
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)12941-6
10.1016/j.heliyon.2024.e36910
e36910
Research Article
Sensitive sandwich-type electrochemical immunosensing of p53 protein based on Ti3C2Tx MXene nanoribbons and ferrocene/gold
Lin Song
Wen Lixin
Zhao Hong
Huang Donghua
Yang Zuwei
Zou Qinge
Jiang Ling JiangLingDoc123456@yeah.net
⁎
Sanming Integrated Medicine Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Sanming, 365000, PR China
⁎ Corresponding author. JiangLingDoc123456@yeah.net
24 8 2024
15 9 2024
24 8 2024
10 17 e369102 7 2024
23 8 2024
23 8 2024
© 2024 Published by Elsevier Ltd.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Since the p53 protein is an important promising biomarker of lung tumor and colorectal tumor, it is very essential to design a highly effective mean to monitor the degree of p53 for the early clinical analysis/therapy of the related tumors. In this work, a sandwich-type electrochemical immunosensing (SES) platform is proposed for the first time to detect p53 via synthesizing Ti3C2Tx MXene nanoribbons (Ti3C2Tx Nb) and ferrocene/gold nanoparticles (Fc/Au) respectively as the sensing substrate and signal-amplifier. The superior electrical property and large surface area of Ti3C2Tx Nb are beneficial to assemble the initial p53-antibodies (Ab1), while the synthesized Fc/Au is devoted to assemble the secondary p53 antibodies (Ab2) and gives a magnified signal. By adopting the Fc molecules as the probes, the experiments reveal the response current of Fc resulted from the SES structure increases along with the p53 increase from 1.0 to 200.0 pg mL−1. A considerable low detection limit (1.0 pg mL−1) is achieved after optimizing several key conditions, it is thus confirmed the as-proposed SES mean exhibits significant application in the detection of p53 protein and other targets.

Keywords

p53 protein
Tumor
Electrochemical immunosensor
MXene
Ti3C2Tx
Ferrocene
==== Body
pmc1 Introduction

The malignant tumors are a kind of diseases with extremely high mortality, generally the early monitor towards the related biomarkers has important significance to offer vital information for the timely and efficient therapy [[1], [2], [3]]. As a reported tumor inhibitor, the p53 protein plays key roles to prevent the gene mutations and maintain the genome integrity [4,5], and generally the physiological degree of p53 in normal human is considerable low (<10 pg mL−1) [[6], [7], [8]]. In such case, the accurate quantification of p53 is extremely useful for the early clinical analysis and therapy of the malignant tumors. Traditional means for the detection of p53 mainly include enzyme-linked immunosorbent assay, chromatography-mass spectrometry and western blotting, immunohistochemistry [[9], [10], [11], [12]], but which were restricted resulted from their cost, operation and analysis times. Sequentially significant efforts have been motivated to design low-cost, simple and rapid methodologies. Recently, the electrochemical immunoassays received some attentions since they exhibit some unique superiorities such as simple operation, inexpensive and time-saving [6,13]. In addition, it has been reported, attributed to the advantages in the feature of signal-amplification, the sandwich-type electrochemical immunosensing (SES) means have aroused considerable attentions to detect various analytes in the past years [[14], [15], [16]]. Therefore, it is very promising to design a sensitive and effective SES platform for p53 detection.

As one of the two key factors in constructing SES platform, designing or selecting appropriate nanomaterial as the substrate of sensor is very important [[17], [18], [19]]. As a type of emerging-representative 2D materials with high electrical conductivity and large surface area recently, the compounds of transition metal carbides/carbonitrides (denoted as MXenes) have been utilized widely in many research fields such as energy storage and conversion, sensors and biomedicine [[20], [21], [22], [23], [24]]. For instance, by growing CoFe-PBA on ferrocene functionalized Ti3C2Tx MXene, Wang et al. [25] developed a sensitive electrochemical sensor of xanthine. In this sensor, the introduction of Ti3C2Tx MXene is dedicated to accommodate ferrocene and give higher conductivity. In general, MXenes are achieved by exfoliating the “A” element in the MAX phase, where “M” is the transition metal and “A” is the element in the IIIA/IVA group, while “X” refers to C or/and N [[26], [27], [28]]. In addition, the MXenes-based nanomaterials can offer good biocompatibility and be easy to functionalizing. These superiorities of MXenes devoted themselves to be a desirable candidate as the substrate to construct a SES platform for p53. In addition, there is no doubt the construction of signal amplifier is also considerable important for the sensing performances of SES platform. Nanogold (Au), as an universally accessible precious metal exhibiting superior conductivity and biocompatibility, is very easy to be functionalized [29,30]. Meanwhile, the ferrocene (Fc) molecule is a common and acceptable signal-probe since it can exhibit high electroactivity [31,32].

Inspired by the above insights, in this work, by synthesizing Ti3C2Tx MXene (a typical MXene material) nanoribbons (Ti3C2Tx Nb) as the substrate to assemble Ab1 of p53 (Ab1-Ti3C2Tx Nb), and functionalizing Fc coupled with Ab2 of p53 to the Au surface as the specific signal-amplifier (Ab2-Au-Fc), we proposed a novel SES mean to detect the degree of p53 (Scheme 1). In the existence of p53 protein, a SES structure consisted of Ab2-Au-Fc/p53/Ab1-Ti3C2Tx Nb would be formed and the relative response signal of the Fc probe is proportional and sensitive to the p53 level, hence achieving a highly sensitive and effective monitoring for the p53 protein. This works provided a reliable and sensitive mean for p53 detection, it's expected which can offer significant real application.Scheme 1 Illustrations for constructing the as-designed SES sensing platform of p53.

Scheme 1

2 Experimental section

2.1 Reagents and equipment

The Ti3AlC2 raw material was purchased from Forsman Technology Company (China). HF (≥40.0 %), KOH, HAuCl4·3H2O, NaBH₄, Fc, NaOH, 4-aminobenzoic acid (PABA), 4-aminobenzoic acid (ABZ) 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), NaNO2 and N-hydroxysuccinimide (NHS) were obtained from Aladdin Biotechnology Co., Ltd (China). Bovine serum albumin (BSA), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), IgG antigen and anti-p53 antibodies were offered by Abcam Co., Ltd. The phosphate buffer solution (PBS) were prepared with KH2PO4 (0.1 M), K2HPO4 (0.1 M) and KCl (0.1 M). Electrochemical CHI 660E Workstation was utilized for all the electrochemical measurements.

2.2 Synthesization of Ti3C2Tx Nb

The Ti3C2Tx MXene nanosheets (Ti3C2Tx NS) were firstly synthesized via etching the Al layer in the Ti3AlC2 powder according to the reported method [33]. Briefly, under stirring at ∼35 °C, 05 g raw material of Ti3AlC2 was slowly added into a HF solution of 10.0 mL. After holding for 20 h, the Ti3C2Tx NS can be obtained via washing and drying.

Next, Ti3C2Tx Nb were synthesized via tearing the above obtained Ti3C2Tx NS as follows: the 0.1 g Ti3C2Tx NS were added into a 3.0 M KOH solution (25.0 mL) under continuous stirring under for 2 days at room temperature, thus the designed Ti3C2Tx Nb can be collected after washing and drying. For further functionalizing Ti3C2Tx Nb with carboxyl dedicated to immobilize Ab1, 0.08 g ABZ and 0.07g NaOH were firstly added to 25.0 mL watery. Next, 3.0 mL HCl solution was added quickly to the solution and maintained for ∼30 min under stirring. In final, the formed mixture were centrifuged and dried to achieve Ti3C2Tx Nb product.

2.3 Synthesization for Au and immobilizing Ab2 coupled with Fc

For preparing Ab2-Au-Fc, the tiny Au nanoparticles were firstly synthesized: 0.1 mL sodium citrate solution (0.2 M) was added dropwise to a 3.0 mL HAuCl4 solution and heated at about 60 °C for 2 h, thus obtaining the Au nanoparticles. Then, 20.0 μL Ab2 solution of 60.0 μg mL−1 and 20.0 μL Fc solution of 0.4 mM were added into the obtained Au solution (1.0 mL), and this mixture was incubated for 1 h at room temperature to obtain Ab2-Au-Fc signaling amplifier.

2.4 Fabrication of the SES structure

Firstly, a definite of Ti3C2Tx Nb suspension of (1.0 mg mL−1) was dropped to the surface of SPCE electrode and a 1:1 mixture solution containing EDC/NHS (0.1 M/0.2 M) were used to activate carboxyls. In sequentially, 8.0 μL solution of Ab1 (10.0 μg mL−1) was coated and immobilized to the activated surface of Ti3C2Tx Nb/SPCE as Ab1/Ti3C2Tx Nb/SPCE. Then, 3.0 μL BSA (100.0 mg mL−1) was utilized to restrict the non-specific immobilization. For sensing p53, the fabricated BSA/Ab1/Ti3C2Tx Nb/SPCE was interacted with p53 at various degrees, and a SES structure would be formed by combining p53/BSA/Ab1/Ti3C2Tx Nb/SPCE with Ab2-Au-Fc, which was then monitored via differential pulse voltammetry (DPV).

3 Results and discussion

3.1 Characterization of the synthesized Ti3C2Tx Nb and Au

Fig. 1 displayed the SEM and TEM images of the as-synthesized Ti3C2Tx Nb and related materials. It was noted the original Ti3AlC2 materials show smooth surface with aligned densely layered-structures (Fig. 1A). After HF etching, the synthesized Ti3C2Tx NS (Fig. 1B and E) layered-structures were very evident and displayed packed loosely accordion-type morphology compared to the original Ti3AlC2 sample. Interestingly, via tearing Ti3C2Tx NS, Ti3C2Tx Nb (Fig. 1C and F) could be well evidenced with minor diameter (∼28 nm). As is evident, the Ti3C2Tx Nb with carboxyl groups have well-defined structures that were almost the same as displayed for Ti3C2Tx Nb (Fig. 1D and G). This indicates that the carboxyl functionalization does not change the microstructure and morphology of the materials, thus which were further characterized by Fourier transform infrared (FT-IR) spectrum (Fig. S1). Compared with the pure Ti3C2Tx Nb, the carboxylated Ti3C2Tx Nb gave a strong and typical peak of the carboxyl at ∼1637 cm−1.Fig. 1 The SEM images of (A) Ti3AlC2, (B) Ti3C2Tx NS, (C) Ti3C2Tx Nb and (D) carboxylated Ti3C2Tx Nb; the TEM images of (E) Ti3C2Tx NS, (F) Ti3C2Tx Nb, (G) carboxylated Ti3C2Tx Nb and (H) Au particles; (I) the particle size distribution of Au.

Fig. 1

Next, the used Au particles were characterized by TEM. As shown in Fig. 1H and I, the as-synthesized Au nanoparticles exhibited very uniform size, and the diameter is tiny to about 4.5 nm through statistical investigation, such small size is beneficial to immobilize Ab2 and Fc molecules.

3.2 Electrochemical evaluation of the SES platform

The impedance spectroscopy (EIS) was firstly utilized to characterize the processes in fabricating SES structure, which was conducted in a [Fe(CN)6]3-/4- solution (5.0 mM) (Fig. 2). In general, the common biomolecules exhibit poor conductive and pose inhibiting effect to the electron channel, thus increasing the impedance values. As displayed in Fig. 2, the charge-transfer resistance (RCT) of Ti3C2Tx Nb/SPCE was smaller compared to the bare SPCE resulted from the superior conductivity of the Ti3C2Tx MXene. When Ab1, p53 and Ab2-Au-Fc were assembled in successive to the surface of Ti3C2Tx Nb/SPCE, the RCT values at the fabricated BSA/Ab1/Ti3C2Tx Nb/SPCE and Ab2-Au-Fc/p53/BSA/Ab1/Ti3C2Tx Nb/SPCE showed an increase in turn. These indicated that the fabricated SES layer was achieved successfully.Fig. 2 The EIS plots of SPCE (a), Ti3C2Tx Nb/SPCE (b), BSA/Ab1/Ti3C2Tx Nb/SPCE (c), and Ab2-Au-Fc/p53/BSA/Ab1/Ti3C2Tx Nb/SPCE (d).

Fig. 2

The feasibility about the as-proposed SES sensor was characterized by DPV technology as it can offer superior sensitivity. Fig. 3 displayed the DPV curves of BSA/Ab1/Ti3C2Tx Nb/SPCE and p53/BSA/Ab1/Ti3C2Tx Nb/SPCE after the incubation with Ab2-Au-Fc. The achieved results revealed there is no DPV signal presented without p53 (300.0 pg mL−1), that is BSA/Ab1/Ti3C2Tx Nb/SPCE. Nevertheless, a strong DPV current of Fc could be noted at p53/BSA/Ab1/Ti3C2Tx Nb/SPCE after incubating with Ab2-Au-Fc to generate a SES structure (Ab2-Au-Fc/p53/BSA/Ab1/Ti3C2Tx Nb). The related reason was that the specific antibody-antigen recognition between p53-antibodies and p53 could induce the Ab2-Au-Fc capture to p53/BSA/Ab1/Ti3C2Tx Nb. These suggested that the as-proposed SES proposal for p53 was feasible.Fig. 3 DPV response of (a) BSA/Ab1/Ti3C2Tx Nb/SPCE and (b) p53/BSA/Ab1/Ti3C2Tx Nb/SPCE after their incubation in Ab2-Au-Fc solution.

Fig. 3

In order to achieve the sensitive determination for p53, several key experiments need to be optimized. Firstly, there is no doubt that the acid-base property of sensing system is very important. Fig. 4A gave the effect of the different pH values of PBS to the DPV signal of Ab2-Au-Fc/p53/BSA/Ab1/Ti3C2Tx Nb/SPCE, it's noted the signals increased along with the pH value increase and the maximum was at 7.0. As for the influence from the dropped amount of Ti3C2Tx Nb to the surface of electrode (Fig. 4B), the peak current increases with the amount increase. Whereas when exceeding 10.0 μL, the DPV signal showed little change, so 10.0 μL Ti3C2Tx Nb dispersion was the amount that coated to the SPCE surface. Meanwhile, Fig. 4C exhibited the effect of Ab1 concentration, the results revealed 10.0 μg mL−1 is enough, thus this concentration was used for the experiments. Fig. 4D displayed the effect about the interaction time between p53 and its antibodies. It can be found the desirable time between p53 and Ab1 was 12 min, while that was 21 min between p53 and Ab2.Fig. 4 Influences of the (A) pH value of PBS; (B) amount of Ti3C2Tx Nb; (C) Ab1 concentration; (D) interaction time of p53 with BSA/Ab1/Ti3C2Tx Nb (a) and p53/BSA/Ab1/Ti3C2Tx Nb with Ab2-Au-Fc (b).

Fig. 4

Finally, the detection capabilities of the as-fabricated SES mean for p53 were evaluated. As displayed in Fig. 5, the DPV signals gradually increased with the p53 level increased ranging from 5.0 to 200.0 pg mL−1 (Fig. 5A), and the linear equation can be written down as ΔI (μA) = 0.314 + 0.034C (pg mL−1) (Fig. 5B). Based on S/N = 3, the limit of detection (LOD) was 1.0 pg mL−1. In order to further understand the as-designed SES mean, the comparisons between this work and other sensors for p53 detection were also performed. From Table 1, it was assured the detection performances of the SES mean were comparable to the previous immunosensors with lower LOD value. In addition, it should be pointed out that the p53 protein can be divided into wild type and mutant type. The wild-type p53 protein is extremely unstable, with a half-life of only a few minutes, while the mutant p53 proteins are more stable, have a longer half-life. Therefore, the p53 protein detected by this sensor is mutant p53 protein.Fig. 5 (A) The DPV responses of p53 with various concentrations (5.0, 15.0, 30.0, 50.0, 80.0, 120.0, 150.0 and 200.0 pg mL−1) based on the developed SES sensor; (B) the calibration plot of p53 detection.

Fig. 5

Table 1 Comparisons of various immunosensing platform with the present method for p53 protein.

Table 1Electrode	Method	Linearity (pg mL−1)	LOD (pg mL−1)	Ref.	
AuNPs	LSV	87000.0–2100000.0	2100.0	[5]	
PEDOT:PSS/AuNPs	DPV	1000.0–120000.0	90.0	[4]	
Au/NiPc	DPV	0.1–500.0	–	[34]	
SAM	LSV	4.3–4370.0	4.3	[35]	
PEG	CV	10.0–10000.0	10.0	[36]	
PTAA/Au/PMB	SWV	1000.0–100000.0	650.0	[37]	
Ti3C2Tx Nb	DPV	5.0–200.0	1.0	This work	
* PEDOT:PSS (poly (3, 4-ethylenedioxythiophene):polystyrenesulfonate); NiPc: nickel phthalocyanine; SAM: Self-assembled monolayer; PEG: pencil graphite electrode; PTAA: poly(thiophene acetic acid); PMB: poly(thiophene acetic acid); LSV: linear sweep voltammograms; CV: cyclic voltammetry; SWV: square wave voltammetry.

3.3 Reliability and real samples analysis

Firstly, the proposed SES mean's selectivity was confirmed after the addition of various interfering substances to the detection system. As displayed in Fig. 6A, it was observed there was little change observed for the signal of Fc after the addition of BSA, AFP, CEA and IgG (10.0 times of p53 level). The stability of the SES mean was also evaluated (Fig. 6B), and the signal responses of SES structure remained almost unchanged via storing the sensing platform for 40 days. Next, the reproducibility was investigated by measuring the signals of Fc at 10-independently-fabricated SES structures. As displayed in Fig. 6C, the RSD value between them was 3.68 %. These indicated the as-fabricated SES mean exhibited desirable reliability.Fig. 6 (A) Selectivity, (B) reproducibility and (C) stability for p53 detection based on the constructed SES sensor.

Fig. 6

Finally, the standard addition technique was adopted to validate the as-proposed SES mean in real application. Various degrees of p53 protein were added in turn to the real human serum samples, and the response signals of the SES sensor towards these samples were recorded. Then, the recoveries were calculated to reveal the capability in the real applications. From Table S1, the obtained recoveries were ranging from 94.7 % to 97.0 %, confirming the as-proposed SES sensing platform exhibited satisfactory real ability for p53 detection.

4 Conclusion

In summary, a novel SES sensing platform for p53 was designed in this work by preparing Ti3C2Tx Nb as sensing platform and Au particles to immobilize Fc and Ab2 as signal amplifier. Owing to the excellent properties (e.g., high electrical conductivity and large surface area) of Ti3C2Tx Nb which are beneficial to immobilize Ab1 and improve conductivity, and the signal amplification function of Ab2-Au-Fc, the as-designed SES sensing platform displayed superior analytical performances under the optimized conditions: wider linearity (5.0–200.0 pg mL−1) coupled with lower LOD (1.0 pg mL−1). Additionally, the as-proposed SES mean displayed good stability, selectivity and reproducibility as well as real applications, suggesting this SES mean for p53 showed important potential application. Through adopting other appropriate antibodies instead of p53 antibodies, we expected the as-designed SES sensing model has a broad application in the detection for other analytes.

Data availability statement

Data will be made available on request.

CRediT authorship contribution statement

Song Lin: Writing – original draft, Visualization, Validation, Methodology, Investigation, Data curation. Lixin Wen: Writing – review & editing, Validation, Supervision, Software, Resources. Hong Zhao: Writing – review & editing, Validation, Resources, Data curation. Donghua Huang: Validation, Resources, Methodology. Zuwei Yang: Validation, Investigation. Qinge Zou: Data curation, Conceptualization. Ling Jiang: Writing – review & editing, Validation, Supervision, Project administration, Methodology, Investigation, 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.

Appendix A Supplementary data

The following is/are the supplementary data to this article:Multimedia component 1

Multimedia component 1

Acknowledgment

This work was financially supported by Fujian Province Natural Science Foundation (No.: 2023J011759 ).

Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e36910.
==== Refs
References

1 Aydın E.B. Aydın M. Sezgintürk M.K. Electrochemical immunosensor based on chitosan/conductive carbon black composite modified disposable ITO electrode: an analytical platform for p53 detection Biosens. Bioelectron. 121 2018 80 89 30199712
2 Cruz-Pacheco A.F. Quinchia J. Orozco J. Cerium oxide–doped PEDOT nanocomposite for label-free electrochemical immunosensing of anti-p53 autoantibodies Microchim. Acta 189 2022 228
3 Zhao J. Blayney A. Liu X. Gandy L. Jin W. Yan L. Ha J.-H. Canning A.J. Connelly M. Yang C. EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction Nat. Commun. 12 2021 986 33579943
4 Kang J. Li Z. Wang G. A novel signal amplification strategy electrochemical immunosensor for ultra-sensitive determination of p53 protein Bioelectrochemistry 137 2021 107647
5 Amor-Gutiérrez O. Costa-Rama E. Arce-Varas N. Martínez-Rodríguez C. Novelli A. Fernández-Sánchez M.T. Costa-García A. Competitive electrochemical immunosensor for the detection of unfolded p53 protein in blood as biomarker for Alzheimer's disease Anal. Chim. Acta 1093 2020 28 34 31735212
6 Cruz-Pacheco A.F. Quinchia J. Orozco J. Nanostructured poly (thiophene acetic acid)/Au/poly (methylene blue) interface for electrochemical immunosensing of p53 protein Microchim. Acta 190 2023 136
7 Yu C.-X. Xiong F. Liu L.-L. Electrochemical biosensors for the detection of p53 proteins and anti-p53 autoantibody Int. J. Electrochem. Sci. 15 2020 6695 6705
8 Silva J.L. Cino E.A. Soares I.N. Ferreira V.F. AP de Oliveira G. Targeting the prion-like aggregation of mutant p53 to combat cancer Accounts Chem. Res. 51 2018 181 190
9 Chen L. Liang J. A proximity ligation assay (PLA) based sensing platform for the ultrasensitive detection of P53 protein-specific SUMOylation Process Biochem. 112 2022 1 5
10 Liang L. Jin L. Ran Y. Sun L.-P. Guan B.-O. Fiber light-coupled optofluidic waveguide (FLOW) immunosensor for highly sensitive detection of p53 protein Anal. Chem. 90 2018 10851 10857 30141911
11 Assah E. Goh W. Zheng X.T. Lim T.X. Li J. Lane D. Ghadessy F. Tan Y.N. Rapid colorimetric detection of p53 protein function using DNA-gold nanoconjugates with applications for drug discovery and cancer diagnostics Colloids Surf. B Biointerfaces 169 2018 214 221 29778960
12 Xia Y. Wu L. Hu Y. He Y. Cao Z. Zhu X. Yi X. Wang J. Sensitive surface plasmon resonance detection of methyltransferase activity and screening of its inhibitors amplified by p53 protein bound to methylation-specific ds-DNA consensus sites Biosens. Bioelectron. 126 2019 269 274 30445302
13 Ostatná V. Černocká H. Galicová T. Hasoň S. Electrochemical analysis of proteins important in cancer. Behavior of anterior gradient receptors, p53 protein and their complexes at charged surfaces Curr. Opin. Electrochem. 2023 101269
14 Lin X. Liu P.P. Yan J. Luan D. Sun T. Bian X. Dual synthetic receptor-based sandwich electrochemical sensor for highly selective and ultrasensitive detection of pathogenic bacteria at the single-cell level Anal. Chem. 95 2023 5561 5567 36961921
15 Kim G. Cho H. Nandhakumar P. Park J.K. Kim K.-S. Yang H. Wash-free, sandwich-type protein detection using direct electron transfer and catalytic signal amplification of multiple redox labels Anal. Chem. 94 2022 2163 2171 35043633
16 Zhang H. Lin Z. Li Y. Lin Z. Yang S. Qiu B. Yu M. Highly sensitive detection of thyroglobulin based on sandwich-type electrochemical immunoassay Anal. Sci. 39 2023 969 975 36877338
17 Chen J. Tong P. Huang L. Yu Z. Tang D. Ti3C2 MXene nanosheet-based capacitance immunoassay with tyramine-enzyme repeats to detect prostate-specific antigen on interdigitated micro-comb electrode Electrochim. Acta 319 2019 375 381
18 Wang Z. Zhao H. Chen K. Cao S. Lan M. Sandwich-type electrochemical aptasensor based on HMCS@ PDA@ AuNPs and PtCu DNs/MUN-CuO-TiO2 for ultrasensitive detection of cardiac troponin I Sensor. Actuator. B Chem. 393 2023 134275
19 Lin S. Wang J. Wang X. Xia S. Wu L. Simple and sensitive sandwich-like electrochemical immunosensing strategy for D-dimer based on cyclodextrin-carbon nanotube and nanogold-ferrocene Heliyon 10 2024 e28793
20 Mohammadniaei M. Koyappayil A. Sun Y. Min J. Lee M.-H. Gold nanoparticle/MXene for multiple and sensitive detection of oncomiRs based on synergetic signal amplification Biosens. Bioelectron. 159 2020 112208
21 Cao F. Zhang Y. Wang H. Khan K. Tareen A.K. Qian W. Zhang H. Ågren H. Recent advances in oxidation stable chemistry of 2D MXenes Adv. Mater. 34 2022 2107554
22 Kalambate P.K. Dhanjai Sinha A. Li Y. Shen Y. Huang Y. An electrochemical sensor for ifosfamide, acetaminophen, domperidone, and sumatriptan based on self-assembled MXene/MWCNT/chitosan nanocomposite thin film Microchim. Acta 187 2020 402
23 Liu F. Han L. Yang Y. Xue Z. Lu X. Liu X. Designable synthesis of a novel layered MXene loaded gold nanocluster composite for efficient electrochemical sensing of homocysteine in biological samples Chem. Eng. J. 461 2023 141928
24 Liu T. Zhou R. Wu K. Zhu G. Colorimetric method transforms into highly sensitive homogeneous voltammetric sensing strategy for mercury ion based on mercury-stimulated Ti3C2Tx MXene nanoribbons@ gold nanozyme activity Anal. Chim. Acta 1250 2023 340975
25 Chu M. Wang Y. Xin J. Zhang L. Liu Y. Yang G. Ma H. Wang Y. Pang H. Wang X. In situ growth of CoFe-prussian blue analog nanospheres on ferrocene-functionalized ultrathin layered Ti3C2Tx MXene frameworks for efficient detection of xanthine Chem. Eng. J. 469 2023 143866
26 Tu X. Gao F. Ma X. Zou J. Yu Y. Li M. Qu F. Huang X. Lu L. Mxene/carbon nanohorn/β-cyclodextrin-Metal-organic frameworks as high-performance electrochemical sensing platform for sensitive detection of carbendazim pesticide J. Hazard Mater. 396 2020 122776
27 Zhang H. Wang Z. Wang F. Zhang Y. Wang H. Liu Y. In situ formation of gold nanoparticles decorated Ti3C2 MXenes nanoprobe for highly sensitive electrogenerated chemiluminescence detection of exosomes and their surface proteins Anal. Chem. 92 2020 5546 5553 32186362
28 Wang D. Zhou C. Filatov A.S. Cho W. Lagunas F. Wang M. Vaikuntanathan S. Liu C. Klie R.F. Talapin D.V. Direct synthesis and chemical vapor deposition of 2D carbide and nitride MXenes Science 379 2023 1242 1247 36952427
29 Han S. Liu W. Zheng M. Wang R. Label-free and ultrasensitive electrochemical DNA biosensor based on urchinlike carbon nanotube-gold nanoparticle nanoclusters Anal. Chem. 92 2020 4780 4787 32054266
30 Yu T. Fu Y. Yi J. Wang Z. Zhang J. Xianyu Y. Sulfhydryl-mediated etching suppression of gold nanostars for rapid and sensitive detection of bacterial pathogens Chem. Eng. J. 481 2024 148650
31 Wu B. Yeasmin S. Liu Y. Cheng L.-J. Sensitive and selective electrochemical sensor for serotonin detection based on ferrocene-gold nanoparticles decorated multiwall carbon nanotubes Sensor. Actuator. B Chem. 354 2022 131216
32 Lee W. Li L. Camarasa-Gómez M. Hernangómez-Pérez D. Roy X. Evers F. Inkpen M.S. Venkataraman L. Photooxidation driven formation of Fe-Au linked ferrocene-based single-molecule junctions Nat. Commun. 15 2024 1439 38365892
33 Wu H. Almalki M. Xu X. Lei Y. Ming F. Mallick A. Roddatis V. Lopatin S. Shekhah O. Eddaoudi M. Alshareef H.N. MXene derived metal-organic frameworks J. Am. Chem. Soc. 141 2019 20037 20042 31825615
34 Chen Y.-J. Peng Y.-R. Lin H.-Y. Hsueh T.-Y. Lai C.-S. Hua M.-Y. Preparation and characterization of Au/NiPc/Anti-p53/BSA electrode for application as a p53 antigen sensor Chemosensors 9 2021 17
35 Hou L. Huang Y. Hou W. Yan Y. Liu J. Xia N. Modification-free amperometric biosensor for the detection of wild-type p53 protein based on the in situ formation of silver nanoparticle networks for signal amplification Int. J. Biol. Macromol. 158 2020 580 586 32380113
36 Nohwal B. Chaudhary R. Pundir C. Amperometric detection of tumor suppressor protein p53 via pencil graphite electrode for fast cancer diagnosis Anal. Biochem. 639 2022 114528
37 Cruz-Pacheco A.F. Quinchia J. Orozco J. Nanostructured poly(thiophene acetic acid)/Au/poly(methylene blue) interface for electrochemical immunosensing of p53 protein Microchim. Acta 190 2023 136
