Novel Aptamer-Based Biosensor Platforms for Detection of Cardiomyopathy Conditions
Abstract
Cardiovascular diseases (CVDs) are the major cause of death worldwide, resulting in ~ 17.5 million deaths in 2012 corresponding to 31% of all global deaths. The American Heart Association (AHA) estimates that more than one-third of American adults have at least one type of CVD and 50% of the affected adults are 60 years of age or older. Furthermore, the AHA cites projections that by the year 2030, 44% of the U.S. population will be afflicted with CVD condition. The term cardiomyopathy broadly encompasses any disease of the myocardium associated with cardiac dysfunction. The incidence of CVDs, cardiomyopathy, and related fatality is projected to rise as risk factors such as obesity, hypertension, and diabetes increase in prominence. This high prevalence is the result of CVDs and cardiomyopathy being clinically silent until signs of serious complications arise, which has led to a lack of standard methods for their diagnosis. As a result, prominent CVD conditions such as congestive heart failure and myocardial infarction are often misdiagnosed at the primary care physician (PCP) level (nearly 20%-40%) and virtually go undetected until further complications arise, thus making it imperative for more in-depth testing and use of sophisticated techniques for disease detection permitting accurate diagnosis. If left untreated, for example, cardiomyopathy conditions may progress to a terminal stage of irreversible myocardial dysfunction marked by systolic and/or diastolic failure, dilation, and an increased likelihood of associated arrhythmias, thromboembolic events, and sudden death. An acute cardiovascular event in a deployed individual thus poses a significant threat to combat mission success and a financial burden to the U.S. government not only for loss of trained personnel and equipment but also for evacuation of the personnel, evaluation, and treatment. Therefore, there is a need for an efficient and robust “point-of-care” (POC) device enabling rapid screening and monitoring of CVD risks to decrease CVD incidence, deaths, and healthcare costs. The goal of this proposal is to simplify biochemical marker testing, one of the methods currently used for CVD diagnosis by developing a portable biosensor specific to cardiac markers utilizing few drops of blood to provide cardiac marker levels in blood within minutes. To achieve this objective, vertically aligned platinum wire aptamer-based multi-array biosensors will be developed to accurately measure the specific levels of relevant cardiomyopathy in the blood using electrochemical impedance spectroscopy. Development of this biosensor will allow for expanding the biochemical marker testing to POC applications in both clinical and non-clinical environments, and will allow for patients and clinicians to screen for and circumvent CVDs at early stages, thus reducing the CVD risks and healthcare costs. Development of such a biosensor will create a simple, inexpensive, and efficient POC device for assessing CVD risk and for monitoring existing CVD conditions circumventing the rise of CVDs and related morbidity and mortality in the future. The following objectives are therefore proposed: (a) Fabricate and optimize the parameters of the platinum wire electrodes. (b) Optimize the concentrations, incubation times, and self-assembled monolayer (SAM) combinations including antigen incubation times to improve and enhance biosensor precision and sensitivity. (c) Determine a single-frequency for cardiac marker detection, optimize aptamer regeneration, and test the biosensor against clinical samples for cardiac marker detection: simplification, regeneration, and clinical testing of the biosensors to create a biosensor with unique qualities compared to those already available on market. (d) Optimize the two electrode approach to eliminate any interference due to nonspecific adsorptions (or bio-fouling) of molecules on the sensor surface, especially in whole blood and plasma. The aim is
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910174
Entities
People
- Moni Datta
Organizations
- United States Army
- University of Pittsburgh