In the ageing society, sick sinus syndrome (SSS) is rapidly becoming one of the major arrhythmia problems. High survival rate with appropriate medical care indicates the paramount importance of early diagnosis. Interests have intensified in plasma biochemical markers to predict susceptibility and aid in patient management. Cardiac troponin I (cTnI) is the most widely used biomarker, due to its nearly complete cardiac tissue specificity. An elevated cTnI concentration was reported to be associated with SSS. A combination of cTnI and myoglobin, one of the earliest biomarkers released into blood circulation, can achieve diagnostic sensitivity of 97% with a 99% negative predictive value within 90 mins of ED presentation. However, blood testing of these biomarkers in current clinical practice represents a challenge for prime time diagnosis due to the time delay caused by laborious analysis and the logistics of sample handling to central labs. Therefore, the objective of this project is to take a multidisciplinary approach to develop an innovative biochip for rapid and simultaneous biosensing of these proteins at point of patient care. Specifically, a nanoparticle surface plasmon resonance (nanoSPR) biochip based on gold nanorod probes will be developed. Effect of the magnetic nanoparticles on the nanoSPR sensitivity and specificity enhancement will be systematically studied. The nano-biochip will then be integrated with a highly sensitive CMOS (complementary metal oxide semiconductor) image sensor and nanohole array to develop an innovative, fully operational lab-on-a-chip biosensor. The fundamental studies will provide innovative insights into MNP mediated nanoSPR mechanism to develop an ultra-sensitive, multiplexed biosensing. System integration of nanoSPR biochip with portable optical detector will transform bio-analysis in clinical environment to a point of care format for prime time medical diagnostics to improve clinical outcome.

Public Health Relevance

Sick sinus syndrome is becoming a significant healthcare problem in a rapidly ageing society and the dysfunction will lead to sudden cardiac death if unattended. This project will develop an innovative, fully operational, ultra-sensitive nano-biosensor. The proposed device in this translational project will improve non-invasive diagnosis by rapid blood testing of SSS associated biomarkers.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Enhancement Award (SC1)
Project #
5SC1HL115833-03
Application #
8685319
Study Section
Special Emphasis Panel (ZGM1-MBRS-1 (SC))
Program Officer
Danthi, Narasimhan
Project Start
2012-06-07
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$252,875
Indirect Cost
$77,875
Name
University of Texas Health Science Center San Antonio
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
800189185
City
San Antonio
State
TX
Country
United States
Zip Code
78249
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Mei, Zhong; Tang, Liang (2017) Surface-Plasmon-Coupled Fluorescence Enhancement Based on Ordered Gold Nanorod Array Biochip for Ultrasensitive DNA Analysis. Anal Chem 89:633-639
Wang, Xuefeng; Mei, Zhong; Wang, Yanyan et al. (2017) Comparison of four methods for the biofunctionalization of gold nanorods by the introduction of sulfhydryl groups to antibodies. Beilstein J Nanotechnol 8:372-380
Mei, Zhong; Dhanale, Ashish; Gangaharan, Ajithkumar et al. (2016) Water dispersion of magnetic nanoparticles with selective Biofunctionality for enhanced plasmonic biosensing. Talanta 151:23-29
Wang, Xuefeng; Mei, Zhong; Wang, Yanyan et al. (2015) Gold nanorod biochip functionalization by antibody thiolation. Talanta 136:1-8
Wang, Yanyan; Tang, Liang (2015) Multiplexed gold nanorod array biochip for multi-sample analysis. Biosens Bioelectron 67:18-24
Tang, Liang; Casas, Justin (2014) Quantification of cardiac biomarkers using label-free and multiplexed gold nanorod bioprobes for myocardial infarction diagnosis. Biosens Bioelectron 61:70-5
Casas, Justin; Venkataramasubramani, Meenakshi; Wang, Yanyan et al. (2013) Replacement of cetyltrimethylammoniumbromide bilayer on gold nanorod by alkanethiol crosslinker for enhanced plasmon resonance sensitivity. Biosens Bioelectron 49:525-30
Tang, Liang; Casas, Justin; Venkataramasubramani, Meenakshi (2013) Magnetic nanoparticle mediated enhancement of localized surface plasmon resonance for ultrasensitive bioanalytical assay in human blood plasma. Anal Chem 85:1431-9
Wang, Yanyan; Tang, Liang (2013) Chemisorption assembly of Au nanorods on mercaptosilanized glass substrate for label-free nanoplasmon biochip. Anal Chim Acta 796:122-9