A first of its kind quantitative functional C1-esterase inhibitor lateral flow assay for hereditary angioedema point-of-care diagnostic testing

2020 ◽  
Vol 83 ◽  
pp. 106526
Author(s):  
Priya S. Chockalingam ◽  
Zhiwei Zhou ◽  
Brijesh K. Garg ◽  
Hans Boehringer ◽  
Roy Chung ◽  
...  

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Xue Jiang ◽  
Peter B. Lillehoj

Abstract Rapid diagnostic tests are one of the most commonly used tests to detect and screen for infectious diseases in the developing world. While these tests are simple, inexpensive, and readily available, they rely on finger-prick blood sampling, which requires trained medical personnel, poses risks of infection, and can complicate cooperation in young children, asymptomatic individuals, and communities with blood taboos. Here, we report a novel microneedle-based skin patch for the rapid detection of protein biomarkers in dermal interstitial fluid. Sample collection is facilitated by a hydrophilic hollow microneedle array that autonomously extracts and transports interstitial fluid to an antibody-based lateral flow test strip via surface tension for colorimetric antigen detection. We employ a simple gold enhancement treatment to enhance the detection sensitivity of this colloidal gold-based lateral flow assay and elucidate the underlying mechanism of this enhancement mechanism through experimental investigation. For proof-of-concept, this device was used to detect Plasmodium falciparum histidine-rich protein 2, a biomarker for malaria infection, which could be detected at concentrations as low as 8 ng/mL. Each test can be completed in <20 min and requires no equipment. To the best of our knowledge, this work is the first demonstration of a microneedle-based lateral flow assay for rapid protein detection in dermal interstitial fluid. In addition to its simplicity, minimally invasive nature, and low cost, this diagnostic device can be readily adapted to detect other protein biomarkers in interstitial fluid, making it a promising tool for point-of-care testing.



Author(s):  
Marco Cicardi ◽  
Lorenza Zingale ◽  
Andrea Zanichelli ◽  
Daniela Lambertenghi Deliliers


Author(s):  
Carla Eiras

Interleukin-6 (IL-6) is a multifunctional cytokine and high bloodstream levels of which have been associated with severe inflammatory diseases, such as dengue fever, sepsis, various cancers, and visceral leishmaniasis (VL). Rapid tests for the quantification of IL-6 would be of great assistance for the bedside diagnosis and treatment of diseases such as VL. We have developed a lateral flow assay (LFA) for rapid and colorimetric IL-6 detection, consisting of anti-IL-6 antibodies conjugated to gold nanoparticles (AuNPs). The optimal concentration of anti-IL-6 used in the conjugate was determined to be 800.0 μg/mL, based on an aggregation assay using LFA. A linear relationship between IL-6 standard concentration and color intensity was observed after 20 min, with a linear range between 1.25 ng/mL and 9,000 ng/mL. The limit of detection for this method was estimated a t0.38 ng/mL. The concentration of IL-6 in five patients with severe VL was measured using LFA, and the results were consistent with those obtained using the cytometric bead array (CBA) method. A thorough analysis of the LFA membranes’ surface morphology, before and after sample contact, was performed using atomic force microscopy (AFM).The prototype described here is still being tested and improved, but this LFA will undoubtedly be of great help in the clinical quantification of IL-6.



Author(s):  
Carla Eiras

Interleukin-6 (IL-6) is a multifunctional cytokine and high bloodstream levels of which have been associated with severe inflammatory diseases, such as dengue fever, sepsis, various cancers, and visceral leishmaniasis (VL). Rapid tests for the quantification of IL-6 would be of great assistance for the bedside diagnosis and treatment of diseases such as VL. We have developed a lateral flow assay (LFA) for rapid and colorimetric IL-6 detection, consisting of anti-IL-6 antibodies conjugated to gold nanoparticles (AuNPs). The optimal concentration of anti-IL-6 used in the conjugate was determined to be 800.0 μg/mL, based on an aggregation assay using LFA. A linear relationship between IL-6 standard concentration and color intensity was observed after 20 min, with a linear range between 1.25 ng/mL and 9,000 ng/mL. The limit of detection for this method was estimated at a t0.38 ng/mL. The concentration of IL-6 in five patients with severe VL was measured using LFA, and the results were consistent with those obtained using the cytometric bead array (CBA) method. A thorough analysis of the LFA membranes’ surface morphology, before and after sample contact, was performed using atomic force microscopy (AFM). The prototype described here is still being tested and improved, but this LFA will undoubtedly be of great help in the clinical quantification of IL-6.



2021 ◽  
Vol 14 (4) ◽  
pp. 100535
Author(s):  
Anna Valerieva ◽  
Maria T. Staevska ◽  
Vesna Grivcheva-Panovska ◽  
Milos Jesenak ◽  
Kinga Viktória Kőhalmi ◽  
...  


2014 ◽  
Vol 2 (1) ◽  
pp. 77-84.e1 ◽  
Author(s):  
Jonathan A. Bernstein ◽  
Michael E. Manning ◽  
Henry Li ◽  
Martha V. White ◽  
James Baker ◽  
...  


2011 ◽  
Vol 4 ◽  
pp. S9-S21 ◽  
Author(s):  
Richard G Gower ◽  
Paula J Busse ◽  
Emel Aygören-Pürsün ◽  
Amin J Barakat ◽  
Teresa Caballero ◽  
...  


2021 ◽  
Vol 42 (4) ◽  
pp. 317-324
Author(s):  
Felix. A. Johnson ◽  
Magdalena Wirth ◽  
Zhaojun Zhu ◽  
Janina Hahn ◽  
Jens Greve ◽  
...  

Introduction: Hereditary angioedema (HAE) is a disease that leads to recurrent swelling of the skin and mucous membranes, including the upper airway tract. Apart from being deadly, these attacks can be debilitating, which leads to a poor quality of life in patients. Clinicians are occasionally confronted with patients who have recurrent attacks despite treatment with C1 esterase inhibitor concentrate or β2-receptor antagonists. The goal of this study was to investigate repeated attacks that occur 48 hours to 7 days (“cluster attacks”) after treatment, to determine why they occur and the factors that may be associated with them, and thus to prevent their occurrence. Methods: We conducted a multicenter mixed retrospective-prospective study with data acquired from all documented attacks in our patients with collective (n = 132) between 2015 and 2018. Results: Eighty-five percent (n = 132) of our total patient collective (N = 156) agreed to participate in the study. Nine percent of these patients (n = 12) had cluster attacks, with a total of 48 cluster attacks. The data procured from the patients were mixed retrospective‐prospective. Approximately 72% of all the cluster attacks were caused by exogenous stimuli (41% due to psychological stress, 29% due to physical stimuli, and 2% due to menstruation). Cluster attacks occurred in 7% of the patients who received prophylactic therapy in comparison with 12.5% of patients who received on-demand therapy. Cluster attacks comprised 48.4% of all the attacks that patients with cluster-attacks (n= 9) experienced. In addition, the patients who were underdosing their C1 esterase inhibitor treatment had cluster attacks more often. A lower “time to repeated attack” was seen in the patients who received on-demand therapy compared with those who received prophylactic therapy. Discussion: The percentage of the patients who had attacks as a result of exogenous triggers was higher in the cluster-attack group (70.5%) compared with the general HAE population (30‐42%). Repeated attacks, therefore, were strongly associated with external triggers. The patients who received prophylactic treatment and who experienced cluster attacks were highly likely to have been underdosing, which may explain the repeated attacks despite treatment. In the patients prone to cluster attacks, prophylaxis should be considered.



2016 ◽  
Vol 6 (1) ◽  
pp. 1600920 ◽  
Author(s):  
Jane Ru Choi ◽  
Kar Wey Yong ◽  
Ruihua Tang ◽  
Yan Gong ◽  
Ting Wen ◽  
...  


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