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Ca -Triggered pH-Response Sodium Alginate Hydrogel Precipitation for Amplified Sandwich-Type Impedimetric Immunosensor of Tumor Marker Lihua Zhao, Shuang Yin, and Zhanfang Ma ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.8b01465 • Publication Date (Web): 14 Jan 2019 Downloaded from http://pubs.acs.org on January 14, 2019
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Ca2+-Triggered pH-Response Sodium Alginate Hydrogel Precipitation for Amplified Sandwich-Type Impedimetric Immunosensor of Tumor Marker Lihua Zhaoa, Shuang Yina, Zhanfang Ma* Department of Chemistry, Capital Normal University, Beijing 100048, China KEYWORDS. cascaded signal amplification; gold nanoparticle-CaCO3 microspheres; Ca2+-triggered alginate hydrogel precipitation; pH-response hydrogel; impedimetric immunosensor; tumor marker
ABSTRACT: Signal amplification is of great significance in the ultrasensitive electrochemical impedimetric immunoassays for tumor marker detection. A cascaded signal amplification approach was designed using gold nanoparticle-CaCO3 microspheres (AuNP-CaCO3) to trigger pH-responsive alginate hydrogel precipitation for sandwich-type impedimetric immunosensor. AuNPCaCO3 exerts a large hindrance effect and can release Ca2+ ions under weak acidic conditions, thus can serve as a multifunctional label. The hindrance effect of AuNP-CaCO3 can significantly enhance the impedance response as the initial signal amplification. Then, part of CaCO3 dissolves under weak acid conditions and releases Ca2+, which can cross-link with alginate to generate an insoluble alginate hydrogel precipitate on the sensing interface, significantly increasing the impedance signal. The impedance signal can be further amplified by making the hydrogel negatively charged based on the pH-responsive surface charge properties of the alginate hydrogel. Benefiting from the cascaded signal amplification, this impedimetric immunosensor exhibits a linear range from 1.0 fg mL-1 to 100 ng mL-1, an detection limit of 0.09 fg mL-1 and ultrahigh sensitivity of 973.01 Ω (lg(ng mL-1))-1 towards the assay of prostate specific antigen (PSA).
Cancer is a serious threat to health worldwide1, 2. Early diagnosis and therapy are imperative to cancer patients 3-5. Sensitive determination of tumor markers is significant to clinical diagnosis of cancers6, 7. Various analytical methods, such as colorimetric8, 9, electrochemiluminescent10, 11, photoelectrochemical12-14 and electrochemical assay15, 16 have been implemented for sensitive and accurate determination of tumor markers. Among them, electrochemical assay is a revolutionary breakthrough due to the inherent superiority including fast response, high sensitivity and simplicity17, 18. Impedimetric immunosensor has attracted considerable attention in the determination of tumor markers19-21. The sensitivity of the impedimetric immunosensor relies on the difference in the charge transfer resistance induced by per unit concentration target (ΔRct)22, 23, whereby various signal amplification strategies have been developed to elevate ΔRct and to achieve ultrasensitive analytical performance. Constructing highly conductive electrochemical sensing interface via conducting polymers, carbon materials, and metal nanoparticles has shown to be effective approach to achieve signal amplification24-26. Negatively charged labels were also utilized to enhance the electrostatic repulsion between sensing interface and negatively charged redox mediator, which usually used [Fe(CN)6]3-/4-, leading to significant signal amplification27-29. Signal amplification strategies based on precipitation reaction catalyzed by bio-enzymes or noble metal catalysts have been widely implemented in sensitive detection
of tumor markers30-33. These precipitation reactions can generate an insoluble layer on sensing interfaces, thus increasing the electrochemical signal response. Despite the considerable progress in signal amplification, the following challenges remain: (1) bio-enzyme-based signal amplification is susceptible to external conditions, such as pH, toxic chemicals, and temperature; (2) the preparation of functionalized labels is complicated and the precipitation reaction is time-consuming; (3) singleness of signal amplification methods because few works integrate multiple approaches to achieve signal amplification. Therefore, developing non-enzymatic, rapid-response and multiple amplification strategy is crucial to improve the analytical performance of impedimetric immunosensors. Hence, a cascaded signal amplification strategy was designed based on Ca2+-triggered pH-response sodium alginate hydrogel precipitation for a sandwich-type impedimetric immunosensor. Gold nanoparticle-CaCO3 microspheres (AuNP-CaCO3), which exert a large hindrance effect and can release Ca2+ ions under weak acidic condition34, 35 to trigger alginate gelation were labeled on immunoprobes. The cascaded signal amplification was accomplished in three steps. First, the large hindrance effect of AuNP-CaCO3 can significantly increase the interface impedance, thus enhancing the impedance signal response. Second, after part of CaCO3 dissolves under weak acid conditions, the released Ca2+ can cross-link alginate to generate an insoluble alginate hydrogel
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precipitate on the sensing interface. The alginate hydrogel with poor conductivity can remarkably hinder the interfacial electron transfer. Third, the pH-responsive surface charge properties of the alginate hydrogel cause the hydrogel surface to become negatively charged, which further amplifies the impedance signal36. To prove the feasibility of this signal amplification strategy, prostate specific antigen (PSA) was analyzed. Due to this cascaded signal amplification strategy, ΔRct was elevated prominently, leading to the ultrasensitive immunoassay of PSA.
EXPERIMENTAL Details about the chemicals, apparatus and protocols used (preparation of AuNPs, CaCO3 microspheres, AuNP-CaCO3, immunoprobes and the sensing platform) are given in the Supporting Information. Measurement procedure In order to carry out the detection process, PSA standard solutions with different levels were incubated on the prepared electrochemical sensing platform at 37°C for 45 min. Then, the prepared immunoprobes (10 μL) were covered on the modified electrodes at 37°C for 45 min, then dipped in SA acetate buffer solution (0.2 mg mL-1, pH = 6.0) for 60 s and carefully washed by ultrapure water. Subsequently, the detection procedure was conducted by electrochemical impedance spectroscopy (EIS) in 5 mM [Fe(CN)6]3-/4- with 100 mM PBS (pH 9.0).
RESULTS AND DISCUSSION Design of the sandwich-type impedimetric immunosensor. Bare GCE was modified with AuNP layer via electrochemical deposition to immobilize Ab1. As a model target, PSA was captured on the electrode surface by Ab1 and then conjugated with immunoprobes (BSA/Ab2-AuNPCaCO3). AuNP-CaCO3 with large hindranceeffect can significantly enhance the impedance response. When the electrode was dipped in sodium alginate acetate (SA) buffer solution, part of CaCO3 dissolved, and the released Ca2+ ions cross-linked with alginate to generate insoluble alginate hydrogel precipitate on the sensing interface to hinder charge transfer.
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Scheme 1. Schematic diagram of Ca2+-triggered pH-response Sodium alginate hydrogel precipitation for amplified sandwich-type impedimetric immunosensor of PSA. With the pH-stimulated response, alginate hydrogel was negatively charged under alkaline detection solution (pH 9.0), which impeded the transmission of [Fe(CN)6]3-/4- to sensing layer. Benefiting from the cascaded signal amplification strategy, a prominent elevation of ΔRct was achieved, resulting in the ultrasensitive determination of PSA (Scheme 1). Characterization of CaCO3 microspheres and AuNP-CaCO3. TEM and SEM were performed to characterize CaCO3 microspheres (Figure 1A) and AuNPCaCO3 (Figure 1B). As displayed in Figure 1a, b, the prepared CaCO3 microspheres have diameters in the range of 900 nm 1 μm. A TEM image (inset in Figure 1d) showed that AuNPs with diameters around 15 nm were synthesized, and well dispersed in ultrapure water. As shown in Figure 1d, e, the AuNPs were uniformly distributed on CaCO3 microspheres. Detailed compositions of CaCO3 microspheres and AuNPCaCO3 were further characterized by EDS (Figure 1c, f). The peaks of C, O, and Ca corresponding to CaCO3 were observed in CaCO3 microspheres. In AuNP-CaCO3, Au peak was appeared, demonstrating the successful assembly of AuNPs and CaCO3 microspheres (Figure 1f). Moreover, the compositions of CaCO3 microspheres and AuNP-CaCO3 were further characterized by XPS (Figure S1A-D). The peaks of Ca2p C1s, and O1s were designated to CaCO3 microspheres (Figure S1A, C). For the AuNP-CaCO3, the emergence of Au 4f peaks was assigned to the AuNPs (Figure 1B, D), which also indicated the successful assembly of AuNPs and CaCO3 microspheres. In order to characterize the assembly of AuNPs on CaCO3, zeta potentials of AuNPs and CaCO3 microspheres were measured. The zeta potential of AuNPs (Figure S2A) and CaCO3 microspheres (Figure S2B) were -22.8 mV and 9.74 mV, respectively. These results indicated that the assembly was occurred mainly due to electrostatic interaction37. Electrochemical Characterization. Cyclic voltammetry (CV) was implemented to research the stepwise construction of this impedimetric immunosensor (Figure 2A). After the modification with AuNPs, the electrochemical signal (curve b) was enhanced in comparison with the observed value of GCE (curve a). The prominent enhancement of conductivity was led
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Figure 1. TEM, SEM photographs and EDS of the CaCO3 microspheres (A) and AuNP-CaCO3 (B). TEM image (a, d), SEM image (b, e), EDS image (c, f). The insert is TEM image of AuNPs. by the modification of AuNPs. After the subsequent incubation of Ab1, BSA, and PSA on the AuNP-GCE (curve c, d, e), the signal decreased successively, indicating that the Ab1, BSA and PSA were successfully immobilized. The peaks current further decreased after incubation of the immunoprobe (BSA/Ab2-AuNP-CaCO3) owing to its poor conductivity (curve f). Again, the current signal decreased after the poorly conductive alginate hydrogel precipitated on the electrode surface (curve g). EIS was performed to research the immunosensing interface properties (Figure 2B). An equivalent circuit was obtained using EC-Lab (inset in Figure 2B). GCE presented a small Rct (charge transfer resistance) (curve a). The AuNP layermodified GCE showed a decreasing Rct (curve b). Rct increased after the incubation of Ab1, BSA, and PSA on the AuNP layer-modified GCE (curve c, d, e), indicating the fixing of Ab1, BSA, and PSA. Rct increased after the incubating with BSA/Ab2-AuNP-CaCO3 (curve f) and more significantly increased after precipitation of the alginate hydrogel (curve g). SEM characterization for stepwise fabrication procedure. SEM was performed to analyze the construction procedures of the immunosensor in more detail. The AuNPs was well distributed on the GCE (Figure 2C). After incubation of the immunoprobes, BSA/Ab2-AuNP-CaCO3 nanocomposites were scattered onto the surface of the modified GCE (Figure 2D). Following the precipitation reaction, SEM results revealed that the insoluble alginate hydrogel was adhered on the BSA/Ab2-AuNP-CaCO3-coated electrode (Figure 2E). Experimental parameters optimization. Immunoreaction time was a crucial parameter for sensitive immunoassay, therefore, the immune time of PSA and Ab1 was optimized.
Figure 2. CV (A), and EIS (B) of the different assembled electrodes in 5 mM [Fe(CN)6]3-/4- with 100 mM KCl (pH 9.0): GCE (a), AuNP/GCE (b), Ab1/AuNP/GCE (c), BSA/Ab1/AuNP/GCE (d), PSA/BSA/Ab1/AuNP/GCE (e), BSA Ab2-AuNP-CaCO3/PSA/BSA/Ab1/AuNP/GCE (f), after Ca2+-triggered pH-response alginate hydrogel precipitation (g). SEM micrographs of AuNP/GCE (C), alginate hydrogel Ab2AuNP-CaCO3/PSA/BSA/Ab1/AuNP/GCE (D), and after Ca2+triggered pH-response alginate hydrogel precipitation (E). The Ab1 modified immunosensing interface was reacted with PSA (1 pg mL-1) at different times. As displayed in Figure S3A, the impedance response was raised up in a range of 15 to 45 min and then leveled off. Therefore, the optimal immunoreaction time was 45 min. To obtain the maximum value of impedance response, the concentration of SA and alginate hydrogel precipitation reaction time were optimized. Rct grew up with SA concentration in the range 0.05 to 0.2 mg mL-1 then leveled off at higher concentration (Figure S3B). Thereby, the optimum concentration of SA was 0.2 mg mL-1. Subsequently, the precipitation time was tested from 30 to 90 s as displayed in Figure 3A. The impedance signal displayed approximate value from 60 to 90 s. Thus, the optimal deposition time for alginate hydrogel was 60 s. The surface charge property of the alginate hydrogel is crucial to performance of signal amplification. With pH response characteristics, the surface charge properties of alginate hydrogel were governed by pH of the electrolyte. In order to obtain the maximum impedance response, the pH value of electrolyte was optimized (Figure S4). Rct was raised up from pH 6.0 to 9.0, and then remained constant with further increase of pH. The alginate hydrogel was positively charged under pH 6.0, while negatively charged under pH 9.0. Thus, the optimal pH of electrolyte was 9.0. A comparison of the impedance response at pH 6.0 and 9.0 were investigated in Figure 3B. After changing the pH of the hydrogel film from 6.0 (curve a) to 9.0 (curve b), the Rct value was increased by 360%. This large increase is accountable to the electrostatic interaction of the sensing interface and [Fe(CN)6]3-/4-. Signal amplification of AuNP-CaCO3 and alginate hydrogel. To characterize the signal amplification of AuNPCaCO3 and alginate hydrogel, comparison experiments were
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performed analyzing 1 ng mL-1 PSA. As displayed in Figure 4A, after the incubation of PSA, the impedance signal (curve b) increased slightly compared with the background signal (curve a). After conjugation with immunoprobes (BSA/Ab2AuNP-CaCO3), the impedance signal (curve b in Figure 4B) increased obviously compared with the background signal (curve a in Figure 4B). After the precipitation of alginate hydrogel, the impedance signal (curve b in Figure 4C) was raised
Figure 3. Effect of precipitation reaction on EIS response (A). EIS response of Ca2+-triggered pH-response alginate hydrogel precipitation in PBS buffer (pH 6.0 and pH 9.0) including 5 mM [Fe(CN)6]3-/4- (B): at pH 6.0 (curve a) and after changing the pH to 9.0 (curve b). more remarkably compared with the background signal (curve a in Figure 4C). The ΔRct before and after signal amplification were also investigated. The ΔRct caused by PSA was 346 Ω (column a in Figure 4D). After the reaction with BSA/Ab2AuNP-CaCO3, ΔRct increased to 1573 Ω (column b in Figure 4D), which is attributed to the large steric hindrance effect of AuNP-CaCO3. After the alginate hydrogel was precipitated on electrode surface, the ΔRct increased to 5390 Ω (column c in Figure 4D) because of the poor electrical conductivity of alginate hydrogel and the enhanced electrostatic interaction of the sensing interface and [Fe(CN)6]3-/4-. Detection performance. Different concentrations of PSA standard samples were analyzed under the optimum experimental parameters. Rct increased with PSA levels ranging from 1 fg mL-1 to 100 ng mL-1 (Figure 5A). The regression equation was fitted to Rct = 973.01 lgC+9256.71(ng mL-1, R2= 0.9961) with an ultralow detection limit of 0.09 fg mL-1 (Figure 5B). Compared to some previous works on impedimetric biosensors, the proposed impedimetric immunosensor exerted higher sensitivity for the assay of PSA (Table S1). In this work, the sensitivity of biosensors is defined as the impedance response (△Rct) caused by unit logarithmic concentration of PSA. The specificity, reproducibility, and stability of the impedimetric immunosensor were evaluated under the optimum experimental parameters. To verify specificity, samples of BSA (10 ng mL-1), AA (10 mM), DA (10 mM), UA (10 mM), IgG (10 ng mL-1), CEA (10 ng mL-1), AFP (10 ng mL-1), PSA (1 pg mL-1), and the mixing of the above samples were tested (Figure S4). It was found that the impedance responses of disturbance substances were almost consistent with the impedance response of the blank value sample. The impedance responses of the mixed sample were
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almost the same as the signal obtained from the sample containing only 1 pg mL-1 PSA,
Figure 4. EIS responses of the proposed impedimetric immunosensor after the incubation with PSA (A), immunoprobes (BSA/Ab2-AuNP-CaCO3) (B) and the gelation of alginate hydrogel (C) without (curve a) and with 1 ng mL-1 PSA (curve b)). (D) ΔRct after the incubation with PSA (column a), BSA/Ab2-AuNP-CaCO3 (column b), and the gelation of alginate hydrogel (column c). suggesting satisfactory selectivity. Four electrodes in the same batch were repeated to assay PSA (1 pg mL-1). The relative standard deviation (RSD) was 4.3%, demonstrating excellent reproducibility. The well-assembled sensing platforms were stored over a period of four weeks at 4°C. The impedance values did not significantly change with the RSD of less than 10%, suggesting satisfying stability. Clinical application of immunosensor. To verify the clinical application potential, ten human serum samples were tested by the developed immunosensing platform and a chemiluminescence immunoassay analyzer (CMIA)38 (Table 1). An acceptable relative error was observed (ranged from 5.88% to 5.00%), demonstrating promising potential in clinical application.
Figure 5. EIS responses toward different levels of PSA standards (A) and calibration curve (B). Table 1. Assay results of the developed immunosensing platformand CMIA (n=3).
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1
Proposed immunosensor (ng mL-1) 0.105
0.100
5.00
2
0.660
0.690
-4.35
3
0.220
0.210
4.76
4
11.9
11.5
3.48
5
0.530
0.550
-3.64
6
0.430
0.450
-4.44
7
0.070
0.067
4.48
8
0.0380
0.0400
-5.00
9
0.320
0.340
-5.88
10
0.480
0.460
4.35
Sample no.
(ng
Recovery error (%)
CONCLUSION In conclusion, a cascaded signal amplification strategy based on AuNP-CaCO3-triggered pH-response sodium alginate hydrogel precipitation is proposed to design an impedimetric immunosensor for PSA detection. This method offers several advantages over existing methods: (1) the cascaded signal amplification of AuNP-CaCO3 and alginate hydrogel prominently increase the impedance signal response, thus leading to ultrahigh sensitivity of 973.01 Ω (lg(ng mL-1))-1; and (2) the sensitivity amplification strategy is more economical and robust and offers a faster response time. Moreover, this method has potential to be extended to almost any target with known antibodies. With pH-response, fast response and cost-saving, hydrogel-based strategy will open up a new way to design innovative immunosensor with ultrahigh sensitivity.
ASSOCIATED CONTENT Supporting Information Details about the chemicals, apparatus and the protocols used (preparation of AuNPs, CaCO3 microspheres, AuNP-CaCO3, immunoprobes and the sensing platform). XPS survey spectra of CaCO3 microspheres and AuNP-CaCO3 (Figure S1), zeta potentials of AuNPs and CaCO3 microspheres (Figure S2), optimization concentration of SA and incubation time of PSA (Figure S3), optimization of pH value of detection solution (Figure S4); the specificity of the proposed immunoassay (Figure S5), comparison of some reported impedimetric biosensors for PSA (Table S1).
AUTHOR INFORMATION Corresponding Author *E-mail:
[email protected] Author Contributions
aThese
authors contributed equally to this work.
Notes The authors declare no competing financial interest.
ACKNOWLEDGMENT This research was financially supported by grants from the National Natural Science Foundation of China (21673143), Natural Science Foundation of Beijing Municipality (2172016), High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan (IDHT20180517) and Capacity Building for Sci-Tech Innovation-Fundamental Scientific Research Funds (025185305000/195).
REFERENCES (1) Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer Statistics 2016. CA Cancer J Clin. 2016, 66, 7-30. (2) Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F., Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. Int. J. Cancer. 2015, 136, E359-E386. (3) Majkić-Singh, N., What is a Biomarker? From its Discovery to Clinical Application. J Med Biochemistry. 2011, 30, 186-192. (4) Ren, J.; Cai, H. Li, Y.; Zhang, X.; Liu, Z.; Wang, J. S.; Hwa, Y. L.; Zhang, Y.; Yang, Y.; Li, Y.; Jiang, S. W., Tumor Markers for Early Detection of Ovarian Cancer. Expert Rev Mol Diagn. 2010, 10, 787-798. (5) Tang, Z. X.; Ma, Z. F., Multiple Functional Strategies for Amplifying Sensitivity of Amperometric Immunoassay for Tumor Markers: A Review. Biosens. Bioelectron. 2017, 98, 100-112. (6) Chikkaveeraiah, B. V.; Bhirde, A. A.; Morgan, N. Y.; Eden, H. S.; Chen, X., Electrochemical Immunosensors for Detection of Cancer Protein Biomarkers. ACS Nano 2012, 6, 6546-6561. (7) Zhang, K. Y.; Lv, S. Z.; Lin, Z. Z.; Li, M. J.; Tang, D. P., Bio-Bar-Code-Based Photoelectrochemical Immunoassay for Sensitive Detection of Prostate-Specific Antigen Using Rolling Circle Amplification and Enzymatic Biocatalytic Precipitation. Biosens. Bioelectron. 2018, 101, 159-166. (8) Ren, X.; Yan, J. R.; Wu, D.; Wei, Q.; Wan, Y. K., Nanobody-Based Apolipoprotein E Immunosensor for Pointof-Care Testing. ACS Sens. 2017, 2, 1267-1271. (9) Hua, X.; Qin, W.; Chai, Y. Q.; Yuan, Y. L.; Yuan, R., Enzyme-Assisted Cycling Amplification and DNA-Templated in-Situ Deposition of Silver Nanoparticles for the Sensitive Electrochemical Detection of Hg2+. Biosens. Bioelectron. 2016, 86, 630-635. (10) Han, E.; Ding, L.; Jin, S.; Ju, H. X., Electrochemiluminescent Biosensing of CarbohydrateFunctionalized CdS Nanocomposites for in Situ Label-Free Analysis of Cell Surface Carbohydrate. Biosens. Bioelectron. 2011, 26, 2500-2505. (11) Zhu, S.; Lin, X.; Ran, P. Y.; Mo, F. J.; Xia, Q.; Fu, Y. Z., A Glassy Carbon Electrode Modified with C-dots and Silver Nanoparticles for Enzymatic Electrochemiluminescent Detection of Glutamate Enantiomers. Microchim. Acta 2017, 184, 4679-4684. (12) Cai, G. N.; Yu, Z. Z.; Ren, R. R.; Tang, D. P., ExcitonPlasmon Interaction between AuNPs/Graphene Nanohybrids and CdS Quantum Dots/TiO2 for Photoelectrochemical
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Aptasensing of Prostate-Specific Antigen. ACS Sens. 2018, 3, 632-639. (13) Luo, Z. B.; Zhang, L. J.; Zeng, R. J.; Su, L. S.; Tang, D. P., Near-Infrared Light-Excited Core-Core-Shell UCNP@Au@CdS Upconversion Nanospheres for Ultrasensitive Photoelectrochemical Enzyme Immunoassay. Anal. Chem. 2018, 90, 9568-9575. (14) Tang, D. P.; Shu, J., Current Advances in Quantum Dots-Based Photoelectrochemical Immunoassays. Chem. Asian J. 2017, 12, 2780-2789. (15) Shan, J.; Ma, Z. F., A Review on Amperometric Immunoassays for Tumor Markers Based on the Use of Hybrid Materials Consisting of Conducting Polymers and Noble Metal Nanomaterials. Microchim. Acta 2017, 184, 969979. (16) Liu, N.; Chen, X.; Ma, Z. F., Ionic Liquid Functionalized Graphene/Au Nanocomposites and Its Application for Electrochemical Immunosensor. Biosens. Bioelectron. 2013, 48, 33-38. (17) Luo, X.; Davis, J. J., Electrical Biosensors and the Label Free Detection of Protein Disease Biomarkers. Chem Soc Rev. 2013, 42, 5944-5962. (18) Wang, L. Y.; Rong, Q. F.; Ma, Z. F., Construction of Electrochemical Immunosensing Interface for Multiple Cancer Biomarkers Detection. Electroanalysis 2016, 28, 1692-1699. (19) Bogomolova, A.; Komarova, E.; Reber, K..; Gerasimov, T.; Yavuz, O.; Bhatt, S.; Aldissi, M., Challenges of Electrochemical Impedance Spectroscopy in Protein Biosensing. Anal. Chem. 2009, 81, 3944-3949. (20) Pejcic, B.; Marco, R. D., Impedance Spectroscopy: Over 35 Years of Electrochemical Sensor Optimization. Electrochim. Acta 2006, 51, 6217-6229. (21) Jin-Young, P.; Su-Moon, P., DNA Hybridization Sensors Based on Electrochemical Impedance Spectroscopy As a Detection Tool. Sensors 2009, 9, 9513-9532. (22) Bin, X. M.; Heinz-Bernhard, K., Interaction of Metal Ions and DNA Films on Gold Surfaces: An Electrochemical Impedance Study. Analyst 2009, 134, 1309-1313. (23) Tang, Z. X.; Fu, Y. Y.; Ma, Z. F., Multiple Signal Amplification Strategies for Ultrasensitive Label-Free Electrochemical Immunoassay for Carbohydrate Antigen 24-2 Based on Redox Hydrogel. Biosens. Bioelectron. 2017, 91, 299-305. (24) Wei, C.; Lu, Z. S.; Li, C. M., Sensitive Human Interleukin 5 Impedimetric Sensor Based on PolypyrrolePyrrolepropylic Acid-Gold Nanocomposite. Anal. Chem. 2008, 80, 8485-8492. (25) Chen, Y.; Jiang, B. Y.; Xiang, Y.; Chai, Y. Q.; Yuan, R., Target Recycling Amplification for Sensitive and LabelFree Impedimetric Genosensing Based on Hairpin DNA and Graphene/Au Nanocomposites. Chem. Commun. 2011, 47, 12798-12800. (26) Adeline Huiling, L.; Alessandra, B.; Martin, P., Impedimetric Thrombin Aptasensor Based on Chemically Modified Graphenes. Nanoscale 2011, 4, 143-147. (27) Zhu, N. N.; Gao, H.; Gu, Y. F.; Xu, Q.; He, P. G.; Fang, Y. Z., PAMAM Dendrimer-Enhanced DNA Biosensors Based on Electrochemical Impedance Spectroscopy. Analyst 2009, 134, 860-866. (28) Patolsky, F.; Lichtenstein, A.; Willner, I., Electronic Transduction of DNA Sensing Processes on Surfaces:
Page 6 of 7
Amplification of DNA Detection and Analysis of Single-Base Mismatches by Tagged Liposomes. J. Am. Chem. Soc. 2001, 123, 5194-5205. (29) Zheng, Y.; Zhao, L. H; Ma, Z. F., pH Responsive Label-Assisted Click Chemistry Triggered Sensitivity Amplification for Ultrasensitive Electrochemical Detection of Carbohydrate Antigen 24-2. Biosens. Bioelectron. 2018, 115, 30-36. (30) Lai, G.; Zhang, H.; Tamanna, T.; Yu, A.; Chem, A., Ultrasensitive Immunoassay Based on Electrochemical Measurement of Enzymatically Produced Polyaniline. Anal. Chem. 2014, 86, 1789-1793. (31) Tang, Z. X.; Wang, L. Y.; Ma, Z. F., Triple Sensitivity Amplification for Ultrasensitive Electrochemical Detection of Prostate Specific Antigen. Biosens. Bioelectron. 2017, 92, 577-582. (32) Hou, L.; Tang, Y.; Xu, M. D; Gao, Z. Q.; Tang, D. P., Tyramine-Based Enzymatic Conjugate Repeats for Ultrasensitive Immunoassay Accompanying Tyramine Signal Amplification with Enzymatic Biocatalytic Precipitation. Anal. Chem. 2014, 86, 8352-8358. (33) Zheng, Y.; Ma, Z. F., Dual-Reaction Triggered Sensitivity Amplification for Ultrasensitive Peptide-Cleavage Based Electrochemical Detection of Matrix Metalloproteinase7. Biosens. Bioelectron. 2018, 108, 46-52. (34) Ogomi, D.; Serizawa, T.; Akashi, M., Controlled Release Based on the Dissolution of A Calcium Carbonate Layer Deposited on Hydrogels. J. Control. Release 2005, 103, 315-323. (35) Tan, W. H.; Takeuchi, S., Monodisperse Alginate Hydrogel Microbeads for Cell Encapsulation. Adv. Mater. 2010, 19, 2696-2701. (36) Dumitriu, R. P.; Mitchell, G. R.; Vasile, C., Multi ‐ responsive Hydrogels Based on N ‐ isopropylacrylamide and Sodium Alginate. Polym. Int. 2011, 60, 222-233. (37) Cai, W. Y.; Xu, Q.; Zhao, X. N.; Zhu, J. J.; Chen, H. Y.; Porous Gold-Nanoparticle-CaCO3 Hybrid Material: Preparation, Characterization, and Application for Horseradish Peroxidase Assembly and Direct Electrochemistry. Chem. Mater. 2006, 18, 279-284. (38) Wesseling, S.; Stephan, C.; Semjonow, A.; Lein, M.; Brux, B.; Sinha, P.; Loening, S. A.; Jung, K., Determination of Non-α1-Antichymotrypsin-Complexed Prostate-Specific Antigen As An Indirect Measurement of Free ProstateSpecific Antigen: Analytical Performance and Diagnostic Accuracy. Clin. Chem. 2003, 49, 887-894.
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