Electrochemical impedimetric detection of stroke biomarker NT-proBNP using disposable screen-printed gold electrodes

Abstract

Stroke is the second top leading cause of death globally. It is caused by an abrupt interruption of blood flow to the brain. In that course, brain natriuretic peptide (BNP) and its derivative N-terminal pro b-type natriuretic peptide (NT-proBNP), neurohormones produced mainly by the heart ventricles in response to excessive stretching of cardiomyocytes (heart muscle cells), are proven to be good biomarkers for heart failure diagnosis. Moreover, there is growing clinical interest of the use of NT-proBNP for stroke diagnosis and prognosis because it is significantly associated with cardioembolic stroke and secondary stroke reoccurrence, with sensitivity >90% and specificity >80%. However, in diagnostic settings, there is still a need to address the encountered analytical problems, particularly assay specificity and set up. In this study, a novel approach for NT-proBNP detection is demonstrated using an electrochemical immunoassay method. A label-free impedimetry immunosensor for stroke biomarker was developed using modified disposable screen-printed gold electrodes (SPGE) hosting specific anti-NT-proBNP capture antibody. The performance of our immunosensor was studied in the presence of NT-proBNP in both buffered and mock (porcine) plasma samples. A linear relation between the relative total resistance (ΔRtot) responses and the NT-proBNP concentrations in buffer was observed in a range from 0.1 to 5 ng mL-1 with a correlation coefficient (R2) of 0.94656. Overall, the biosensor has demonstrated the capability to quantitate NT-proBNP and differentiate such concentrations in a low concentration range, especially among 0, 0.1, 0.5, 1, and 3 ng mL-1 in plasma samples within 25 min. This range is valuable not only for classifying cardioembolic stroke (higher or equal to 0.5 ng mL-1), but also predicting the risk of secondary stroke reoccurrence (higher than 0.255 ng mL-1). Our biosensor has the potential to be used as an easy-to-use point-of-care test that is both accurate and affordable.

Timely and Blood-Based Multiplex Molecular Profiling of Acute Stroke

“…The EIS system comprises a sensing component with multiple functionalized electrodes to transduce biomarkers concentrations in considerably small blood sample volumes into electrochemical signals. The second combines a flow test strip with a screen-printed electrode and relies on immune-electroactive nanobeads for ultrasensitive recognition of biomarkers, and the results are measured electrochemically [ 85 , 86 , 87 ]. The third platform is based on stacked and differently functionalized membranes, from which a measurable signal is obtained via biomarker migration linked, for example, to an antibody conjugated with enzyme horseradish peroxidase [ 88 , 89 , 90 ].…”

B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor

“…The sensing of b-type natriuretic peptides for clinically useful diagnostic assays demonstrates analytical problems, mainly with circulating NT-proBNP [ 161 ], assay specificity, and analyte stability [ 162 , 163 , 164 , 165 ]. Several previous studies examined the development of NT-proBNP immunoassays [ 166 , 167 , 168 ]. There is no consensus on the exact circulating peptides that are derived from proBNP [ 80 , 169 , 170 ].…”

Blood-Based Biomarkers Are Associated with Different Ischemic Stroke Mechanisms and Enable Rapid Classification between Cardioembolic and Atherosclerosis Etiologies

“…Lastly, the transducer allows the signal measurement that is from optical, electrochemical, or acoustic origin [ 147 , 148 ]. There are different POC biosensor analytical formats such as paper-based [ 149 , 150 , 151 ], optical [ 152 , 153 ], electrochemical [ 154 ] and microfluidics [ 155 ]. Most of the POC biosensor platforms allow the detection of a single chosen biomarker.…”