Semiconductor Electronic Label-Free Assay (SELFA) for Diagnosing Heart Disease

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In United States and Europe alone, about 15 million patients are annually admitted to emergency departments with acute coronary syndrome. These patients are immediately screened for potential acute myocardial infarction (AMI) via electrocardiogram and biomarker detection in blood samples. Due to its high specificity and elevated concentrations in blood for hours past an incident, cardiac troponin I (cTnI) has become one of the most reliable biomarkers for diagnosing AMI where a cTnI concentration of less than 0.10 ng/mL is considered a negative result, while a cTnI concentration of 0.10 ng/mL or greater is considered a positive result. Furthermore, recent studies have shown that cTnI could also be used for AMI risk stratification. However, for this intended use, ultra-sensitive assays are required to detect slightly elevated levels of cTnI in blood samples. Currently there are two methods available for determining the concentration of cTnI in patient samples: lab-based assays and point-of-care (POC) assays. While lab-based assays are more sensitive, they have a longer turnaround time (TAT) of typically 45 minutes to 1 hour, which is not ideal for application such as diagnosing AMI where speed is crucial. On the other hand, while current POC assays have much improved TAT of 10-15 minutes and could be implemented at bed-side, they have inferior sensitivity, and hence found to not be as reliable as lab-based assays. Additionally, even the current lab-based assays do not have the necessary analytical sensitivity in quantifying cTnI in patient samples to aid in AMI risk stratification. We at Selfa Inc. aim to develop a novel and sensitive label-free POC assay for rapid, reliable, and accurate detection of cTnI in patient blood samples that could aid in diagnosing and risk stratification of AMI. This assay will be based on a novel semiconductor nanowire field-effect transistor technology that utilizes anti-cTnI antibodies to quantify cTnI in a patient sample. In or preliminary studies, we have demonstrated a 1000-fold improved sensitivity in detecting cTnI concentrations compared to current lab-based assays. Our novel assay will consist of disposable, one-time-use test strips, and an easy-to-use and portable reader. In Phase I of this Fast-Track proposal, we will (a) examine various anti-cTnI antibody-cTnI combinations to maximize the sensitivity of our biosensor, and (b) develop and optimize the 0th generation, lab-grade SELFA test strips prototype and validate their analytical and clinical performance. Upon successful completion of Phase I, in Phase II of this proposal, we will (c) develop and optimize the 1st generation, commercial-grade SELFA test strips and portable reader device, (d) establish and evaluate a robust strategy for high throughput calibration of the test strips, and finally (f) validate the analytical and clinical performance of the commercial-grade test strips an reader, and prepare and initial the FDA regulatory approval process.