Abstract
The detection signal of carbohydrate antigen 125 (CA125) can be quantitatively amplified via the dual metal–organic framework (MOF) sandwich strategy. We propose a versatile method for synthesizing uniform MXene and MIL-101(Fe)-NH2 composites that combine the advantages of both materials to build a base layer with superb performance. MXene exhibits excellent electrical conductivity and high surface area. The mesoporous MIL-101(Fe)-NH2 not only increases the loading capacity of the primary antibody but also possesses the catalytic activity of the metal center (Fe). UiO66 loaded with methylene blue (MB) was fabricated as an electrochemical immunosensor signal tag to enable the detection of CA125. The mixture of MXene and MIL-101(Fe)-NH2 prepared as the substrate was fixed by chitosan rich in amino groups. As the signal amplification sector, UiO66@MB enhanced secondary antibody loading capacity and generated a redox signal enabling the detection of antigenic substances. The proposed electrochemical immunosensor demonstrated high sensitivity with a low limit of detection (LOD) of 0.006 U/mL. Therefore, the dual MOF sandwich-based immunosensor provides a novel method for the early diagnosis of CA125.
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Sjövall K, Nilsson B, Einhorn N (2002) The significance of serum CA 125 elevation in malignant and nonmalignant diseases. Gynecol Oncol 85(1):175–178. https://doi.org/10.1006/gyno.2002.6603
Al-Ogaidi I, Aguilar ZP, Suri S, Gou H, Wu N (2013) Dual detection of cancer biomarker CA125 using absorbance and electrochemical methods. Analyst 138:5647–5653. https://doi.org/10.1039/c3an00668a
Luo S, Ou Y, Zheng T, Jiang H, Wu Y, Zhao J, Zhang Z (2021) Optimal strategy for colorectal cancer patients’ diagnosis based on circulating tumor cells and circulating tumor endothelial cells by subtraction enrichment and immunostaining-fluorescence in situ hybridization combining with CEA and CA19-9. J Oncol 2021:1–9. https://doi.org/10.1155/2021/1517488
Wang M, Hu M, Li Z, He L, Song Y, Jia Q, Zhang Z, Du M (2019) Construction of Tb-MOF-on-Fe-MOF conjugate as a novel platform for ultrasensitive detection of carbohydrate antigen 125 and living cancer cells. Biosens Bioelectron 142:111536. https://doi.org/10.1016/j.bios.2019.111536
Rebelo TSCR, Ribeiro JA, Sales MGF, Pereira CM (2021) Electrochemical immunosensor for detection of CA 15–3 biomarker in point-of-care. Sens Bio-Sens Res 33:100446. https://doi.org/10.1016/j.sbsr.2021.100445
Gao H, Zhang Z, Zhang Y, Yu H, Rong S, Meng L, Song S, Mei Y, Pan H, Chang D (2021) Electrochemiluminescence immunosensor for cancer antigen 125 detection based on novel resonance energy transfer between graphitic carbon nitride and NIR CdTe/CdS QDs. J Electroanal Chem 886:115104. https://doi.org/10.1016/j.jelechem.2021.115104
Mo G, He X, Qin D, Meng S, Wu Y, Deng B (2021) Spatially-resolved dual-potential sandwich electrochemiluminescence immunosensor for the simultaneous determination of carbohydrate antigen 19–9 and carbohydrate antigen 24–2. Biosens Bioelectron 178:113024. https://doi.org/10.1016/j.bios.2021.113024
Fonseca J, Gong T, Jiao L, Jiang H (2021) Metal-organic frameworks (MOFs) beyond crystallinity: amorphous MOFs, MOF liquids and MOF glasses. Journal of materials chemistry. Mater Energy Sustain 9:1562–1611. https://doi.org/10.1039/d1ta01043c
Lin Y, Li Y, Cao Y, Wang X (2021) Two-dimensional MOFs: design & synthesis and applications. Chem Asian J 16:3281–3298. https://doi.org/10.1002/asia.202100884
Masoomi MY, Morsali A, Dhakshinamoorthy A, Garcia H (2019) Mixed-metal MOFs: unique opportunities in metal–organic framework (MOF) functionality and design. Angew Chem Int Ed 131:15330–15347. https://doi.org/10.1002/ange.201902229
Zhong X, Zhang M, Guo L, Xie Y, Luo R, Chen W, Cheng F, Wang L (2021) A dual-signal self-checking photoelectrochemical immunosensor based on the sole composite of MIL-101(Cr) and CdSe quantum dots for the detection of α-fetoprotein. Biosens Bioelectron 189:113389. https://doi.org/10.1016/j.bios.2021.113389
Daglar H, Gulbalkan HC, Avci G, Aksu GO, Altundal OF, Altintas C et al (2021) Effect of metal-organic framework (MOF) database selection on the assessment of gas storage and separation potentials of MOFs. Angew Chem Int Ed 60:7828–7837. https://doi.org/10.1002/anie.202015250
Rivera-Torrente M, Mandemaker L, Filez M, Delen G, Seoane B, Meirer F, Weckhuysen BM (2020) Spectroscopy, microscopy, diffraction and scattering of archetypal MOFs: formation, metal sites in catalysis and thin films. Chem Soc Rev 49:6694–6732. https://doi.org/10.1039/d0cs00635a
AbánadesLázaro I, Haddad S, Rodrigo-Muñoz JM, Marshall RJ, Sastre B, Del Pozo V, Fairen-Jimenez D, Forgan RS (2018) Surface-functionalization of Zr-fumarate MOF for selective cytotoxicity and immune system compatibility in nanoscale drug delivery. ACS Appl Mater Inter 10:31146–31157. https://doi.org/10.1021/acsami.8b11652
Yao MS, Xiu JW, Huang QQ, Li WH, Wu WW, Wu AQ, Cao LA, Deng WH, Wang GE, Xu G (2019) Van der Waals Heterostructured MOF-on-MOF thin films: cascading functionality to realize advanced chemiresistive sensing. Angew Chem Int Ed 58:14915–14919. https://doi.org/10.1002/anie.201907772
Wang Z, Yan Z, Wang F, Cai J, Guo L, Su J, Liu Y (2017) Highly sensitive photoelectrochemical biosensor for kinase activity detection and inhibition based on the surface defect recognition and multiple signal amplification of metal-organic frameworks. Biosens Bioelectron 97:107–114. https://doi.org/10.1016/j.bios.2017.05.011
Huang K, Li Z, Lin J, Han G, Huang P (2018) Two-dimensional transition metal carbides and nitrides (MXenes) for biomedical applications. Chem Soc Rev 47:5109–5124. https://doi.org/10.1039/c7cs00838d
Naguib M, Mochalin VN, Barsoum MW, Gogotsi Y (2014) 25th Anniversary Article: MXenes: a new family of two-dimensional materials. Adv Mater 26:992–1005. https://doi.org/10.1002/adma.201304138
Anasori B, Xie Y, Beidaghi M, Lu J, Hosler BC, Hultman L, Kent PRC, Gogotsi Y, Barsoum MW (2015) Two-dimensional, ordered, double transition metals carbides (MXenes). ACS Nano 9:9507–9516. https://doi.org/10.1021/acsnano.5b03591
Zhu J, Ha E, Zhao G, Zhou Y, Huang D, Yue G, Hu L, Sun N, Wang Y, Lee LYS, Xu C, Wong K, Astruc D, Zhao P (2017) Recent advance in MXenes: a promising 2D material for catalysis, sensor and chemical adsorption. Coordin Chem Rev 352:306–327. https://doi.org/10.1016/j.ccr.2017.09.012
Wang S, Zhao X, Yan X, Liu C, Yang X (2019) Regulating fast anionic redox for high-voltage aqueous hydrogen-ion based energy storage. Angew Chem Int Ed 131:211–216. https://doi.org/10.1002/anie.201811220
Guo R, Xiao M, Wan Z, Zhou S, Hu Y, Liao M, Wang S, Yang X, Chai R, Tang M (2022) 2D Ti3C2TxMXene couples electrical stimulation to promote proliferation and neural differentiation of neural stem cells. Acta Biomater 139:105–117. https://doi.org/10.1016/j.actbio.2020.12.035
Zhao H, Lv J, Xu H, Zhao X, Jia X, Tan L (2019) In-situ synthesis of MXene/ZnCo2O4 nanocomposite with enhanced catalytic activity on thermal decomposition of ammonium perchlorate. J Solid State Chem 279:120947. https://doi.org/10.1016/j.jssc.2019.12094
Lu X, Huang H, Zhang X, Lin P, Huang J, Sheng X, Zhang L, Qu J (2019) Novel light-driven and electro-driven polyethylene glycol/two-dimensional MXene form-stable phase change material with enhanced thermal conductivity and electrical conductivity for thermal energy storage. Compos Part B: Eng 177:107. https://doi.org/10.1016/j.compositesb.2019.107372
Li J, Kuang D, Feng Y, Zhang F, Xu Z, Liu M (2012) A graphene oxide-based electrochemical sensor for sensitive determination of 4-nitrophenol. J Hazard Mater 201–202:250–259. https://doi.org/10.1016/j.jhazmat.2011.11.076
de Castro ACH, Alves LM, Siquieroli ACS, Madurro JM, Brito-Madurro AG (2020) Label-free electrochemical immunosensor for detection of oncomarker CA125 in serum. Microchem J 155:104746. https://doi.org/10.1016/j.microc.2020.104746
Szymańska B, Lukaszewski Z, Hermanowicz-Szamatowicz K, Gorodkiewicz E (2020) A biosensor for determination of the circulating biomarker CA125/MUC16 by Surface Plasmon Resonance Imaging. Talanta 206:120187. https://doi.org/10.1016/j.talanta.2019.120187
SamadiPakchin P, Fathi M, Ghanbari H, Saber R, Omidi Y (2020) A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer. Biosens Bioelectron 153:112029. https://doi.org/10.1016/j.bios.2020.112029
SamadiPakchin P, Ghanbari H, Saber R, Omidi Y (2018) Electrochemical immunosensor based on chitosan-gold nanoparticle/carbon nanotube as a platform and lactate oxidase as a label for detection of CA125 oncomarker. Biosens Bioelectron 122:68–74. https://doi.org/10.1016/j.bios.2018.09.016
Zhang X, Wang Y, Deng H, Xiong X, Zhang H, Liang T, Li C (2021) An aptamer biosensor for CA125 quantification in human serum based on upconversion luminescence resonance energy transfer. Microchem J 161:105761. https://doi.org/10.1016/j.microc.2020.105761
Wu L, Sha Y, Li W, Wang S, Guo Z, Zhou J, Su X, Jiang X (2016) One-step preparation of disposable multi-functionalized g-C3N4 based electrochemiluminescence immunosensor for the detection of CA125. Sens Actuators, B Chem 226:62–68. https://doi.org/10.1016/j.snb.2015.11.133
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This work was supported by the National Natural Science Foundation of China (22108170, 22008011, 81973097).
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Qu, L., Wu, M., Zhao, L. et al. A sandwich electrochemical immunosensor based on MXene@dual MOFs for detection of tumor marker CA125. Microchim Acta 190, 147 (2023). https://doi.org/10.1007/s00604-023-05719-w
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DOI: https://doi.org/10.1007/s00604-023-05719-w