A Self-Calibrated Single Wavelength Biosensor for Measuring Oxygen Saturation.

Traditional methods for measuring blood oxygen use multiple wavelengths, which produce an intrinsic error due to ratiometric measurements. These methods assume that the absorption changes with the wavelength, but in fact the scattering changes as well and cannot be neglected. We found that if one measures in a specific angle around a cylindrical tissue, called the iso-pathlength (IPL) point, the reemitted light intensity is unaffected by the tissue's scattering. Therefore, the absorption can be isolated from the scattering, which allows the extraction of the subject's oxygen saturation. In this work, we designed an optical biosensor for reading the light intensity reemitted from the tissue, using a single light source and multiple photodetectors (PDs), with one of them in the IPL point's location. Using this bio-device, we developed a methodology to extract the arterial oxygen saturation using a single wavelength light source. We proved this method is not dependent on the light source and is applicable to different measurement locations on the body, with an error of 0.5%. Moreover, we tested thirty-eight males and females with the biosensor under normal conditions. Finally, we show the results of measuring subjects in a hypoxic chamber that simulates extreme conditions with low oxygen.

Optical Method for Detection and Classification of Heavy Metal Contaminants in Water Using Iso-pathlength Point Characterization.

Water pollution caused by hazardous substances, particularly heavy metal (HM) ions, poses a threat to human health and the environment. Traditional methods for measuring HM in water are expensive and time-consuming and require extensive sample preparation. Therefore, developing robust, simple, and sensitive techniques for the detection and classification of HM is needed. We propose an optical approach that exploits the full scattering profile, meaning the angular intensity distribution, and utilizes the iso-pathlength (IPL) point. This point appears where the intensity is constant for different scattering coefficients, while the absorption coefficient is set. The absorption does not affect the IPL point position, it only reduces its intensity. In this paper, we explore the wavelength influence on the IPL point both in Monte Carlo simulations and experimentally. Next, we present the characterization of ferric chloride (FeCl2) by this phenomenon. Eventually, we exhibit the detection of FeCl2 and intralipid mixed in concentrations of 50-100 and 20-30 ppm, respectively. These findings endorse the idea that the IPL point is an intrinsic parameter of a system serving as an absolute calibration point. The method provides an efficient way of differentiating contamination in water. Its characterization technique is easy, precise, and versatile making it preferable for water monitoring.

Bioimaging based on Poly(ethylenimine)-Coated Carbon Dots and Gold Nanoparticles for pH Sensing and Metal Enhanced Fluorescence.

When exposed to specific light wavelengths, carbon dots (CDs), which tend to be fluorescent, can emit colorful light. It provides them with a lot of adaptability for different applications including bioimaging, optoelectronics, and even environmental sensing. Poly(ethylenimine) (PEI) coated carbon dots (PEI-CDs) with a long emission wavelength were synthesized via the hydrothermal method. The resultant CDs show strong fluorescence with quantum yield up to 20.2%. The PEI-CDs exist with distinct pH-sensitive features with pH values in the range of 2-14. The optical characteristics of CDs are pH-responsive due to the presence of different amine groups on PEI, which is a functional polycationic polymer. One of the most widely employed nanoparticles for improving the fluorescence plasmonic characteristics of a nanocomposite is gold. Gold nanoparticles were coupled with PEI-CDs in this assay by using the EDC-NHS coupling to increase the photoluminescence property of the PEI-CDs by using the metal-enhanced fluorescence approach. In the presence of gold nanoparticles, the fluorescence is enhanced 5-6 times. The likely mechanism in our investigation was primarily derived from enhancement of the intrinsic radiative decay rate rather than the local electric field impact. Moreover, PEI-CDs can be used as a bioimaging agent, as these molecules are nontoxic to the cells, and the positively charged PEI-CDs have the potential for nuclear targeting, allowing for electrostatic contact with DNA in the nucleus. This finding will expand the application that the PEI-CDs can be used in the future for targeted imaging applications.

Probing Polarity and pH Sensitivity of Carbon Dots in Escherichia coli through Time-Resolved Fluorescence Analyses.

Intracellular monitoring of pH and polarity is crucial for understanding cellular processes and functions. This study employed pH- and polarity-sensitive nanomaterials such as carbon dots (CDs) for the intracellular sensing of pH, polarity, and viscosity using integrated time-resolved fluorescence anisotropy (FA) imaging (TR-FAIM) and fluorescence lifetime (FLT) imaging microscopy (FLIM), thereby enabling comprehensive characterization. The functional groups on the surface of CDs exhibit sensitivity to changes in the microenvironment, leading to variations in fluorescence intensity (FI) and FLT according to pH and polarity. The FLT of CDs in aqueous solution changed gradually from 6.38 ± 0.05 ns to 8.03 ± 0.21 ns within a pH range of 2-8. Interestingly, a complex relationship of FI and FLT was observed during measurements of CDs with decreasing polarity. However, the FA and rotational correlation time (θ) increased from 0.062 ± 0.019 to 0.112 ± 0.023 and from 0.49 ± 0.03 ns to 2.01 ± 0.27 ns, respectively. This increase in FA and θ was attributed to the higher viscosity accompanying the decrease in polarity. Furthermore, CDs were found to bind to three locations in Escherichia coli: the cell wall, inner membrane, and cytoplasm, enabling intracellular characterization using FI and FA decay imaging. FLT provided insights into cytoplasmic pH (7.67 ± 0.48), which agreed with previous works, as well as the decrease in polarity in the cell wall and inner membrane. The CD aggregation was suspected in certain areas based on FA, and the θ provided information on cytoplasmic heterogeneity due to the aggregation and/or interactions with biomolecules. The combined TR-FAIM/FLIM system allowed for simultaneous monitoring of pH and polarity changes through FLIM and viscosity variations through TR-FAIM.

Detecting Contaminants in Water Based on Full Scattering Profiles within the Single Scattering Regime.

Clean water is essential for maintaining human health. To ensure clean water, it is important to use sensitive detection methods that can identify contaminants in real time. Most techniques do not rely on optical properties and require calibrating the system for each level of contamination. Therefore, we suggest a new technique to measure water contamination using the full scattering profile, which is the angular intensity distribution. From this, we extracted the iso-pathlength (IPL) point which minimizes the effects of scattering. The IPL point is an angle where the intensity values remain constant for different scattering coefficients while the absorption coefficient is set. The absorption coefficient does not affect the IPL point but only attenuates its intensity. In this paper, we show the appearance of the IPL in single scattering regimes for small concentrations of Intralipid. We extracted a unique point for each sample diameter wherein light intensity remained constant. The results describe a linear dependency between the angular position of the IPL point and the sample diameter. In addition, we show that the IPL point separates the absorption from the scattering, which allows the absorption coefficient to be extracted. Eventually, we present how we used the IPL point to detect the contamination levels of Intralipid and India ink in concentrations of 30-46 and 0-4 ppm, respectively. These findings suggest that the IPL point is an intrinsic parameter of a system that can be used as an absolute calibration point. This method provides a new and efficient way of measuring and differentiating between various types of contaminants in water.

Ultrafast Temporal SU(1,1) Interferometer.

Interferometers are highly sensitive to phase differences and are utilized in numerous schemes. Of special interest is the quantum SU(1,1) interferometer which is able to improve the sensitivity of classical interferometers. We theoretically develop and experimentally demonstrate a temporal SU(1,1) interferometer based on two time lenses in a 4f configuration. This temporal SU(1,1) interferometer has a high temporal resolution, imposes interference on both time and spectral domains, and is sensitive to the phase derivative which is important for detecting ultrafast phase changes. Therefore, this interferometer can be utilized for temporal mode encoding, imaging, and studying the ultrafast temporal structure of quantum light.

Imaging the rotational mobility of carbon dot-gold nanoparticle conjugates using frequency domain wide-field time-resolved fluorescence anisotropy.

Significance: Wide-field measurements of time-resolved fluorescence anisotropy (TR-FA) provide pixel-by-pixel information about the rotational mobility of fluorophores, reflecting changes in the local microviscosity and other factors influencing the fluorophore's diffusional motion. These features offer promising potential in many research fields, including cellular imaging and biochemical sensing, as demonstrated by previous works. Nevertheless, θ imaging is still rarely investigated in general and in carbon dots (CDs) in particular. Aim: To extend existing frequency domain (FD) fluorescence lifetime (FLT) imaging microscopy (FLIM) to FD TR-FA imaging (TR-FAIM), which produces visual maps of the FLT and θ, together with the steady-state images of fluorescence intensity (FI) and FA (r). Approach: The proof of concept of the combined FD FLIM/ FD TR-FAIM was validated on seven fluorescein solutions with increasing viscosities and was applied for comprehensive study of two types of CD-gold nano conjugates. Results: The FLT of fluorescein samples was found to decrease from 4.01±0.01 to 3.56±0.02 ns, whereas both r and θ were significantly increased from 0.053±0.012 to 0.252±0.003 and 0.15±0.05 to 11.25±1.87 ns, respectively. In addition, the attachment of gold to the two CDs resulted in an increase in the FI due to metal-enhanced fluorescence. Moreover, it resulted in an increase of r from 0.100±0.011 to 0.150±0.013 and θ from 0.98±0.13 to 1.65±0.20 ns for the first CDs and from 0.280±0.008 to 0.310±0.004 and 5.55±1.08 to 7.95±0.97 ns for the second CDs. These trends are due to the size increase of the CDs-gold compared to CDs alone. The FLT presented relatively modest changes in CDs. Conclusions: Through the combined FD FLIM/ FD TR-FAIM, a large variety of information can be probed (FI, FLT, r, and θ). Nevertheless, θ was the most beneficial, either by probing the spatial changes in viscosity or by evident variations in the peak and full width half maximum.

Fluorescence attenuated by a thick scattering medium: Theory, simulations and experiments.

Fluorescence-based imaging has an enormous impact on our understanding of biological systems. However, in vivo fluorescence imaging is greatly influenced by tissue scattering. A better understanding of this dependence can improve the potential of noninvasive in vivo fluorescence imaging. In this article, we present a diffusion model, based on an existing master-slave model, of isotropic point sources imbedded in a scattering slab, representing fluorophores within a tissue. The model was compared with Monte Carlo simulations and measurements of a fluorescent slide measured through tissue-like phantoms with different reduced scattering coefficients (0.5-2.5 mm-1 ) and thicknesses (0.5-5 mm). Results show a good correlation between our suggested theory, simulations and experiments; while the fluorescence intensity decays as the slab's scattering and thickness increase, the decay rate decreases as the reduced scattering coefficient increases in a counterintuitive manner, suggesting fewer fluorescence artifacts from deep within the tissue in highly scattering media.

Recent Advances in the Spintronic Application of Carbon-Based Nanomaterials.

The term "carbon-based spintronics" mostly refers to the spin applications in carbon materials such as graphene, fullerene, carbon nitride, and carbon nanotubes. Carbon-based spintronics and their devices have undergone extraordinary development recently. The causes of spin relaxation and the characteristics of spin transport in carbon materials, namely for graphene and carbon nanotubes, have been the subject of several theoretical and experimental studies. This article gives a summary of the present state of research and technological advancements for spintronic applications in carbon-based materials. We discuss the benefits and challenges of several spin-enabled, carbon-based applications. The advantages include the fact that they are significantly less volatile than charge-based electronics. The challenge is in being able to scale up to mass production.

Noninvasive Nanodiamond Skin Permeation Profiling Using a Phase Analysis Method: Ex Vivo Experiments.

Carbon-based nanoparticles (NPs) are widely used in nanotechnology. Among them, nanodiamonds (NDs) are suitable for biotechnology and are especially interesting for skin delivery and topical treatments. However, noninvasive detection of NDs within the different skin layers or analyzing their penetration ability is complicated due to the turbid nature of the tissue. The iterative multiplane optical properties extraction (IMOPE) technique detects differences in the optical properties of the measured item by a phase-image analysis method. The phase image is reconstructed by the multiplane Gerchberg-Saxton algorithm. This technique, traditionally, detects differences in the reduced scattering coefficients. Here, however, due to the actual size of the NDs, the IMOPE technique's detection relies on absorption analysis rather than relying on scattering events. In this paper, we use the IMOPE technique to detect the presence of the NDs within tissue-like phantoms. In addition, we perform ex vivo pigskin experiments to estimate the penetration of the NDs to the different skin layers and show that their presence reduces at deeper layers. The significance signal of the NDs within the epidermis, dermis, and fat layers gradually reduces, with t test significance values that are smaller than 10-4, 10-3, and 10-2, respectively. The IMOPE results are corroborated by TEM results and Franz-cell experiments. These results confirm that the IMOPE profiled the skin-permeation of the NDs noninvasively.

Design and Use of a Gold Nanoparticle-Carbon Dot Hybrid for a FLIM-Based IMPLICATION Nano Logic Gate.

The interest in nanomaterials resides in the fact that they can be used to create smaller, faster, and more portable systems. Nanotechnology is already transforming health care. Nanoparticles are being used by scientists to target malignancies, improve drug delivery systems, and improve medical imaging. Integration of biomolecular logic gates with nanostructures has opened new paths in illness detection and therapy that need precise control of complicated components. Most studies have used fluorescence intensity techniques to implement the logic function. Its drawbacks, mainly when working with nanoparticles in intracellular media, include fluctuations in excitation power, fluorophore concentration dependence, and interference from cell autofluorescence. We suggest using fluorescence lifetime imaging microscopy (FLIM) in order to circumvent these constraints. Designing a nanohybrid composed of gold nanoparticles (AuNPs) and red-emitting carbon dots (CDs) can be used to develop a FLIM-based logic gate that can respond to multiple input parameters. Our findings indicate a nanohybrid that can serve as a nano-computer to receive and integrate chemical and biochemical stimuli and produce a definitive output measured by FLIM. This can open a new research avenue for enhanced diagnostics and therapy that require complicated factor handling and precise control. The AuNPs are conjugated to CDs' surfaces through a strong covalent linkage. The AuNP-CD nanohybrid shows fluorescence lifetime (FLT) quenching of pristine CDs after conjugation to AuNPs. The FLT was reduced from 3.61 ± 0.037 to 2.48 ± 0.040 ns. This quenched FLT can be recovered back by using trypsin as a recovering agent, giving us a reversible logic output. The FLT was recovered to 3.01 ± 0.01 ns after trypsin addition. This "on-off-on" response can be used to construct the IMPLICATION logic gate.

Simultaneous Noninvasive Detection and Therapy of Atherosclerosis Using HDL Coated Gold Nanorods.

Cardiovascular disease (CVD) is a major cause of death and disability worldwide. A real need exists in the development of new, improved therapeutic methods for treating CVD, while major advances in nanotechnology have opened new avenues in this field. In this paper, we report the use of gold nanoparticles (GNPs) coated with high-density lipoprotein (HDL) (GNP-HDL) for the simultaneous detection and therapy of unstable plaques. Based on the well-known HDL cardiovascular protection, by promoting the reverse cholesterol transport (RCT), injured rat carotids, as a model for unstable plaques, were injected with the GNP-HDL. Noninvasive detection of the plaques 24 h post the GNP injection was enabled using the diffusion reflection (DR) method, indicating that the GNP-HDL particles had accumulated in the injured site. Pathology and noninvasive CT measurements proved the recovery of the injured artery treated with the GNP-HDL. The DR of the GNP-HDL presented a simple and highly sensitive method at a low cost, resulting in simultaneous specific unstable plaque diagnosis and recovery.

Single-shot analysis of amplified correlated light.

Correlated beams are important in classical and quantum communication as well as other technologies. However, classical amplifiers, which are essential for long transmission of correlated beams, degrade the correlation due to noise and due to the amplifier spectral response. We measure, with a novel high resolution single-shot measurement system, the impact of amplifiers on correlated beams. We develop a new method for analyzing the correlation between the signal and idler beams by choosing peaks in the pulses according to their power levels. We demonstrate how to tailor the correlation after the amplifier to obtain either higher or lower correlation. Our research may influence the future use of amplifiers in non-classical communication systems as well as the transmission of quantum information over long distances.

Classification of fluorescent anisotropy decay based on the distance approach in the frequency domain.

Frequency-domain (FD) fluorometry is a widely utilized tool to probe unique features of complex biological structures, which may serve medical diagnostic purposes. The conventional data analysis approaches used today to extract the fluorescence intensity or fluorescence anisotropy (FA) decay data suffer from several drawbacks and are inherently limited by the characteristics and complexity of the decay models. This paper presents the squared distance (D2) technique, which categorized samples based on the direct frequency response data (FRD) of the FA decay. As such, it improves the classification ability of the FD measurements of the FA decay as it avoids any distortion that results from the challenged translation into time domain data. This paper discusses the potential use of the D2 approach to classify biological systems. Mathematical formulation of D2 technique adjusted to the FRD of the FA decay is described. In addition, it validates the D2 approach using 2 simulated data sets of 6 groups with similar widely and closely spaced FA decay data as well as in experimental data of 4 samples of a fluorophore-solvent (fluorescein-glycerol) system. In the simulations, the classification accuracy was above 95% for all 6 groups. In the experimental data, the classification accuracy was 100%. The D2 approach can help classify samples whose FA decay data are difficult to extract making FA in the FD a realistic diagnostic tool. The D2 approach offers an advanced method for sorting biological samples with differences beyond the practical temporal resolution limit in a reliable and efficient manner based on the FRD of their time-resolved fluorescence measurements thereby achieving better diagnostic quality in a shorter time.

Diffused reflectance measurements to detect tattoo ink location in skin using the crossover point.

Tattoos are highly trendy in western culture, but many people regret their tattoos for many reasons. It is essential to be aware of the ink location in advance to reduce the long and short-term side effects. In this study, diffuse reflectance (DR) experiments were conducted on two-layer (2L) tissue-mimicking phantoms, where ink was sandwiched between the layers. An appreciable difference in the DR profile was found between the 2L phantom with and without the tattoo ink using the crossover point (Cp) method. Our technique was applied to ex vivo porcine skin. A point of intersection was found, between the skin and the tattooed skin. In the shorter wavelengths (500-600 nm), a distinguishable 2L behavior was found, and in longer wavelengths (600-850 nm), a single layer behavior was found between the tattooed skin before and after the intersection. In biological tissue, this Cp indeed finds the tattoo ink without harm to the surrounding skin.

Bottom layer absorption coefficients extraction from two-layer phantoms based on crossover point in diffuse reflectance.

SIGNIFICANCE: Numerous optical imaging and spectroscopy techniques are used to study the tissue-optical properties; the majority of them are limited in information regarding the penetration depth. A simple, safe, easily applicable diagnostic technique is required to get deeper tissue information in a multilayer structure. AIM: A fiber-based diffuse reflectance (DR) technique is used to extract and quantify the bottom layer absorption coefficients in two-layer (2L) tissue-mimicking solid phantoms. We determine the Indian black ink concentrations in a deep-hidden layer that is sandwiched between agar and silicone-based phantom layers. APPROACH: A fiber-based DR experiment was performed to study the optical properties of the tissue at higher penetration depth, with different fiber core diameters and a constant numerical aperture (0.5 NA). The optimal core diameter of the fiber was chosen by measuring solid phantoms. In 2L phantoms, the thickness of the top layer was kept 5.5 mm with a constant absorption and reduced scattering coefficients (µa = 0.045 mm - 1 and µs ' = 2.622 mm - 1), whereas the absorption coefficients of the bottom layers were varied from 0.014 to 0.037 mm - 1 keeping the µs ' the same as the top layer. A unique crossover point (Cp) was found in the DR intensity profile against distance. We examined the slope before and after the Cp. These two slopes indicate the difference between the optical properties of the top and bottom layers. Our technique got further verification, as we successfully determined the Cp with different Indian black ink concentrations, placed at the junction between the agar and silicone-based phantom layers. RESULTS: The DR measurements were applied to 2L phantoms. Two different slopes were found in 2L phantoms compared to the one-layer (optical properties equal to the top layer of 2L). We extracted the slopes before and after the Cp in the 2L phantoms. The calculated absorption coefficients before the Cp were 0.014 ± 0.0004, 0.022 ± 0.0003, 0.028 ± 0.0003, and 0.036 ± 0.0014 mm - 1, and the absorption coefficients after the Cp were 0.019 ± 0.0013, 0.013 ± 0.0004, 0.014 ± 0.0006, and 0.031 ± 0.0001 mm - 1, respectively. The calculated absorption coefficients before the Cp were in good agreement with the optical properties of the bottom layer. The calculated absorption coefficients after the Cp were not the same as the top layer. Our DR system successfully determines the crossover points 12.14 ± 0.11 and 11.73 ± 0.15 mm for 70% and 100% ink concentrations placed at the junction of the agar and silicone layers. CONCLUSIONS: In a 2L tissue structure, the Cp depends on the absorption coefficients of top and bottom layers and the thickness of the top layer. With the help of the Cp and the absorption coefficients, one can determine the thickness of the top layer or vice versa. The slope value before the Cp in the DR profile allowed us to determine the absorption properties of the bottom layer instead of having the average behavior of the 2L phantom in the far detection range (11.0 to 17.0 mm).

Iterative optical technique for detecting anti-leishmania nanoparticles in mouse lesions.

Nanoparticles (NPs) based drugs for topical administration are gaining interest in the biomedical world. However, a study tool of their penetration depth to the different tissue layers without additional markers or contrast agents is required in order to relieve safety concerns. While common diagnostic tools, e.g. X-ray, computed tomography or magnetic resonance imaging, can provide in vivo detection of the metallic NPs, their resolution cannot determine the exact penetration depth to the thin skin layers. In this work, we propose the noninvasive nanophotonics iterative multi-plane optical property extraction (IMOPE) technique for the novel iron-based NPs detection in leishmaniasis lesions. The optical properties of the different tissue layers: epidermis, dermis, subcutaneous fat and muscle, were examined before and after topical drug administration. The potential topical drug was detected in the epidermis (∼13µm) and dermis (∼160µm) layers in mice lesions at different stages of the disease (two or four weeks post infection). The lesion size influence on the detection was also observed, where in larger lesions the IMOPE senses a greater presence of the topical drug.

Cross-phase modulation aberrations in time lenses.

We study the aberrations of four-wave mixing based time lenses resulting from the cross-phase modulations of the pump wave. These temporal aberrations have no spatial equivalent and are important when imaging weak signals with strong pump waves. We show that as the pump power increases, the cross-phase modulations of the pump are responsible for shifting, defocusing, and imposing temporal coma aberrations on the image. We present experimental results of these aberrations with high agreement to analytical and numerical calculations.

Effect of optical magnification on the detection of the reduced scattering coefficient in the blue regime: theory and experiments.

Imaging turbid media is range limited. In contrast, sensing the medium's optical properties is possible in larger depths using the iterative multi-plane optical properties extraction technique. It analyzes the reconstructed reemitted light phase image. The root mean square of the phase image yields two graphs with opposite behaviors that intersect at µ's,cp. These graphs enable the extraction of a certain range of the reduced scattering coefficient, µ's. Here, we aim to extend the range of µ's detection by optical magnification. We use a modified diffusion theory and show how µ's,cp shifts with the varying magnification. The theoretical results were tested experimentally, showing that the technique can be adapted to different ranges of µ's by changing the magnification.

Polarization dynamics of ultrafast solitons.

We study the polarization dynamics of ultrafast solitons in mode-locked fiber lasers. We find that when a stable soliton is generated, its state of polarization shifts toward a stable state, and when the soliton is generated with excess power levels it experiences relaxation oscillations in its intensity and timing. On the other hand, when a soliton is generated in an unstable state of polarization, it either decays in intensity until it disappears, or its temporal width decreases until it explodes into several solitons, and then it disappears. We also found that when two solitons are simultaneously generated close to each other, they attract each other until they collide and merge into a single soliton. Although these two solitons are generated with different states-of-polarization, they shift their state of polarization closer to each other until the polarization coincides when they collide. We support our findings by numerical calculations of a non-Lagrangian approach by simulating the Ginzburg-Landau equation governing the dynamics of solitons in a laser cavity. Our model also predicts the relaxation oscillations of stable solitons and the two types of unstable solitons observed in the experimental measurements.