Detection Of Brain Natriuretic Peptide Research Articles

Fluorescent aptasensor based on competitive recognition strategies and point-of-care testing system for brain natriuretic peptide detection

Brain natriuretic peptide (BNP) is the preferred biomarker for clinical analysis, widely used in early screening and prognostic monitoring of cardiovascular and neurological diseases. Due to the low concentration and short half-life of BNP in the blood, its sensitive detection remains a challenge that must be overcome. With the rapid development of molecular diagnosis and point-of-care testing (POCT), developing a BNP biosensor with high sensitivity, good stability, accuracy, speed, and low-cost is of great significance for clinical applications and emergency diagnosis. However, BNP in human blood exists in various forms, and traditional fluorescence sensors may lead to overestimation of the concentration. In this work, we constructed an “on” fluorescent aptasensor based on competitive recognition strategy for quantitative detection of BNP, and built a fluorescence sensing detection system based on smartphone to achieve rapid on-site detection. We designed a specific aptamer labeled with carboxyfluorescein (FAM) with a simple structure and high biological affinity for selective capture of BNP, and utilized the large specific surface area and excellent fluorescence quenching effect of carboxylated graphene oxide (GO-COOH) as a carrier and quencher for the aptasensor. By optimizing experimental parameters such as aptamer and GO-COOH concentrations, as well as quenching/recovery time, linear sensitive detection of BNP was achieved in the concentration range of 0.01 ng/mL–10 ng/mL, with a detection limit as low as 10 pg/mL, good specificity, and excellent application potential in artificial serum spiking experiments. Additionally, a stable and sensitive fluorescence signal collection system has been developed to meet the needs of portable detection, breaking through the usage environment of traditional fluorescence detection equipment and filling the gap of portable fluorescence biosensing. In summary, we have creatively proposed a fluorescent aptasensor that enables rapid and sensitive detection of BNP and the development of low-cost fluorescent biosensors. The combination with POCT has shown broad application prospects and also provides some ideas for the fluorescence detection of other protein biomarkers.

A novel electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH for rapid detecting warning markers-BNP of heart failure caused by myocardial infarction

Heart failure (HF) is an insidious and dangerous disease that significantly impairs a patient’s quality of life and safety. It is not easy to detect in mild cases, and once it progresses to severe stages, deterioration can be rapid and challenging to reverse. Currently, early warning and prognostic risk assessment technologies are lacking, and there is an urgent need for precise early warning, risk assessment and diagnosis and treatment of HF at the cellular or molecular level. In this study, an electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH was prepared to detect brain natriuretic peptide (BNP), a biomarker for early warning of HF caused by myocardial infarction. Among them, the CS@MWCNTs-COOH nanocomposites and the polymerized neutral red (PNR) films on the electrode surface effectively enhanced the conductivity of the modified electrodes and significantly increased the specific surface area through the formation of three-dimensional nanostructures. AuNPs loaded on PNR/CS@MWCNTs-COOH provided a stable gold-ammonia bond for the specific antibody loading of BNP, facilitating the development of an electrochemical immunosensor with high selectivity for BNP detection. Furthermore, this work used cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to improve aspects that influence the immunosensor’s analytical performance. Under ideal conditions, the immunosensor was tested for immunological qualities using differential pulse voltammetry (DPV), resulting in sensitive measurement of BNP concentration in undiluted serum samples.The peak current Ip of the response signal is linearly proportional to the LgCBNP in the range of 1.95 × 10−3 ng mL−1 to 8.0 ng mL−1, with a detection limit of 0.80 × 10−3 ng mL−1 (S/N=3). It can achieve highly sensitive identification and detection of trace BNP in complex biological samples and provide a convenient and efficient method for HF-related marker detection. Furthermore, it also can serve as a scientific basis and a new method for the development of early warning technology for HF and related pathological mechanism research.

Luminescence "Turn-On" Sensing of Brain Natriuretic Peptide (BNP) - Dilated Cardiomyopathy Biomarker Based on the MoS2 Nanosheet Quenched Terbium Citrate Complex.

Dilated cardiomyopathy (DCM), known as myocardial metabolic dysfunction, is recognized as a clinical condition characterized by left ventricular dilation or improper contraction of cardiac muscles in the absence of coronary atherosclerosis and hypertension. It is an independent risk factor for cardiac function caused by a hyperglycemic condition in diabetic patients leading to heart failure (HF), which renders the early diagnosis of DCM highly challenging. Hence, detection of early diagnostic biomarkers in blood serum to identify DCM conditions is quite requisite. Brain natriuretic peptide (BNP) is a well-recognized biomarker for heart failure and reported as an early diagnostic biomarker for DCM. In this work, we developed a terbium citrate based MoS2 nanosheet (NS) coupled immunoprobe for the sensitive detection of BNP. The antibody conjugated Tb-citrate complex exhibits green fluorescence, which is quenched by the introduction of MoS2 NS. On subsequent addition of antigen BNP, the fluorescence is enhanced because of specific antigen-antibody interaction. The probe is selective and sensitive toward BNP in a linear range from 30.76 to 849.85 pg/mL with a low LOD of 3.87 pg/mL. The probe is validated in spiked human serum samples with good recovery percentage.

Gold nanoclusters – 2D MoS2 nano couple: An immunosensor for the fluorescence turn-on detection of heart failure Biomarker Brain Natriuretic Peptide (BNP)

In the context of elevated morbidity and mortality risk of heart failure (HF), the establishment of prompt and sensitive diagnosis of HF is vital. A nanostructured fluorescence immuno sensing probe was constructed out of noble metal nanoclusters / two-dimensional transition metal dichalcogenide nano couple to target brain natriuretic peptide (BNP) antigen, a potential multi-utility heart failure biomarker. The green fluorescence of BNP-specific monoclonal antibody-conjugated gold nanoclusters was pre-quenched by a MoS2 two-dimensional nanosheet, which is subsequently enhanced in the presence of BNP antigen via target-specific antigen–antibody interaction. The probe is free from interferences by other potentially interfering possible co-existing biomolecules and offers easy, low-cost linear detection of BNP in the concentration range 0 to 360.82 pg/mL.

Exploring T7 RNA polymerase-assisted CRISPR/Cas13a amplification for the detection of BNP via electrochemiluminescence sensing platform

Brain natriuretic peptide (BNP) is considered to be an important biomarker of heart failure (HF) attracting attention. However, its low concentration and short half-life in blood lead to a low-sensitivity detection of BNP, which is a challenge that has to be overcome. In this work, we propose a highly specific, highly sensitive T7 RNA polymerase-assisted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system to detect BNP via an electrochemiluminescence (ECL) sensing platform and incorporate exonuclease III (Exo III)-hairpin and dumbbell-shaped hybridization chain reaction (HCR) technologies. In this detection scheme, the ECL sensing platform possesses low background signal and high sensitivity. Firstly, the T7 promoter-initiated T7 RNA polymerase acts as a signal amplification technique to generate large amounts of RNAs that can activate CRISPR/Cas13a activity. Secondly, CRISPR/Cas13a is able to trans-cleave the surrounding trigger strand to produce DNA1. Thirdly, DNA1 is involved in the co-amplification reaction of Exo III and hairpin DNA, which subsequently triggers a dumbbell-shaped HCR technology. Eventually, a large number of Ru (II) molecules are inserted into the interstitial space of the dumbbell-shaped HCR to generate a strong ECL signal. The CRISPR/Cas13a possesses outstanding specificity for a single base and increased sensitivity. The tightly conformed dumbbell-shaped HCR provides higher sensitivity than the traditional linear HCR amplification technique. Ultimately, the clever combination of several amplification reactions enables the limit of detection (LOD) as low as 3.2 fg/mL. It showed promise for clinical sample testing, with recovery rates ranging from 98.4% to 103% in 5% human serum samples. This detection method offered a valuable tool for early HF detection, emphasizing the synergy of amplification strategies and specificity conferred by CRISPR/Cas13a technology.

The Value of Combined Detection of Serum BNP, Cardiac Troponin-I and Dynamic Electrocardiogram in Early Clinical Diagnosis and Prognosis of Patients with Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease resulting from myocardial ischemia and necrosis due to coronary artery occlusion. AMI is characterized by a sudden onset and high mortality, underscoring the significance of early diagnosis and treatment for improving patient prognosis. This study endeavors to assess the utility of a combined assessment involving serum brain natriuretic peptide (BNP), cardiac troponin-I (cTnI), and dynamic electrocardiogram (ECG) in the early clinical diagnosis and prognosis prediction of AMI. This paper constitutes a retrospective study. All enrolled patients underwent dynamic ECG examination. The study compared the serum levels of BNP and cTnI, along with pertinent dynamic ECG parameters [turbulence slope (TS) and standard deviation (SDNN) of the 24-hour interval between normal atrial depolarization and ventricular depolarization (R-R)], between the observation group (AMI patients) and the control group (patients with unstable angina (UA)). To evaluate the early diagnostic potential of AMI, we utilized receiver operating characteristic (ROC) curves to analyze serum BNP, cTnI, dynamic ECG, and their combined utility. Furthermore, a follow-up period of 6 months was conducted for AMI patients to record major adverse cardiovascular events (MACE). In the observation group, the serum levels of BNP and cTnI were significantly higher than those in the control group (p < 0.001), while dynamic ECG parameters, specifically TS and SDNN, were significantly lower in the observation group compared to the control group (p < 0.001). The results obtained from the ROC curve analysis revealed that the area under the curve (AUC) for BNP, cTnI, dynamic ECG, and their combination in early AMI diagnosis were 0.838, 0.887, 0.874, and 0.974, respectively. The 95% confidence intervals (CI) were 0.781~0.884, 0.836~0.926, 0.822~0.915, and 0.942~0.991, respectively. Sensitivity values were 64.29%, 82.14%, 91.07%, and 88.39%, and specificity values were 91.00%, 88.00%, 70.00%, and 98.00%, respectively. Significantly, the combination of all three markers demonstrated superior efficacy in early AMI diagnosis compared to any single index (p < 0.05). During the 6-month follow-up of 112 AMI patients, 22 experienced MACE. The MACE group exhibited notably higher serum BNP and cTnI levels compared to the non-MACE group. Additionally, dynamic electrocardiogram parameters TS and SDNN demonstrated a significant decrease (p < 0.05) in the MACE group. The combined assessment of serum BNP, cTnI, and dynamic electrocardiogram enhances the early clinical diagnostic potential for AMI and holds value in assessing the prognosis of AMI patients.

An impedimetric immunosensor based on chitosan-Au nanoparticles-reduced graphene oxide nanosheet composite modified PG electrode for detection of brain natriuretic peptide.

The online version contains supplementary material available at 10.1007/s13205-023-03704-x.

Impedimetric immunosensor based on chitosan-modified gold wire with Au@rGO nanocomposite for the detection of brain natriuretic peptide (BNP)

Impedimetric immunosensor based on chitosan-modified gold wire with Au@rGO nanocomposite for the detection of brain natriuretic peptide (BNP)

Solid-Phase Screening and Synthesis of Molecularly Imprinted Nanoparticles for Selective Recognition and Detection of Brain Natriuretic Peptide.

A new recognition method is explored for the rapid detection of B-type natriuretic peptide (BNP) based on the rational design and solid-phase synthesis of molecularly imprinted nanoparticles (nanoMIP) encapsulated with carbon dots. The nanosized magnetic template is first prepared by attaching the epitope of BNP on amino-functionalized magnetic carriers. High-dilution polymerization of monomers in the presence of magnetic template generates lightly crosslinked imprinted nanoparticles. To obtain the optimal MIP formulation, a new combinatorial screening approach is developed by a competitive fluorescence assay using the magnetic template. The resultant nanoMIP exhibits high affinity and selectivity toward BNP with an equilibrium dissociation constant (KD ) of ≈10-11 m. The proposed assay allows fast BNP detection within ≈7min with a linear range of its concentration from 0.25 to 5000 pg mL-1 and a limit of detection of 0.208 pg mL-1 (S/N = 3). To demonstrate its practicability in clinical diagnosis, unknown real serum samples from 160 individuals are analyzed and the relative standard deviation is less than 4.43%. Compared with the routine electrochemiluminescence detection method that is widely used in hospital, the relative error is less than 4.98% and the correlation coefficient is 0.994.

Clinical value of combined plasma brain natriuretic peptide and serum cystatin C measurement on the prediction of heart failure in patients after acute myocardial infarction.

This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

A Raman immunosensor based on SERS and microfluidic chip for all-fiber detection of brain natriuretic peptide

Early diagnosis of chronic heart failure (CHF) relies on the ultra-sensitive detection assay of its main biomarker, Brain natriuretic peptide (BNP). To meet such demand, we designed a near-infrared immunoassay biosensor, utilizing a fiber-embedded microfluidic chip for surface-enhanced Raman scattering (SERS) detection. A SERS probe, consisting of metal–organic framework and Au-HEPES coupling nanoparticles (AuHPs), was used to enhance the Raman signal of the toluidine blue (TB) dye. The probe anchored with TB is used as a SERS tag, which is linked to BNP through sandwich method. To enhance the Raman signal further, we embedded a SERS substrate at the bottom of the microfluidic channel, which serves an enhancer when the SERS tagged BNP passes through the microfluidic chip. The amplified Raman signal was collected by an optical fiber probe of a simple and portable Raman detection system with an all-fiber connected configuration. Such design resulted in the lowest detection limit of pg/mL, indicating that the proposed platform can be used for rapid and highly sensitive detection of BNP. In addition, our platform also has the advantages of low sample consumption and high throughput rate, providing an effective scheme for the early diagnosis of CHF.

The enhanced photoelectrochemical platform constructed by N-doped ZnO nanopolyhedrons and porphyrin for ultrasensitive detection of brain natriuretic peptide

Nowadays, brain natriuretic peptide (BNP-32) is fundamental to early cardiovascular clinical diagnosis, whose accurate assay is of significance by photoelectrochemistry (PEC) for the low background and high precision. Herein, a novel enhanced PEC platform was built by successive deposition of N-doped ZnO nanopolyhedra (N–ZnO NP) and protoporphyrin IX (PPIX). Specifically, the N–ZnO NP with a narrow bandgap of 2.60 eV was synthesized by direct calcination of zeolitic imidazole framework-8 (ZIF-8), and performed as the substrate to enhance the photocurrents of PPIX (as photosensitizer) whose photoelectron transfer pathway and enhanced PEC mechanism were studied in detail. Under such foundation, a label-free PEC aptasensor was developed by deposition of DNA aptamer onto the PEC platform and then ultrasensitive assay of BNP-32 based on a “signal off” model. The biosensor showed a wide linear range (1 pg mL−1- 0.1 μg mL−1) with a limit of detection (LOD) as low as 0.14 pg mL−1. This doping technique of ZnO nanomaterials provides some valuable guidelines for synthesis of advanced PEC probes in bioanalysis.

The Prognostic Value of the Serum Levels of Brain Natriuretic Peptide, Troponin I, and D-Dimer, in Addition to the Neutrophil-to-Lymphocyte Ratio, for the Disease Evaluation of Patients with Acute Pulmonary Embolism.

ObjectiveThe present study aims to investigate whether the serum levels of brain natriuretic peptide (BNP), troponin I (TnI), and D-dimer, in addition to the neutrophil-to-lymphocyte ratio (NLR), can be used to determine the prognosis of patients with acute pulmonary embolism (APE).MethodsData were collected from 72 patients that were diagnosed with APE in our hospital from January 2015 to December 2018. These patients were divided into three groups: a high-risk group (n = 10), a moderate-risk group (n = 33), and a low-risk group (n = 29). The serum levels of BNP, TnI, and D-dimer were determined, and the NLR was measured. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of the single and combined detection of BNP, TnI, and D-dimer, and the NLR was used to determine the prognosis of patients with APE.ResultsThe serum levels of BNP, TnI, and D-dimer were significantly higher in the high-risk group than they were in the moderate-risk and low-risk groups (P < 0.05). The serum levels of BNP, TnI, and D-dimer were also significantly higher in the moderate-risk group than they were in the low-risk group (P < 0.05). The serum levels of BNP, TnI, and D-dimer, as well as the NLR, were all significantly higher in the death group than they were in the survival group (P < 0.05). For the combined detection of the four indices, the area under the ROC curve was 0.92, the sensitivity was 0.889, and the specificity was 0.904; each of these values was higher than the corresponding values of single detection.ConclusionIn patients with APE, higher serum levels of BNP, TnI, D-dimer and NLR are associated with a higher risk stratification, greater severity of disease, and an increased risk of death.

Correlation of serum BNP and ET-1 levels with cardiac pump function and ventricular remodeling in patients with heart failure

This study aimed to explore the correlation of serum brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels with cardiac pump function and ventricular remodeling in patients with heart failure. Eighty-one patients with chronic heart failure admitted to our hospital from March 2016 to November 2018 were enrolled as the study group, and 80 healthy individuals as the control group. Immunofluorescence was used for the detection of serum BNP, ELISA for serum ET-1, and ultrasound for related indexes of cardiac pump function and ventricular remodeling. Moreover, correlation analysis and prognostic factors analysis were carried out. Both BNP and ET-1 were highly expressed in the serum of patients with heart failure. Cardiac pump function related indexes (left atrial ejection fraction (LAEF), left atrial passive ejection fraction (LAPEF), and left atrial active ejection fraction (LAAEF)) in the study group were significantly lower than those in the control group (P&lt; 0.05). While ventricular remodeling related indexes (left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPM), and left ventricular mass index (LVMI) in the study group were significantly higher than those in the control group (P&lt; 0.05). BNP and ET-1 were negatively correlated with LAEF, LAPEF and LAAEF (P&lt; 0.05), and were positively correlated with LVEDD, IVST, LVPM and LVMI (P&lt; 0.05). The expressions of serum BNP and ET-1 were higher in patients with cardiovascular events than those without cardiovascular events. Hypertension, hyponatremia, high BNP, high ET-1, NYHA classification, decreased LAEF and increased LVEDD were independent risk factors for cardiovascular adverse events. Serum BNP and ET-1 are closely related to cardiac pump function and ventricular remodeling in patients with heart failure and can be used as important reference indexes for prognosis evaluation.

Electrochemiluminescence behaviour of m-CNNS quenched by CeO2@PDA composites for sensitive detection of BNP

Heart failure is one of the common disabling states and serious illness among medical disorders that may lead to death. Brain natriuretic peptide (BNP) has been recognized as a new biomarker of outstanding prognosis-predictive capability for heart failure. In this work, modified carbon nitride nanosheets (m-CNNS) were used as the part of this sensing platform could generate stronger ECL emission and the CeO2@Polydopamine (CeO2@PDA) composites firstly worked as effective ECL signal quencher. Moreover, there was a suitable overlap between the absorption spectra of CeO2@PDA and ECL spectra of m-CNNS, causing the remarkable decline in ECL signal. In particular, a novel ECL-RET (electrochemiluminescence resonance energy transfer) system between m-CNNS as ECL donor while CeO2@PDA as ECL acceptor was established. CeO2@PDA composites were tightly linked to the secondary antibody (Ab2) via covalent bonding owing to the reactive quinones on the surface of the PDA film. The primary antibody (Ab1) and m-CNNS are connected via carboxylic groups of 1-pyrene butyric acid (Py-COOH, sodium salt) easily employing EDC/NHS activation, a common crosslinking approach. By employing K2S2O8 as a coreactant, ECL behaviour of m-CNNS was observed. Under optimal conditions, BNP concentration was detected in the range of 0.5 pg/mL–100 ng/mL with the detection limit of 0.01 pg/mL (S/N = 3). Featuring high sensitivity, wider linear range, excellent repeatability and selectivity, this ECL-RET immunosensor opened a novel path to realize a reliable sensitive detection of BNP, which may also be applied to determine other biomarkers. It was noteworthy that the proposed method was applied to real serum samples accompanied by good recovery range of 102.8–103.2%, indicating that the recommended method was of good accuracy for BNP detection.

Three-dimensional CdS nanosheet-enwrapped carbon fiber framework: Towards split-type CuO-mediated photoelectrochemical immunoassay

This work reports a customized methodology for the fabrication of 3D CdS nanosheet (NS)-enwrapped carbon fiber framework (CFF) and its utilization for sensitive split-type CuO-mediated PEC immunoassay. Specifically, the 3D CdS NS-CFF was fabricated via a solvothermal process, while the sandwich immunocomplexing was allowed in a 96 well plate with CuO nanoparticles (NPs) as the signaling labels. The subsequent release of the Cu2+ ions was directed to interact with the CdS NS, generating trapping sites and thus inhibiting its photocurrent generation. In such a protocol, the 3D CdS NS-CFF photoelectrode could not only guarantee its sufficient contact with the Cu2+-containing solution but also supply plenty CdS surface for the Cu2+ ions. Because of the target-dependent release of the Cu2+ ions and its proper coupling with the 3D CdS NS-CFF photoelectrode, a sensitive split-type PEC immunoassay was achieved for the detection of brain natriuretic peptide (BNP). This proposed system exhibited good stability and selectivity, and its applicability for real sample analysis was also demonstrated via comparison with the commercial BNP enzyme-linked immunosorbent assay (ELISA) kit. We expect this work could stimulate more interest in the design and utilization of 3D photoelectrodes for novel PEC bioanalysis.

(Invited) Detection of Heart Failure-Related Biomarker in Whole Blood with Graphene Field Effect Transistor Biosensor

Since brain natriuretic peptide (BNP) has become internationally recognized biomarkers in the diagnosis and prognosis of heart failure (HF), it is highly desirable to search for a novel sensing tool for detecting the patient’s BNP level at the early stage. Here we report a platinum nanoparticles (PtNPs)-decorated reduced graphene oxide (rGO) field effect transistor (FET) biosensor coupled with a microfilter system for label-free and highly sensitive detection of BNP in whole blood. The PtNPs-decorated rGO FET sensor was obtained by drop-casting rGO onto the pre-fabricated FET chip and subsequently assembling PtNPs on the graphene surface. After anti-BNP was bound to the PtNPs surface, BNP was successfully detected by the anti-BNP immobilized FET biosensor. It was found that the developed FET biosensor was able to achieve a low detection limitation of 100 fM. Moreover, BNP was successfully detected in human whole blood sample treated by a custom-made microfilter, suggesting the sensor’s capability of working in a complex sample matrix. The developed FET biosensor provides a new sensing platform for protein detection, showing its potential applications in clinic sample.

Platinum aptasensor wire arrays for cardiac biomarker detection

There is clinical diagnostic power in developing point-of-care diagnostic biosensors offering rapid and sensitive detection of cardiac biomarkers. This could provide outpatient screening and monitoring of cardiovascular diseases in outpatient settings via portable technology. This study focuses on development of platinum wire platforms functionalized with aptamers to impedimetrically detect Brain Natriuretic Peptide (BNP) and Troponin T (TnT), biomarkers, the currently accepted gold standard indicators of congestive heart failure and myocardial infarction. Various platinum wire diameters and surface preparation conditions were selected to determine ideal electrode parameters for impedimetric detection of BNP and TnT without loss of precision and sensitivity. Ideal parameters of 0.5 mm diameter wire polished to 5 μm demonstrated optimal linearity, correlation, and precision when detecting BNP and TnT. The authors have thus developed a simplistic platinum wire multi-array apatasensor platform for detecting BNP and TnT easily expandable to detecting various biomarkers in portable or handheld POC biosensing device configurations.

Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides.

Brain natriuretic peptide (BNP) and the N-terminal fragment of the BNP precursor (NT-proBNP) are widely used as heart failure (HF) biomarkers. Since the discovery of BNP in 1988, much effort has been allocated to the precise detection of BNP and NT-proBNP levels for reliable HF diagnostics. As a result, measurements of these biomarkers are globally accepted and used in clinical practice for the diagnosis of acute and chronic HF, risk stratification, and monitoring response to therapy. Several immunoassays specific for BNP and NT-proBNP are currently commercially available. Recent comparative studies show that there are marked differences between different BNP and NT-proBNP assays and platforms, and the results of measurements are not comparable enough. The lack of equivalence between the assays complicates the interpretation of the results and renders the cut-off points for diagnostic decisions to be method dependent. Presently, there is no agreement on what kind of BNP or NT-proBNP standard should be used for calibration, and a certified reference material as well as reference measurement procedures are lacking. The aim of this chapter is to summarize the available data on the complex nature of BNP-related peptides, specificity for existing BNP and NT-proBNP immunoassays, and to discuss potential approaches for standardization of BNP and NT-proBNP measurements.

Household Fluorescent Lateral Flow Strip Platform for Sensitive and Quantitative Prognosis of Heart Failure Using Dual-Color Upconversion Nanoparticles.

Heart failure (HF) is the end-stage of cardiovascular diseases, which is associated with a high mortality rate and high readmission rate. Household early diagnosis and real-time prognosis of HF at bedside are of significant importance. Here, we developed a highly sensitive and quantitative household prognosis platform (termed as UC-LFS platform), integrating a smartphone-based reader with multiplexed upconversion fluorescent lateral flow strip (LFS). Dual-color core-shell upconversion nanoparticles (UCNPs) were synthesized as probes for simultaneously quantifying two target antigens associated with HF, i.e., brain natriuretic peptide (BNP) and suppression of tumorigenicity 2 (ST2). With the fluorescent LFS, we achieved the specific detection of BNP and ST2 antigens in spiked samples with detection limits of 5 pg/mL and 1 ng/mL, respectively, both of which are of one order lower than their clinical cutoff. Subsequently, a smartphone-based portable reader and an analysis app were developed, which could rapidly quantify the result and share prognosis results with doctors. To confirm the usage of UC-LFS platform for clinical samples, we detected 38 clinical serum samples using the platform and successfully detected the minimal concentration of 29.92 ng/mL for ST2 and 17.46 pg/mL for BNP in these clinical samples. Comparing the detection results from FDA approved clinical methods, we obtained a good linear correlation, indicating the practical reliability and stability of our developed UC-LFS platform. Therefore, the developed UC-LFS platform is demonstrated to be highly sensitive and specific for sample-to-answer prognosis of HF, which holds great potential for risk assessment and health monitoring of post-treatment patients at home.