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An efficient electrochemical nano-biosensor based on hydrothermally engineered ultrathin nanostructures of hexagonal boron nitride nanosheets for label-free detection of carcinoembryonic antigen

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Abstract

Advancements in nanostructure engineering have evolved ultrathin geometry and controlled morphology in inorganic layered materials consequently endowing ultrahigh specific surface area, highly permeable mass transport channels, and bio-compatible, bio-sensitive, bio-selective sites that render them appealing candidate as nano-biosensor. In the present work, engineered nanostructures of hexagonal boron nitride nanosheets (h-BNNS) were harnessed as electroanalytical sensing platform for label-free detection of carcinoembryonic antigen (CEA). The cytotoxicity analysis carried using MTT assay on the HEK 293 human cell line revealed the bio-compatible nature of ultrathin h-BNNS. Structural and morphological studies of h-BNNS nanostructures were investigated by XRD, SEM, TEM, Raman, and UV–visible spectroscopic techniques. Further, electrophoretic deposition (EPD) technique was employed at low DC potential (20 V) to fabricate micro-electrodes of h-BNNS onto hydrolysed indium tin oxide (ITO) glass substrates. Hydrothermally exfoliated ultrathin h-BNNS terminated with –OH, –NH, and –BH groups specifically crosslinks as well as anchors monoclonal antibodies of CEA by utilising synergy of EDC-NHS and BSA corroborated by FT-IR and diffusivity measurement. Under optimised working condition, nano-biosensor exhibited highly sensitive response (24.84 μA mL/ng/cm2) and remarkable lower limit of detection (LOD) of 22.5 pg/mL with correlation coefficient of 0.99988 in a wide physiological range from 0 to 50 ng/mL. As-fabricated nano-biosensor displayed negligible cross-reactivity, excellent shelf life, and great clinical performance for detection of CEA in human serum samples.

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References

  • Alduais Y, Zhang H, Fan F, Chen J, Chen B (2023) Non-small cell lung cancer (NSCLC): a review of risk factors, diagnosis, and treatment. Medicine 102:e32899–e32899

    Article  CAS  Google Scholar 

  • Amarasiri C, Nguyen TB, Nguyen LT, Thu VT, Thuy NTM, Dai Lam T (2017) Electrochemical immunosensor based on Fe3O4/PANI/AuNP detecting interface for carcinoembryonic antigen biomarker. J Electron Mater 46:5755–5763

    Article  CAS  Google Scholar 

  • Aref H, Refaat S (2014) CRP evaluation in non-small cell lung cancer. Egypt J Chest Dis Tuberc 63:717–722

    Article  Google Scholar 

  • Arya SK, Bhansali S (2011) Lung cancer and its early detection using biomarker-based biosensors. Chem Rev 111:6783–6809

    Article  CAS  Google Scholar 

  • Aydın EB, Sezgintürk MK (2017) Indium tin oxide (ITO): a promising material in biosensing technology. Trends Anal Chem 97:309–315

    Article  Google Scholar 

  • Boulet-Audet M, Byrne B, Kazarian SG (2014) High-throughput thermal stability analysis of a monoclonal antibody by attenuated total reflection FT-IR spectroscopic imaging. Anal Chem 86:9786–9793

    Article  CAS  Google Scholar 

  • Cai Q, Du A, Gao G, Mateti S, Cowie BC, Qian D, Zhang S, Lu Y, Fu L, Taniguchi T (2016) Molecule-induced conformational change in boron nitride nanosheets with enhanced surface adsorption. Adv Funct Mater 26:8202–8210

    Article  CAS  Google Scholar 

  • Cairns J (1981) The origin of human cancers. Nature 289:353–357

    Article  CAS  Google Scholar 

  • Chandra P, Prakash R (2020) Nanobiomaterial engineering: concepts and their applications in biomedicine and diagnostics. Springer International Publishing, New York

    Book  Google Scholar 

  • Chang AE, Ganz PA, Hayes DF, Kinsella T, Pass HI, Schiller JH, Stone RM, Strecher VO (2007) An evidence-based approach. Springer, Berlin

    Google Scholar 

  • Chen C, Liu J-B, Bian Z-P, Xu J-D, Wu H-F, Gu C-R, Shi Y, Zhang J-N, Chen X-J, Yang D (2014) Cardiac troponin I is abnormally expressed in non-small cell lung cancer tissues and human cancer cells. Int J Clin Exp Pathol 7:1314

    Google Scholar 

  • Chen JL, Lv XD, Ma H, Chen JR, Huang JA (2016) Detection of cancer embryo antigen and endothelin-1 in exhaled breath condensate: a novel approach to investigate non-small cell lung cancer. Mol Clin Oncol 5:124–128

    Article  CAS  Google Scholar 

  • Curigliano G (2020) Cancer patients and risk of mortality for COVID-19. Cancer Cell 38:161–163

    Article  CAS  Google Scholar 

  • De Mello RA, Veloso AF, Catarina PE, Nadine S, Antoniou G (2017) Potential role of immunotherapy in advanced non-small-cell lung cancer. Onco Targets Ther 10:21

    Article  Google Scholar 

  • Elgrishi N, Rountree KJ, McCarthy BD, Rountree ES, Eisenhart TT, Dempsey JL (2018) A practical beginner’s guide to cyclic voltammetry. J Chem Educ 95:197–206

    Article  CAS  Google Scholar 

  • Ganti AK, Mulshine JL (2006) Lung cancer screening. Oncologist 11:481–487

    Article  Google Scholar 

  • Hua Li L, Chen Y, Cheng B-M, Lin M-Y, Chou S-L, Peng Y-C (2012) Photoluminescence of boron nitride nanosheets exfoliated by ball milling. Appl Phys Lett 100:261108

    Article  Google Scholar 

  • Jozghorbani M, Fathi M, Kazemi SH, Alinejadian N (2021) Determination of carcinoembryonic antigen as a tumor marker using a novel graphene-based label-free electrochemical immunosensor. Anal Biochem 613:114017

    Article  CAS  Google Scholar 

  • Kelly JG, Trevisan J, Scott AD, Carmichael PL, Pollock HM, Martin-Hirsch PL, Martin FL (2011) Biospectroscopy to metabolically profile biomolecular structure: a multistage approach linking computational analysis with biomarkers. J Proteome Res 10:1437–1448

    Article  CAS  Google Scholar 

  • Kumar S, Kumar V, Abhilasha A, Garg M, Jain D (2010) Fourier transform infra red spectroscopic studies on epilepsy, migraine and paralysis. Int J Eng Trans B Appl 23:277

    Google Scholar 

  • Kumar S, Kumar S, Pandey CM, Malhotra BD (2016a) Conducting paper based sensor for cancer biomarker detection. J Phys Conf Ser 2016:012010

    Article  Google Scholar 

  • Kumar S, Sen A, Kumar S, Augustine S, Yadav BK, Mishra S, Malhotra BD (2016b) Polyaniline modified flexible conducting paper for cancer detection. Appl Phys Lett 108:203702

    Article  Google Scholar 

  • Kumar S, Umar M, Saifi A, Kumar S, Augustine S, Srivastava S, Malhotra BD (2019) Electrochemical paper based cancer biosensor using iron oxide nanoparticles decorated PEDOT: PSS. Anal Chim Acta 1056:135–145

    Article  CAS  Google Scholar 

  • Lee DS, Kim SJ, Kang JH, Hong SH, Jeon EK, Kim YK, Yoo IR, Park JG, Jang HS, Lee HC (2014) Serum carcinoembryonic antigen levels and the risk of whole-body metastatic potential in advanced non-small cell lung cancer. J Cancer 5:663

    Article  Google Scholar 

  • Li LH, Chen Y (2016) Atomically thin boron nitride: unique properties and applications. Adv Funct Mater 26:2594–2608

    Article  CAS  Google Scholar 

  • Li LH, Cervenka J, Watanabe K, Taniguchi T, Chen Y (2014) Strong oxidation resistance of atomically thin boron nitride nanosheets. ACS Nano 8:1457–1462

    Article  CAS  Google Scholar 

  • Liang H, Luo Y, Li Y, Song Y, Wang L (2022) An immunosensor using electroactive COF as signal probe for electrochemical detection of carcinoembryonic antigen. Anal Chem 94:5352–5358

    Article  CAS  Google Scholar 

  • Malik P, Katyal V, Malik V, Asatkar A, Inwati G, Mukherjee TK (2013) Nanobiosensors: concepts and variations. Int Sch Res Not 2013

  • Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T, Nakagawa A, Tsubota N (2004) Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease. Ann Thorac Surg 78:216–221

    Article  Google Scholar 

  • Passaro A, Bestvina C, Velez MV, Garassino MC, Garon E, Peters S (2021) Severity of COVID-19 in patients with lung cancer: evidence and challenges. J Immunother Cancer 9

  • Pavithra M, Muruganand S, Parthiban C (2018) Development of novel paper based electrochemical immunosensor with self-made gold nanoparticle ink and quinone derivate for highly sensitive carcinoembryonic antigen. Sens Actuators B Chem 257:496–503

    Article  CAS  Google Scholar 

  • Sadeghi M, Kashanian S, Naghib SM, Askari E, Haghiralsadat F, Tofighi D (2022a) A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells. Nanotechnol Rev 11:793–810

    Article  CAS  Google Scholar 

  • Sadeghi M, Kashanian S, Naghib SM, Arkan E (2022b) A high-performance electrochemical aptasensor based on graphene-decorated rhodium nanoparticles to detect HER2-ECD oncomarker in liquid biopsy. Sci Rep 12:3299

    Article  CAS  Google Scholar 

  • Satoh H, Ishikawa H, Kurishima K, Yamashita YT, Ohtsuka M, Sekizawa K (2002) Cut-off levels of NSE to differentiate SCLC from NSCLC. Oncol Rep 9:581–583

    CAS  Google Scholar 

  • Sharma K, Puri NK (2021) Enhanced electrochemical performance of hydrothermally exfoliated hexagonal boron nitride nanosheets for applications in electrochemistry. J Electrochem Soc 168:056512

    Article  CAS  Google Scholar 

  • Sharma P, Hasan MR, Khanuja M, Rawal R, Pilloton R, Narang J (2023) Aptamer-based silver nanoparticle decorated paper platform for electrochemical detection ovarian cancer biomarker PDGF. Mater Chem Phys 2023:128114

    Article  Google Scholar 

  • Sibai A, Elamri K, Barbier D, Jaffrezic-Renault N, Souteyrand E (1996) Analysis of the polymer-antibody-antigen interaction in a capacitive immunosensor by FTIR difference spectroscopy. Sens Actuators B Chem 31:125–130

    Article  CAS  Google Scholar 

  • Singh B, Kaur G, Singh P, Singh K, Kumar B, Vij A, Kumar M, Bala R, Meena R, Singh A (2016) Nanostructured boron nitride with high water dispersibility for boron neutron capture therapy. Sci Rep 6:1–10

    Article  Google Scholar 

  • Sun W, Meng Y, Fu Q, Wang F, Wang G, Gao W, Huang X, Lu F (2016) High-yield production of boron nitride nanosheets and its uses as a catalyst support for hydrogenation of nitroaromatics. ACS Appl Mater Interfaces 8:9881–9888

    Article  CAS  Google Scholar 

  • Sun C, Zhao J, Zhang D, Guo H, Wang X, Hu H (2020) Covalent functionalization of boron nitride nanosheets via reductive activation. Nanoscale 12:18379–18389

    Article  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA 71:209–249

    Google Scholar 

  • Suys O, Derenne A, Goormaghtigh E (2022) ATR-FTIR biosensors for antibody detection and analysis. Int J Mol Sci 23:11895

    Article  CAS  Google Scholar 

  • Tolosa L, Donato MT, Gómez-Lechón MJ (2015) General cytotoxicity assessment by means of the MTT assay, protocols in in vitro hepatocyte research 333–348

  • Tothill IE (2009) Biosensors for cancer markers diagnosis. In: Seminars in cell & developmental biology. Elsevier, Amsterdam, pp 55–62

  • Vashist SK (2012) Comparison of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide based strategies to crosslink antibodies on amine-functionalized platforms for immunodiagnostic applications. Diagnostics 2:23–33

    Article  CAS  Google Scholar 

  • Wang Q-L, Cui H-F, Song X, Fan S-F, Chen L-L, Li M-M, Li Z-Y (2018) A label-free and lectin-based sandwich aptasensor for detection of carcinoembryonic antigen. Sens Actuators B Chem 260:48–54

    Article  CAS  Google Scholar 

  • Yang G, Park S-J (2019) Conventional and microwave hydrothermal synthesis and application of functional materials: a review. Materials 12:1177

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are greatly thankful to Prof. JP Saini, Vice chancellor, DTU, Delhi, India for arranging the research facilities. We gratefully acknowledged SERB, DST, India (EMR/2016/007479) for supporting this research. The authors are very thankful for the help extended by Dr. Saurabh Srivastava, Dr. Deepika Sandil, Anurag Bhandari, and Niharika Gupta for their support. The authors acknowledge the great cooperation of SAIF, AIIMS (Delhi) for providing sophisticated characterisation techniques.

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Correspondence to Nitin K. Puri.

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Sharma, K., Puri, N.K. & Singh, B. An efficient electrochemical nano-biosensor based on hydrothermally engineered ultrathin nanostructures of hexagonal boron nitride nanosheets for label-free detection of carcinoembryonic antigen. Appl Nanosci 14, 217–230 (2024). https://doi.org/10.1007/s13204-023-02971-7

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