Geiger-Mode Avalanche Photodiodes in Standard CMOS Technologies

Photodiodes are the simplest but most versatile semiconductor optoelectronic devices. They can be used for direct detection of light, of soft X and gamma rays, and of particles such as electrons or neutrons. For many years, the sensors of choice for most research and industrial applications needing photon counting or timing have been vacuum-based devices such as Photo-Multiplier Tubes, PMT, and Micro-Channel Plates, MCP (Renker, 2004). Although these photodetectors provide good sensitivity, noise and timing characteristics, they still suffer from limitations owing to their large power consumption, high operation voltages and sensitivity to magnetic fields, as well as they are still bulky, fragile and expensive. New approaches to high-sensitivity imagers tend to use CCD cameras coupled with either MCP Image Intensifiers, I-CCDs, or Electron Multipliers, EM-CCDs (Dussault & Hoess, 2004), but they still have limited performances in extreme time-resolved measurements. A fully solid-state solution can improve design flexibility, cost, miniaturization, integration density, reliability and signal processing capabilities in photodetectors. In particular, Single- Photon Avalanche Diodes, SPADs, fabricated by conventional planar technology on silicon can be used as particle (Stapels et al., 2007) and photon (Ghioni et al., 2007) detectors with high intrinsic gain and speed. These SPAD are silicon Avalanche PhotoDiodes biased above breakdown. This operation regime, known as Geiger mode, gives excellent single-photon sensitivity thanks to the avalanche caused by impact ionization of the photogenerated carriers (Cova et al., 1996). The number of carriers generated as a result of the absorption of a single photon determines the optical gain of the device, which in the case of SPADs may be virtually infinite. The basic concepts concerning the behaviour of G-APDs and the physical processes taking place during their operation will be reviewed next, as well as the main performance parameters and noise sources

Epidemiological characteristics and outcomes of COVID-19 cases: mortality inequalities by socio-economic status, Barcelona, Spain, 24 February to 4 May 2020

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiologia; Situació socioeconòmicaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiología; Estatus socioeconómicoCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiology; Socio-economic statusBackground: Population-based studies characterising outcomes of COVID-19 in European settings are limited, and effects of socio-economic status (SES) on outcomes have not been widely investigated. Aim: We describe the epidemiological characteristics of COVID-19 cases, highlighting incidence and mortality rate differences across SES during the first wave in Barcelona, Catalonia, Spain. Methods: This population-based study reports individual-level data of laboratory-confirmed COVID-19 cases diagnosed from 24 February to 4 May 2020, notified to the Public Health Agency of Barcelona and followed until 15 June 2020. We analysed end-of-study vital status and the effects of chronic conditions on mortality using logistic regression. Geocoded addresses were linked to basic health area SES data, estimated using the composed socio-economic index. We estimated age-standardised incidence, hospitalisation, and mortality rates by SES. Results: Of 15,554 COVID-19-confirmed cases, the majority were women (n =9,028; 58%), median age was 63 years (interquartile range: 46–83), 8,046 (54%) required hospitalisation, and 2,287 (15%) cases died. Prevalence of chronic conditions varied across SES, and multiple chronic conditions increased risk of death (≥3, adjusted odds ratio: 2.3). Age-standardised rates (incidence, hospitalisation, mortality) were highest in the most deprived SES quartile (incidence: 1,011 (95% confidence interval (CI): 975–1,047); hospitalisation: 619 (95% CI: 591–648); mortality: 150 (95% CI: 136–165)) and lowest in the most affluent (incidence: 784 (95% CI: 759–809); hospitalisation: 400 (95% CI: 382–418); mortality: 121 (95% CI: 112–131)). Conclusions: COVID-19 outcomes varied markedly across SES, underscoring the need to implement effective preventive strategies for vulnerable populations

Active gating as a method to inhibit the crosstalk of Single Photon Avalanche Diodes in a shared well

This work presents low noise readout circuits for silicon pixel detectors based on Geiger mode avalanche photodiodes. Geiger mode avalanche photodiodes offer a high intrinsic gain as well as an excellent timing accuracy. In addition, they can be compatible with standard CMOS technologies. However, they suffer from a high intrinsic noise, which induces false counts indistinguishable from real events and represents an increase of the readout electronics area to store the false counts. We have developed new front-end electronic circuitry for Geiger mode avalanche photodiodes in a conventional 0.35 µm HV-CMOS technology based on a gated mode of operation that allows low noise operation. The performance of the pixel detector is triggered and synchronized with the particle beam thanks to the gated acquisition. The circuits allow low reverse bias overvoltage operation which also improves the noise figures. Experimental characterization of the fabricated front-end circuit is presented in this work

Characterization of linear-mode avalanche photodiodes in standard CMOS

Linear-mode Avalanche PhotoDiodes (APDs) can be fabricated in standard CMOS processes for obtaining high multiplication gains that allow to determine the number of incident photons with great precision. This idea can be exploited in several application domains, such as image sensors, optical communications and quantum information. In this work, we present a linear-mode APD fabricated in a 0.35 µm CMOS process and report its noise and gain characterization by means of two different experimental set-ups. Good matching is observed between the results obtained by means of the two different methods

Modelling the SARS-COV-2 outbreak: assessing the usefulness of protective measures to reduce the pandemic at population level

A new bioinspired computational model was developed for the SARS-CoV-2 pandemic using the available epidemiological information, high-resolution population density data, travel patterns, and the average number of contacts between people. The effectiveness of control measures such as contact reduction measures, closure of communities (lockdown), protective measures (social distancing, face mask wearing, and hand hygiene), and vaccination were modelled to examine possibilities for control of the disease under several protective vaccination levels in the population. Lockdown and contact reduction measures only delay the spread of the virus in the population because it resumes its previous dynamics as soon as the restrictions are lifted. Nevertheless, these measures are probably useful to avoid hospitals being overwhelmed in the short term. Our model predicted that 56% of the Spanish population would have been infected and subsequently recovered over a 130 day period if no protective measures were taken but this percentage would have been only 34% if protective measures had been put in place. Moreover, this percentage would have been further reduced to 41.7, 27.7, and 13.3% if 25, 50 and 75% of the population had been vaccinated, respectively. Finally, this percentage would have been even lower at 25.5, 12.1 and 7.9% if 25, 50 and 75% of the population had been vaccinated in combination with the application of protective measures, respectively. Therefore, a combination of protective measures and vaccination would be highly efficacious in decreasing not only the number of those who become infected and subsequently recover, but also the number of people who die from infection, which falls from 0.41% of the population over a 130 day period without protective measures to 0.15, 0.08 and 0.06% if 25, 50 and 75% of the population had been vaccinated in combination with protective measures at the same time, respectively.This study was partially funded by the University of Lleida (UdL). The comments of four anonymous reviewers improved a previous version of this article

Modeling of Vaccination and Contact Tracing as Tools to Control the COVID-19 Outbreak in Spain

We developed an agent-based stochastic model, based on P Systems methodology, to decipher the effects of vaccination and contact tracing on the control of COVID-19 outbreak at population level under different control measures (social distancing, mask wearing and hand hygiene) and epidemiological scenarios. Our findings suggest that without the application of protection social measures, 56.1% of the Spanish population would contract the disease with a mortality of 0.4%. Assuming that 20% of the population was protected by vaccination by the end of the summer of 2021, it would be expected that 45% of the population would contract the disease and 0.3% of the population would die. However, both of these percentages are significantly lower when social measures were adopted, being the best results when social measures are in place and 40% of contacts traced. Our model shows that if 40% of the population can be vaccinated, even without social control measures, the percentage of people who die or recover from infection would fall from 0.41% and 56.1% to 0.16% and 33.5%, respectively compared with an unvaccinated population. When social control measures were applied in concert with vaccination the percentage of people who die or recover from infection diminishes until 0.10% and 14.5%, after vaccinating 40% of the population. Vaccination alone can be crucial in controlling this disease, but it is necessary to vaccinate a significant part of the population and to back this up with social control measures.This research was funded by University of Lleida

Factors associated with risk behavior in travelers to tropical and subtropical regions

BACKGROUND: Recent decades have seen a rise in population movements and, therefore, the spread of tropical diseases and changes in the epidemiology of global disease patterns. Only 50% of travelers to tropical areas receive pre-travel advice and most of them present risk behaviors for acquiring infections. The aim of this study was to describe the clinical and epidemiological characteristics of travelers and identify factors associated with risk behaviors. METHODS: We made a retrospective, descriptive and analytical study of 772 travelers consulting a tropical medicine clinic in Barcelona in 2010. Data on demographic and clinical variables, travel characteristics and risk behaviors were collected. RESULTS: Among all travelers studied, 65.8% (466/708) received pre-travel advice and 30.7% (209/680) took malaria prophylaxis. At least one risk behavior was reported by 82.6% (587/711) of travelers. People travelling for 1-6 months had a 3-fold higher likelihood of experiencing risk behaviors than people travelling for <1 month (95% CI 1.54-5.81, p=0.001), and those travelling for >6 months had a 13-fold higher likelihood (95% CI 3.11-56.14, p<0.001) compared with the same group. Increasing age was associated with presenting less risk behaviors. CONCLUSIONS: Younger travelers and those making longer trips have a higher number of risk behaviors. Strategies emphasizing advice on risk behavior should focus on these groups

Economic Impact of a New Rapid PCR Assay for Detecting Influenza Virus in an Emergency Department and Hospitalized Patients

Seasonal influenza causes significant morbidity and mortality and has a substantial economic impact on the healthcare system. The main objective of this study was to compare the cost per patient for a rapid commercial PCR assay (Xpert1 Flu) with an in-house real-time PCR test for detecting influenza virus. Community patients with influenza like-illness attending the Emergency Department (ED) as well as hospitalized patients in the Hospital Clínic of Barcelona were included. Costs were evaluated from the perspective of the hospital considering the use of resources directly related to influenza testing and treatment. For the purpose of this study, 366 and 691 patients were tested in 2013 and 2014, respectively. The Xpert1 Flu test reduced the mean waiting time for patients in the ED by 9.1 hours and decreased the mean isolation time of hospitalized patients by 23.7 hours. This was associated with a 103€ (or about $113) reduction in the cost per patient tested in the ED and 64€ ($70) per hospitalized patient. Sensitivity analyses showed that Xpert1 Flu is likely to be cost-saving in hospitals with different contexts and prices

Readout electronics for low dark count pixel detectors based on geiger mode avalanche photodiodes fabricated in conventional CMOS technologies for future linear colliders

The high sensitivity and excellent timing accuracy of Geiger mode avalanche photodiodes makes them ideal sensors as pixel detectors for particle tracking in high energy physics experiments to be performed in future linear colliders. Nevertheless, it is well known that these sensors suffer from dark counts and afterpulsing noise, which induce false hits (indistinguishable from event detection) as well as an increase of the necessary area of the readout system. In this work, we present a comparison between APDs fabricated in a high voltage 0.35 µm and a high integration 0.13 µm commercially available CMOS technologies that has been performed to determine which of them best fits the particle collider requirements. In addition, a readout circuit that allows low noise operation is introduced. Experimental characterization of the proposed pixel is also presented in this work

A DIGE proteomic analysis of wheat flag leaf treated with TERRA-SORB® foliar, a free amino acid high content biostimulant

The flag leaf is the most important source of carbohydrate during wheat kernel filling. Around a 75% of all sugars stored in the kernel come from carbon fixed by this leaf. Terra-Sorb® foliar is an L-α-amino acid-based product from enzymatic hydrolysis for foliar application with a high ratio of free to total amino acids. Previous agronomical studies carried out on grassy, horticultural and tree crops have shown that the application of Terra-Sorb® increases photosynthetic plant activity and chlorophyll content, promotes rapid recovery from stress and improves fruit set. In this work, we have undertaken a proteomic approach to explore molecular mechanisms potentially involved in the stimulating effect of Terra-Sorb® Foliar on wheat yield when applied in commercial fields. Wheat plants at the flag leaf stage were treated, and a DIGE approach was used to compare the proteomes of treated vs. control plants in four biological replicates. Thirty-seven protein spots were found to change in abundance (ANOVA p<0.05) out of which 8 were down-regulated and 29 up-regulated in treated leaves. Twenty protein spots (1.2<fold change <1.9) encoded by 11 different genes were successfully identified by nLC-ESI-MS/MS and NCBInr database search. The deregulated proteins identified were mainly related to the life cycle of Rubisco. Importantly, two proteins involved in the positive regulation of Rubisco activity, namely Rubisco activase, and the large subunit of Rubisco binding protein, were found up-regulated in treated plants, suggesting a better performance of Rubisco. Down-regulated proteins were of metabolic and anti-stress enzymes, including Cu/Zn superoxide dismutase that protects photosystem 11 from photooxidation. In conclusion, significant changes were shown to occur in the wheat flag leaf proteome upon Terra-Sorb® Foliar application. The deregulated proteins identified are directly or indirectly involved in the C02 fixation which may correlate with the known stimulating effect of Terra-Sorb® Foliar of wheat yield, although further functional experiments are needed to validate the proposed hypothesis.This work was supported by Bioibérica, S.A. MJME acknowledged a grant contract from Fundación CajaMurcia-Universidad de Alicante