Precise date for the Laacher See eruption synchronizes the Younger Dryas.

The Laacher See eruption (LSE) in Germany ranks among Europe's largest volcanic events of the Upper Pleistocene1,2. Although tephra deposits of the LSE represent an important isochron for the synchronization of proxy archives at the Late Glacial to Early Holocene transition3, uncertainty in the age of the eruption has prevailed4. Here we present dendrochronological and radiocarbon measurements of subfossil trees that were buried by pyroclastic deposits that firmly date the LSE to 13,006 ± 9 calibrated years before present (BP; taken as AD 1950), which is more than a century earlier than previously accepted. The revised age of the LSE necessarily shifts the chronology of European varved lakes5,6 relative to the Greenland ice core record, thereby dating the onset of the Younger Dryas to 12,807 ± 12 calibrated years BP, which is around 130 years earlier than thought. Our results synchronize the onset of the Younger Dryas across the North Atlantic-European sector, preclude a direct link between the LSE and Greenland Stadial-1 cooling7, and suggest a large-scale common mechanism of a weakened Atlantic Meridional Overturning Circulation under warming conditions8-10.

Diffuse reflectance spectroscopy for colorectal cancer surgical guidance: towards real-time tissue characterization and new biomarkers.

Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide, representing 11.3% of the diagnosed cancer cases and resulting in 10.2% (0.88 million) of the cancer related deaths in 2020. CRCs are typically detected at the late stage, which leads to high mortality and morbidity. Mortality and poor prognosis are partially caused by cancer recurrence and postoperative complications. Patient survival could be increased by improving precision in surgical resection using accurate surgical guidance tools based on diffuse reflectance spectroscopy (DRS). DRS enables real-time tissue identification for potential cancer margin delineation through determination of the circumferential resection margin (CRM), while also supporting non-invasive and label-free approaches for laparoscopic surgery to avoid short-term complications of open surgery as suitable. In this study, we have estimated the scattering properties and chromophore concentrations based on 2949 DRS measurements of freshly excised ex vivo specimens of 47 patients, and used this estimation to classify normal colorectal wall (CW), fat and tumor tissues. DRS measurements were performed with fiber-optic probes of 630 µm source-detector distance (SDD; probe 1) and 2500 µm SDD (probe 2) to measure tissue layers ∼0.5-1 mm and ∼0.5-2 mm deep, respectively. By using the 5-fold cross-validation of machine learning models generated with the classification and regression tree (CART) algorithm, we achieved 95.9 ± 0.7% sensitivity, 98.9 ± 0.3% specificity, 90.2 ± 0.4% accuracy, and 95.5 ± 0.3% AUC for probe 1. Similarly, we achieved 96.9 ± 0.8% sensitivity, 98.9 ± 0.2% specificity, 94.0 ± 0.4% accuracy, and 96.7 ± 0.4% AUC for probe 2.

Fabrication and characterization of multi-biomarker optimized tissue-mimicking phantoms for multi-modal optical spectroscopy.

Rapid advancement of novel optical spectroscopy and imaging systems relies on the availability of well-characterised and reproducible protocols for phantoms as a standard for the validation of the technique. The tissue-mimicking phantoms are also used to investigate photon transport in biological samples before clinical trials that require well-characterized phantoms with known optical properties (reduced scattering (µ's) and absorption (µa) coefficients). However, at present, there is limited literature available providing well-characterized phantom recipes considering various biomarkers and tested over a wide range of optical properties covering most of the human organs and applicable to multimodal optical spectroscopy. In this study, gelatin-based phantoms were designed to simulate tissue optical properties where India ink and Intralipid were used as absorbing and scattering agents, respectively. Multiple biomarkers were simulated by varying the gelatin concentration to mimic the change in tissue hydration and hydroxyapatite concentration to mimic bone signature. The recipe along with biomarkers were optimized and characterised over a wide range of optical properties (µa from 0.1 to 0.5 cm-1; µ's from 5 to 15 cm-1) relevant to human tissue using a broadband time-domain diffuse optical spectrometer. The data collected showed a linear relationship between the concentration of ink/lipids and µa/µ's values with negligible coupling between µa and µ's values. While being stored in a refrigerator post-fabrication, the µa and µ's did not change significantly (<4% coefficient of variation, 'CV') over three weeks. The reproducibility in three different sets was validated experimentally and found to be strong with a variation of ≤6% CV in µa and ≤9% CV in µ's. From the 3 × 3 data of µa and µ's matrices, one can deduce the recipe for any target absorption or reduced scattering coefficient. The applicability of the phantoms was tested using diffuse reflectance and Raman spectrometers. A use case application was demonstrated for Raman spectroscopy where hydration and hydroxyapatite phantoms were designed to characterize the Raman instrument. The Raman instrument could detect the change in 1% of HA and 5% of hydration. This study presents a first-of-its-kind robust, well-characterized, multi-biomarker phantom recipe for calibration and benchmarking of multimodal spectroscopy devices assisting in their clinical translation.

Mobile multi-configuration clinical translational Raman system for oral cancer application.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

Multi-variable compensated quantum yield measurements of upconverting nanoparticles with high dynamic range: a systematic approach.

Non-linear materials such as upconverting nanoparticles (UCNPs) are emerging technology with fast-growing applications in various fields. The power density dependence of the emission quantum yield (QY) of these non-linear materials makes them challenging to characterize using currently available commercial QY systems. We propose a multimodal system to measure QY over a wide dynamic range (1:104), which takes into account and compensates for various distorting parameters (scattering, beam profile, inner filter effect and bandwidth of emission lines). For this, a beam shaping approach enabling speckle free beam profiles of two different sizes (530 µm or 106 µm) was employed. This provides low noise high-resolution QY curves. In particular, at low power densities, a signal-to-noise ratio of >50 was found. A Tm-based core-shell UCNP with excitation at 976 nm and emission at 804 nm was investigated with the system.

Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care.

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care. IMPACT: This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses. This review summarises the current literature investigating the concept of optical lung oxygen measurement. Information from this review can guide researchers in future studies.

Temperature change as a driver of spatial patterns and long-term trends in chironomid (Insecta: Diptera) diversity.

Anthropogenic activities have led to a global decline in biodiversity, and monitoring studies indicate that both insect communities and wetland ecosystems are particularly affected. However, there is a need for long-term data (over centennial or millennial timescales) to better understand natural community dynamics and the processes that govern the observed trends. Chironomids (Insecta: Diptera: Chironomidae) are often the most abundant insects in lake ecosystems, sensitive to environmental change, and, because their larval exoskeleton head capsules preserve well in lake sediments, they provide a unique record of insect community dynamics through time. Here, we provide the results of a metadata analysis of chironomid diversity across a range of spatial and temporal scales. First, we analyse spatial trends in chironomid diversity using Northern Hemispheric data sets overall consisting of 837 lakes. Our results indicate that in most of our data sets, summer temperature (Tjul ) is strongly associated with spatial trends in modern-day chironomid diversity. We observe a strong increase in chironomid alpha diversity with increasing Tjul in regions with present-day Tjul between 2.5 and 14°C. In some areas with Tjul  > 14°C, chironomid diversity stabilizes or declines. Second, we demonstrate that the direction and amplitude of change in alpha diversity in a compilation of subfossil chironomid records spanning the last glacial-interglacial transition (~15,000-11,000 years ago) are similar to those observed in our modern data. A compilation of Holocene records shows that during phases when the amplitude of temperature change was small, site-specific factors had a greater influence on the chironomid fauna obscuring the chironomid diversity-temperature relationship. Our results imply expected overall chironomid diversity increases in colder regions such as the Arctic under sustained global warming, but with complex and not necessarily predictable responses for individual sites.

Beam-profile-compensated quantum yield measurements of upconverting nanoparticles.

The quantum yield is a critically important parameter in the development of lanthanide-based upconverting nanoparticles (UCNPs) for use as novel contrast agents in biological imaging and optical reporters in assays. The present work focuses on the influence of the beam profile in measuring the quantum yield (ϕ) of nonscattering dispersions of nonlinear upconverting probes, by establishing a relation between ϕ and excitation light power density from a rate equation analysis. A resulting 60% correction in the measured ϕ due to the beam profile utilized for excitation underlines the significance of the beam profile in such measurements, and its impact when comparing results from different setups and groups across the world.

Quasi-Continuous Wave Near-Infrared Excitation of Upconversion Nanoparticles for Optogenetic Manipulation of C. elegans.

Optogenetics is an emerging powerful tool to investigate workings of the nervous system. However, the use of low tissue penetrating visible light limits its therapeutic potential. Employing deep penetrating near-infrared (NIR) light for optogenetics would be beneficial but it cannot be used directly. This issue can be tackled with upconversion nanoparticles (UCNs) acting as nanotransducers emitting at shorter wavelengths extending to the UV range upon NIR light excitation. Although attractive, implementation of such NIR-optogenetics is hindered by the low UCN emission intensity that necessitates high NIR excitation intensities, resulting in overheating issues. A novel quasi-continuous wave (quasi-CW) excitation approach is developed that significantly enhances multiphoton emissions from UCNs, and for the first time NIR light-triggered optogenetic manipulations are implemented in vitro and in C. elegans. The approach developed here enables the activation of channelrhodopsin-2 with a significantly lower excitation power and UCN concentration along with negligible phototoxicity as seen with CW excitation, paving the way for therapeutic optogenetics.

Diode laser spectroscopy for noninvasive monitoring of oxygen in the lungs of newborn infants.

BACKGROUND: Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants. METHODS: Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode. RESULTS: Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of >3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight. CONCLUSION: The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care.

Computationally effective solution of the inverse problem in time-of-flight spectroscopy.

Photon time-of-flight (PTOF) spectroscopy enables the estimation of absorption and reduced scattering coefficients of turbid media by measuring the propagation time of short light pulses through turbid medium. The present investigation provides a comparison of the assessed absorption and reduced scattering coefficients from PTOF measurements of intralipid 20% and India ink-based optical phantoms covering a wide range of optical properties relevant for biological tissues and dairy products. Three different models are used to obtain the optical properties by fitting to measured temporal profiles: the Liemert-Kienle model (LKM), the diffusion model (DM) and a white Monte-Carlo (WMC) simulation-based algorithm. For the infinite space geometry, a very good agreement is found between the LKM and WMC, while the results obtained by the DM differ, indicating that the LKM can provide accurate estimation of the optical parameters beyond the limits of the diffusion approximation in a computational effective and accurate manner. This result increases the potential range of applications for PTOF spectroscopy within industrial and biomedical applications.

Potential of multi-photon upconversion emissions for fluorescence diffuse optical imaging.

The spatial resolution of fluorescence molecular imaging is a critical issue for the success of the technique in biomedical applications. One important method for increasing the imaging resolution is to utilize multi-photon emissions. In this study, we thoroughly investigate the potential of the multi-photon upconversion emissions from rare-earth-doped upconverting nanoparticles for the improvement in spatial resolution of diffuse optical imaging. It is found that the imaging resolution is increased by a factor of 1.45 through employing two-photon upconversion emission compared with using the linear emission, and can be further elevated by a factor of 1.23 by using three-photon upconversion emission. In addition, we demonstrate that the pulsed excitation approach holds the promise of overcoming the low quantum yield associated with the high-order upconversion emissions.

Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications.

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355-1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.

Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Teaching and learning in biophotonics: Crossing the bridge between educators and students.

As a rapidly growing field, biophotonics demonstrates an increasingly higher demand for interdisciplinary professionals and requires the implementation of a structured approach to educational and outreach activities focused on appropriate curriculum, and teaching and learning for audiences with diverse technical backgrounds and learning styles. Our study shows the main findings upon applying this approach to biophotonics workshops delivered 2 consecutive years while updating and improving learning outcomes, teaching strategies, workshop content based on student and teacher feedback. We provided resources for a variety of lecture-based, experimental, computer simulation activities. Quality of subject matter, teaching, and overall learning was rated as "Very good" or "Good" by 88%, 76%, and 82% of students in average, respectively. Application of our teaching strategies and materials during short- and long-term workshops/courses could potentially increase the interest in pursuing careers in the biophotonics field and related areas, leading to standardized approaches in designing education and outreach events across centers.

High contrast breast cancer biomarker semi-quantification and immunohistochemistry imaging using upconverting nanoparticles.

Breast cancer is the second leading cause of cancer death in women. Current clinical treatment stratification practices open up an avenue for significant improvements, potentially through advancements in immunohistochemistry (IHC) assessments of biopsies. We report a high contrast upconverting nanoparticles (UCNP) labeling to distinguish different levels of human epidermal growth factor receptor 2 (HER2) in HER2 control pellet arrays (CPAs) and HER2-positive breast cancer tissue. A simple Fourier transform algorithm trained on CPAs was sufficient to provide a semi-quantitative HER2 assessment tool for breast cancer tissues. The UCNP labeling had a signal-to-background ratio of 40 compared to the negative control.

Hybrid heterogeneous phantoms for biomedical applications: a demonstration to dosimetry validation.

Phantoms simultaneously mimicking anatomical and optical properties of real tissues can play a pivotal role for improving dosimetry algorithms. The aim of the paper is to design and develop a hybrid phantom model that builds up on the strengths of solid and liquid phantoms for mimicking various anatomical structures for prostate cancer photodynamic therapy (PDT) dosimetry validation. The model comprises of a photosensitizer-embedded gelatin lesion within a liquid Intralipid prostate shape that is surrounded by a solid silicone outer shell. The hybrid phantom was well characterized for optical properties. The final assembled phantom was also evaluated for fluorescence tomographic reconstruction in conjunction with SpectraCure's IDOSE software. The developed model can lead to advancements in dosimetric evaluations. This would improve PDT outlook as a clinical treatment modality and boost phantom based standardization of biophotonic devices globally.

Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly scattering plastics in the VIS and close NIR spectral ranges.

We present extended spectroscopic analysis of pharmaceutical tablets in the close near infrared spectral range performed using broadband photon time-of-flight (PTOF) absorption and scattering spectra measurements. We show that the absorption spectra can be used to perform evaluation of the chemical composition of pharmaceutical tablets without need for chemo-metric calibration. The spectroscopic analysis was performed using an advanced PTOF spectrometer operating in the 650 to 1400 nm spectral range. By employing temporal stabilization of the system we achieve the high precision of 0.5% required to evaluate the concentration of tablet ingredients. In order to further illustrate the performance of the system, we present the first ever reported broadband evaluation of absorption and scattering spectra from pure and doped Spectralon®.

Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications.

The editorial introduces the JBO Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications.