scholarly journals Detection and quantification of Mycobacterium tuberculosis antigen CFP10 in serum and urine for the rapid diagnosis of active tuberculosis disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marva Seifert ◽  
Eva Vargas ◽  
Victor Ruiz-Valdepeñas Montiel ◽  
Joseph Wang ◽  
Timothy C. Rodwell ◽  
...  
Keyword(s):  
Point Of Care ◽  
Low Cost ◽  
Specific Antigen ◽  
Active Tuberculosis ◽  
Serum Samples ◽  
Tuberculosis Patients ◽  
Tuberculosis Antigen ◽  
Highly Sensitive ◽  
Tuberculosis Disease ◽  
Serum And Urine

AbstractOutside of the ongoing COVID-19 pandemic, tuberculosis is the leading cause of infectious disease mortality globally. Currently, there is no commercially available point-of-care diagnostic that is rapid, inexpensive, and highly sensitive for the diagnosis of active tuberculosis disease. Here we describe the development and optimization of a novel, highly sensitive prototype bioelectronic tuberculosis antigen (BETA) assay to detect tuberculosis-specific antigen, CFP10, in small-volume serum and urine samples. In this proof-of-concept study we evaluated the performance of the BETA assay using clinical specimens collected from presumptive tuberculosis patients from three independent cohorts. Circulating CFP10 antigen was detected in ALL serum (n = 19) and urine (n = 3) samples from bacteriologically confirmed tuberculosis patients who were untreated or had less than one week of treatment at time of serum collection, successfully identifying all culture positive tuberculosis patients. No CFP10 antigen was detected in serum (n = 7) or urine (n = 6) samples from individuals who were determined to be negative for tuberculosis disease. Additionally, antigen quantification using the BETA assay of paired serum samples collected from tuberculosis patients (n = 8) both before and after treatment initiation, indicate consistently declining within-person levels of CFP10 antigen during treatment. This novel, low-cost assay demonstrates potential as a rapid, non-sputum-based, point-of-care tool for the diagnosis of tuberculosis disease.

scholarly journals An Ultra-Rapid Biosensory Point-of-Care (POC) Assay for Prostate-Specific Antigen (PSA) Detection in Human Serum

Sensors ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 3834 ◽  
Author(s):  
Sophie Mavrikou ◽  
Georgia Moschopoulou ◽  
Athanasios Zafeirakis ◽  
Konstantina Kalogeropoulou ◽  
Georgios Giannakos ◽  
...  
Keyword(s):  
Human Serum ◽  
Prostate Specific Antigen ◽  
High Throughput ◽  
Early Stage ◽  
Point Of Care ◽  
Low Cost ◽  
Specific Antigen ◽  
Serum Samples ◽  
Stage Of Development ◽  
Better Than

Prostate-specific antigen (PSA) is the established routine screening tool for the detection of early-stage prostate cancer. Given the laboratory-centric nature of the process, the development of a portable, ultra rapid high-throughput system for PSA screening is highly desirable. In this study, an advancedpoint-of-care system for PSA detection in human serum was developed based on a cellular biosensor where the cell membrane was modified by electroinserting a specific antibody against PSA. Thirty nine human serum samples were used for validation of this biosensory system for PSA detection. Samples were analyzed in parallel with a standard immunoradiometric assay (IRMA) and an established electrochemical immunoassay was used for comparison purposes. They were classified in three different PSA concentration ranges (0, <4 and ≥4 ng/mL). Cells membrane-engineered with 0.25 μg/mL anti-PSA antibody demonstrated a statistically lower response against the upper (≥4 ng/mL) PSA concentration range. In addition, the cell-based biosensor performed better than the immunosensor in terms of sensitivity and resolution against positive samples containing <4 ng/mL PSA. In spite of its preliminary, proof-of-concept stage of development, the cell-based biosensor could be used as aninitiative for the development of a fast, low-cost, and high-throughput POC screening system for PSA.

scholarly journals Trimodal Waveguide Demonstration and Its Implementation as a High Order Mode Interferometer for Sensing Application

Sensors ◽  
2019 ◽  
Vol 19 (12) ◽  
pp. 2821 ◽  
Author(s):  
Jhonattan C. Ramirez ◽  
Lucas H. Gabrielli ◽  
Laura M. Lechuga ◽  
Hugo E. Hernandez-Figueroa
Keyword(s):  
Free Spectral Range ◽  
Point Of Care ◽  
Low Cost ◽  
High Order Mode ◽  
Sio2 Substrate ◽  
Polymer Waveguide ◽  
Sensing Applications ◽  
Highly Sensitive ◽  
Different Types ◽  
Mode Order

This work implements and demonstrates an interferometric transducer based on a trimodal optical waveguide concept. The readout signal is generated from the interference between the fundamental and second-order modes propagating on a straight polymer waveguide. Intuitively, the higher the mode order, the larger the fraction of power (evanescent field) propagating outside the waveguide core, hence the higher the sensitivity that can be achieved when interfering against the strongly confined fundamental mode. The device is fabricated using the polymer SU-8 over a SiO2 substrate and shows a free spectral range of 20.2 nm and signal visibility of 5.7 dB, reaching a sensitivity to temperature variations of 0.0586 dB/ ∘ C. The results indicate that the proposed interferometer is a promising candidate for highly sensitive, compact and low-cost photonic transducer for implementation in different types of sensing applications, among these, point-of-care.

scholarly journals Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Eliana Peresi ◽  
Larissa Ragozo Cardoso Oliveira ◽  
Weber Laurentino da Silva ◽  
Érika Alessandra Pellison Nunes da Costa ◽  
João Pessoa Araujo ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Plasma Levels ◽  
Gene Polymorphisms ◽  
Essential Role ◽  
Active Tuberculosis ◽  
Mrna Levels ◽  
Tuberculosis Patients ◽  
Antituberculosis Treatment ◽  
Cytokine Levels ◽  
Tuberculosis Disease

Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify ifIFNG, IL12B, TNF, IL17A, IL10, and TGFB1gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations:IFNG+874 T allele andIFNG+2109 A allele with higher IFN-γlevels;IL12B+1188 C allele with higher IL-12 levels;TNF−308 A allele with higher TNF-αplasma levels in controls and mRNA levels in PTB patients at T1;IL17AA allele at rs7747909 with higher IL-17 levels;IL10−819 T allele with higher IL-10 levels; andTGFB1+29 CC genotype higher TGF-βplasma levels in PTB patients at T2. The present study suggests thatIFNG+874T/A,IFNG+2109A/G,IL12B+1188A/C,IL10−819C/T, andTGFB1+21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.

Field deployable platform for prognostic hepatic cancer screening.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 267-267
Author(s):  
Jill E. Shea ◽  
Jennifer H Granger ◽  
Mark D Porter ◽  
Courtney L. Scaife
Keyword(s):  
High Risk ◽  
Point Of Care ◽  
Low Cost ◽  
Serum Levels ◽  
Blood Levels ◽  
Vertical Flow ◽  
Serum Samples ◽  
Point Of Care System ◽  
Risk Patients ◽  
Care System

267 Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.

scholarly journals A low-cost smartphone-based platform for highly sensitive point-of-care testing with persistent luminescent phosphors

Lab on a Chip ◽  
2017 ◽  
Vol 17 (6) ◽  
pp. 1051-1059 ◽  
Author(s):  
Andrew S. Paterson ◽  
Balakrishnan Raja ◽  
Vinay Mandadi ◽  
Blane Townsend ◽  
Miles Lee ◽  
...  
Keyword(s):  
Point Of Care ◽  
Low Cost ◽  
Test Strip ◽  
Lateral Flow ◽  
Point Of Care Testing ◽  
Flow Test ◽  
Highly Sensitive ◽  
Lateral Flow Test ◽  
Gated Imaging

Time-gated imaging on a smartphone of a lateral flow test strip run with persistent luminescent nanophosphors.

scholarly journals Deep Learning-Enabled Point-of-Care Sensing Using Multiplexed Paper-Based Sensors

2019 ◽  
Author(s):  
Zachary Ballard ◽  
Hyou-Arm Joung ◽  
Artem Goncharov ◽  
Jesse Liang ◽  
Karina Nugroho ◽  
...  
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Point Of Care ◽  
Low Cost ◽  
High Sensitivity ◽  
Cost Effective ◽  
Serum Samples ◽  
Cvd Risk ◽  
Medical Test ◽  
Sensing Membrane

ABSTRACTWe present a deep learning-based framework to design and quantify point-of-care sensors. As its proof-of-concept and use-case, we demonstrated a low-cost and rapid paper-based vertical flow assay (VFA) for high sensitivity C-Reactive Protein (hsCRP) testing, a common medical test used for quantifying the degree of inflammation in patients at risk of cardio-vascular disease (CVD). A machine learning-based sensor design framework was developed for two key tasks: (1) to determine an optimal configuration of immunoreaction spots and conditions, spatially-multiplexed on a paper-based sensing membrane, and (2) to accurately infer the target analyte concentration based on the signals of the optimal VFA configuration. Using a custom-designed mobile-phone based VFA reader, a clinical study was performed with 85 human serum samples to characterize the quantification accuracy around the clinically defined cutoffs for CVD risk stratification. Results from blindly-tested VFAs indicate a competitive coefficient of variation of 11.2% with a linearity of R2 = 0.95; in addition to the success in the high-sensitivity CRP range (i.e., 0-10 mg/L), our results further demonstrate a mitigation of the hook-effect at higher CRP concentrations due to the incorporation of antigen capture spots within the multiplexed sensing membrane of the VFA. This paper-based computational VFA that is powered by deep learning could expand access to CVD health screening, and the presented machine learning-enabled sensing framework can be broadly used to design cost-effective and mobile sensors for various point-of-care diagnostics applications.

scholarly journals Immunoproteomic analysis of Borrelia miyamotoi for the identification of serodiagnostic antigens

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Emma K. Harris ◽  
Marisa R. Harton ◽  
Maria Angela de Mello Marques ◽  
John T. Belisle ◽  
Claudia R. Molins ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Specific Antigen ◽  
Disease Patient ◽  
Borrelia Miyamotoi ◽  
Serum Samples ◽  
Human Patient ◽  
Highly Sensitive ◽  
Associated Proteins ◽  
Multiple Variable ◽  
Health Significance

AbstractThe tick-borne spirochete, Borrelia miyamotoi, is an emerging pathogen of public health significance. Current B. miyamotoi serodiagnostic testing depends on reactivity against GlpQ which is not highly sensitive on acute phase serum samples. Additionally, anti-B. miyamotoi antibodies can cross-react with C6 antigen testing for B. burgdorferi, the causative agent of Lyme disease, underscoring the need for improved serological assays that produce accurate diagnostic results. We performed an immunoproteomics analysis of B. miyamotoi proteins to identify novel serodiagnostic antigens. Sera from mice infected with B. miyamotoi by subcutaneous inoculation or tick bite were collected for immunoblotting against B. miyamotoi membrane-associated proteins separated by 2-dimensional electrophoresis (2DE). In total, 88 proteins in 40 2DE immunoreactive spots were identified via mass spectrometry. Multiple variable large proteins (Vlps) and a putative lipoprotein were among those identified and analyzed. Reactivity of anti-B. miyamotoi sera against recombinant Vlps and the putative lipoprotein confirmed their immunogenicity. Mouse anti-B. burgdorferi serum was cross-reactive to all recombinant Vlps, but not against the putative lipoprotein by IgG. Furthermore, antibodies against the recombinant putative lipoprotein were present in serum from a B. miyamotoi-infected human patient, but not a Lyme disease patient. Results presented here provide a comprehensive profile of B. miyamotoi antigens that induce the host immune response and identify a putative lipoprotein as a potentially specific antigen for B. miyamotoi serodetection.

iLluminate-miRNA: Paradigm for high-throughput, low-cost, and sensitive miRNA detection in serum samples at point-of-care

2018 ◽  
Vol 52 (5) ◽  
pp. 055401 ◽  
Author(s):  
Logeeshan Velmanickam ◽  
Manpreet Bains ◽  
Michael Fondakowski ◽  
Glenn Paul Dorsam ◽  
Dharmakeerthi Nawarathna
Keyword(s):  
High Throughput ◽  
Point Of Care ◽  
Low Cost ◽  
Serum Samples ◽  
Mirna Detection

scholarly journals The TBAg/PHA ratio in T-SPOT.TB assay has high prospective value in the diagnosis of active tuberculosis: a multicenter study in China

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yidian Liu ◽  
Lan Yao ◽  
Feng Wang ◽  
Ziyong Sun ◽  
Yaoju Tan ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Threshold Value ◽  
Active Tuberculosis ◽  
Tuberculosis Patients ◽  
Specificity And Sensitivity ◽  
Positive Rate ◽  
Tertiary Hospitals ◽  
High Prediction ◽  
Improved Performance ◽  
Multicenter Prospective Study

Abstract Background The positive rate of pathogenic examination about tuberculosis is low. It is still difficult to achieve early diagnosis for some TB patients. The value of Interferon-gamma release assays (IGRA) in the diagnosis of active tuberculosis remains controversial. The purpose of this multicenter prospective study was to verify and validate the role of TBAg/PHA ratio (TB-specific antigen to phytohaemagglutinin) of T-SPOT.TB assay in diagnosing ATB. Methods We prospectively enrolled 2390 suspected pulmonary tuberculosis patients with positive T-SPOT assay results from three tertiary hospitals. Results A total of 1549 ATB (active tuberculosis) patients (including 1091 confirmed and 458 probable ATB) and 724 non-tuberculosis (non-TB) patients with positive T-SPOT results were included. The results of this study showed that ESAT-6 and CFP-10 in the T-SPOT.TB assay were significantly higher in the ATB group compared with the non-TB group, while PHA was lower in the ATB group. Results of ESAT-6, CFP-10 and PHA show a certain diagnostic performance, but moderate sensitivity and specificity. The TBAg/PHA ratio, a further calculation of ESAT-6, CFP-10 and PHA in T-SPOT.TB assay showed improved performance in the diagnosis of active Tuberculosis. If using the threshold value of 0.2004, the specificity and sensitivity of TBAg/PHA ratio in distinguishing ATB from non-TB were 92.3% and 74.4%, PPV was 95.4, PLR was 9.6. Conclusion By recalculating the results of T-SPOT.TB Assay, the TBAg/PHA ratio shows high prospect value in the diagnosis of active tuberculosis in high prediction areas.

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