Zinc ion mediated synthesis of cuprous oxide crystals for non-enzymatic glucose detection

Jian Lv a, Chuncai Kong ab, Xuanxuan Hu a, Xiaojing Zhang a, Ke Liu c, Shengchun Yang ab, Jinglei Bi a, Xiaoyan Liu a, Ge Meng d, Jianhui Li e, Zhimao Yang *ab and Sen Yang *ab
aSchool of Science, MOE Key Laboratory for Non-Equilibrium Synthesis and Modulation of Condensed Matter, State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an 710049, Shaanxi, China. E-mail: zmyang@xjtu.edu.cn; yangsen@xjtu.edu.cn
bCollaborative Innovation Center of Suzhou Nano Science and Technology, Xi’an Jiaotong University Suzhou Academy, Suzhou 21500, China
cHubei Key Laboratory of Advanced Textile Materials & Application, College of Materials Science and Engineering, Wuhan Textile University, Wuhan 430200, China
dSchool of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an 710049, Shaanxi, China
eDepartment of Surgical Oncology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an 710049, Shaanxi, China

Received 23rd July 2017 , Accepted 29th September 2017

First published on 2nd October 2017


Morphology control is expected to be an effective method to enhance the electrochemical properties of materials. In this work, zinc cation-mediated growth of Cu2O crystals was achieved via an aqueous chemical route at room temperature. Thus, by simply increasing the concentration of Zn2+, concave cube-like (C-Cu2O), porous (P-Cu2O), and hierarchical (H-Cu2O) Cu2O crystals were selectively obtained. The morphologies and structures of the as-prepared Cu2O crystals were characterized by SEM, TEM, XRD and XPS. The three materials were subsequently employed as active materials for the non-enzymatic detection of glucose. The H-Cu2O-based electrode exhibited the highest sensitivity (3076 μA mM−1 cm−2) in virtue of its highest surface area, while the P-Cu2O-based electrode showed the widest linear range (up to 24 mM). The reliability of the Cu2O-based glucose sensors was proved by determining their detection limit, response time, selectivity, and stability characteristics on human serum samples. This work provides a novel strategy for the morphology-controlled Zn2+-mediated fabrication of Cu2O crystals with different glucose sensing performances depending on their structures.


Introduction

Effective control of the shape and size of metal oxide nanostructures is important for nanotechnology, because their applications are highly related to the special physical and chemical properties which could be assigned to certain morphologies.1 In general, excellent morphology-dependent properties can be obtained via crystalline structure modification, this typically leading to materials with a high surface area and specific crystallography. The need for materials with superior properties, particularly surface-sensitive properties, has motivated researchers to synthesize metal oxide nanostructures with various morphologies.

Cuprous oxide (Cu2O), as an environmentally friendly p-type semiconductor with a direct band gap of 2.2 eV, has been used in various fields including photocatalysis,2 gas sensors,3 solar energy conversion,4 lithium-ion batteries (as anode components),5 and templates.6 In the past few decades, various Cu2O micro/nanostructures have been prepared using different methods in an attempt to prepare materials with improved performances. For example, Cu2O superstructures were constructed via recrystallization-induced self-assembly.7 Cu2O nanowire mesocrystals were synthesized by the conjugation of reduced graphene oxide (rGO),8 and Cu2O nanospheres were prepared with the assistance of polyvinylpyrrolidone (PVP).9 Among these techniques, inorganic ion-directing synthesis is particularly relevant since the rate and direction of Cu2O crystal growth can be effectively altered by simply adding inorganic ions to the reaction system, thereby achieving Cu2O crystals with various morphologies.10,11 Remarkably, these inorganic ions do not prevent the Cu2O surface from being in contact with the surrounding substances, which is extremely important for surface-related applications. However, inorganic ion-directing methods mostly result in polyhedral Cu2O materials with a relatively low surface area, while materials with monodispersed irregular shapes (e.g., porous and hierarchical structures) are rarely produced. Unlike polyhedral morphologies, irregular morphologies usually present a higher surface area and a high index surface, thereby providing a higher number of active sites for surface-related applications.

Fast and reliable monitoring of glucose levels in blood is of great importance for the control and treatment of diabetes, an illness that usually derives from other diseases such as cardiopathy, blindness, and kidney failure.12,13 Owing to their low cost and high sensitivity characteristics, various metal oxides have been used as sensing materials to manufacture enzyme-free glucose sensors.14 Among these materials, Cu2O or Cu2O composites have been extensively used in non-enzymatic sensing of glucose since effective electron transfer can be achieved via the Cu3+/Cu2+/Cu+ redox couple that enables the effective electron transfer.15–17 The synthesis of Cu2O composite-based non-enzymatic glucose sensors typically involves multiple steps,18 which results in low yields and high costs. In contrast, the synthesis of single Cu2O-based glucose sensors is significantly easier.19 Porous and hierarchical Cu2O particles possessing more active sites and charge-transport channels normally show superior glucose sensing performances compared with the Cu2O crystals with smooth surfaces.20,21 However, most of the reported methods always require high temperature (above room temperature),22 ultrasound,23 microwave,24 or a surfactant,20 which is either energy-consuming or blocks the active sites on the surface of Cu2O.

Herein, we demonstrated a surfactant-free solution-chemistry approach to prepare Cu2O structures at room temperature, as shown in Scheme 1. Interestingly, homogeneous concave cube-like (C-Cu2O), porous (P-Cu2O), and hierarchical (H-Cu2O) Cu2O materials were successfully fabricated by simply controlling the amount of Zn2+ added. These three materials were subsequently used as active materials for manufacturing enzyme-free glucose sensors. The shape-dependent glucose sensing properties of these sensors were evaluated. While the large surface area of H-Cu2O resulted in this material exhibiting the highest sensitivity among the three Cu2O structures studied (ca. 19 times higher versus p-Cu2O and C-Cu2O), P-Cu2O showed the widest linear range. This work provides a facile strategy to modify the morphology of Cu2O nanomaterials with the aim to provide these materials with excellent glucose sensing performance.


image file: c7tb01971h-s1.tif
Scheme 1 Schematic presentation of the formation of C-Cu2O, P-Cu2O and H-Cu2O.

Experimental

Chemicals

Cupric chloride (CuCl2), zinc chloride (ZnCl2), sodium assorbate (SA), sodium hydroxide (NaOH), glucose, ascorbic acid (AA), uric acid (UA), sodium chloride (NaCl), fructose, lactose and sucrose were purchased from Aladdin Reagent. All chemicals were of analytical grade and used without further purification. The deionized water (18.25 MΩ cm) used in all of the preparation was from a MilliQ Academic water purification system (Millipore Corp.).

Synthesis of Cu2O nanomaterials

All the Cu2O materials were produced via a facile aqueous route at room temperature (25 °C). Firstly, 1 ml of CuCl2 solution with a concentration of 0.1 M, 1 ml of sodium hydroxide solution (0.4 M) and ZnCl2 solution (0.1 M) in different volumes, 0 ml, 0.25 ml and 0.5 ml, respectively, were injected into ultrapure water (43 ml, 42.75 ml and 42.5 ml, respectively, to make sure the total volume is constant) under stirring at room temperature. After constant stirring for 5 minutes, SA solution (0.1 M, 5 ml) was added dropwise to the beaker, and further stirring was processed for 60 minutes. The products synthesized by using different volumes of ZnCl2 solution were referred to as C-Cu2O, P-Cu2O and H-Cu2O, respectively. Finally, the obtained precipitates were washed with ultrapure water and ethanol several times and then dried in a vacuum oven at 50 °C for 12 h. The reagents required for the three samples are listed in Table S1 (ESI).

Instruments

The crystal phases of the as-obtained Cu2O structures were characterized using an X-ray diffractometer (Bruker-AXS D8 ADVANCE) equipped with a Cu Kα radiation source (λ = 1.54 Å). A Kratos Axis Ultra DLD spectrometer equipped with an Al mono Kα X-ray source was utilized to record X-ray photoelectron spectra. A JSM-7000F field-emission scanning electron microscope (FE-SEM, JEOL, Japan) was used to observe the morphologies of different Cu2O materials. A JEOL JEM-2100 transmission electron microscope was used to characterize transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) at an acceleration voltage of 200 kV. A N2 adsorption experiment was conducted at −196 °C on a Quantachrome Quadrasorb SI-3.

Preparation of Cu2O/Nafion/GCE electrodes

Enzyme-free amperometric electrochemical sensors were fabricated by coating Nafion-impregnated Cu2O powders onto glassy carbon electrodes (GCE) at room temperature. Before modification, bare GCEs (Φ 5 mm) were polished to a mirror-like surface with 0.5 μm and 50 nm alumina powders, respectively, followed by washing ultrasonically in deionized water and ethanol several times. The modified electrodes were prepared as follows: homogeneous Cu2O suspensions were obtained by mixing the as-prepared Cu2O powders (5 mg) with 5 ml of Nafion solution (0.05%, Sigma-Aldrich), and sonication for approximately 20 minutes. 20 μl of the Cu2O mixtures were dropped onto cleaned GCEs (denoted as Cu2O/Nafion/GCE), and allowed to dry at room temperature, respectively. The quantity of the Nafion is based on our previous studies, endowing electrodes with good stability to entrap active materials and anti-interference abilities without hugely deteriorating the sensitivities of the as-prepared electrodes. Three electrodes made from C-Cu2O, P-Cu2O and H-Cu2O are denoted as C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE and H-Cu2O/Nafion/GCE, respectively.

Electrochemical measurement

A standard three-electrode system (CHI-660E, Shanghai Chenhua, China) was applied to perform all the electrochemical experiments at room temperature. The as-prepared Cu2O/Nafion/GCE electrodes were used as the working electrodes, with Ag/AgCl as the reference electrode and Pt foil as the counter electrode. All the cyclic voltammetry (CV) measurements and chronoamperometry measurements (CA) were performed in 100 ml of NaOH aqueous solution (0.1 M) with or without various concentrations of glucose aqueous solution. Continuous magnetic stirring was needed in amperometric measurements to make sure of the absolute mixing of glucose with the NaOH solution. All the electrochemical measurements were performed at room temperature.

Results and discussion

Structural and compositional characterizations

The structures of the Cu2O materials were dramatically altered upon increasing the Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ ratio from 0 to 1[thin space (1/6-em)]:[thin space (1/6-em)]2. Fig. 1a shows the XRD patterns of the three Cu2O materials under study. All the patterns can be assigned to Cu2O crystals (JCPDS: no. 05-0667), and no peaks ascribed to impurities (e.g., CuO, Cu, ZnO, and Zn) were found. With the aim to further confirm the purity of the prepared samples, the chemical composition of P-Cu2O (i.e., the material with the highest percentage of zinc chloride) was analyzed by XPS. Fig. 1b shows the detailed Cu 2p spectrum of P-Cu2O. The peaks at 932.3 eV and 952.2 eV were assigned to the Cu 2p3/2 and Cu 2p1/2 of Cu2O, respectively, with no shake-up satellite peak being found.25 As shown in Fig. 1c, the Zn 2p spectrum showed no peaks, thereby suggesting that Zn2+ was completely removed after washing. The above XPS results further confirmed that the synthesis approach used herein led to the formation of pure Cu2O in all cases. In addition, the XRD peaks broadened (i.e., higher FWHM) upon increasing the amount of zinc chloride in the synthesis. Thus, high zinc chloride amounts resulted in Cu2O materials with small grain sizes.
image file: c7tb01971h-f1.tif
Fig. 1 (a) XRD patterns of the three different Cu2O crystal materials and Cu2O standard (JCPDS 05-0667). XPS spectra of H-Cu2O prepared with a Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ ratio of 1[thin space (1/6-em)]:[thin space (1/6-em)]2: (b) Cu 2p, (c) Zn 2p, and (d) O 1s.

The morphology and structure of Cu2O were studied by SEM and TEM. The size of the Cu2O particles was measured by means of the Nanomeasure software (Fig. S1, ESI). Fig. 2a and b show SEM and TEM images of C-Cu2O prepared without adding zinc chloride, respectively. The edge length of the as-prepared C-Cu2O cubes was ca. 304 nm. As clearly shown in the inset of Fig. 2c, the single particle in Fig. 2c generated a selected area electronic diffraction pattern typical of single crystalline materials, thereby revealing the single crystal nature of the as-obtained C-Cu2O. The HRTEM image (Fig. 2d), corresponding to the area labeled with a red circle in Fig. 2c, showed the presence of only one type of lattice fringes with a spacing of about 0.207 nm, which is comparable to that of the (200) planes in Cu2O crystals (JCPDS: no. 05-0667). The addition of zinc chloride to the reaction system in low amounts (Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ = 1[thin space (1/6-em)]:[thin space (1/6-em)]4) resulted in samples with more uneven surfaces, and some holes were formed in the inner part of the Cu2O materials (Fig. 2e and f). These P-Cu2O crystals were slightly larger in size (326 nm) as compared to C-Cu2O cubes. As shown in Fig. 2h (HRTEM patterns of the area highlighted in Fig. 2g), the surface lattice fringes were still assigned to the (200) crystallographic planes of Cu2O. H-Cu2O materials were prepared by increasing the Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ ratio to 1[thin space (1/6-em)]:[thin space (1/6-em)]2, resulting in spherical particles of ca. 309 nm diameter (Fig. 2i), with their surface being composed of numerous small nanoparticles (Fig. 2j). The SAED pattern of the nanosphere highlighted in Fig. 2k showed a ring-like form, thereby revealing that the obtained H-Cu2O nanospheres were polycrystalline, in good agreement with the above XRD results. The H-Cu2O nanospheres showed two surface lattice fringes with measured spacings of 0.241 and 0.296 nm, which corresponded to the (111) and (110) planes of Cu2O crystals (JCPDS: no. 05-0667), respectively.


image file: c7tb01971h-f2.tif
Fig. 2 FESEM, TEM, and HRTEM images of Cu2O crystals synthesized with different Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ ratios: (a–d) C-Cu2O, (e–h) P-Cu2O, and (i–l) H-Cu2O. Insets (c, g, and k) show the corresponding SAED patterns.

Based on the above discussion, it is easy to deduce that an increase in the concentration of zinc chloride can result in Cu2O materials with higher surface areas, and this was confirmed by isothermal N2 adsorption/desorption measurements (Fig. 3). The BET surface area of P-Cu2O was slightly higher than that of C-Cu2O (8.397 versus 5.487 m2 g−1) as a result of the presence of inner holes. Remarkably, H-Cu2O showed a high surface area of 49.577 m2 g−1, and this was probably ascribed to the hierarchical structure comprising of numerous small particles. The morphological and surface area characteristics of the three samples under study are summarized in Table S2 (ESI).


image file: c7tb01971h-f3.tif
Fig. 3 N2 adsorption/desorption isotherms for the three different Cu2O samples.

Electrochemical performances of the three Cu2O/Nafion/GCE electrodes

Three different Cu2O crystals were incorporated into Nafion and GCE to serve as the working electrodes for glucose sensing in the absence of glucose oxidase. Fig. 4 shows the electrocatalytic responses of the Nafion/GCE, C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE, and H-Cu2O/Nafion/GCE electrodes towards 1 mM glucose in a 0.1 M NaOH solution (scan rate = 50 mV s−1). No oxidation peak was found for the Nafion/GCE electrode, whereas three Cu2O/Nafion/GCE electrodes showed several oxidation peaks at ca. +0.55 V. This voltage was employed for the following chronoamperometry (CA) tests. These oxidation responses resulted from the transformation of Cu+ into Cu3+.26 Among the three electrodes under study, H-Cu2O/Nafion/GCE showed the highest glucose oxidation peak. The hierarchical structure of H-Cu2O provided this material with abundant active sites for the oxidation of glucose. Fig. S2 (ESI) shows the CV curves of the three electrodes while varying the concentration of glucose (0–3 mM). Very weak glucose oxidation signals were found in the absence of glucose for the three electrodes. In contrast, large peaks were found after glucose addition, and the intensity of these peaks increased with the concentration of glucose.
image file: c7tb01971h-f4.tif
Fig. 4 CV curves of the different electrodes in a 0.1 M NaOH solution at a concentration of glucose of 1 mM (scan rate = 50 mV s−1).

Fig. 5a–c show the effect of the scan rate on the oxidation of glucose for C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE, and H-Cu2O/Nafion/GCE, respectively. These results were obtained by performing CV measurements for three different electrodes (0.1 M NaOH, 2 mM glucose) while increasing the scan rate at 25 mV s−1 intervals up to 150 mV s−1. The peak potentials shifted to more positive values with the scan rate in all cases. Meanwhile, the peak currents corresponding to glucose oxidation varied linearly with the scan rate, and the fitting equations of the C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE, and H-Cu2O/Nafion/GCE electrodes were IC (mA) = 0.000467 V + 0.0500 (mV s−1), IP (mA) = 0.00240 V + 0.0743 (mV s−1), and IH (mA) = 0.00472 V + 0.424 (mV s−1), respectively (Fig. 5d–f). These linear relationships revealed that the electrochemical kinetics of the three electrodes is governed by the adsorption of glucose on the surface of the electrodes.33


image file: c7tb01971h-f5.tif
Fig. 5 CV curves of: (a) C-Cu2O/Nafion/GCE, (b) P-Cu2O/Nafion/GCE, and (c) H-Cu2O/Nafion/GCE electrodes at different scan rates (0.1 M NaOH, 2 mM glucose). (d–f) Peak current versus scan rate plots corresponding to the CV curves represented in Fig. 5a–c, respectively.

Fig. 6a depicts the amperometric response curves of the C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE, and H-Cu2O/Nafion/GCE electrodes (0.1 M NaOH, +0.55 V) while gradually increasing the glucose concentration. During the tests, the solutions were vigorously stirred to ensure a complete mixing of glucose and the electrolyte. The three electrodes showed fast response towards glucose concentration changes, and the sensing currents increased with glucose concentration. H-Cu2O/Nafion/GCE showed the highest response among the electrodes tested herein (19 times higher than those of C-Cu2O/Nafion/GCE and P-Cu2O/Nafion/GCE) and the narrowest response range. At the beginning of the tests, P-Cu2O/Nafion/GCE and C-Cu2O/Nafion/GCE showed nearly similar responses upon continuation of glucose injection. A further increase in the concentration of glucose resulted in P-Cu2O/Nafion/GCE exhibiting stronger responses than C-Cu2O/Nafion/GCE. Fig. 6b shows the corresponding calibration curves of the three Cu2O-based electrodes based on the results in Fig. 6a (n = 3) The H-Cu2O/Nafion/GCE electrode showed a sensitivity of 3076 μA mM−1 cm−2 (R = 0.996), with a linear range of up to 2 mM and a detection limit of 1.89 μM, as determined by 3σ/s (where σ and s represent the standard deviation of the background current and the slope of the calibration curve, respectively). The sensitivities of C-Cu2O/Nafion/GCEs and P-Cu2O/GCEs were significantly lower (165 μA mM−1 cm−2 and 157 μA mM−1 cm−2, respectively) than that of H-Cu2O/Nafion/GCE. However, C-Cu2O/Nafion/GCE and P-Cu2O/Nafion/GCE showed wider linear ranges than H-Cu2O/Nafion/GCE, especially in the case of P-Cu2O/Nafion/GCEs (a linear range of up to 24 mM).


image file: c7tb01971h-f6.tif
Fig. 6 (a) Amperometric responses of the three electrodes at +0.55 V vs. Ag/AgCl with the successive addition of glucose to 100 mM NaOH solutions per 60 s. (b) Corresponding calibration curves of the three electrodes (n = 3).

The different responses to glucose are mainly due to the morphological differences among the three materials. Compared to C-Cu2O and P-Cu2O, H-Cu2O possesses the highest surface area, which will inevitably increase the chance of glucose molecules to be oxidized,34 thus the sensitivity of the H-Cu2O modified electrode is much higher than those of C-Cu2O and P-Cu2O modified electrodes. The C-Cu2O and P-Cu2O crystals have almost the same surface area (8.397 versus 5.487 m2 g−1), causing the similar sensitivities of the Cu2O crystal modified electrodes. Another possible reason is the exposed facets of Cu2O crystals which have the significant influence on the sensing performance of Cu2O modified electrodes. The {111} facets with higher surface energy showed better electrocatalytic activity compared with {100} facets, Meanwhile, {111} facets possess higher density of Cu dangling bonds which make them positively charged, promoting the electron transfer in the oxidation of glucose.31,35 Three Cu2O crystals have different proportions of exposed facets and H-Cu2O crystals seem to have the lowest proportion of low surface energy facets {100}, thus making the H-Cu2O modified electrode exhibit highest sensitivity towards the sensing of glucose. The use of Nafion film also affects the performances of the three electrodes. The Nafion film reduces the mass transport of glucose to the surfaces of Cu2O materials thus making the sensing reaction determined by the diffusion rate instead of the catalysis rate.36 This effect lowers the sensitivity of glucose sensors but will generally increase their linear regions.37 Compared with C-Cu2O and P-Cu2O modified electrodes, H-Cu2O modified electrodes were not fully capped by Nafion as the other two materials when a small amount of Nafion solution was casted on the modified electrodes in our experiments. This difference causes C-Cu2O and P-Cu2O modified electrodes to show much wider linear regions than the H-Cu2O modified electrode. Even compared with the reported Cu2O-based glucose sensors,27–32 our C-Cu2O and P-Cu2O exhibit superior linear regions, endowing these two sensors with great potential to directly detect glucose in human blood (the normal concentration of glucose in human blood is about 3–8 mM). The aforementioned reasons might work together to determine the glucose sensing performances of the three Cu2O modified electrodes.

Fig. S3a–c (ESI) show the sensing behaviors at low glucose concentrations for the three electrodes. The three electrodes showed remarkable amperometric increases, even at glucose concentrations as low as 1 μM. The response times of the three Cu2O-based electrodes (defined as the time required for the electrodes to reach 95% of steady-state values) were also tested (Fig. S3d–f, ESI). C-Cu2O/Nafion/GCE and H-Cu2O/Nafion/GCE only required 1 s to achieve stable values, while 2 s is required for P-Cu2O/Nafion/GCE. The analytical performances of the three Cu2O-based electrodes were compared with other Cu2O-based non-enzymatic glucose sensors (Table 1).

Table 1 Sensing performances of the electrode prepared herein and other enzyme-free glucose sensors
Electrode materials Electrolyte Applied potential (V) Sensitivity (μA mM−1 cm−2) Linear range (mM) Response time (s) Detection limit (μM) Ref.
CQDs-carbon quantum dots; GO-graphene oxide; NS-nanosheet; NW-nanowire; MCHN-mesocrystalline Cu2O hollow nanocubes.
CQDs/Cu2O/Nafion/GCE 0.1 M NaOH +0.60 298 0.02–4.3 2.8 27
RGOs-Cu2O/Nafion/GCE 0.05 M KOH +0.60 2619 0.01–6 <3 0.05 28
Cu2O/NiOx/GO/GC 0.1 M NaOH +0.60 285 0.002–2.95 0.4 29
Cu2O/Carbon Vulcan XC-72 0.1 M KOH +0.75 629 Up to 1 2.4 30
Cu@Cu2O NS-NWs/Nafion/GCE 0.05 M NaOH +0.60 1420 Up to 2 <0.1 0.04 16
Octahedral Cu2O 0.1 M NaOH +0.65 294 0.1–5 5.11 31
Hierarchical Cu2O 0.1 M NaOH +0.50 190 0.05–1.1 47.2 20
MCHNs/Nafion/GCE 0.1 M NaOH +0.60 743 0.001–1.7 0.87 32
C-Cu2O/Nafion/GCE 0.1 M NaOH +0.55 165 Up to 12 ∼1 3.79 Our work
P-Cu2O/Nafion/GCE 0.1 M NaOH +0.55 157 Up to 24 ∼1 2.71 Our work
H-Cu2O/Nafion/GCE 0.1 M NaOH +0.55 3076 Up to 2 ∼1 1.89 Our work


The selectivity of the Cu2O-based sensors was studied since there are several easily oxidized substances such as uric acid, ascorbic acid, fructose, lactose, and sucrose in human blood that could mask the sensing signals of the electrodes. Chloride ion is a very powerful poison for enzyme-free glucose sensors. However, glucose is typically present in the human body at significantly higher concentrations as compared to the aforementioned species. Considering the above facts, anti-interference tests were carried out by first injecting 100 μM glucose, followed by the addition of 10 μM uric acid, ascorbic acid, fructose, lactose, and sucrose to the 0.1 M NaOH solution at a potential of +0.55 V. Fig. 7a–c show the current responses of the three electrodes towards various interfering species. The three electrodes displayed low responses towards the added species, except for glucose. These results were further confirmed by obtaining the exact contrasts among the different interfering species (Fig. 7d–f). These contrasts, obtained by denoting the current responses of the three Cu2O-based electrodes at 100 μM of glucose, were 100% in all cases, thus revealing good sensing selectivities of the electrodes. The difference in responses of three electrodes towards reducing sugars, like fructose and lactose, is probably due to the different structures of the three materials. While the reason why H-Cu2O modified electrode shows less efficiency in rejecting uric acid and ascorbic acid than the other two electrodes is that Nafion film does not cover H-Cu2O as thoroughly as the other two surfaces. The negatively charged Nafion not only serves as the stabilizing agent for Cu2O materials, but also as an effective perm-selective barrier to circumvent electroactive interferences such as uric acid and ascorbic acid.38


image file: c7tb01971h-f7.tif
Fig. 7 Anti-interference tests of the three electrodes in a 0.1 M NaOH solution at +0.55 V: (a) C-Cu2O/Nafion/GCE, (b) P-Cu2O/Nafion/GCE, and (c) H-Cu2O/Nafion/GCE. (d)–(f) Represent the corresponding percentages of interfering signals as compared to the target analyte. (g)–(i) Represent the corresponding long-term stabilities of the three electrodes.

The stabilities of the electrodes were investigated by measuring their amperometric responses towards 0.1 mM glucose for 7 days. The three electrodes were used under air without specific protection. C-Cu2O/Nafion/GCE, P-Cu2O/Nafion/GCE, and H-Cu2O/Nafion/GCE retained 88%, 96%, and 87% of their original responses towards 0.1 mM glucose, respectively (Fig. 7g–i). These results were indicative of the good stability of the three Cu2O-based electrodes under air. Furthermore, the reusability of three types of Cu2O crystal modified electrodes was measured by their five times responses toward 0.1 M glucose in 0.1 M NaOH at a potential of +0.55 V vs. Ag/AgCl. For each Cu2O crystal, we fabricate three electrodes to make the error bars. As shown in Fig. S5 (ESI), three types of Cu2O modified electrodes could be used for at least 5 times with acceptable relative standard deviations.

Real blood serum tests

To verify the practical applicability of the Cu2O-based electrodes, all three electrodes are applied to test the glucose concentrations in human blood serum samples. Table 2 summarizes the results acquired by the as-prepared electrodes, together with the data obtained using an automatic biochemical analyzer. The concentrations of glucose in various blood serums were similar to those provided by the biochemical analyzer, indicating the potential applicability of the Cu2O-based electrodes.
Table 2 Determination of glucose in human blood serum samples (n = 3)
Samples Biochemical analyzer (mM) Developed glucose sensor (mM) RSD (%)
C-Cu2O 3.80 3.71 1.2
6.95 6.31 1.3
P-Cu2O 4.71 4.69 6.7
6.88 6.87 4.5
H-Cu2O 5.15 5.11 1.6
7.19 6.88 2.2


Glucose sensing mechanism of the Cu2O-based electrodes

It is commonly accepted that the oxidation of glucose is caused by the deprotonation of the glucose and isomerization to its enediol form, followed by the attachment on the electrode and oxidation by Cu(I), Cu(II) and Cu(III) surface states.39 Instead of Cu(I) and Cu(II), Cu(III) species act as the mediator for electron transfer phenomena,40 which is confirmed by CV curves of the modified electrodes towards glucose. In those CV curves, the oxidations of glucose occur in the potential range of 0.4–0.8 V, where the oxidation wave of the Cu(II)/Cu(III) is.41,42 Cu2O is first oxidized to Cu(OH)2, and finally to CuOOH in the alkaline solution.43 The Cu(OH)2/CuOOH redox couple serves as the mediator for the oxidation of glucose. The oxidation could not simply produce gluconic or glucuronic acid, but might instead entail C–C bond cleavage.44 Light-weight products, such as formates and carbonates, would be generated in the cleavage, which involves the electron transfer resulting in an increase of anodic currents and a decrease of cathodic currents.45

Conclusions

In summary, a facile Zn2+-mediated approach has been used to synthesize various homogenous Cu2O materials at room temperature. Without Zn2+, uniform C-Cu2O crystals were obtained. P-Cu2O crystals were synthesized upon the addition of small amounts of Zn2+ to the reaction medium (Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ = 1[thin space (1/6-em)]:[thin space (1/6-em)]4). A further increase in the concentration of Zn2+ (Zn2+[thin space (1/6-em)]:[thin space (1/6-em)]Cu2+ = 1[thin space (1/6-em)]:[thin space (1/6-em)]2), resulted in the formation of H-Cu2O materials with a high surface area. The shape-regulated non-enzymatic glucose sensing performances of these materials were investigated by performing CV and CA tests. H-Cu2O showed the highest sensitivity towards glucose due to the high surface area which can result in higher electrocatalytic active areas and fast electron transfer during glucose oxidation. P-Cu2O showed the widest linear range among the Cu2O materials. In addition, the three materials showed low detection limits, fast response times, good selectivities, and acceptable stabilities. The detection capabilities were maintained during human serum tests for all the electrodes, indicating their potential as the candidates for non-enzymatic glucose sensing. This work provides an applicable strategy that allows easy control of the morphology of Cu2O nanomaterials with the aim to enhance their non-enzymatic glucose sensing performances.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC no. 51501140), Shaanxi Province Science Foundation for Youth (no. 2016JQ5028), China Postdoctoral Science Foundation (2016M602808), Natural Science Foundation of Jiangsu Province (BK20161250, BK20171235), Public welfare technology application research project of Zhejiang Province (2016C31G4181807) and the Fundamental Research Funds for the Central Universities.

Notes and references

  1. S. Konar, H. Kalita, N. Puvvada, S. Tantubay, M. K. Mahto, S. Biswas and A. Pathak, J. Catal., 2016, 336, 11–22 CrossRef CAS .
  2. L. Tang, J. Lv, S. Sun, X. Zhang, C. Kong, X. Song and Z. Yang, New J. Chem., 2014, 38, 4656–4660 RSC .
  3. H. Zhang, Q. Zhu, Y. Zhang, Y. Wang, L. Zhao and B. Yu, Adv. Funct. Mater., 2007, 17, 2766–2771 CrossRef CAS .
  4. C. G. Moralesguio, L. Liardet, M. T. Mayer, S. D. Tilley, M. Grätzel and X. Hu, Angew. Chem., Int. Ed., 2015, 54, 664–667 CAS .
  5. Y. T. Xu, Y. Guo, C. Li, X. Y. Zhou, M. C. Tucker, X. Z. Fu, R. Sun and C. P. Wong, Nano Energy, 2015, 11, 38–47 CrossRef CAS .
  6. S. Sun and Z. Yang, Chem. Commun., 2014, 50, 7403–7415 RSC .
  7. Y. Shang, Y. M. Shao, D. F. Zhang and L. Guo, Angew. Chem., Int. Ed., 2014, 53, 11514–11518 CrossRef CAS PubMed .
  8. S. Deng, V. Tjoa, H. M. Fan, H. R. Tan, D. C. Sayle, M. Olivo, S. Mhaisalkar, J. Wei and C. H. Sow, J. Am. Chem. Soc., 2012, 134, 4905–4917 CrossRef CAS PubMed .
  9. S. Zhang, R. Jiang, Y. M. Xie, Q. Ruan, B. Yang, J. Wang and H. Q. Lin, Adv. Mater., 2015, 27, 7432–7439 CrossRef CAS PubMed .
  10. M. J. Siegfried and K.-S. Choi, J. Am. Chem. Soc., 2006, 128, 10356–10357 CrossRef CAS PubMed .
  11. B. Heng, T. Xiao, W. Tao, X. Hu, X. Chen, B. Wang, D. Sun and Y. Tang, Cryst. Growth Des., 2012, 12, 3998–4005 CAS .
  12. J. Wang, Chem. Rev., 2008, 108, 4473–4491 Search PubMed .
  13. E. Witkowska-Nery, M. Kundys, P. S. Jelen and M. JönssonNiedziółka, Anal. Chem., 2016, 88, 11271–11282 CrossRef CAS PubMed .
  14. M. M. Rahman, A. Ahammad, J.-H. Jin, S. J. Ahn and J.-J. Lee, Sensors, 2010, 10, 4855–4886 CrossRef CAS PubMed .
  15. L. Zhang, Y. Ni and H. Li, Microchim. Acta, 2010, 171, 103–108 CrossRef CAS .
  16. Y. Zhao, L. Fan, Y. Zhang, H. Zhao, X. Li, Y. Li, L. Wen, Z. Yan and Z. Huo, ACS Appl. Mater. Interfaces, 2015, 7, 16802–16812 CAS .
  17. X. Zhang, G. Wang, W. Zhang, Y. Wei and B. Fang, Biosens. Bioelectron., 2009, 24, 3395–3398 CrossRef CAS PubMed .
  18. J. Ding, W. Sun, G. Wei and Z. Su, RSC Adv., 2015, 5, 35338–35345 RSC .
  19. X. Liu, Y. Sui, X. Yang, L. Jiang, F. Wang, Y. Wei and B. Zou, RSC Adv., 2015, 5, 59099–59105 RSC .
  20. S. Li, Y. Zheng, G. W. Qin, Y. Ren, W. Pei and L. Zuo, Talanta, 2011, 85, 1260–1264 CrossRef CAS PubMed .
  21. L. Zhang, H. Li, Y. Ni, J. Li, K. Liao and G. Zhao, Electrochem. Commun., 2009, 11, 812–815 CrossRef CAS .
  22. S. Sun, X. Zhang, X. Song, S. Liang, L. Wang and Z. Yang, CrystEngComm, 2012, 14, 3545–3553 RSC .
  23. B. G. Mao, D. Q. Chu, L. M. Wang, A. X. Wang, Y. J. Wen and X. Z. Yang, Mater. Lett., 2013, 109, 62–65 CrossRef CAS .
  24. S. K. Li, X. Guo, Y. Wang, F. Z. Huang, Y. H. Shen, X. M. Wang and A. J. Xie, Dalton Trans., 2011, 40, 6745–6750 RSC .
  25. X. Zhao, Y. Li, Y. Guo, Y. Chen, Z. Su and P. Zhang, Adv. Mater. Interfaces, 2016, 3, 1600658 CrossRef .
  26. J. Lv, C. Kong, Y. Xu, Z. Yang, X. Zhang, S. Yang, G. Meng, J. Bi, J. Li and S. Yang, Sens. Actuators, B, 2017, 248, 630–638 CrossRef CAS .
  27. Y. Li, Y. Zhong, Y. Zhang, W. Weng and S. Li, Sens. Actuators, B, 2015, 206, 735–743 CrossRef CAS .
  28. D.-L. Zhou, J.-J. Feng, L.-Y. Cai, Q.-X. Fang, J.-R. Chen and A.-J. Wang, Electrochim. Acta, 2014, 115, 103–108 CrossRef CAS .
  29. B. Yuan, C. Xu, L. Liu, Q. Zhang, S. Ji, L. Pi, D. Zhang and Q. Huo, Electrochim. Acta, 2013, 104, 78–83 CrossRef CAS .
  30. K. El Khatib and R. A. Hameed, Biosens. Bioelectron., 2011, 26, 3542–3548 CrossRef CAS PubMed .
  31. L. Tang, J. Lv, C. Kong, Z. Yang and J. Li, New J. Chem., 2016, 40, 6573–6576 RSC .
  32. Z. Gao, J. Liu, J. Chang, D. Wu, J. He, K. Wang, F. Xu and K. Jiang, CrystEngComm, 2012, 14, 6639–6646 RSC .
  33. C. Kong, L. Tang, X. Zhang, S. Sun, S. Yang, X. Song and Z. Yang, J. Mater. Chem. A, 2014, 2, 7306–7312 CAS .
  34. H. Cao, A. Yang, H. Li, L. Wang, S. Li, J. Kong, X. Bao and R. Yang, Sens. Actuators, B, 2015, 214, 169–173 CrossRef CAS .
  35. Y. Zhong, Y. Li, S. Li, S. Feng and Y. Zhang, RSC Adv., 2014, 4, 40638–40642 RSC .
  36. T. J. Ohara, R. Rajagopalan and A. Heller, Anal. Chem., 1994, 66, 2451–2457 CrossRef CAS PubMed .
  37. H. Tang, J. H. Chen, S. Z. Yao, L. H. Nie, G. H. Deng and Y. F. Kuang, Anal. Biochem., 2004, 331, 89–97 CrossRef CAS PubMed .
  38. L. Zhang, Y. H. Ni and H. Li, Microchim. Acta, 2010, 171, 103–108 CrossRef CAS .
  39. J. M. Marioli and T. Kuwana, Electrochim. Acta, 1992, 37, 1187–1197 CrossRef CAS .
  40. X. Kang, Z. Mai, X. Zou, P. Cai and J. Mo, Anal. Biochem., 2007, 363, 143–150 CrossRef CAS PubMed .
  41. Z. Zhuang, X. Su, H. Yuan, Q. Sun, D. Xiao and M. M. Choi, Analyst, 2008, 133, 126–132 RSC .
  42. M. Z. Luo and R. P. Baldwin, J. Electroanal. Chem., 1995, 387, 87–94 CrossRef .
  43. X. Niu, J. Pan, F. Qiu, X. Li, Y. Yan, L. Shi, H. Zhao and M. Lan, Talanta, 2016, 161, 615–622 CrossRef CAS PubMed .
  44. K. B. Male, S. Hrapovic, Y. Liu, D. Wang and J. H. Luong, Anal. Chim. Acta, 2004, 516, 35–41 CrossRef CAS .
  45. S. K. Meher and G. R. Rao, Nanoscale, 2013, 5, 2089–2099 RSC .

Footnotes

Electronic supplementary information (ESI) available. See DOI: 10.1039/c7tb01971h
These authors contributed equally to this work.

This journal is © The Royal Society of Chemistry 2017