Ultrasensitive dynamic light scattering immunosensing platform for NT-proBNP detection using boronate affinity amplification.
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ABSTRACT:
SUBMITTER: Hu J
PROVIDER: S-EPMC8740487 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this paper, we demonstrate an electrochemical method for detection of the heart failure biomarker, N-terminal prohormone brain natriuretic peptide (NT-proBNP). The approach is based on a paper electrode assembly and a metalloimmunoassay; it is intended for eventual integration into a home-use sensor. Sensing of NT-proBNP relies on the formation of a sandwich immunoassay and electrochemical quantification of silver nanoparticle (AgNP) labels attached to the detection antibodies (Abs). There are four important outcomes reported in this article. First, compared to physisorption of the detection Abs on the AgNP labels, a 27-fold increase in signal is observed when a heterobifunctional cross-linker is used to facilitate this labeling. Second, the assay is selective in that it does not cross-react with other cardiac natriuretic peptides. Third, the assay forms in undiluted human serum (though the electrochemical analysis is carried out in buffer). Finally, and most important, the assay is able to detect NT-proBNP at concentrations between 0.58 and 2.33 nM. This performance approaches the critical NT-proBNP concentration threshold often used by physicians for risk stratification purposes: ?0.116 nM.
| S-EPMC7103555 | biostudies-literature
Project description:ObjectiveTo compare in-hospital mortality in unselected adult patients according to N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.MethodRetrospective study including 3833 adult patients (median age 72 years, 45% women) hospitalized between January 2013 and April 2015 in a Swiss university hospital, with at least one NT-proBNP level measurement during hospitalization. Patients were categorized in quintiles regarding their highest NT-proBNP level. In-hospital mortality and length of stay (LOS) were compared between the highest and the other quintiles.ResultsIn-hospital mortality rate and LOS (average±standard deviation) were higher in the fifth quintile than in the others (6.5% vs 20.3%, and 20.8±24.0 vs. 14.9±26.5 days respectively, both p<0.001). After multivariate adjustment on age, gender, principal diagnoses, stage 5 renal failure and type of management, patients in the fifth quintile had a hazard ratio [95% confidence interval] of 1.97 [1.57-2.46] for in-hospital mortality and an adjusted LOS (average±standard error) of 20.4±1.0 vs. 14.9±0.5 days for the other quintiles (p<0.001). Further stratification on the main diagnosis at discharge led to similar findings.ConclusionPatients with high levels of NT-proBNP are at higher risk of in-hospital mortality and longer LOS, regardless of their clinical characteristics. NT-proBNP level can be a helpful tool for predicting in-hospital patient outcome in unselected adult patients.
| S-EPMC6224094 | biostudies-literature
Project description:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a myocardial stress biomarker that can be found in serum or plasma, saliva, and urine in the context of cardiovascular disease. In this study, we developed a rapid (~25 min) and straightforward localized surface plasmon resonance (LSPR)-based assay for detecting NT-proBNP in urine. The assay employs citrate-capped gold nanoparticles (AuNPs) and an aptamer specific for NT-proBNP, which initially interacts with NT-proBNP. The remaining unbound aptamer then interacts with the AuNPs, and the addition of NaCl induces the aggregation of the unprotected AuNPs, resulting in a decrease in absorbance at the LSPR band (A521) and an increase in absorbance at 750 nm (A750). The concentration of NT-proBNP showed a linear correlation with the aggregation ratio (A521/A750), and the assay demonstrated a limit of detection (LOD) of 0.303 µg·L-1 and a detection range of 0.566-8 µg·L-1. However, the presence of sulfur-containing proteins in saliva and fetal bovine serum hindered the detection of NT-proBNP in these biofluids. Nevertheless, the assay successfully detected NT-proBNP in diluted urine with an LOD of 0.417 µg·L-1 and a detection range of 0.589-6 µg·L-1. The observed values in urine samples from preterm infants with cardiovascular disease fell within this range, indicating the potential clinical relevance of the assay. The recovery percentages ranged from 92.3 to 116.3%. Overall, our findings suggest that the LSPR-based assay for NT-proBNP detection in urine can be a valuable tool for the diagnosis and treatment of cardiovascular disease.
| S-EPMC10377000 | biostudies-literature
Project description:Background: We evaluated the performance of the Abbott N-terminal pro-brain natriuretic peptide (NT-proBNP) assay against the Roche NT-proBNP immunoassay across two sites. Methods: Precision, linearity, and sensitivity studies were performed. A combined method of comparison and regression analysis was performed between the Roche and Abbott assays using samples from both sites (n = 494). To verify biotin interference, lyophilised biotin powder was reconstituted and spiked into serum samples at two medical decision levels (final concentration 500/4250 ng/mL) and compared to controls. NT-proBNP was also measured in anonymised leftover sera (n = 388) in a cardio-renal healthy population and stratified into three age bands-<50 (n = 145), 50-75 (n = 183) and >75 (n = 60). Results: Between-run precision (CV%) for NT-proBNP was 4.17/4.50 (139.5/142.0 pg/mL), 3.83/2.17 (521.6/506.3), and 4.60/2.51 (5053/4973), respectively. The assay was linear from 0.7-41,501 pg/mL. The limit of blank/quantitation was 1.2/7.9 pg/mL. The assay showed no interference from biotin up to 4250 ng/mL. Passing-Bablok regression analysis showed excellent agreement between the two assays (r = 0.999, 95% CI 0.999 to 0.999, p < 0.0001). The Roche assay had a slightly persistent, negative bias across different levels of NT-proBNP. ESC age cut-offs for diagnosing acute heart failure are applicable for the Abbott assay, with the median NT-proBNP of subjects < 50 years old at 43.0 pg/mL (range 4.9-456 pg/mL), 50-75 years old at 95.1 pg/mL (range 10.5-1079 pg/mL), and >75 years old at 173.1 pg/mL (range 23.2-1948 pg/mL). Conclusions: The Abbott Architect NT-proBNP assay has good performance that agrees with the manufacturer's specifications. ESC/AHA recommended NT-proBNP age groups for acute heart failure diagnosis are applicable to this assay.
| S-EPMC9140882 | biostudies-literature
Project description:We describe an adaptation of the rolling circle amplification (RCA) reporter system for the detection of protein Ags, termed "immunoRCA. " In immunoRCA, an oligonucleotide primer is covalently attached to an Ab; thus, in the presence of circular DNA, DNA polymerase, and nucleotides, amplification results in a long DNA molecule containing hundreds of copies of the circular DNA sequence that remain attached to the Ab and that can be detected in a variety of ways. Using immunoRCA, analytes were detected at sensitivities exceeding those of conventional enzyme immunoassays in ELISA and microparticle formats. The signal amplification afforded by immunoRCA also enabled immunoassays to be carried out in microspot and microarray formats with exquisite sensitivity. When Ags are present at concentrations down to fM levels, specifically bound Abs can be scored by counting discrete fluorescent signals arising from individual Ag-Ab complexes. Multiplex immunoRCA also was demonstrated by accurately quantifying Ags mixed in different ratios in a two-color, single-molecule-counting assay on a glass slide. ImmunoRCA thus combines high sensitivity and a very wide dynamic range with an unprecedented capability for single molecule detection. This Ag-detection method is of general applicability and is extendable to multiplexed immunoassays that employ a battery of different Abs, each labeled with a unique oligonucleotide primer, that can be discriminated by a color-coded visualization system. ImmunoRCA-profiling based on the simultaneous quantitation of multiple Ags should expand the power of immunoassays by exploiting the increased information content of ratio-based expression analysis.
| S-EPMC27732 | biostudies-literature
Project description:A major challenge in the development of bioanalytical methods is to achieve a rapid and robust quantification of disease biomarkers present at very low concentration levels in complex biological samples. An immunoassay platform is presented herein for ultrasensitive and fast detection of the prostate-specific antigen (PSA), a well-recognized cancer biomarker. A sandwich type immunosensor has been developed employing a detection antibody labeled with inorganic nanoparticles acting as tags for further indirect quantification of the analyte. The required high sensitivity is then achieved through a controlled gold deposition on the nanoparticle surface, carried out after completing the recognition step of the immunoassay, thus effectively amplifying the size of the nanoparticles from nm to µm range. Due to such an amplification procedure, quantification of the biomolecule could be carried out directly on the immunoassay plates using confocal microscopy for measurement of the reflected light produced by gold-enlarged nanostructures. The high specificity of the immunoassay was demonstrated with the addition of a major abundant protein in serum (albumin) at much higher concentrations. An extremely low detection limit for PSA quantification (LOD of 1.1 fg·mL-1 PSA) has been achieved. Such excellent LOD is 2-3 orders of magnitude lower than the clinically relevant PSA levels present in biological samples (4-10 ng·mL-1) and even to monitor eventual recurrence after clinical treatment of a prostate tumor (0.1 ng·mL-1). In fact, the broad dynamic range obtained (4 orders of magnitude) would allow the PSA quantification of diverse samples at very different relevant levels.
| S-EPMC7571086 | biostudies-literature
Project description:Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) level is useful to diagnose or exclude acutely decompensated heart failure (ADHF) in dyspnoeic patients presenting to the emergency department (ED).To evaluate the impact of ED NT-proBNP testing on admission, length of stay (LOS), discharge diagnosis and long-term outcome.Dyspnoeic patients were randomized in the ED to NT-proBNP testing. Admission and discharge diagnoses, and outcomes were examined.During 17 months, 470 patients were enrolled and followed for 2.0±1.3 years. ADHF likelihood, determined at study conclusion by validated criteria, established ADHF diagnosis as unlikely in 86 (17%), possible in 120 (24%), and likely in 293 (59%) patients. The respective admission rates in these subgroups were 80, 91, and 96%, regardless of blinding, and 61.9% of blinded vs. 74.5% of unblinded ADHF-likely patients were correctly diagnosed at discharge (p=0.029), with similar LOS. 2-year mortality within subgroups was unaffected by test, but was lower in ADHF-likely patients with NT-proBNP levels below median (5000 pg/ml) compared with those above median (p=0.002). Incidence of recurrent cardiac events tracked NT-proBNP levels.ED NT-proBNP testing did not affect admission, LOS, 2-year survival, or recurrent cardiac events among study patients but improved diagnosis at discharge, and allowed risk stratification even within the ADHF-likely group. (ClinicalTrials.gov#NCT00271128).
| S-EPMC3760533 | biostudies-literature
Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.
| S-EPMC8603582 | biostudies-literature
Project description:BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown.MethodsThe study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records.ResultsThe best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death.ConclusionNT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19.Trial registrationClinicalTrials, NCT04292964. Registered 03 March 2020.
| S-EPMC7156898 | biostudies-literature
Project description:We conducted a prospective cohort study in newly diagnosed systemic light chain (AL) amyloidosis patients (N = 59) to study patient-reported outcomes (PROs) through the first year. The median age was 68 years with 42% female, 8% Black, and 78% lambda subtype. Organ involvement was cardiac in 66%, renal in 58%, with 25% having 3 or greater organs involved. Between baseline and 3 months, all PROMIS®-29 domain scores worsened by 0.4-4.1 points except anxiety which improved by 2.1 points. By 1 year, scores improved compared to the greatest decline at 3 months, most statistically significant for global physical health, physical function, and fatigue. On stage-adjusted survival analysis, in addition to baseline global physical and mental health, domains measuring physical function, fatigue, anxiety, depression, and social roles were associated with 1-year survival. At 1 year, PROMIS measures were associated with NT-proBNP changes and hematologic response. Among patients with an NT-proBNP response, the improvement was seen in physical function, social roles, global mental health, and anxiety. Among patients with an NT-proBNP progression, worsening was seen with anxiety, depression, sleep, and global mental health. Measuring and tracking PROs in patients with AL amyloidosis is important and these important outcomes can be used as correlative endpoints in clinical care/research.
| S-EPMC7873213 | biostudies-literature