Disposable electrochemical flow cell with paper-based electrode assemble

https://doi.org/10.1016/j.jelechem.2021.115268Get rights and content

Highlights

  • A novel flow-cell design was constructed.

  • Disposable and low-cost paper-based electrodes were simply fabricated and characterized.

  • AuNPs and MWCNTs showed a significant increase in current response against catecholamines.

  • HPLC-EC technique provided high selectivity and sensitivity for the determination of some catecholamines.

  • The applicability of the developed system was demonstrated by the analysis of biological samples.

Abstract

High performance liquid chromatography-electrochemical detector (HPLC-EC) is employed as a reliable device for the detection of catecholamines in blood or urine samples without any time-consuming extraction procedure. However, there is a need for the construction of cheap and easy-to-operate electrode assemble systems embedded in HPLC-EC. In this study, we present a disposable and low-cost paper-based electrode (PBE) assemble utilizing a nitrocellulose membrane, which serves support material in flow-cell device for HPLC-EC. A custom-built flow cell was inventively designed as specific to the prepared PBEs via stereolithography 3D printing. To gain the electrochemical signal enhancement, the working electrode was modified with gold nanoparticles and carboxylated-multi-walled carbon nanotubes (MWCNTs). Here, we focused on the construction of the paper-based electrode assemble and characterization of the flow cell device performance. To demonstrate the functionality of the flow cell device, we analyzed common catecholamines from spiked biological fluids using the optimized experimental parameters. Amperometric detection of the catecholamines was carried out at the potential of + 0.5 V and linear range was found to be 0.5–20.0 μg/mL, with a limit of detection in the range of 4.0–15.0 ng/mL. The obtained results confirmed our disposable paper-based electrode assemble to be promising for the construction of an electrochemical platform for reliable and fast detection of electroactive species.

Introduction

Paper was utilized as an analytical substrate since the 1930s [1]. The first usage of paper-based sensors emerged for the detection of glucose in the 1950s [2]. Furthermore, paper was used as a substrate to create a pregnancy test in the 1980s [3]. The paper-based analytical devices have been renewed by George Whiteside’s group in 2007 [4]. In recent years, they have been started over again to be used because of their unique properties such as low cost, biocompatible, disposable, flexible, easily prepared, and simple to use [5], [6]. Besides, the hydrophilic and porous structure of cellulose provides a capillary flow without external pumps [7]. Basically, a paper-based sensor is composed of hydrophobic barriers, channels, and a reaction cell. The fabrication techniques such as wax patterning, inkjet printing, photolithography, chemical vapor-phase deposition have been reported by providing various architectures and designs [8]. In the literature, several applications of paper-based sensors were reported for chemical industry fields [9], food safety [10], environmental [11], and clinical analysis [12]. Furthermore, researchers focus on working with paper-based sensors as point-of-care (POC) diagnostics because of their eco-friendly behavior [13].

There are several studies in the literature regarding the use of various techniques such as colorimetric, fluorescence, chemiluminescence, electrochemical (EC), which can be combined with paper-based sensors [14]. Due to the excellent properties of electrochemical techniques such as high sensitivity and selectivity, paper-based sensors can be coupled with electrochemistry with a low cost-portable design. The first time in 2009, the electrochemical application of paper-based analytical devices was reported by Henry and co-workers [15]. Subsequently, paper-based sensors have been started to use by coupling with several electrochemical techniques such as cyclic voltammetry, amperometry, coulometry, potentiometry, and impedance [8], [16], [17].

Recently, different types of nanomaterials were reported in the literature to increase the surface area and enhance the conductivity of electrochemical sensors. Carbon nanotube (CNT), one of the unique nanomaterials, has been started to be used with the increasing interest for various applications since they were discovered by Iijima in 1991 [18]. It was reported that CNTs could increase the electrochemical reactivity of several molecules. Besides, they provide high chemical stability and sensitivity with a high current response [19]. The reason for their electrocatalytic activity is having the functional groups on their surface [20]. Additionally, their tubular structure leads to enhance the electron transfer by changing the level of energy bands [21]. CNTs can be fabricated at two different groups as to be single-wall (SWCNT) and multi-wall carbon nanotubes (MWCNT). MWCNTs can be imagined as a combination of hexagonal structures, which are occurred by rolling up graphene sheets layer by layer [22]. Previously, MWCNTs were used by Britto and co-workers [23] for the determination of dopamine, and they reported a remarkable enhancement in its electrochemical signal. Gold nanoparticles (AuNPs) have unique characteristics such as high surface energy and high surface area [24]. Therefore, AuNPs can be used to serve an efficient conducting interface and unique catalytic activity for the construction of robust and sensitive electrochemical sensors [25].

Catecholamines are a group of biogenic amines, placed in the central nervous system and act neurotransmitters and/or hormones. This group mainly consists of epinephrine (EPI), norepinephrine (NE), dopamine (DA) and their metabolites such as levodopa (l-Dopa) [26]. The detection of catecholamines is crucial for the diagnosis of various diseases such as neuroblastoma and pheochromocytoma [27]. Besides, they are therapeutics in patients of Parkinson’s disease, bronchial asthma, cardiac surgery, and myocardial infarction [28]. Carbidopa (C-Dopa) can also be used in the treatment of Parkinson's disease. Hence, the sensitive, selective, and accurate determination of EPI, NE, DA, l-Dopa, and C-Dopa has an importance in both blood and urine samples. In order to achieve multiple analysis of catecholamines, high performance liquid chromatography (HPLC) is a convenient option with several detection techniques [29], [30].

Furthermore, the usage of flow-cell combined with paper-electrode assemble as a detection technique can provide an attractive analysis of the catecholamines because of its excellent properties mentioned above. According to HPLC-EC methodology, the usage of high flow rates provides high mass transport, and the microelectrodes used in HPLC-EC systems provide low background signal improving diffusion rates [31], [32]. Thus, signal to noise ratio can be substantially enhanced, and the amperometric detection with high sensitivity can be achieved. We also benefitted from the same methodology by using a flow-cell system. Despite the remarkable potential of electrochemical flow cell for electroactive species, an absence of robust and cheap electrode assemble is still a challenge. Herein, we report on a simple, disposable, and user-friendly electrochemical flow cell device with size of 4 × 3 × 2 cm. To the best of our knowledge, this approach represents the first reported three-dimensional low-cost electrochemical flow cell device, which utilizes a paper-based electrode (PBE) for the detection of catecholamines in blood and urine samples. For this reason, we prepared a PBE modified with AuNPs and MWCNT, which provides high surface area and efficient electrocatalytic activity for EC detection. We also fabricated a flow-cell with a specially designed for the PBE, and five different catecholamines (EPI, NE, DA, l-Dopa, and C-Dopa) were utilized as model target molecules. The characterization of the prepared PBE was carried out using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy with energy dispersive X-Ray analysis (SEM-EDX) and Raman spectroscopy. Furthermore, the analytical figure of merits was demonstrated for the usability and the applicability of the developed method with performing the analytical validation tests from bulk forms and biological samples.

Section snippets

Reagents

EPI, NE, DA, l-Dopa, and C-Dopa standards were purchased from Sigma-Aldrich (St. Louis, MO, USA). Sodium chloride (NaCl), potassium chloride (KCl), disodium hydrogen phosphate (Na2HPO4), and potassium dihydrogen phosphate (KH2PO4) were obtained from J.T. Baker (Deventer, Netherlands). Chloroauric acid (HAuCl4), potassium ferricyanide (K3Fe(CN)6), potassium ferrocyanide (K4Fe(CN)6), sodium dihydrogen phosphate (NaH2PO4), ethylenediaminetetraacetic acid (EDTA) were purchased from Sigma-Aldrich

Paper electrode assemble design and construction of flow cell

In the present study, nitrocellulose membrane was preferred as a support of the PBE to provide the most proper construction. We also benefited from the stencil printing method to fabricate the PBE as shown in Schema S1. Two different types of steel stencil in the name of long and short electrode type with 0.1 mm and 0.15 mm thickness were used to decide the most proper electrode design. The prepared electrodes were tested in 5.0 mM [Fe(CN)6]3–/4− including 0.1 M KCl, using CV (Fig. S3). Usage

Conclusions

In this report, we fabricated a flow-cell coupled with a paper-based electrode assemble, using a specific architecture for the determination of catecholamines in both blood and urine samples. The flow-cell system, combined with an HPLC-EC method, was applied for the quantitative analysis of NE, EPI, l-Dopa DA, and C-Dopa with high accuracy. The main recovery values in blood and urine samples were calculated for NE, EPI, l-Dopa and DA as 103.0 ± 6.9 and 103.6 ± 2.6, respectively. The new design

CRediT authorship contribution statement

Hilal Torul: Conceptualization, Methodology, Validation, Investigation, Writing - original draft, Review & editing. Mehmet Gumustas: Conceptualization, Writing - review & editing. Berat Urguplu: Validation. Aytekin Uzunoglu: Validation. I. Hakki Boyaci: Funding acquisition. Huseyin Celikkan: Formal analysis, Investigation. Ugur Tamer: Conceptualization, Methodology, Funding acquisition.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We thank to Alparslan Kılıç for providing technical support. This study was supported by Gazi University Scientific Research Department (Ankara, Turkey; Project No. 02/2019-16).

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