Project Summary
Cardiovascular disease is the leading cause of death in the United States. Among them, silent heart attack, also
known as silent myocardial infarction (SMI) that occurs without apparent symptoms, accounts for approximately
half of the total number of heart attacks. When cardiac myocytes are damaged, cardiac troponin (cTn), a
component of the heart muscle, is released into circulation. Currently, blood cTn is routinely measured in patients
suspected of having Acute Myocardial Infarction (AMI). However, SMI is often undiagnosed until it is too late,
although SMI causes similar level of damage to the heart as symptomatic typical AMI. We hypothesize that an
implantable cTn sensor providing a real-time and continuous data on the blood levels of cTn will allow a timely
diagnosis at the very time when a SMI occurs to a subject, enabling timely treatment. For an in vivo biosensor,
the sensing reactions not only need to be sensitive and selective to the analyte but also need to be self-sustaining
for a long time in complex physiological conditions. This requires that the sensing reactions can be self-
regenerating while at the same time developing a signal related to the analytes. Currently there is no cTn sensors
that can be operated in real-time and continuously. We propose to use a radically new biosensor approach to
develop highly sensitive, specific, and self-sustaining biosensors based on our years of research and innovations
in 1) uniquely designed peptide mimotope biosensing interface for label-free affinity based electrochemical
biosensor; 2) the unique properties of bifunctional Pd/Au bimetallic substrate electrode for sensing interface self-
regeneration; and 3) miniaturized, low cost and real-time electrochemical sensor platform. Peptide mimotopes,
in lieu of antibodies, when immobilized on the surface via self-assemble monolayer (SAM) can significantly
reduce the structural variability, retain biological activity, and minimize or eliminate non-specific adsorption from
interfering proteins and provide real-time, highly sensitive and selective detection of protein antigens in human
blood samples. In addition, our multifunctional bimetallic nanostructured Pd/Au electrode will allow the formation
of stable and robust peptide SAM on gold (Au) as well as controlled rapid regeneration of the protein complex
using palladium (Pd) chemistry to induce rapid local pH change. We have two research Aims to develop and
validate this novel biosensing technology: 1. Develop self-regenerable electrochemical cTn biosensor for
real-time detection of cTn; 2. Develop miniaturized implantable cTn biosensor and validate its in vivo
sensing using rat cardiac ischemia model. Successful completing these Aims will validate the capability
of our cTn biosensor for real-time, sensitive and selective sensing of cTn in vivo for early detection and monitoring
of SMI. The sensor will have great potential in the diagnosis and monitoring of a variety of other forms of heart
injuries including (but not limited to) viral myocarditis (such as myocardial injury related to COVID-19 infection),
drug-induced cardiac toxicities, and radiation-induced cardiac injuries. The biosensor methods developed can
also be applied to many other implantable real-time sensing applications.
