Lab-on-chip system for point-of-care cardiac biomarker screening utilizing sensitive photonic sensor
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abstract
Cardiovascular diseases (CVD) are the leading cause of death world-wide that needs to be treated with immediate hospitalization and revascularization. Based on data released for 2013, 12.9 percent of registered deaths in Qatar were related to CVD. Among the Qatari population, the share of mortality related to CVD was 12.2 percent. Diagnosis of acute coronary syndrome (ACS) and assessment of the underlying risk factors of CVD at the point-of-care (PoC) will likely play a crucial role in enabling rapid diagnosis and treatment, and thus reducing morbidity, mortality, and healthcare costs. The main goal of this proposal is to develop a low-cost, compact, rapid, reliable, sensitive, and easy-to-use PoC CVD diagnostic tool that determines concentrations of several cardiac biomarkers (in blood). This information can then be processed to provide immediate information regarding cardiovascular risk factors. Such comprehensive biomarker analysis can potentially provide additional immediately actionable information, not available by current standard methodologies that are expensive and subject to delays. Our approach aims for establishing a rapid and reliable diagnostic method that can detect CVD risk factors and ACS. To achieve the envisioned goal, we will develop a high throughput and highly sensitive multiplexed sensing platform based on a simple single-step assay enabled by integration of 1) a compact and high-throughput continuous flow sample preparation module for blood plasma extraction and filtering, 2) a continuous-flow electrokinetic analyte pre-concentrator that can provide 100 to 1000 fold enhancement of target biomarker concentrations, 3) a compact multiplexed sensing platform based on resonance wavelength shift measurement in a densely-integrated array of high-quality factor (Q) photonic resonators, 4) a panel of high-quality biomarker-specific capture antibodies with a non-fouling surface coating to minimize the nonspecific binding to the sensor surface, and 5) an array of on-chip reference elements to calibrate the sensor measurement and compensate for the effect of nonspecific binding and drift errors caused by sensing device drifts or other environmental effects. The resulting sensing platform enables the rapid detection of multiple cardiac biomarkers at the point-of-care with reasonable sensitivity. The final outcome of this project will be a prototype system for PoC detection of cardiac biomarkers with the ability to simultaneously screen up to 10 biomarkers using a single drop of blood. To reduce the overall costs, the proposed solution will be designed in such a way that it can be miniaturized in the form of a compact reader system working with disposable sensor cartridges. The experimental demonstrations in this program will be performed using a bench-top reader system with the possibility of being miniaturized into a hand-held reader system in a follow-on program. As such, the focus of this program (with the requested budget) is to address the fundamental challenges for the development of such a transformative sensing approach with a practical (manufacturable) solution
