Development Toward a Triple-Marker Biosensor for Diagnosing Cardiovascular Disease
Anna Deng1, Daniel Matloff1, Chi-En Lin1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona.
Insights
New biosensors offer rapid, label-free detection of key cardiac biomarkers, including B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein (CRP). These advancements aim to simplify cardiovascular disease diagnosis and management.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Cardiovascular Medicine
Background:
- Cardiovascular disease (CVD) is a leading global cause of mortality, necessitating accurate and efficient diagnostic methods.
- Current assays for cardiac biomarkers are often complex and time-consuming, hindering timely diagnosis and management.
- There is a critical need for rapid, sensitive, and user-friendly biosensors for monitoring multiple cardiac biomarkers.
Purpose of the Study:
- To develop and report rapid, label-free biosensor prototypes for three FDA-approved cardiac biomarkers: BNP, cTnI, and CRP.
- To demonstrate the capability of these biosensors for sensitive, multi-marker detection using electrochemical impedance spectroscopy (EIS).
- To evaluate the clinical relevance of the developed biosensors, particularly for BNP detection in blood samples.
Main Methods:
- Fabrication of biosensors by immobilizing antibodies for BNP, cTnI, and CRP onto gold working electrodes.
- Utilized electrochemical impedance spectroscopy (EIS) for label-free detection and quantification of biomarkers.
- Determined the optimal frequency (OF) for each biomarker to enable sensitive and specific detection.
Main Results:
- Successfully identified optimal frequencies (OFs) for BNP (1.74 Hz), cTnI (37.56 Hz), and CRP (253.9 Hz).
- Demonstrated femto-molar sensitivity using EIS, enabling label-free detection of multiple biomarkers.
- The BNP biosensor achieved a clinically relevant detection limit of 100 pg/mL when tested in blood samples.
Conclusions:
- Developed rapid, label-free biosensor prototypes for key cardiac biomarkers (BNP, cTnI, CRP).
- EIS proves to be a sensitive technique for multi-marker detection when optimal frequencies are identified.
- These biosensors hold significant potential for simplifying and improving cardiovascular disease diagnostics.
Abstract:
Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 30% of all deaths globally. The diagnosis and management of CVD requires monitoring of multiple biomarkers, which comprehensively represents the state of the disease. However, many assays for cardiac biomarkers today are complicated and laborious to perform. Rapid and sensitive biosensors capable of giving accurate measurements of vital cardiac biomarkers without complex procedures are thus in high demand. In the work presented below, rapid, label-free biosensor prototypes for three Food and Drug Administration-approved biomarkers are reported: B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein (CRP). The sensors were prepared by immobilizing each biomarker's antibody onto gold working electrodes with platinum counter and silver/silver chloride reference electrodes. The sensors were tested using electrochemical impedance spectroscopy (EIS), a femto-molar sensitive technique capable of label-free, multi-marker detection if a biomarker's optimal frequency (OF) can be identified. The OFs of BNP, cTnI, and CRP were found to be 1.74, 37.56, and 253.9 Hz, respectively. The performance of the BNP biosensor was also evaluated in blood and achieved clinically relevant detection limits of 100 pg/mL.
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