Development of nanomaterials and molecularly imprinted polymer based chemical sensors for selective and sensitive determination of biomarkers

TitleDevelopment of nanomaterials and molecularly imprinted polymer based chemical sensors for selective and sensitive determination of biomarkers
Publication Typeวิทยานิพนธ์/Thesis
Year of Publication2021
AuthorsNongyao Nontawong
DegreeDoctor of Philosophy -- Major in Chemistry
InstitutionFaculty of Science, Ubon Rachathani University
Keywordsbiomarkers, chemical sensors, molecularly imprinted polymer, nanomaterials

This thesis focuses on the development of a new chemical sensor based on electrochemical measurements for the analysis of important biomarkers for medical diagnostic applications, which can be divided into 3 main parts. The first part focuses on the development of a three-dimensional electrochemical paper-based analytical device (3D-ePAD) with screen-printed graphite electrodes for the determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) in pharmaceutical and urine samples. The device was fabricated by alkyl ketene dimer (AKD)-inkjet printing to form a circular hydrophobic zone on filter paper for the application of aqueous samples coupled with screen-printed electrodes on the paper. The electrochemical detection performed consists of three electrodes of graphite modified Fe3O4@Au-Cys/PANI nanocomposites. The three Fe3O4@Au-Cys/PANI/GFE electrodes screen-printed on the layout paper served as the working electrode, reference electrode, and counter electrode, respectively. Under optimum conditions, the fabricated device gave a linearity range of 20-700 μM for AA, and 20-1,000 μM for DA and UA. The detection limits were 3.20, 2.19, and 1.80 μM for AA, DA and UA, respectively. Additionally, the fabricated paper-based 3D electrochemical device has the following advantages: it is easy-to-use, inexpensive, and is a portable alternative for point of care monitoring. The second part focuses on the development of a novel amperometric flow-injection analysis (AMP-FIA) for determination of creatinine (Cre) based on a sensor consisting of copper oxide nanoparticles coated with a molecularly-imprinted polymer (CuO@MIP). The CuO@MIP was synthesized using CuO as the supporting core, Cre as the template, methacrylic acid (MAA) as functional monomer, N, N-(1,2-dihydroxyethylene)bis(acrylamide) (DHEBA) as cross-linker, and 2,2-azobis(2-methylpropionitrile) (AIBN) as initiates the polymerization process. CuO@MIP was then decorated on carbon-paste electrodes to obtain the CuO@MIP/CPE. The AMP-FIA system was used to quantitatively determine Cre at the CuO@MIP/CPE sensor, in a 0.1 M phosphate buffer (pH 8.0) carrier. The imprinted sensor exhibits excellent performance for Cre oxidation at an applied potential of +0.35V and a flow rate of 0.6 mL min-1. The sensor exhibits a linear dynamic range for Cre detection from 0.5 to 200 M (r2 = 0.995) with a limit of detection of 0.083 M (S/N = 3). The developed sensor was successfully applied for Cre determination in urine samples with accuracy and precision. The final part is the development of a novel dual-imprinted amperometric sensor for simultaneous determination of Cre and 8-hydroxy-2′-deoxyguanosine or 8-OHdG in human urine and serum. The determination used multiple-pulse amperometric detection coupled with flow injection analysis (MPA-FIA). For Cre sensing, CuO@MIP was applied. For 8-OHdG sensing, platinum nanoparticles embedded on reduced graphene oxide and then coated with guanosine poly-dopamine MIP to obtain PtNPs-rGO@MIP were applied. A dual MIP sensor (CuO@MIP and PtNPs-rGO@MIP/CPE) was then formed by CPE modified with both nanocomposites. A dual-potential waveform as a function of time, with Edet.1 at +0.4 V/150 ms to determine Cre selectively and Edet.2 at +0.6 V/250 ms for simultaneous analysis of both (Cre and 8-OHdG) compounds. Subtraction of a +0.6 V signal and +0.4 V signal using the respective correction factor, allows the developed sensor to perform quantitative analysis of 8-OHdG without Cre interference. The dual-imprinted sensor has a linear range of 0.5-150 μM for Cre and 0.005-50 μM for 8-OHdG, with limits of detection at the nano-molar level. The proposed method has been successfully applied in the accurate quantitative determination of Cre and 8-OHdG in urine and serum samples.

Title Alternate การพัฒนาเคมีคัลเซนเซอร์ด้วยวัสดุนาโนและพอลิเมอร์ที่มีรอยพิมพ์ประทับโมเลกุลสำหรับการตรวจวัดสารบ่งชี้ทางชีวภาพอย่างจำเพาะเจาะจงและมีสภาพไวสูง