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Quantitative Detection of Uric Acid by Electrochemical-Surface Enhanced Raman Spectroscopy Using a Multilayered Au/Ag Substrate Lili Zhao,† Jonathan Blackburn,‡ and Christa L. Brosseau*,† †

Department of Chemistry, Saint Mary’s University, Halifax, Nova Scotia B3H 3C3, Canada Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925 South Africa



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ABSTRACT: Uric acid is a potential important biomarker in urine and serum samples for early diagnosis of preeclampsia, a lifethreatening hypertensive disorder that occurs during pregnancy. Preeclampsia is a leading cause of maternal death, especially in developing nation settings. Quantitative detection of uric acid for rapid and routine diagnosis of early preeclampsia using electrochemical-surface enhanced Raman spectroscopy (EC-SERS) is presented herein. A uniform EC-SERS active Au/Ag substrate was developed by depositing nearly monodisperse gold and silver nanoparticles on the carbon working electrode surface of screen printed electrodes. The multilayered Au/Ag substrates were characterized by electron microscopy and used for quantitative detection of uric acid in 0.1 M NaF and synthetic urine at clinically relevant concentrations. These results showed a linear relationship between the EC-SERS signal intensity and the uric acid concentration. Relative errors calculated for selected concentrations were all within the Clinical Laboratory Improvement Amendments (CLIA) criterion for uric acid analysis (±17%). It is believed that routine and early diagnosis of disease could be possible through such quantitative detection of biomarkers in patient samples using this EC-SERS method.

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In past decades, great effort was devoted toward the development of new methods for early diagnosis of preeclampsia in order to reduce maternal and infant mortality rates.1,4,15−21 It has been shown that uric acid, an end product of purine metabolism, is an important biomarker in urine and serum samples and may be key for the development of a test for early onset of gestational hypertension (preeclampsia).22−32 A uric acid concentration of approximately 0.4 mM in urine and serum is an indication for patients experiencing low to moderate hypertension and proteinuria. A higher concentration of uric acid (>0.4 mM) is associated with patients experiencing severe preeclampsia.23 The most commonly used methods for determination of uric acid in urine and serum are based on costly enzymes, which need to be stored and used under special conditions.33−35 In addition, assay-based tests are time-

reeclampsia is a hypertensive disorder that occurs during pregnancy and remains a leading cause of maternal death, especially in developing nation settings.1−3 Approximately 10− 15% of maternal deaths worldwide are currently caused by preeclampsia.4 When preeclampsia appears in the second or third trimester of pregnancy, there is no means of treatment other than premature delivery of the baby. However, accumulated clinical evidence has begun to show that early detection of the disorder, leading to careful monitoring and appropriate management, is crucial in the prevention of preeclampsia-related deaths. So far, diagnosis of preeclampsia is mostly based on blood pressure readings and a urine protein test, arising from two hallmarked symptoms of this disease (elevated blood pressure and significant protein in the urine).5,6 However, it is usually late stage preeclampsia which is diagnosed using these tests.7−14 Therefore, rapid, routine, and early diagnosis of preeclampsia has become a challenge worldwide, especially in areas with insufficient clinical support and limited resources. © 2014 American Chemical Society

Received: July 15, 2014 Accepted: December 6, 2014 Published: December 6, 2014 441

dx.doi.org/10.1021/ac503967s | Anal. Chem. 2015, 87, 441−447

Analytical Chemistry

Article

EC-SERS signal intensity and the uric acid concentration was observed over the desired clinically relevant concentration range (0.1−1.0 mM). As such, electrochemical SERS has the potential for rapid, quantitative detection of uric acid in urine and could be developed in the future as a diagnostic tool for noninvasive, routine testing of early stage preeclampsia.

consuming and require multiple reagents. These factors limit the applicability of such tests for rapid and routine diagnosis in resource-limited settings. Recently, an EasyTouch self-monitoring system was developed for determination of uric acid in blood, which realized rapid, in-home detection of uric acid.36 However, this method requires the collection of blood samples, which can be problematic for in-home use. Furthermore, a uricase-based electrochemical technique is used in this system, resulting in high cost per patient. To this end, a diagnostic method that is rapid, portable, and affordable to determine uric acid concentration in urine is in urgent need. Recently, electrochemical-surface enhanced Raman spectroscopy (EC-SERS), combining both electrochemistry37−39 and surface enhanced Raman spectroscopy (SERS),40−50 has been developed for routine spectroelectrochemical analysis. A simple, portable EC-SERS system, consisting of a small benchtop Raman spectrometer, a laptop computer, and a portable USB potentiostat, has been reported by Brosseau et al. for real-time on-site monitoring of patient biomarkers.51 It was revealed that this EC-SERS system was capable of easily detecting uric acid at concentrations

Ag substrate.

Uric acid is a potential important biomarker in urine and serum samples for early diagnosis of preeclampsia, a life-threatening hypertensive disorder ...
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