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Conductive metal–organic framework based label-free electrochemical detection of circulating tumor DNA

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Abstract  

An ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of circulating tumor DNA (ctDNA, EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal–organic frameworks (MOFs), which is termed Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGE were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA over a wide concentration range and the detection limit down to the femtomolar level. The sensor was applied to the determination of ctDNA in serum samples with high sensitivity. This simple, efficient, and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment, and prognosis of tumors.

Graphical abstract

Herein, an ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of ctDNA (EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal–organic frameworks (MOFs), which is termed as Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGEs were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA in the concentration range of 1 × 10−15 M to 1 × 10−6 M and with a detection limit as low as 0.32 fM. The sensor was applied for determination of ctDNA in serum samples and gave high sensitivity. This simple, efficient and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment and prognosis of tumors.

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References 

  1. Bronkhorst AJ, Ungerer V, Holdenrieder S (2019) The emerging role of cell-free DNA as a molecular marker for cancer management. Biomolecular Detection and Quantification 17:100087. https://doi.org/10.1016/j.bdq.2019.100087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. de Lima LTF, Broszczak D, Zhang X, Bridle K, Crawford D, Punyadeera C (2020) The use of minimally invasive biomarkers for the diagnosis and prognosis of hepatocellular carcinoma. Biochimica et Biophysica Acta (BBA) Reviews on Cancer 1874(2):188451

    Article  Google Scholar 

  3. Volckmar AL, Sultmann H, Riediger A, Fioretos T, Schirmacher P, Endris V et al (2018) A field guide for cancer diagnostics using cell-free DNA: from principles to practice and clinical applications. Genes Chromosom Cancer 57(3):123–139. https://doi.org/10.1002/gcc.22517

    Article  CAS  PubMed  Google Scholar 

  4. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N et al (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Research 17(7):2503–2516

    Article  CAS  Google Scholar 

  5. Mao X, Pan S, Zhou D, He X, Zhang Y (2019) Fabrication of DNAzyme-functionalized hydrogel and its application for visible detection of circulating tumor DNA. Sens Actuators, B Chem 285:385–390. https://doi.org/10.1016/j.snb.2019.01.076

    Article  CAS  Google Scholar 

  6. Zhang J, Dong Y, Zhu W, Xie D, Zhao Y, Yang D et al (2019) Ultrasensitive detection of circulating tumor dna of lung cancer via an enzymatically amplified SERS-based frequency shift assay. ACS Appl Mater Interfaces 11(20):18145–18152. https://doi.org/10.1021/acsami.9b02953

    Article  CAS  PubMed  Google Scholar 

  7. Chaibun T, Puenpa J, Ngamdee T, Boonapatcharoen N, Athamanolap P, O’Mullane AP et al (2021) Rapid electrochemical detection of coronavirus SARS-CoV-2. Nat Commun 12(1):802. https://doi.org/10.1038/s41467-021-21121-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Miao P, Tang YG (2020) DNA walking and rolling nanomachine for electrochemical detection of miRNA. Small 16(47):2004518. https://doi.org/10.1002/smll.202004518

    Article  CAS  Google Scholar 

  9. Wang L-L, Chen W-Q, Wang Y-R, Zeng L-P, Chen T-T, Chen G-Y et al (2020) Numerous long single-stranded DNAs produced by dual amplification reactions for electrochemical detection of exosomal microRNAs. Biosens Bioelectron 169:112555. https://doi.org/10.1016/j.bios.2020.112555

    Article  CAS  PubMed  Google Scholar 

  10. Zhang R, Chen W (2015) Fe3C-functionalized 3D nitrogen-doped carbon structures for electrochemical detection of hydrogen peroxide. Science Bulletin 60(5):522–531. https://doi.org/10.1007/s11434-015-0740-0

    Article  CAS  Google Scholar 

  11. Ramachandran R, Leng X, Zhao C, Xu Z-X, Wang F (2020) 2D siloxene sheets: a novel electrochemical sensor for selective dopamine detection. Appl Mater Today 18:100477. https://doi.org/10.1016/j.apmt.2019.100477

    Article  Google Scholar 

  12. Small LJ, Henkelis SE, Rademacher DX, Schindelholz ME, Krumhansl JL, Vogel DJ et al (2020) Near-zero power MOF-based sensors for NO2 detection. Adv Func Mater 30(50):2006598. https://doi.org/10.1002/adfm.202006598

    Article  CAS  Google Scholar 

  13. Song J, Huang M, Lin X, Li SFY, Jiang N, Liu Y et al (2022) Novel Fe-based metal–organic framework (MOF) modified carbon nanofiber as a highly selective and sensitive electrochemical sensor for tetracycline detection. Chem Eng J 427:130913. https://doi.org/10.1016/j.cej.2021.130913

    Article  CAS  Google Scholar 

  14. Rubio-Gimenez V, Almora-Barrios N, Escorcia-Ariza G, Galbiati M, Sessolo M, Tatay S et al (2018) Origin of the chemiresistive response of ultrathin films of conductive metal-organic frameworks. Angewandte Chemie-International Edition 57(46):15086–15090. https://doi.org/10.1002/anie.201808242

    Article  CAS  PubMed  Google Scholar 

  15. Duan H, Zhao Z, Lu J, Hu W, Zhang Y, Li S et al (2021) When conductive MOFs meet MnO2: high electrochemical energy storage performance in an aqueous asymmetric supercapacitor. ACS Appl Mater Interfaces 13(28):33083–33090. https://doi.org/10.1021/acsami.1c08161

    Article  CAS  PubMed  Google Scholar 

  16. Cai D, Lu MJ, Li L, Cao JM, Chen D, Tu HR et al (2019) A highly conductive MOF of graphene analogue Ni3(HITP)2 as a sulfur host for high-performance lithium-sulfur batteries. Small 15(44):1902605. https://doi.org/10.1002/smll.201902605

    Article  CAS  Google Scholar 

  17. Xu Z, Wang Q, Zhangsun H, Zhao S, Zhao Y, Wang L (2021) Carbon cloth-supported nanorod-like conductive Ni/Co bimetal MOF: a stable and high-performance enzyme-free electrochemical sensor for determination of glucose in serum and beverage. Food Chem 349:129202. https://doi.org/10.1016/j.foodchem.2021.129202

    Article  CAS  PubMed  Google Scholar 

  18. Ko M, Mendecki L, Eagleton AM, Durbin CG, Stolz RM, Meng Z et al (2020) Employing conductive metal–organic frameworks for voltammetric detection of neurochemicals. J Am Chem Soc 142(27):11717–11733. https://doi.org/10.1021/jacs.9b13402

    Article  CAS  PubMed  Google Scholar 

  19. Vicentini FC, Ravanini AE, Figueiredo-Filho LCS, Iniesta J, Banks CE, Fatibello-Filho O (2015) Imparting improvements in electrochemical sensors: evaluation of different carbon blacks that give rise to significant improvement in the performance of electroanalytical sensing platforms. Electrochim Acta 157:125–133. https://doi.org/10.1016/j.electacta.2014.11.204

    Article  CAS  Google Scholar 

  20. Hmadeh M, Lu Z, Liu Z, Gándara F, Furukawa H, Wan S et al (2012) New porous crystals of extended metal-catecholates. Chem Mater 24(18):3511–3513. https://doi.org/10.1021/cm301194a

    Article  CAS  Google Scholar 

  21. Nagarajan S, Vairamuthu R, Angamuthu R, Venkatachalam G (2019) Electrochemical fabrication of reusable pencil graphite electrodes for highly sensitive, selective and simultaneous determination of hydroquinone and catechol. J Electroanal Chem 846:113156. https://doi.org/10.1016/j.jelechem.2019.05.038

    Article  CAS  Google Scholar 

  22. Nguyen NTT, Furukawa H, Gándara F, Trickett CA, Jeong HM, Cordova KE et al (2015) Three-dimensional metal-catecholate frameworks and their ultrahigh proton conductivity. J Am Chem Soc 137(49):15394–15397. https://doi.org/10.1021/jacs.5b10999

    Article  CAS  PubMed  Google Scholar 

  23. Lee S-M, Lee S-H, Roh J-S (2021) Analysis of activation process of carbon black based on structural parameters obtained by XRD analysis. Crystals 11(2):153 (https://www.mdpi.com/2073-4352/11/2/153)

    Article  CAS  Google Scholar 

  24. Qiao Y, Liu Q, Lu S, Chen G, Gao S, Lu W et al (2020) High-performance non-enzymatic glucose detection: using a conductive Ni-MOF as an electrocatalyst. Journal of Materials Chemistry B 8(25):5411–5415. https://doi.org/10.1039/D0TB00131G

    Article  CAS  PubMed  Google Scholar 

  25. Tezerjani MD, Benvidi A, Jahanbani S, Moshtaghioun SM, Mazloum-Ardakani M (2016) A comparative investigation for prostate cancer detection using two electrochemical biosensors based on various nanomaterials and the linker of thioglycolic acid. J Electroanal Chem 778:23–31. https://doi.org/10.1016/j.jelechem.2016.08.009

    Article  CAS  Google Scholar 

  26. Hájková A, Barek J, Vyskočil V (2017) Electrochemical DNA biosensor for detection of DNA damage induced by hydroxyl radicals. Bioelectrochemistry 116:1–9. https://doi.org/10.1016/j.bioelechem.2017.02.003

    Article  CAS  PubMed  Google Scholar 

  27. Guo L, Mu Z, Yan B, Wang J, Zhou J, Bai L (2022) A novel electrochemical biosensor for sensitive detection of non-small cell lung cancer ctDNA using NG-PEI-COFTAPB-TFPB as sensing platform and Fe-MOF for signal enhancement. Sens Actuators, B Chem 350:130874. https://doi.org/10.1016/j.snb.2021.130874

    Article  CAS  Google Scholar 

  28. Chen M, Wu D, Tu S, Yang C, Chen D, Xu Y (2021) CRISPR/Cas9 cleavage triggered ESDR for circulating tumor DNA detection based on a 3D graphene/AuPtPd nanoflower biosensor. Biosens Bioelectron 173:112821. https://doi.org/10.1016/j.bios.2020.112821

    Article  CAS  Google Scholar 

  29. Huang Y, Tao M, Luo S, Zhang Y, Situ B, Ye X et al (2020) A novel nest hybridization chain reaction based electrochemical assay for sensitive detection of circulating tumor DNA. Anal Chim Acta 1107:40–47. https://doi.org/10.1016/j.aca.2020.02.006

    Article  CAS  PubMed  Google Scholar 

  30. Li D, Xu Y, Fan L, Shen B, Ding X, Yuan R et al (2020) Target-driven rolling walker based electrochemical biosensor for ultrasensitive detection of circulating tumor DNA using doxorubicin@tetrahedron-Au tags. Biosens Bioelectron 148:111826. https://doi.org/10.1016/j.bios.2019.111826

    Article  CAS  PubMed  Google Scholar 

  31. Chen K, Zhao H, Wang Z, Lan M (2021) A novel signal amplification label based on AuPt alloy nanoparticles supported by high-active carbon for the electrochemical detection of circulating tumor DNA. Anal Chim Acta 1169:338628. https://doi.org/10.1016/j.aca.2021.338628

    Article  CAS  PubMed  Google Scholar 

  32. Chen KC, Zhao HL, Wang ZX, Lan MB (2022) Three-dimensional graphene-like homogeneous carbon architecture loaded with gold-platinum for the electrochemical detection of circulating tumor DNA. Materials Today Chemistry 24:100892. https://doi.org/10.1016/j.mtchem.2022.100892

    Article  CAS  Google Scholar 

  33. Su J, Zhong WZ, Zhang XC, Huang Y, Yan HH, Yang JJ et al (2017) Molecular characteristics and clinical outcomes of EGFR exon 19 indel subtypes to EGFR TKIs in NSCLC patients. Oncotarget 8(67):111246–111257. https://doi.org/10.18632/oncotarget.22768

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 81271930 and 31000425), the Research Project of Chongqing Science and Technology Commission of China (cstc2020jcyj-msxmX0861), the Fundamental Research Funds for the Central Universities (No. 2020CDJ-LHZZ-033), and we would like to thank the Analytical and Testing Center of Chongqing University for SEM images, XRD, and XPS spectrum.

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Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Juan Liu, Siyi Yang, Jinhui Shen, Changjun Hou & Mei Yang

  2. College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Huanbao Fa

  3. College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Changjun Hou & Mei Yang

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  1. Juan Liu
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Liu, J., Yang, S., Shen, J. et al. Conductive metal–organic framework based label-free electrochemical detection of circulating tumor DNA. Microchim Acta 189, 391 (2022). https://doi.org/10.1007/s00604-022-05482-4

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