Optical fiber-based sensing method for nanoparticle detection through supervised back-scattering analysis: A potential contributor for biomedicine

Background: In view of the growing importance of nanotechnologies, the detection/identification of nanoparticles type has been considered of utmost importance. Although the characterization of synthetic/organic nanoparticles is currently considered a priority (eg, drug delivery devices, nanotextiles, theranostic nanoparticles), there are many examples of “naturally” generated nanostructures - for example, extracellular vesicles (EVs), lipoproteins, and virus - that provide useful information about human physiology or clinical conditions. For example, the detection of tumor-related exosomes, a specific type of EVs, in circulating fluids has been contributing to the diagnosis of cancer in an early stage. However, scientists have struggled to find a simple, fast, and low-cost method to accurately detect/identify these nanoparticles, since the majority of them have diameters between 100 and 150 nm, thus being far below the diffraction limit. Methods: This study investigated if, by projecting the information provided from short-term portions of the back-scattered laser light signal collected by a polymeric lensed optical fiber tip dipped into a solution of synthetic nanoparticles into a lower features dimensional space, a discriminant function is able to correctly detect the presence of 100 nm synthetic nanoparticles in distilled water, in different concentration values. Results and discussion: This technique ensured an optimal performance (100% accuracy) in detecting nanoparticles for a concentration above or equal to 3.89 µg/mL (8.74E+10 particles/mL), and a performance of 90% for concentrations below this value and higher than 1.22E-03 µg/mL (2.74E+07 particles/mL), values that are compatible with human plasmatic levels of tumorderived and other types of EVs, as well as lipoproteins currently used as potential biomarkers of cardiovascular diseases. Conclusion: The proposed technique is able to detect synthetic nanoparticles whose dimensions are similar to EVs and other “clinically” relevant nanostructures, and in concentrations equivalent to the majority of cell-derived, platelet-derived EVs and lipoproteins physiological levels. This study can, therefore, provide valuable insights towards the future development of a device for EVs and other biological nanoparticles detection with innovative characteristics.This work was partly developed under the project NanoSTIMA, funded by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF). It was also funded by the Portuguese Foundation for Science and Technology (PhD research grant PD/BD/135023/2017). Rita SR Ribeiro is currently working at 4Dcell and Elvesys, Paris, France

Author Correction: iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification

An amendment to this paper has been published and can be accessed via a link at the top of the paper.This work was partially funded by the projects NanoSTIMA and NORTE-01-0145-FEDER-000029, both supported by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF); and by the Portuguese Foundation for Science and Technology, within the scope of the PhD grant PD/BD/135023/2017 and the projects: PTDC/BBB-EBI/0567/2014 (to CAR) and UID/BIM/04293/2013. It was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; PPBI-POCI-01-0145-FEDER-022122). MB acknowledges the Marie Sklodowska-Curie grant agreement No. 748880

Exploring the sub-eV neutrino mass range with supernova neutrinos

A new method to study the effects of neutrino masses on a supernova neutrino signal is proposed. The method relies exclusively on the analysis of the full statistics of neutrino events, it is independent of astrophysical assumptions, and does not require the observation of any additional phenomenon to trace possible delays in the neutrino arrival times. The sensitivity of the method to the sub-eV neutrino mass range, defined as the capability of disentangling at 95% c.l. the case $m_\nu=1$eV from $m_\nu=0$, is tested by analyzing a set of synthetic neutrino samples modeled according to the signal that could be detected at SuperKamiokande. For a supernova at the Galactic center success is achieved in more than 50% of the cases. It is argued that a future Galactic supernova yielding several thousands of inverse $\beta$ decays might provide enough information to explore a neutrino mass range somewhat below 1 eV.Comment: Included analysis with numerical neutrino energy spectrum and oscillations effects. 7 pages, 6 figure

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

High sensitivity LPG Mach-Zehnder sensor for real-time fuel conformity analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)A high sensitivity refractive index sensor based on the combination of mechanically induced long period gratings (LPG) and fiber tapers was developed for real-time fuel quality analysis. The sensor was built in a Mach-Zehnder configuration by employing a pair of in-series gratings. In order to enhance sensor sensitivity, the region between both LPGs was tapered down from 125 to 10 mu m. The system was tested by measuring water concentration in ethanol and ethanol concentration in commercial gasoline. The tapered sensor has shown an average sensitivity of 930 nm/RIU, 18 times higher than the non-tapered version. The resolution limit of the system using spectral interrogation was estimated to be 0.06% of ethanol dissolved in gasoline. For the purpose of real-time monitoring, an interrogation system based on white light interferometry (WLI) and virtual instrumentation was employed to evaluate ethanol evaporation in water, avoiding the use of spectral analysis. The WLI system, using phase tracking techniques, enabled us to record the evolution of the ethanol concentration in water with a resolution of 0.005% (v/v).241Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Building a robust Middle Cambrian astrochronology using deep-water rhythmites and parsequences in the Marjum Formation of western North America

peer reviewe

iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification

With the advent of personalized medicine, there is a movement to develop “smaller” and “smarter” microdevices that are able to distinguish similar cancer subtypes. Tumor cells display major differences when compared to their natural counterparts, due to alterations in fundamental cellular processes such as glycosylation. Glycans are involved in tumor cell biology and they have been considered to be suitable cancer biomarkers. Thus, more selective cancer screening assays can be developed through the detection of specific altered glycans on the surface of circulating cancer cells. Currently, this is only possible through time-consuming assays. In this work, we propose the “intelligent” Lab on Fiber (iLoF) device, that has a high-resolution, and which is a fast and portable method for tumor single-cell type identification and isolation. We apply an Artificial Intelligence approach to the back-scattered signal arising from a trapped cell by a micro-lensed optical fiber. As a proof of concept, we show that iLoF is able to discriminate two human cancer cell models sharing the same genetic background but displaying a different surface glycosylation profile with an accuracy above 90% and a speed rate of 2.3 seconds. We envision the incorporation of the iLoF in an easy-to-operate microchip for cancer identification, which would allow further biological characterization of the captured circulating live cells.This work was partially funded by the projects NanoSTIMA and NORTE-01-0145-FEDER-000029, both supported by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF); and by the Portuguese Foundation for Science and Technology, within the scope of the PhD grant PD/BD/135023/2017 and the projects: PTDC/BBB-EBI/0567/2014 (to CAR) and UID/BIM/04293/2013. It was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; PPBI-POCI-01-0145-FEDER-022122). MB acknowledges the Marie Sklodowska-Curie grant agreement No. 748880