Abstract
Human epididymis protein 4 (HE4) is a vital biomarker for early diagnosis of epithelial ovarian cancer (EOC). Herein, a new label-free biosensor was developed using K3[Fe(CN)6] as the electrochemical probe for ultrasensitive immunoassay of HE4 based on PtNi nanocubes assemblies (NCAs) as efficient biosensing interfaces. The PtNi NCAs were synthesized by a simple solvothermal approach, where N-hexadecyltrimethylammonium chloride (HTAC) and 2,2′-bis(4,5-dimethylimidazole) (BDMM) behaved as co-structuring directors. Under the optimal conditions, the obtained HE4 immunosensor displayed a wide detection range from 0.001 to 100 ng mL−1 and a low detection limit (0.11 pg mL−1, S/N = 3). As a result, the current sensing platform would serve as a useful reference for detecting cancer biomarkers in the clinical assay and diagnosis.
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Yan Q, Cao L, Dong H, Tan Z, Hu Y, Liu Q, Liu H, Zhao P, Chen L, Liu Y, Li Y, Dong Y (2019) Label-free immunosensors based on a novel multi-amplification signal strategy of TiO2-NGO/Au@Pd hetero-nanostructures. Biosens Bioelectron 127:174–180
Vaughan S, Coward JI, Bast RC, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR (2011) Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 11:719–725
Chen K, Xue J, Zhou Q, Zhang Y, Zhang M, Zhang Y, Zhang H, Shen Y (2020) Coupling metal-organic framework nanosphere and nanobody for boosted photoelectrochemical immunoassay of human epididymis protein 4. Anal Chim Acta 1107:145–154
Cadkova M, Kovarova A, Dvorakova V, Metelka R, Bilkova Z, Korecka L (2018) Electrochemical quantum dots-based magneto-immunoassay for detection of HE4 protein on metal film-modified screen-printed carbon electrodes. Talanta 182:111–115
Ran Z, Yang H, Li Z, Wang K, Zhao J, Ran X, Du G, Yang L (2020) Pillar[6]arene@AuNPs functionalized N-CQDs@Co3O4 hybrid composite for ultrasensitive electrochemical detection of human epididymis protein 4. ACS Sustain Chem Eng 8:10161–10172
Luo CH, Zhao M, Tang YX, Shahabi S, Fang KN, Chen Y, Tang Y, Chen XY, Wang J, Zhou HH (2018) Increased HE4 mRNA expression correlates with high level of eIF3a mRNA and better survival in women with epithelial ovarian cancer. J Cancer 9:1088–1095
Wang C, Wu J, Zong C, Xu J, Ju HX (2012) Chemiluminescent immunoassay and its applications. Chinese J Anal Chem 40:3–10
Bonyár A (2020) Label-free nucleic acid biosensing using nanomaterial-based localized surface plasmon resonance imaging: a review. ACS Appl Nano Mater 3:8506–8521
Wang S, Yang G, Yang S (2015) Pt-frame@Ni quasi core–shell concave octahedral PtNi3 bimetallic nanocrystals for electrocatalytic methanol oxidation and hydrogen evolution. J Phys Chem C 119:27938–27945
Chikkaveeraiah BV, Bhirde AA, Morgan NY, Eden HS, Chen X (2012) Electrochemical immunosensors for detection of cancer protein biomarkers. ACS Nano 6:6546–6561
Kim WH, Lee JU, Jeon MJ, Park KH, Sim SJ (2022) Three-dimensional hierarchical plasmonic nano-architecture based label-free surface-enhanced Raman spectroscopy detection of urinary exosomal miRNA for clinical diagnosis of prostate cancer. Biosens Bioelectron 205:114116
Rizwan M, Elma S, Lim SA, Ahmed MU (2018) AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen. Biosens Bioelectron 107:211–217
Sun D, Li H, Li M, Li C, Qian L, Yang B (2019) Electrochemical immunosensors with AuPt-vertical graphene/glassy carbon electrode for alpha-fetoprotein detection based on label-free and sandwich-type strategies. Biosens Bioelectron 132:68–75
Laochai T, Yukird J, Promphet N, Qin J, Chailapakul O, Rodthongkum N (2022) Non-invasive electrochemical immunosensor for sweat cortisol based on L-cys/AuNPs/MXene modified thread electrode. Biosens Bioelectron 203:114039
Velayutham R, Palanisamy K, Manikandan R, Velumani T, Kumar Ap S, Puigdollers J, Chul Kim B (2022) Synergetic effect induced/tuned bimetallic nanoparticles (Pt-Ni) anchored graphene as a catalyst for oxygen reduction reaction and scalable SS-314L serpentine flow field proton exchange membrane fuel cells (PEMFCs). Mater Sci Eng B 282:115780
Sun X, Zhou L, Zhao W (2022) A novel electrochemical immunosensor for dibutyl phthalate based on Au@Pt/PEI-rGO and DNA hybridization chain reaction signal amplification strategy. Bioelectrochemistry 145:108104
Kim SJ, Choi SJ, Jang JS, Cho HJ, Koo WT, Tuller HL, Kim ID (2017) Exceptional high-performance of Pt-based bimetallic catalysts for exclusive detection of exhaled biomarkers. Adv Mater 29:1700737
Cao Z, Chen Q, Zhang J, Li H, Jiang Y, Shen S, Fu G, Lu BA, **e Z, Zheng L (2017) Platinum-nickel alloy excavated nano-multipods with hexagonal close-packed structure and superior activity towards hydrogen evolution reaction. Nat Commun 8:15131
Dong L, Yin L, Tian G, Wang Y, Pei H, Wu Q, Cheng W, Ding S, **a Q (2020) An enzyme-free ultrasensitive electrochemical immunosensor for calprotectin detection based on PtNi nanoparticles functionalized 2D Cu-metal organic framework nanosheets. Sens Actuators B Chem 308:127687
Wang AJ, Zhu XY, Chen Y, Xl L, Xue Yd, Feng JJ (2019) Ultrasensitive label-free electrochemical immunoassay of carbohydrate antigen 15–3 using dendritic Au@Pt nanocrystals/ferrocene-grafted-chitosan for efficient signal amplification. Sens Actuators B Chem 292:164–170
Chang F, Yu G, Shan S, Skeete Z, Wu J, Luo J, Ren Y, Petkov V, Zhong C-J (2017) Platinum–nickel nanowire catalysts with composition-tunable alloying and faceting for the oxygen reduction reaction. J Mater Chem A 5:12557–12568
Guo DJ, Cui SK, Cheng D, Zhang P, Jiang L, Zhang CC (2014) One-pot synthesis of PtNi alloy nanoflowers supported on multi-walled carbon nanotubes with superior electrocatalytic activity for the oxygen reduction. J Power Sources 255:157–162
Choi SI, **e S, Shao M, Odell JH, Lu N, Peng HC, Protsailo L, Guerrero S, Park J, **a X, Wang J, Kim MJ, **a Y (2013) Synthesis and characterization of 9 nm Pt–Ni octahedra with a record high activity of 3.3 A/mgPt for the oxygen reduction reaction. Nano Lett 13:3420–3425
Wang Y, Sha H, Ke H, Jia N (2018) An ultrasensitive electrochemiluminescence immunosensor based on platinum nickel nanocubes-L-cysteine-luminol nanocomposite. Talanta 186:322–329
Chen F, Wang D, Chen J, Ling J, Yue H, Gou L, Tang H (2020) PtNi nanocubes-catalyzed tyramine signal amplification electrochemiluminescence sensor for nonenzymatic and ultrasensitive detection of hepatocellular carcinoma cells. Sens Actuators B Chem 305:127472
Fan Y, Tan X, Ou X, Chen S, Wei S (2017) An ultrasensitive electrochemiluminescence biosensor for the detection of concanavalin A based on Au nanoparticles-thiosemicarbazide functionalized PtNi nanocubes as signal enhancer. Biosens Bioelectron 87:802–806
Yan H, Tang X, Zhu X, Zeng Y, Lu X, Yin Z, Lu Y, Yang Y, Li L (2018) Sandwich-type electrochemical immunosensor for highly sensitive determination of cardiac troponin I using carboxyl-terminated ionic liquid and helical carbon nanotube composite as platform and ferrocenecarboxylic acid as signal label. Sens Actuators B Chem 277:234–240
Gao S, Yang X, Liang S, Wang YH, Zang HY, Li YG (2019) One step synthesis of PtNi electrocatalyst for methanol oxidation. Inorg Chem 106:104–110
Ding H, Yang L, Jia H, Fan D, Zhang Y, Sun X, Wei Q, Ju H (2020) Label-free electrochemical immunosensor with palladium nanoparticles functionalized MoS2/NiCo heterostructures for sensitive procalcitonin detection. Sens Actuators B Chem 312:127980
Zhang W, Chen YP, Zhang L, Feng JJ, Li XS, Wang AJ (2022) Theophylline-regulated pyrolysis synthesis of nitrogen-doped carbon nanotubes with iron-cobalt nanoparticles for greatly boosting oxygen reduction reaction. J Colloid Interface Sci 626:653–661
Guan H, Zhao Y, Zhang J, Liu Y, Yuan S, Zhang B (2018) Uniformly dispersed PtNi alloy nanoparticles in porous N-doped carbon nanofibers with high selectivity and stability for hydrogen peroxide detection. Sens Actuators B Chem 261:354–363
Feng YG, Wang XY, Wang ZW, Wang AJ, Mei LP, Xl L, Feng JJ (2021) A label-free electrochemical immunosensor based on encapsulated signal molecules in mesoporous silica-coated gold nanorods for ultrasensitive assay of procalcitonin. Bioelectrochemistry 140:107753
Han Z, Feng JJ, Yao YQ, Wang ZG, Zhang L, Wang AJ (2021) Mn, N, P-tridoped bamboo-like carbon nanotubes decorated with ultrafine Co2P/FeCo nanoparticles as bifunctional oxygen electrocatalyst for long-term rechargeable Zn-air battery. J Colloid Interface Sci 590:330–340
Senkovskiy BV, Usachov DY, Fedorov AV, Vilkov OY, Shelyakov AV, Adamchuk VK (2012) Electronic structure of Ti–Ni alloys: an XPS and NEXAFS study. J Alloys Compd 537:190–196
Han F, Wu J, Sun P, Zhang Y, Tan F, Li W, Xu M, Min C, Wang J, Yang X (2022) Elucidating growth mechanism and shape evolution of highly branched PtNi alloy nanocrystals and their electrocatalytic performance. J Alloys Compd 927:166867
Guan H, Zhang J, Liu Y, Zhao Y, Zhang B (2019) Rapid quantitative determination of hydrogen peroxide using an electrochemical sensor based on PtNi alloy/CeO2 plates embedded in N-doped carbon nanofibers. Electrochim Acta 295:997–1005
Song D, Zheng J, Myung NV, Xu J, Zhang M (2021) Sandwich-type electrochemical immunosensor for CEA detection using magnetic hollow Ni/C@SiO2 nanomatrix and boronic acid functionalized CPS@PANI@Au probe. Talanta 225:122006
Huang XY, Wang AJ, Zhang L, Fang KM, Wu LJ, Feng JJ (2018) Melamine-assisted solvothermal synthesis of PtNi nanodentrites as highly efficient and durable electrocatalyst for hydrogen evolution reaction. J Colloid Interface Sci 531:578–584
Li X, Du Y, Xu P, Li Y, Ren X, Ma H, Wang H, Wei Q, Ju H (2020) Signal-off electrochemiluminescence immunosensor based on Mn-Eumelanin coordination nanoparticles quenching PtCo-CuFe2O4-reduced graphene oxide enhanced luminol. Sens Actuators B Chem 323:128702
Zhu X, Gao L, Tang L, Peng B, Huang H, Wang J, Yu J, Ouyang X, Tan J (2019) Ultrathin PtNi nanozyme based self-powered photoelectrochemical aptasensor for ultrasensitive chloramphenicol detection. Biosens Bioelectron 146:111756
Huang XY, Zhu XY, Zhang XF, Zhang L, Feng JJ, Wang AJ (2018) Simple solvothermal synthesis of uniform Pt66Ni34 nanoflowers as advanced electrocatalyst to significantly boost the catalytic activity and durability of hydrogen evolution reaction. Electrochim Acta 271:397–405
Chen XL, Zhang H, Huang XY, Feng JJ, Han DM, Zhang L, Chen JR, Wang AJ (2018) Facile solvothermal fabrication of Pt47Ni53 nanopolyhedrons for greatly boosting electrocatalytic performances for oxygen reduction and hydrogen evolution. J Colloid Interface Sci 525:260–268
Li M, Zhe T, Li F, Li R, Bai F, Jia P, Bu T, Xu Z, Wang L (2022) Hybrid structures of cobalt-molybdenum bimetallic oxide embedded in flower-like molybdenum disulfide for sensitive detection of the antibiotic drug nitrofurantoin. J Hazard Mater 435:129059
Li L, Liu X, Su B, Zhang H, Li R, Liu Z, Chen Q, Huang T, Cao H (2022) An innovative electrochemical immunosensor based on nanobody heptamer and AuNPs@ZIF-8 nanocomposites as support for the detection of alpha fetoprotein in serum. Microchem J 179:107463
Medetalibeyoglu H, Kotan G, Atar N, Yola ML (2020) A novel and ultrasensitive sandwich-type electrochemical immunosensor based on delaminated MXene@AuNPs as signal amplification for prostate specific antigen (PSA) detection and immunosensor validation. Talanta 220:121403
Medetalibeyoglu H, Beytur M, Akyıldırım O, Atar N, Yola ML (2020) Validated electrochemical immunosensor for ultra-sensitive procalcitonin detection: carbon electrode modified with gold nanoparticles functionalized sulfur doped MXene as sensor platform and carboxylated graphitic carbon nitride as signal amplification. Sens Actuators B Chem 319:128195
Huang X, Miao J, Fang J, Xu X, Wei Q, Cao W (2022) Ratiometric electrochemical immunosensor based on L-cysteine grafted ferrocene for detection of neuron specific enolase. Talanta 239:123075
Ranjan P, Abubakar Sadique M, Yadav S, Khan R (2022) An electrochemical immunosensor based on gold-graphene oxide nanocomposites with ionic liquid for detecting the breast cancer CD44 biomarker. ACS Appl Mater Interfaces 14:20802–20812
Lu L, Liu B, Zhao Z, Ma C, Luo P, Liu C, **e G (2012) Ultrasensitive electrochemical immunosensor for HE4 based on rolling circle amplification. Biosens Bioelectron 33:216–221
Lan Q, Ren C, Lambert A, Zhang G, Li J, Cheng Q, Hu X, Yang Z (2020) Platinum nanoparticle-decorated graphene oxide@polystyrene nanospheres for label-free electrochemical immunosensing of tumor markers. ACS Sustain Chem Eng 8:4392–4399
Liu D, Wang A, Zhou J, Wang X, Liu H, Ding P, Zhang Y, Zhu X, Zhou Y, Zhang G (2022) A label-free electrochemical immunosensor based on AuNPs/GO-PEI-Ag-Nf for olaquindox detection in feedstuffs. Microchem J 177:107287
Funding
This research was supported by Zhejiang Public Welfare Technology Application Research Project (LGG19B050001) and National Students’ Innovation and Entrepreneurship Training Program of Zhejiang Normal University (202210345026).
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Research highlights.
•PtNi nanocube assemblies were synthesized by a solvothermal method.
•BDMM and HTAC were acted as co-structuring directors.
•PtNi NCAs showed highly catalytic activity.
•The hierarchical superstructure provided abundant binding sites.
•The immunosensor was applied for ultrasensitive detection of HE4.
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Chen, DN., Jiang, LY., Zhang, JX. et al. Electrochemical label-free immunoassay of HE4 using 3D PtNi nanocubes assemblies as biosensing interfaces. Microchim Acta 189, 455 (2022). https://doi.org/10.1007/s00604-022-05553-6
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DOI: https://doi.org/10.1007/s00604-022-05553-6