| 1. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 2. |
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| 3. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 4. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 5. |
- da Silva, P. G., et al.
(författare)
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Airborne spread of infectious SARS-CoV-2 : Moving forward using lessons from SARS-CoV and MERS-CoV
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 764
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although an increasing body of data reports the detection of SARS-CoV-2 RNA in air, this does not correlate to the presence of infectious viruses, thus not evaluating the risk for airborne COVID-19. Hence there is a marked knowledge gap that requires urgent attention. Therefore, in this systematic review, viability/stability of airborne SARS-CoV-2, SARS-CoV and MERS-CoV viruses is discussed. Methods: A systematic literature review was performed on PubMed/MEDLINE, Web of Science and Scopus to assess the stability and viability of SARS-CoV, MERS-CoV and SARS-CoV-2 on air samples. Results and discussion: The initial search identified 27 articles. Following screening of titles and abstracts and removing duplicates, 11 articles were considered relevant. Temperatures ranging from 20 °C to 25 °C and relative humidity ranging from 40% to 50% were reported to have a protective effect on viral viability for airborne SARS-CoV and MERS-CoV. As no data is yet available on the conditions influencing viability for airborne SARS-CoV-2, and given the genetic similarity to SARS-CoV and MERS-CoV, one could extrapolate that the same conditions would apply. Nonetheless, the effect of these conditions seems to be residual considering the increasing number of cases in the south of USA, Brazil and India, where high temperatures and humidities have been observed. Conclusion: Higher temperatures and high relative humidity can have a modest effect on SARS-CoV-2 viability in the environment, as reported in previous studies to this date. However, these studies are experimental, and do not support the fact that the virus has efficiently spread in the tropical regions of the globe, with other transmission routes such as the contact and droplet ones probably being responsible for the majority of cases reported in these regions, along with other factors such as human mobility patterns and contact rates. Further studies are needed to investigate the extent of aerosol transmission of SARS-CoV-2 as this would have important implications for public health and infection-control policies.
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| 6. |
- Petrov, Dmitry, et al.
(författare)
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Machine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging
- 2017
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Ingår i: Machine learning in medical imaging. MLMI (Workshop). - Cham : Springer International Publishing. ; 10541, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.
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| 7. |
- Silva, Priscilla G., et al.
(författare)
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SARS-CoV-2 air sampling : A systematic review on the methodologies for detection and infectivity
- 2022
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Ingår i: Indoor Air. - : Wiley. - 0905-6947 .- 1600-0668. ; 32:8
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Forskningsöversikt (refereegranskat)abstract
- This systematic review aims to present an overview of the current aerosol sampling methods (and equipment) being used to investigate the presence of SARS-CoV-2 in the air, along with the main parameters reported in the studies that are essential to analyze the advantages and disadvantages of each method and perspectives for future research regarding this mode of transmission. A systematic literature review was performed on PubMed/MEDLINE, Web of Science, and Scopus to assess the current air sampling methodologies being applied to SARS-CoV-2. Most of the studies took place in indoor environments and healthcare settings and included air and environmental sampling. The collection mechanisms used were impinger, cyclone, impactor, filters, water-based condensation, and passive sampling. Most of the reviewed studies used RT-PCR to test the presence of SARS-CoV-2 RNA in the collected samples. SARS-CoV-2 RNA was detected with all collection mechanisms. From the studies detecting the presence of SARS-CoV-2 RNA, fourteen assessed infectivity. Five studies detected viable viruses using impactor, water-based condensation, and cyclone collection mechanisms. There is a need for a standardized protocol for sampling SARS-CoV-2 in air, which should also account for other influencing parameters, including air exchange ratio in the room sampled, relative humidity, temperature, and lighting conditions.
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| 8. |
- Soares, Ruben R. G., et al.
(författare)
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Silica bead-based microfluidic device with integrated photodiodes for the rapid capture and detection of rolling circle amplification products in the femtomolar range
- 2019
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 128, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and sensitive detection of specific nucleic acid sequences at the point-of-care (PoC) is becoming increasingly in demand for a variety of emergent biomedical applications ranging from infectious disease diagnostics to the screening of antimicrobial resistance. To meet such demand, considerable efforts have been invested towards the development of portable and integrated analytical devices combining microfluidics with miniaturized signal transducers. Here, we demonstrate the combination of rolling circle amplification (RCA)-based nucleic acid amplification with an on-chip size-selective trapping of amplicons on silica beads (similar to 8 nL capture chamber) coupled with a thin-film photodiode (200 x 200 mu m area) fluorescence readout. Parameters such as the flow rate of the amplicon solution and trapping time were optimized as well as the photodiode measurement settings, providing minimum detection limits below 0.5 fM of targeted nucleic acids and requiring only 5 mu L of pre-amplified sample. Finally, we evaluated the analytical performance of our approach by benchmarking it against a commercial instrument for RCA product (RCP) quantification and further investigated the effect of the number of RCA cycles and elongation times (ranging from 10 to 120 min). Moreover, we provide a demonstration of the application for diagnostic purposes by detecting RNA from influenza and Ebola viruses, thus highlighting its suitability for integrated PoC systems.
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| 9. |
- Gomes da Silva, Priscilla, et al.
(författare)
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Evidence of Air and Surface Contamination with SARS-CoV-2 in a Major Hospital in Portugal
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- As the third wave of the COVID-19 pandemic hit Portugal, it forced the country to reintroduce lockdown measures due to hospitals reaching their full capacities. Under these circumstances, environmental contamination by SARS-CoV-2 in different areas of one of Portugal’s major Hospitals was assessed between 21 January and 11 February 2021. Air samples (n = 44) were collected from eleven different areas of the Hospital (four COVID-19 and seven non-COVID-19 areas) using Coriolis® μ and Coriolis® Compact cyclone air sampling devices. Surface sampling was also performed (n = 17) on four areas (one COVID-19 and three non-COVID-19 areas). RNA extraction followed by a one-step RT-qPCR adapted for quantitative purposes were performed. Of the 44 air samples, two were positive for SARS-CoV-2 RNA (6575 copies/m3 and 6662.5 copies/m3, respectively). Of the 17 surface samples, three were positive for SARS-CoV-2 RNA (200.6 copies/cm2, 179.2 copies/cm2, and 201.7 copies/cm2, respectively). SARS-CoV-2 environmental contamination was found both in air and on surfaces in both COVID-19 and non-COVID-19 areas. Moreover, our results suggest that longer collection sessions are needed to detect point contaminations. This reinforces the need to remain cautious at all times, not only when in close contact with infected individuals. Hand hygiene and other standard transmission-prevention guidelines should be continuously followed to avoid nosocomial COVID-19.
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| 10. |
- Saha, Udiptya, et al.
(författare)
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Plasmonic Fiber Optic Absorbance Biosensor for MDR-Mtb detection using Padlock Probing
- 2022
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Ingår i: 2022 Workshop on Recent Advances in Photonics (WRAP 2022). - Piscataway, New Jersey : Institute of Electrical and Electronics Engineers (IEEE). - 9781665407038 ; , s. 170-171
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Konferensbidrag (refereegranskat)abstract
- India is one among the 14 countries that have a high burden of Multidrug Resistant-Tuberculosis (MDR-TB), thereby demanding robust clinical and diagnostic attention. This study explores the development of a plasmonic fiber optic absorbance biosensor (P-FAB) for the detection of Rolling Circle Amplification (RCA) products to detect MDR genes of Mycobacterium tuberculosis. RCA is used as a nucleic acid amplification strategy for the specific and sensitive detection of DNA samples using the P-FAB platform. RCA-generated amplicons, when detected using U-bent optical fiber probe sensor with a nanoparticle-labeled DNA assay, provides adequate scope for the required clinical sensitivity towards multiplexed TB detection.
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| 11. |
- Varela, João C., et al.
(författare)
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Rolling circle amplification-on-a-chip towards portable isothermal detection of SARS-COV-2 RNA
- 2021
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Ingår i: Proceedings MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 865-866
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Konferensbidrag (refereegranskat)abstract
- Rolling Circle Amplification (RCA) has shown significant potential for pathogen diagnostics providing high specificity and sensitivity combined with relatively low temperature (<37 °C) isothermal amplification. In the context of the ongoing COVID-19 pandemic, we report the development of an RCA-based method allowing direct detection of SARS-CoV-2 RNA in microfluidics. The viral RNA was hybridized to biotinylated oligos and L-probes in solution, enriched in a microchannel and subsequently amplified in situ using padlock probes against the L-probes. This method allowed the detection of 1x103 viral copies/μL within 90 minutes of amplification, demonstrating an alternative approach to current isothermal amplification methods.
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| 12. |
- Akhtar, Ahmad Saleem, et al.
(författare)
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A portable and low-cost centrifugal microfluidic platform for multiplexed colorimetric detection of protein biomarkers
- 2023
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 1245
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines play a very important role in our immune system by acting as mediators to put up a coordinated defense against foreign elements in our body. Elevated levels of cytokines in the body can signal to an ongoing response of the immune system to some abnormality. Thus, the quantification of a panel of cytokines can provide valuable information regarding the diagnosis of specific diseases and state of overall health of an individual. Conventional Enzyme Linked Immunosorbent Assay (ELISA) is the gold-standard for quantification of cytokines, however the need for trained personnel and expensive equipment limits its application to centralized laboratories only. In this context, there is a lack of simple, low-cost and portable devices which can allow for quantification of panels of cytokines at point-of-care and/or resource limited settings.Here, we report the development of a versatile, low-cost and portable bead-based centrifugal microfluidic platform allowing for multiplexed detection of cytokines with minimal hands-on time and an integrated colorimetric signal readout without the need for any external equipment. As a model, multiplexed colorimetric quantification of three target cytokines i.e., Tumor necrosis factor alpha (TNF-α), Interferon gamma (IFN-γ) and Interleukin-2 (IL-2) was achieved in less than 30 min with limits of detection in ng/mL range. The developed platform was further evaluated using spiked-in plasma samples to test for matrix interference. The ease of use, low-cost and portability of the developed platform highlight its potential to serve as a sample-to-answer solution for detection of cytokine panels in resource limited settings.
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| 13. |
- Akhtar, Ahmad Saleem, et al.
(författare)
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An integrated centrifugal microfluidic platform for multiplexed colorimetric immunodetection of protein biomarkers in resource-limited settings
- 2021
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Ingår i: Proceedings MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 947-948
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Konferensbidrag (refereegranskat)abstract
- The up- and down- regulation of inflammatory biomarkers such as cytokines can be indicative of several diseases such as primary cancers and/or metastatic tumors, as well as less serious conditions. For point-of-care clinical applications, the detection of these biomarkers requires a combination of a sensitive assay and multiplexing capabilities, together with fit-for-purpose signal transduction strategies. Here, we report the development of a versatile and cost-effective integrated centrifugal microfluidic platform compatible with resource-limited settings using nanoporous microbeads for immunoaffinity-based profiling of cytokines. With an automated colorimetric readout at the end, the platform allows for profiling of cytokines in < 30 mins.
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| 14. |
- Akhtar, Ahmad Saleem, et al.
(författare)
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Centrifugal microfluidic platform comprising an array of bead microcolumns for the multiplexed colorimetric quantification of inflammatory biomarkers at the point-of-care
- 2019
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Ingår i: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. - : Chemical and Biological Microsystems Society. ; , s. 1230-1231
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Konferensbidrag (refereegranskat)abstract
- The detection of panels of inflammatory biomarkers such as cytokines has potential for the rapid and specific diagnostic of several devastating diseases such as primary cancers and/or metastatic tumors, as opposed to less serious conditions. For point-of-care clinical applications, the detection of these biomarkers requires a combination of pg/mL sensitivities and multiplexing capabilities, coupled with fit-for-purpose signal transduction strategies. Here, we report the development of a versatile centrifugal microfluidic platform combined with nanoporous microbeads for immunoaffinity-based profiling of cytokines. The device allows sample and analyte multiplexing and detection limits below 1 ng/mL were achieved within 30 minutes, using colorimetric detection.
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| 15. |
- Damiati, Samar, et al.
(författare)
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Flex Printed Circuit Board Implemented Grapene-Based DNA Sensor for Detection of SARS-CoV-2
- 2021
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Ingår i: IEEE Sensors Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 1530-437X .- 1558-1748. ; 21:12, s. 13060-13067
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Tidskriftsartikel (refereegranskat)abstract
- Since the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO) in March 2020, ongoing efforts have been made to develop sensitive diagnostic platforms. Detection of viral RNA provides the highest sensitivity and specificity for detection of early and asymptomatic infections. Thus, this work aimed at developing a label-free genosensor composed of graphene as a working electrode that could be embedded into a flex printed circuit board (FPCB) for the rapid, sensitive, amplification-free and label-free detection of SARS-CoV-2. To facilitate liquid handling and ease of use, the developed biosensor was embedded with a user-friendly reservoir chamber. As a proof-of-concept, detection of a synthetic DNA strand matching the sequence of ORF1ab was performed as a two-step strategy involving the immobilization of a biotinylated complementary sequence on a streptavidin-modified surface, followed by hybridization with the target sequence recorded by the differential pulse voltammetric (DPV) technique in the presence of a ferro/ferricyanide redox couple. The effective design of the sensing platform improved its selectivity and sensitivity and allowed DNA quantification ranging from 100 fg/mL to 1 mu g/mL. Combining the electrochemical technique with FPCB enabled rapid detection of the target sequence using a small volume of the sample (5-20 mu L). We achieved a limit-of-detection of 100 fg/mL, whereas the predicted value was similar to 33 fg/mL, equivalent to approximately 5 x 10(5) copies/mL and comparable to sensitivities provided by isothermal nucleic acid amplification tests. We believe that the developed approach proves the ability of an FPCB-implemented DNA sensor to act as a potentially simpler and more affordable diagnostic assay for viral infections in Point-Of-Care (POC) applications.
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| 16. |
- Kazemzadeh, Amin, et al.
(författare)
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Towards integrated, autonomous and low-cost diagnostics at the point-of-care from whole blood to answer
- 2019
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Ingår i: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. - : Chemical and Biological Microsystems Society. ; , s. 705-706
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Konferensbidrag (refereegranskat)abstract
- The growing popularity of smartphones has been allowing new opportunities towards the development of low-cost and integrated point-of-care diagnostic platforms. Here, we combine (1) the capabilities of smartphones as both imaging devices and power sources; (2) centrifugal microfluidic devices and; (3) our recently reported microdispenser technology allowing reagent storage, dispensing and blood-plasma separation, to pave the way towards cost-effective and portable point-of-care devices with potential to meet the ASSURED criteria outlined by the World Health Organization.
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| 17. |
- Krishnan, Sowmya Ramaswamy, et al.
(författare)
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AutoPLP : A Padlock Probe Design Pipeline for Zoonotic Pathogens
- 2023
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Ingår i: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 9:3, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of novel zoonotic infections among the human population has increased the burden on global healthcare systems to curb their spread. To meet the evolutionary agility of pathogens, it is essential to revamp the existing diagnostic methods for early detection and characterization of the pathogens at the molecular level. Padlock probes (PLPs), which can leverage the power of isothermal nucleic acid amplification techniques (NAAT) such as rolling circle amplification (RCA), are known for their high sensitivity and specificity in detecting a diverse pathogen panel of interest. However, due to the complexity involved in deciding the target regions for PLP design and the need for optimization of multiple experimental parameters, the applicability of RCA has been limited in point-of-care testing for pathogen detection. To address this gap, we have developed a novel and integrated PLP design pipeline named AutoPLP, which can automate the probe design process for a diverse pathogen panel of interest. The pipeline is composed of three modules which can perform sequence data curation, multiple sequence alignment, conservation analysis, filtration based on experimental parameters (Tm, GC content, and secondary structure formation), and in silico probe validation via potential cross-hybridization check with host genome. The modules can also take into account the backbone and restriction site information, appropriate combinations of which are incorporated along with the probe arms to design a complete probe sequence. The potential applications of AutoPLP are showcased through the design of PLPs for the detection of rabies virus and drug-resistant strains of Mycobacterium tuberculosis.
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| 18. |
- Kumar, Tharagan, et al.
(författare)
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Multi-layer assembly of cellulose nanofibrils in a microfluidic device for the selective capture and release of viable tumor cells from whole blood
- 2020
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Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 12:42, s. 21788-21797
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Tidskriftsartikel (refereegranskat)abstract
- According to reports by the World Health Organization (WHO), cancer-related deaths reached almost 10 million in 2018. Nearly 65% of these deaths occurred in low- to middle-income countries, a trend that is bound to increase since cancer diagnostics are not currently considered a priority in resource-limited settings (RLS). Thus, cost-effective and specific cancer screening and diagnostics tools are in high demand, particularly in RLS. The selective isolation and up-concentration of rare cells while maintaining cell viability and preventing phenotypic changes is a powerful tool to allow accurate and sensitive downstream analysis. Here, multi-layer cellulose nanofibril-based coatings functionalized with anti-EpCAM antibodies on the surface of disposable microfluidic devices were optimized for specific capture of target cells, followed by efficient release without significant adverse effects. HCT 116 colon cancer cells were captured in a single step with >97% efficiency at 41.25 mu L min(-1) and, when spiked in whole blood, an average enrichment factor of similar to 200-fold relative to white blood cells was achieved. The release of cells was performed by enzymatic digestion of the cellulose nanofibrils which had a negligible impact on cell viability. In particular, >80% of the cells were recovered with at least 97% viability in less than 30 min. Such performance paves the way to expand and improve clinical diagnostic applications by simplifying the isolation of circulating tumor cells (CTCs) and other rare cells directly from whole blood.
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| 19. |
- Parker, Helen E., et al.
(författare)
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A Lab-in-a-Fiber optofluidic device using droplet microfluidics and laser-induced fluorescence for virus detection
- 2022
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Microfluidics has emerged rapidly over the past 20 years and has been investigated for a variety of applications from life sciences to environmental monitoring. Although continuous-flow microfluidics is ubiquitous, segmented-flow or droplet microfluidics offers several attractive features. Droplets can be independently manipulated and analyzed with very high throughput. Typically, microfluidics is carried out within planar networks of microchannels, namely, microfluidic chips. We propose that fibers offer an interesting alternative format with key advantages for enhanced optical coupling. Herein, we demonstrate the generation of monodisperse droplets within a uniaxial optofluidic Lab-in-a-Fiber scheme. We combine droplet microfluidics with laser-induced fluorescence (LIF) detection achieved through the development of an optical side-coupling fiber, which we term a periscope fiber. This arrangement provides stable and compact alignment. Laser-induced fluorescence offers high sensitivity and low detection limits with a rapid response time making it an attractive detection method for in situ real-time measurements. We use the well-established fluorophore, fluorescein, to characterize the Lab-in-a-Fiber device and determine the generation of ∼ 0.9 nL droplets. We present characterization data of a range of fluorescein concentrations, establishing a limit of detection (LOD) of 10 nM fluorescein. Finally, we show that the device operates within a realistic and relevant fluorescence regime by detecting reverse-transcription loop-mediated isothermal amplification (RT-LAMP) products in the context of COVID-19 diagnostics. The device represents a step towards the development of a point-of-care droplet digital RT-LAMP platform. © 2022, The Author(s).
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| 20. |
- Parker, Helen E., et al.
(författare)
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Digital detection and quantification of SARS-CoV-2 in a droplet microfluidic all-fiber device
- 2021
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Ingår i: Proceedings MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 1047-1048
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Konferensbidrag (refereegranskat)abstract
- Silica fibers and capillaries offer opportunities for compact integration of optics with microfluidics while adding advantages such as; flexibility within a high aspect ratio format, uniaxial arrangements, and measurement-at-a-distance. Here, we describe droplet microfluidics-based nucleic acid detection of SARS-CoV-2 in a lab-in-a-fiber platform. The fiber component integrates three modules with key functions: droplet generation, incubation, and fluorescence detection. Within the scope of this work, we developed the component specifically to target the quantification of SARS-CoV-2 viral RNA through reverse-transcription loop-mediated isothermal amplification (RT-LAMP). The all-fiber component could successfully generate uniform droplets and differentiate pre-amplified positive LAMP reaction from negative sample.
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| 21. |
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| 22. |
- Parker, Helen E., et al.
(författare)
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Viral detection and quantification in a digital droplet microfluidic lab-in-a-fiber device
- 2021
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9781510643802
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Konferensbidrag (refereegranskat)abstract
- In this work, we present the design and fabrication of a fiber device that performs digital droplet microfluidics for molecular diagnostics. A variety of fibers and capillaries were used to build three connected modules dedicated to droplet generation, incubation, and fluorescence detection which enables a uniaxial arrangement. This is in contrast to the traditional 2-dimensional lab-on-a-chip architecture. We characterize our fiber device using a fluorescein dilution series. Our observed detection limit is on the order of 10 nM fluorescein. We demonstrate our all-fiber device for the fluorescence readout after loop-mediated isothermal amplification (LAMP) of synthetic SARS-CoV-2. Our results suggest that this fiber device can successfully distinguish between positive and negative samples in molecular diagnostics. We propose that our fiber device offers benefits over microfluidic chip techniques such as easier optical integration, much simpler sample loading, and faster diagnosis with high specificity and sensitivity. Keywords: All-fiber device, microfluidics, optofluidics, loop-mediated isothermal amplification (LAMP), molecular diagnostics, SARS-CoV2.
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| 23. |
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| 24. |
- Pinto, Ines Fernandes, et al.
(författare)
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Multiplexed Microfluidic Cartridge for At-Line Protein Monitoring in Mammalian Cell Culture Processes for Biopharmaceutical Production
- 2021
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Ingår i: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 6:3, s. 842-851
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Tidskriftsartikel (refereegranskat)abstract
- The biopharmaceutical market has been rapidly growing in recent years, creating a highly competitive arena where R&D is critical to strike a balance between clinical safety and profitability. Toward process optimization, the recent development and adoption of new process analytical technologies (PAT) highlight the dynamic complexity of mammalian/human cell culture processes, as well as the importance of fine-tuning and modeling key metabolites and proteins. In this context, simple, rapid, and cost-effective devices allowing routine at-line monitoring of specific proteins during process development and production are currently lacking. Here, we report the development of a versatile microfluidic protein analysis cartridge allowing the multiplexed bead-based immunodetection of specific proteins directly from complex mixtures with minimal hands-on time. Colorimetric quantification of Chinese hamster ovary (CHO) host cell proteins as key impurities, monoclonal antibodies as target biopharmaceuticals, and lactate dehydrogenase as a marker of cell viability was achieved with limits of detection in the 1-10 ng/mL range and analysis times as short as 30 min. The device was further demonstrated for the monitoring of a Rituximab-producing CHO cell bioreactor over the course of 8 days, providing comparable recoveries to standard enzyme-linked immunosorbent assay (ELISA) kits. The high sensitivity combined with robustness to matrix interference highlights the potential of the device to perform at-line measurements spanning from the bioreactor to the downstream processing.
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| 25. |
- Pinto, Ines F., et al.
(författare)
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Single-Step Quantification of Specific Nucleic Acid Sequences in Microfluidics Using a Multilabeled Hybrid DNA Duplex
- 2021
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Ingår i: MicroTAS 2021. - : Chemical and Biological Microsystems Society. ; , s. 757-758
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Konferensbidrag (refereegranskat)abstract
- The rapid and specific detection of nucleic acid sequences is highly demanded for several applications including pathogen diagnostics, quality control of biopharmaceutical products and forensics. Nucleic acid amplification methods based on mixtures of primers and polymerase enzymes such as polymerase chain reaction (PCR) and other isothermal methods are typically the standard approach. Here, using SARS-CoV-2 ORF1ab sequence as a model, we report the development of a simple enzyme-free and single-step competitive hybridization method allowing the specific detection of any type of nucleic acid sequence (ss/dsDNA or RNA) within 15 min with 89% sequence homology and sensitivity in the pM-range.
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| 26. |
- Soares, Ruben R. G., et al.
(författare)
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Circle-to-circle amplification coupled with microfluidic affinity chromatography enrichment for in vitro molecular diagnostics of Zika fever and analysis of anti-flaviviral drug efficacy
- 2021
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier BV. - 0925-4005 .- 1873-3077. ; 336
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive viral diagnostic methods are increasingly in demand to tackle emerging epidemics. The Zika virus (ZIKV) is particularly relevant in tropical resource limited settings (RLS) and is associated with intermittent epidemics such as the recent 2016 ZIKV outbreak in South America, wherein Zika fever was classified by WHO as a public health emergency of international concern. Thus, there is an urgent need for widespread Zika fever diagnostics and efficient drug therapies. ZIKV diagnostics are typically performed using RT-qPCR in centralized laboratories. While extremely sensitive, RT-qPCR requires rapid heating-cooling cycles, combined with continuous fluorescence measurements to allow quantification, implying high costs and limiting availability of molecular diagnostics in RLS. Here, we report isothermal amplification of ZIKV cDNA using padlock probes followed by two rounds of Rolling Circle Amplification (RCA), termed as circle-to-circle amplification (C2CA), combined with a microfluidic affinity chromatography enrichment (mu ACE) platform. This platform allowed the detection of <17 vRNA copies per reaction mixture, equivalent to similar to 3 aM, showed a positive correlation with RT-qPCR in both average (r = 0.80) and discrete (r = 0.95) signal modes, and was validated for drug efficiency tests using in vitro infected peripheral blood mononuclear cells from 3 healthy donors. This performance shows significant promise towards highly sensitive, albeit simple and cost-effective point-of-care viral diagnostics.
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| 27. |
- Soares, Ruben R. G., et al.
(författare)
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Point-of-care isothermal nucleic acid amplification platform for COVID-19 diagnostics in resource-limited settings
- 2021
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Ingår i: Proceedings MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 863-864
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Konferensbidrag (refereegranskat)abstract
- The demand for scalable, rapid and sensitive COVID-19 diagnostics is particularly pressing at present to help contain the spread of infection and prevent overwhelming the capacity of health systems. While high-income countries have managed to rapidly expand diagnostic capacities, such is not the case in resource-limited settings of low- to medium-income countries. We report the development of an integrated modular centrifugal microfluidic platform costing less than 250 USD to perform loop-mediated isothermal amplification (LAMP) of viral RNA directly from heat-inactivated nasopharyngeal swab samples. The platform was validated with a panel of 131 nasopharyngeal swab samples collected from symptomatic COVID-19 patients.
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| 28. |
- Soares, Ruben R. G., et al.
(författare)
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Rolling Circle Amplification in Integrated Microsystems : An Uncut Gem toward Massively Multiplexed Pathogen Diagnostics and Genotyping
- 2021
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Ingår i: Accounts of Chemical Research. - : American Chemical Society (ACS). - 0001-4842 .- 1520-4898. ; 54:21, s. 3979-3990
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Forskningsöversikt (refereegranskat)abstract
- The development of robust methods allowing the precise detection of specific nucleic acid sequences is of major societal relevance, paving the way for significant advances in biotechnology and biomedical engineering. These range from a better understanding of human disease at a molecular level, allowing the discovery and development of novel biopharmaceuticals and vaccines, to the improvement of biotechnological processes providing improved food quality and safety, efficient green fuels, and smart textiles. Among these applications, the significance of pathogen diagnostics as the main focus of this Account has become particularly clear during the recent SARS-CoV-2 pandemic. In this context, while RT-PCR is the gold standard method for unambiguous detection of genetic material from pathogens, other isothermal amplification alternatives circumventing rapid heating-cooling cycles up to similar to 95 degrees C are appealing to facilitate the translation of the assay into point-of-care (PoC) analytical platforms. Furthermore, the possibility of routinely multiplexing the detection of tens to hundreds of target sequences with single base pair specificity, currently not met by state-of-the-art methods available in clinical laboratories, would be instrumental along the path to tackle emergent viral variants and antimicrobial resistance genes. Here, we advocate that padlock probes (PLPs), first reported by Nilsson et al. in 1994, coupled with rolling circle amplification (RCA), termed here as PLP-RCA, is an underexploited technology in current arena of isothermal nucleic acid amplification tests (NAATs) providing an unprecedented degree of multiplexing, specificity, versatility, and amenability to integration in miniaturized PoC platforms. Furthermore, the intrinsically digital amplification of PLP-RCA retains spatial information and opens new avenues in the exploration of pathogenesis with spatial multiomics analysis of infected cells and tissue. The Account starts by introducing PLP-RCA in a nutshell focusing individually on the three main assay steps, namely, (1) PLP design and ligation mechanism, (2) RCA after probe ligation, and (3) detection of the RCA products. Each subject is touched upon succinctly but with sufficient detail for the reader to appreciate some assay intricacies and degree of versatility depending on the analytical challenge at hand. After familiarizing the reader with the method, we discuss specific examples of research in our group and others using PLP-RCA for viral, bacterial, and fungal diagnostics in a variety of clinical contexts, including the genotyping of antibiotic resistance genes and viral subtyping. Then, we dissect key developments in the miniaturization and integration of PLPRCA to minimize user input, maximize analysis throughput, and expedite the time to results, ultimately aiming at PoC applications. These developments include molecular enrichment for maximum sensitivity, spatial arrays to maximize analytical throughput, automation of liquid handling to streamline the analytical workflow in miniaturized devices, and seamless integration of signal transduction to translate RCA product titers (and ideally spatial information) into a readable output. Finally, we position PLP-RCA in the current landscape of NAATs and furnish a systematic Strengths, Weaknesses, Opportunities and Threats analysis to shine light upon unpolished edges to uncover the gem with potential for ubiquitous, precise, and unbiased pathogen diagnostics.
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| 29. |
- Soares, Ruben R. G., et al.
(författare)
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Sample-to-answer COVID-19 nucleic acid testing using a low-cost centrifugal microfluidic platform with bead-based signal enhancement and smartphone read-out
- 2021
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 21:15, s. 2932-2944
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Tidskriftsartikel (refereegranskat)abstract
- With its origin estimated around December 2019 in Wuhan, China, the ongoing SARS-CoV-2 pandemic is a major global health challenge. The demand for scalable, rapid and sensitive viral diagnostics is thus particularly pressing at present to help contain the rapid spread of infection and prevent overwhelming the capacity of health systems. While high-income countries have managed to rapidly expand diagnostic capacities, such is not the case in resource-limited settings of low- to medium-income countries. Aiming at developing cost-effective viral load detection systems for point-of-care COVID-19 diagnostics in resource-limited and resource-rich settings alike, we report the development of an integrated modular centrifugal microfluidic platform to perform loop-mediated isothermal amplification (LAMP) of viral RNA directly from heat-inactivated nasopharyngeal swab samples. The discs were pre-packed with driedn-benzyl-n-methylethanolamine modified agarose beads used to selectively remove primer dimers, inactivate the reaction post-amplification and allowing enhanced fluorescence detectionviaa smartphone camera. Sample-to-answer analysis within 1 hour from sample collection and a detection limit of approximately 100 RNA copies in 10 μL reaction volume were achieved. The platform was validated with a panel of 162 nasopharyngeal swab samples collected from patients with COVID-19 symptoms, providing a sensitivity of 96.6% (82.2-99.9%, 95% CI) for samples with Ct values below 26 and a specificity of 100% (90-100%, 95% CI), thus being fit-for-purpose to diagnose patients with a high risk of viral transmission. These results show significant promise towards bringing routine point-of-care COVID-19 diagnostics to resource-limited settings.
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| 30. |
- Soares, Ruben R. G., et al.
(författare)
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Sub-attomole detection of HIV-1 using padlock probes and rolling circle amplification combined with microfluidic affinity chromatography
- 2020
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 166
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Tidskriftsartikel (refereegranskat)abstract
- Despite significant progress in diagnostics and disease management during the past decades, human immunodeficiency virus (HIV) infections are still responsible for nearly 1 million deaths every year, mostly in resource-limited settings. Thus, novel, accurate and cost-effective tools for viral load monitoring become crucial to allow specific diagnostics and the effective monitoring of the associated antiviral therapies. Herein, we report an effective combination of a (1) padlock probe (PLP)-mediated rolling circle amplification (RCA) bioassay and an (2) agarose bead-based microfluidic device for the affinity chromatography-based capture and detection of RCA products (RCPs) pre-labelled simultaneously with biotin and an organic fluorophore. This method allowed the efficient capture of similar to 1 mu m-sized RCPs followed by their quantification either as discrete signals or an average fluorescence signal, thus being compatible with both high-resolution imaging for maximum sensitivity as well as simpler optical detection setups. A limit of detection < 30 fM was obtained for HIV-1 synthetic target with just a single round of RCA, comparable to recently reported procedures requiring technically complex amplification strategies such as hyperbranching and/or enzymatic digestion/amplification. Furthermore, targeting a set of five conserved regions in the HIV-1 gag gene, the method could specifically detect HIV-1 in 293T cell culture supernatants, as well as a set of 11 HIV-1 NIH reference samples with four different subtypes. The reported method provides simplicity of operation, unique versatility of signal transduction (i.e. average or discrete signals), and potential coupling with previously reported miniaturized photodetectors. These combined features hold promise for bringing RCA-based molecular diagnostics closer to the point-of-care.
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| 31. |
- Soares, Ruben R. G., et al.
(författare)
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Towards point-of-care HIV diagnostics using dual-labelled rolling circle products for efficient capture and detection in a microfluidic device
- 2019
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Ingår i: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. - : Chemical and Biological Microsystems Society. ; , s. 734-735
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Konferensbidrag (refereegranskat)abstract
- HIV infections are devastating in resource-limited settings, where portable, fit-for-purpose and affordable diagnostic devices would allow effective monitoring of infection spread and aid therapeutics. Here, a rolling circle amplification (RCA)-based assay using multiple specific padlock probes (PLP) targeting a conserved pol gene of HIV-1 subtype B is presented. These PLPs were designed to allow (1) fluorescence detection of the rolling circle products (RCP), as well as (2) their specific capture in a microfluidic device resorting to streptavidin-biotin interactions. The device provided detection limits as low as 10 fM and allowed the detection of HIV in infected 293T cell culture supernatants.
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