Dedicated low-cost spectrophotometer to assist in cystic fibrosis diagnosis

Author(s):  
Daniel Saverio Spozito ◽  
Francisco Ubaldo Vieira Junior ◽  
Eduardo Tavares Costa
Keyword(s):  
Author(s):  
David Gaibor ◽  
Mehdi Goulamaly ◽  
Nilu Jariwala ◽  
Mark Piontkowski ◽  
Mansour Zenouzi ◽  
...  

It is common knowledge that an early diagnosis of a disease improves the treatment provided to a patient. With the advent of nanotechnology, engineers and scientists are beginning to utilize these nanoscale capabilities in the hope of - early disease detection. Viral, bacterial infections and other chronic diseases seem to alter the concentrations of some compounds present in sweat [1,2]. This project attempts to detect some of these diseases by measuring the variation in salinity of sweat that differs from the commonly accepted level [2]. By creating a low-cost, reusable and portable microsensor, it can then apply the same principles to construct a nanosensor to yield even more accurate results. The electrical signals obtained by the sensor produce data that translates into diagnostic medical results for sweat-related illnesses such as cystic fibrosis [3]. For a deeper and thorough understanding of all aspects of the sensor, multiple concepts for measuring sweat using electrical signals were considered. Ultimately, the concept chosen to measure varying sweat concentrations was through a capacitor. Multiple capacitor designs were simulated to determine the best way of maximizing performance. After the sensors were constructed, they were tested using various concentrations of sodium chloride (NaCl), from 0.1 grams per liter to 5 grams per liter, dissolved in distilled water to mimic the effect of authentic human sweat [4]. The designed sensor is successfully able to determine the likelihood of a person having cystic fibrosis using a sweat sample as their sweat sodium chloride concentration will correspond to an electrical signal obtained throughout the testing process.


Author(s):  
Mira Tafa ◽  
Sevim Naz Karışık ◽  
Ece Begüm Aksoy ◽  
Rüya Aslan

Cystic Fibrosis is a rare genetic disease that affects the transmission of chloride ions due to mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Even though there are nearly 2000 mutations identified to be related to the condition, the most common mutation is F508del; deletion of a phenylalanine residue at 508. On the other hand, G542X which is a Class I mutation is also found very commonly and there are no modulator treatments available for it. Furthermore, it was investigated that R553X mutation can as well be corrected simultaneously with G542X mutation. Therefore, the main focus is on designing a gene therapy project that can correct all these three mutations at once by utilizing the prime editing technique via lipid-based delivery. In this way, the mutations can be edited through plasmids that were designed containing 2 pegRNAs and the Cas enzyme. To implement such an approach efficiently, both ex vivo, an animal model, and in vivo steps are to be designed. For the cell line, fibroblasts are selected due to their simplicity and low cost. The animal model of the experiment is determined to be a ferret concerning the high similarity to the human's CFTR protein and finally, the procedure will follow on a direct application in human Cystic Fibrosis patients. The plasmids are thought to be delivered through a cationic liposome that will reach the lungs with the aid of a nebulizer. At the last stage of the experimental procedure, Sanger Sequencing will be done to see if the desired edit within the CFTR has been performed successfully, and Next Generation Sequencing will be executed to see if there has been an off-target mutation in the remainder of the genome. Whereas for detecting the presence and expression of CFTR protein in humans, immunodetection with flow cytometry will be conducted.


Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 123 ◽  
Author(s):  
Alicia Hauke ◽  
Susanne Oertel ◽  
Leona Knoke ◽  
Vanessa Fein ◽  
Christoph Maier ◽  
...  

Analysis of sweat chloride levels in cystic fibrosis (CF) patients is essential not only for diagnosis but also for the monitoring of therapeutic responses to new drugs, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and potentiators. Using iontophoresis as the gold standard can cause complications like burns, is uncomfortable, and requires repetitive hospital visits, which can be particularly problematic during a pandemic, where distancing and hygiene requirements are increased; therefore, it is necessary to develop fast and simple measures for the diagnosis and monitoring of CF. A screen-printed, low-cost chloride sensor was developed to remotely monitor CF patients. Using potentiometric measurements, the performance of the sensor was tested. It showed good sensitivity and a detection limit of 2.7 × 10−5 mol/L, which covered more than the complete concentration range of interest for CF diagnosis. Due to its fast response of 30 s, it competes well with standard sensor systems. It also offers significantly reduced costs and can be used as a portable device. The analysis of real sweat samples from healthy subjects, as well as CF patients, demonstrates a proper distinction using the screen-printed sensor. This approach presents an attractive remote measurement alternative for fast, simple, and low-cost CF diagnosis and monitoring


2017 ◽  
Author(s):  
Cibele Zanardi Esteves ◽  
Letícia de Aguiar Dias ◽  
Estela de Oliveira Lima ◽  
Diogo Noin de Oliveira ◽  
Carlos Fernando Odir Rodrigues Melo ◽  
...  

ABSTRACTBackgroundCystic fibrosis is a disabling genetic disease with an increased prevalence in populations with European heritage. Currently, the most used technique for collection of cystic fibrosis samples and diagnosis is provided through uncomfortable tests, with uncertain results, mostly based on chloride concentration in sweat. Since cystic fibrosis mutation induces many metabolic changes in patients, exploring these alterations might be an alternative to visualize potential biomarkers that could be used as interesting tools for further diagnostic upgrade, prioritizing simplicity, low cost and quickness.MethodsThis contribution describes an accurate strategy to provide potential biomarkers related to cystic fibrosis, which may be understood as a potential tool for new diagnostic approaches and/or for monitoring disease evolution. Therefore, the present proposal consists of using skin imprints on silica plates as a way of sample collection, followed by direct-infusion high-resolution mass spectrometry and multivariate data analysis, intending to identify metabolic changes in skin composition of cystic fibrosis patients.ResultsMetabolomics analysis allowed identifying chemical markers that can be traced back to cystic fibrosis in patients’ skin imprints, differently from control subjects. Seven chemical markers from several molecular classes were elected, represented by bile acids, a glutaric acid derivative, thyrotropin releasing hormone, an inflammatory mediator, a phosphatidic acid, and diacylglycerol isomers, all reflecting metabolic disturbances that occur due to of cystic fibrosis.ConclusionThe comfortable method of sample collection combined with the identified set of biomarkers represent potential tools that open the range of possibilities to manage cystic fibrosis and follow the disease evolution. This exploratory approach points to new perspectives about cystic fibrosis management and maybe to further development of a new diagnostic assay based on them.


2019 ◽  
Vol 39 (5) ◽  
pp. 593-604 ◽  
Author(s):  
Joseph F. Levy ◽  
Marjorie A. Rosenberg

Introduction. Estimating costs of medical care attributable to treatments over time is difficult due to costs that cannot be explained solely by observed risk factors. Unobserved risk factors cannot be accounted for using standard econometric techniques, potentially leading to imprecise prediction. The goal of this work is to describe methodology to account for latent variables in the prediction of longitudinal costs. Methods. Latent class growth mixture models (LCGMMs) predict class membership using observed risk factors and class-specific distributions of costs over time. Our motivating example models cost of care for children with cystic fibrosis from birth to age 17. We compare a generalized linear mixed model (GLMM) with LCGMMs. Both models use the same covariates and distribution to predict average costs by combinations of observed risk factors. We adopt a Bayesian estimation approach to both models and compare results using the deviance information criterion (DIC). Results. The 3-class LCGMM model has a lower DIC than the GLMM. The LCGMM latent classes include a low-cost group where costs increase slowly over time, a medium-cost group with initial higher costs than the low-cost group and with more rapidly increasing costs at older ages, and a high-cost group with a U-shaped trajectory. The risk profile-specific mixtures of classes are used to predict costs over time. The LCGMM model shows more delineation of costs by age by risk profile and with less uncertainty than the GLMM model. Conclusions. The LCGMM approach creates flexible prediction models when using longitudinal cost data. The Bayesian estimation approach to LCGMM presented fits well into cost-effectiveness modeling where the estimated trajectories and class membership can be used for prediction.


Author(s):  
Leire Martin-Souto ◽  
Idoia Buldain ◽  
Maialen Areitio ◽  
Leire Aparicio-Fernandez ◽  
Aitziber Antoran ◽  
...  

The detection and diagnosis of the opportunistic fungi Scedosporium spp. and Lomentospora prolificans still relies mainly on low-sensitive culture-based methods. This fact is especially worrying in Cystic Fibrosis (CF) patients in whom these fungal species are frequently isolated and may increase the risk of suffering from an infection or other health problems. Therefore, with the purpose of developing a serologic detection method for Scedosporium/Lomentospora, four different Scedosporium boydii protein extracts (whole cell protein extract, secretome, total cell surface and conidial surface associated proteins) were studied by ELISA to select the most useful for IgG detection in sera from CF patients. The four extracts were able to discriminate the Scedosporium/Lomentospora-infected from Aspergillus-infected and non-infected patients. However, the whole cell protein extract was the one selected, as it was the one with the highest output in terms of protein concentration per ml of fungal culture used, and its discriminatory capacity was the best. The ELISA test developed was then assayed with 212 sera from CF patients and it showed to be able to detect Scedosporium spp. and Lomentospora prolificans with very high sensitivity and specificity, 86%–100% and 93%–99%, respectively, depending on the cut-off value chosen (four values were proposed A450nm= 0.5837, A450nm= 0.6042, A450nm= 0.6404, and A450nm= 0.7099). Thus, although more research is needed to reach a standardized method, this ELISA platform offers a rapid, low-cost and easy solution to detect these elusive fungi through minimally invasive sampling, allowing the monitoring of the humoral response to fungal presence.


2017 ◽  
Vol 8 (1) ◽  
pp. 550-558 ◽  
Author(s):  
Jimin P. Kim ◽  
Zhiwei Xie ◽  
Michael Creer ◽  
Zhiwen Liu ◽  
Jian Yang

A new class of fluorescence chloride sensors are derived from a facile citrate-based synthesis platform, enabling low-cost chloride sensing for clinical diagnosis of Cystic Fibrosis through dynamic quenching mechanisms. We demonstrate for the first time a selective multi-halide sensing strategy using a single fluorophore.


2018 ◽  
Vol 199 ◽  
pp. 272-277.e3 ◽  
Author(s):  
Thaiane Rispoli ◽  
Simone Martins de Castro ◽  
Tarciana Grandi ◽  
Mayara Prado ◽  
Letícia Filippon ◽  
...  

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 993-1000 ◽  
Author(s):  
R. J. Grand
Keyword(s):  

Author(s):  
Y. L. Chen ◽  
S. Fujlshiro

Metastable beta titanium alloys have been known to have numerous advantages such as cold formability, high strength, good fracture resistance, deep hardenability, and cost effectiveness. Very high strength is obtainable by precipitation of the hexagonal alpha phase in a bcc beta matrix in these alloys. Precipitation hardening in the metastable beta alloys may also result from the formation of transition phases such as omega phase. Ti-15-3 (Ti-15V- 3Cr-3Al-3Sn) has been developed recently by TIMET and USAF for low cost sheet metal applications. The purpose of the present study was to examine the aging characteristics in this alloy.The composition of the as-received material is: 14.7 V, 3.14 Cr, 3.05 Al, 2.26 Sn, and 0.145 Fe. The beta transus temperature as determined by optical metallographic method was about 770°C. Specimen coupons were prepared from a mill-annealed 1.2 mm thick sheet, and solution treated at 827°C for 2 hr in argon, then water quenched. Aging was also done in argon at temperatures ranging from 316 to 616°C for various times.


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