete optics to PICs and iii) investigate detection schemes for a fully integrated on-chip sensing.
This paper reviews recent key achievements in the miniaturization and the co-integration of photonics devices at chip and packaging level to address cost, size and power consumption. Perspectives on potential applications will also be presented.
In this paper, we discuss a new methodology based on lens-free imaging to perform wound healing assay with unprecedented statistics. Our video lens-free microscopy setup is a simple optical system featuring only a CMOS sensor and a semi coherent illumination system. Yet it is a powerful means for the real-time monitoring of cultivated cells. It presents several key advantages, e.g., integration into standard incubator, compatibility with standard cell culture protocol, simplicity and ease of use. It can perform the follow-up in a large field of view (25 mm2) of several crucial parameters during the culture of cells i.e. their motility, their proliferation rate or their death. Consequently the setup can gather large statistics both in space and time. But in the case of tissue growth experiments, the field of view of 25 mm2 remains not sufficient and results can be biased depending on the position of the device with respect to the recipient of the cell culture. Hence, to conduct exhaustive wound healing assay, here we propose to enlarge the field of view up to 10 cm2 through two different approaches. The first method consists in performing a scan of the cell culture by moving the source/sensor couple and then stitch the stack of images. The second is to make an acquisition by scanning with a line scan camera. The two approaches are compared in term of resolution, complexity and acquisition time. Next we have performed acquisitions of wound healing assay (keratinocytes HaCaT) both in real-time (25 mm2) and in final point (10 cm2) to assess the combination of these two complementary modalities. In the future, we aim at combining directly super wide field of view acquisitions (>10 cm2) with real time ability inside the incubator.
Innovative imaging methods are continuously developed to investigate the function of biological systems at the microscopic scale. As an alternative to advanced cell microscopy techniques, we are developing lensfree video microscopy that opens new ranges of capabilities, in particular at the mesoscopic level. Lensfree video microscopy allows the observation of a cell culture in an incubator over a very large field of view (24 mm2) for extended periods of time. As a result, a large set of comprehensive data can be gathered with strong statistics, both in space and time. Video lensfree microscopy can capture images of cells cultured in various physical environments. We emphasize on two different case studies: the quantitative analysis of the spontaneous network formation of HUVEC endothelial cells, and by coupling lensfree microscopy with 3D cell culture in the study of epithelial tissue morphogenesis. In summary, we demonstrate that lensfree video microscopy is a powerful tool to conduct cell assays in 2D and 3D culture experiments. The applications are in the realms of fundamental biology, tissue regeneration, drug development and toxicology studies.
We demonstrated that the use of thin wetting film focusing allows detection of single micrometer-size objects with 24 mm2 lensfree imaging. In order to refine the technique and push the detection limit down to the nanometer scale, a deep insight in the imaging mechanisms is necessary. We constructed a model based on wetting film microfluidics and Fresnel diffraction of light. This model properly fits the intensity measurements acquired on micro-particles with our lensfree imaging setup. When the particle diameter is 1 µm, a microlens is formed by a liquid surface deformation of about 100 nm in height over few microns radial distance. The measured point spread function of the light deflected by such microlens presents a constant beam intensity over a long range, between 50 µm and 250 µm from the object plane. This is very similar to what is obtained by illuminating an axicon with a Gaussian beam, i.e. the central beam propagates for several Rayleigh ranges without appreciable divergences. In the lensfree imaging setup, the detector plane is far apart from the object (≈500 µm). Thus, it is a true advantage to form axicon lens that can propagate strong intensity beams up to the detector plane. Most important, our model predicts that the detection of smaller objetcs needs thinner films. These results are important for further detecting viruses with lensfree imaging techniques.
This article [J. Biomed. Opt.. 17, , 106014 (2012)] was originally published online on 10 October 2012 with an error on page 5, column 2, line 5. The unit of measure "88 mW/cm2" should have read "8 mW/cm2."
This article was corrected online on 11 October 2012. The article appears correctly in print.
Over the last few years, near-infrared (NIR) fluorescence imaging has witnessed rapid growth and is already used in clinical trials for various procedures. However, most clinically compatible imaging systems are optimized for large, open-surgery procedures. Such systems cannot be employed during head and neck oncologic surgeries because the system is not able to image inside deep cavities or allow the surgeon access to certain tumors due to the large footprint of the system. We describe a miniaturized, low-cost, NIR fluorescence system optimized for clinical use during oral oncologic surgeries. The system, termed FluoSTIC, employs a miniature, high-quality, consumer-grade lipstick camera for collecting fluorescence light and a novel custom circular optical fiber array for illumination that combines both white light and NIR excitation. FluoSTIC maintains fluorescence imaging quality similar to that of current large-size imaging systems and is 22 mm in diameter and 200 mm in height and weighs less than 200 g.
In the context of continuous wave fluorescence-enhanced diffuse optical tomography, we show that the reconstructed
fluorescence depends on the local diffusion coefficient and demonstrate that the a priori knowledge of specific optical
parameters may lead to the reconstruction of absolute quantification of the fluorophore distribution. In this context, we
point out the potentiality of a bimodal instrument coupling functional and morphological information to provide
knowledge of the distribution of optical parameters of internal organs. We show some quantitative results on simulated
and experimental data on phantoms and conclude suggesting the use of optical parameters atlases to achieve an absolute
quantification of fluorophore distribution in real contexts.
KEYWORDS: Bacteria, 3D image reconstruction, Thin films, Holograms, Holography, CMOS sensors, Sensors, Microlens, Imaging systems, Signal to noise ratio
Due to low light scattering, bacteria are difficult to detect using lensless imaging systems. In
order to detect individual bacteria, we report a method based on a thin wetting film imaging
that produces a micro-lens effect on top of each bacterium when the sample dries up. The
imaging using a high-end CMOS sensor is combined with an in-line holographic
reconstruction to improve positive detection rate up to 95% with micron-sized beads at high
density of ~103 objects/mm2. The system allows detecting from single bacterium to densely
packed objects (103 bacteria/μl) within 10μl sample. As an example, E.coli, Bacillus subtilis
and Bacillus thuringiensis, has been successfully detected with strong signal to noise ratio across a 24mm2 field of view.
Lensless imaging has recently attracted a lot of attention as a compact, easy-to-use method to image or detect biological
objects like cells, but failed at detecting micron size objects like bacteria that often do not scatter enough light. In order
to detect single bacterium, we have developed a method based on a thin wetting film that produces a micro-lens effect.
Compared with previously reported results, a large improvement in signal to noise ratio is obtained due to the presence
of a micro-lens on top of each bacterium. In these conditions, standard CMOS sensors are able to detect single
bacterium, e.g. E.coli, Bacillus subtilis and Bacillus thuringiensis, with a large signal to noise ratio. This paper presents our sensor optimization to enhance the SNR; improve the detection of sub-micron objects; and increase the imaging
FOV, from 4.3 mm2 to 12 mm2 to 24 mm2, which allows the detection of bacteria contained in 0.5μl to 4μl to 10μl, respectively.
An instrument dedicated to the co-registration of optical and X-ray measurements is presented: specific acquisition
protocol and reconstruction software have been developed for carrying out fluorescence diffuse optical tomography in a
cylindrical geometry consistent with XCT. Actual animal geometry provided by the X-ray tomography is used to give
animal boundaries to the diffuse optical tomography reconstruction algorithm. To evaluate performances of this new
optical imaging system, experiments have been conducted on phantoms, mice with fluorescent capillaries, and finally on
mice bearing tumors. The fluorescence reconstructions are shown to be geometrically consistent with X-ray ones. We
determined that the sensibility limit of the system to detect fluorescence signal over intrinsic ones is 2 pmol for lungs
area and 5 pmol for the abdomen area.
We present first results of a fluorescence optical diffusion tomography experiment coupled to a X-ray computed
tomography reconstruction. An instrument, dedicated to the co-registration of optical and X-ray measurements, has been
developed: specific acquisition protocol and reconstruction software have been developed for carrying out fluorescence
diffuse optical tomography in a cylindrical geometry consistent with X-ray tomography. Actual animal geometry
provided by the X-ray tomography is used to give animal boundaries to the diffuse optical tomography reconstruction
algorithm. Experiments have been conducted on sacrificed mice and fluorescence reconstructions have been evaluated
and are geometrically consistent with X-ray ones.
Laser damage at 3ω, 351 nm, of fused silica optical components is a major concern for LMJ maintenance.
Indeed, even a low density of damage sites is unacceptable due to the exponential growth of surface damage with a series
of laser shots. A technique is now used to prevent the growth of initiated damage sites : this mitigation technique consists
in a local melting and evaporation of silica by CO2 laser irradiation on the damage site. Even if the growth is stopped in
most cases, we showed previously that some of the mitigated sites re-initiate on their peripheral area, where most of redeposited
debris are located. To further increase the efficiency of mitigation technique, the treatment was improved by
varying the spatial profile of the CO2 laser beam. We present here the new set-up and the results obtained in terms of
laser damage resistance: about 98% of the mitigated sites sustained 200 shots of a 10 J/cm2 3ω YAG laser without
damage.
Surface incandescence properties of proton implanted fused silica have been researched with a focused CO2
laser. We have discovered that in the initial stage of incandescence a thermoluminescent peak appears. We call it
blackbody thermoluminescence. In our silica samples, with a 100 micron spatial resolution, the blackbody
thermoluminescence mapping reveals surface and sub surfaces defects made by the polishing process. We show how
laser damage and laser conditioning are the same two facets of this blackbody thermoluminescence occurrence.
The lifetime of optical components submitted to high laser fluences is degraded under organic contaminant environment.
The molecular background of the Ligne d'Integration Laser (LIL), prototype of the future Laser Megajoule, might reduce
the laser damage threshold of exposed fused silica surfaces. This paper reports the interaction effects between pure
model contaminant deposits and a pulsed 1064 nm laser radiation on the coming out of mirror damage. The experimental
setup allowed us to condense nanolayers of model contaminants on optics, the deposit impacts were then investigated by
Laser Induced Damage Threshold (LIDT) tests in Rasterscan mode. In order to highlight physical processes emphasizing
the emergence of optics damage, we characterized the irradiated deposit using interferometric microscopy analysis and
spectrophotometric analysis. The challenge was to determine physical and phenomenological processes occurring during
the irradiation of a pure contaminant deposit with a 1064 nm pulsed laser and to study the impact of this model
contaminant on the LIDT of dielectric SiO2/HfO2 mirrors.
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