Determination of aristolochic acid using a piezoelectric immunosensor based on magnetic carbon nanocomposites

A technique for the determination of aristolochic acid (AA) in food products using a piezoelectric immunosensor is presented. Magnetic carbon nanocomposites (MCNC) were used as the recognition layer of the sensor, on the surface of which protein conjugates of AA were immobilized. Abstract-Methods for the synthesis of Fe₃O₄ magnetic nuclei and their attachment to the surface of multi-walled carbon nanotubes (CNTs) have been studied. Using IR spectrometry, it was found that the formation of the recognition layer of the sensor occurs due to the formation of covalent bonds between the amino groups of AA conjugates and carboxyl groups of CNTs. The concentrations of protein conjugates based on ovalbumin (OVA) and bovine serum albumin (BSA) (0.3 and 0.2 mg/ml) and the degree of antibody dilution (0.25) were determined, which provide optimal characteristics of the piezoelectric immunosensor. The metrological characteristics of the method for determining AA have been established. The range of determined concentrations of AA and the limit of detection when using a piezoelectric immunosensor with a recognition layer based on MUNA/AA-OVA and MUNA/AA-BSA are (ng/ml): 50 – 400 and 10; 100 – 300 and 50, respectively. The sensor has been tested in the determination of AA in samples of Chinese herbal tea and dietary supplements for weight loss. No acid was found in tea, and in dietary supplements, the acid content is 3.2 μg/g.

1. Wang X., Giusti A., Ny A., De Witte P. A. Nephrotoxic effects in zebrafish after prolonged exposure to aristolochic acid / Toxins. 2020. Vol. 12. N 4. P. 217 – 235. DOI: 10.3390/toxins12040217

2. Nie W., Lv Y., Yan L., et al. Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms / Sci. Rep. 2015. Vol. 5. P. 17646 – 17658. DOI: 10.1038/srep17646

3. Xu D., Zhao X., Yin L. Aristolochic acid i-induced hepatotoxicity in tianfu broilers is associated with oxidative-stress-mediated apoptosis and mitochondrial damage / Animals. 2021. Vol. 11. N 12. P. 3437 – 3449. DOI: 10.3390/ani11123437

4. Al-Barham M. B., Al-Jaber H. L., Al-Qudah M. A., Abu Zarga M. H. New aristolochic acid and other chemical constituents of Aristolochia maurorum growing wild in Jordan / Nat. Prod. Res. 2017. Vol. 31. N 3. P. 245 – 252. DOI: 10.1080/14786419.2016.1226833

5. Rebhan K., Ertl I. E., Shariat S. F., et al. Aristolochic acid and its effect on different cancers in uro-oncology / Curr. Opin. Urol. 2020. Vol. 30. N 5. P. 689 – 695. DOI: 10.1097/MOU.0000000000000806

6. Jadot I., Declèves A-E., Nortier J., Caron N. An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature / Int. J. Mol. Sci. 2017. Vol. 18. N 2. P. 297 – 320. DOI: 10.3390/ijms18020297

7. Guo W., Shi Z., Zhang J., et al. Analysis of aristolochic acid I in mouse serum and tissues by using magnetic solid-phase extraction and UHPLC-MS/MS / Talanta. 2021. Vol. 235. P. 122774 – 122782. DOI: 10.1016/j.talanta.2021.122774

8. Zhang J., Wang Y., Sun Y., et al. QuEChERS pretreatment combined with high-performance liquid chromatography-tandem mass spectrometry for determination of aristolochic acids I and II in Chinese herbal patent medicines / RSC Adv. 2020. Vol. 10. N 42. P. 25319 – 25324. DOI: 10.1039/D0RA03200J

9. Li W., Chan C.-K., Wong Y.-L., et al. Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains / Food Chem. 2018. Vol. 264. P. 270 – 276. DOI: 10.1016/j.foodchem.2018.05.052

10. Karaseva N. A., Ermolaeva T. N. Piezoelectric immunosensors for the detection of individual antibiotics and the total content of penicillin antibioticsin foodstuffs / Talanta. 2014. Vol. 120. P. 312 – 317. DOI: 10.1016/j.talanta.2013.12.018

11. Zyablov A. N., Shapovalova A. A. Determination of residual amounts of cefotaxime in liquid media using a piezoelectric sensor / Zavod. Lab. Diagn. Mater. 2022. Vol. 88. N 2. P. 15 – 21 [in Russian]. DOI: 10.26896/1028-6861-2022-88-2-15-20

12. Alsoveydi A. K. M., Karavaeva O. A., Guliy O. I. Methods and approaches for the determination of antibiotics / Antibiot. Khimioter. 2022. Vol. 67. N 1 – 2. P. 53 – 61 [in Russian]. DOI: 10.37489/0235-2990-2022-67-1-2-53-61

13. Vu Hoang Yen, Zyablov A. N. The use of MIP sensors for the determination of preservatives in soft drinks / Zavod. Lab. Diagn. Mater. 2022. Vol. 88. N 8. P. 10 – 16 [in Russian]. DOI: 10.26896/1028-6861-2022-88-8-10-16

14. Guliy O. I., Karavaeva O. A., Lovtsova L. G., et al. Biosensor systems for antibiotic detection / Biophysics. 2021. Vol. 66. N 4. P. 555 – 564. DOI: 10.1134/S0006350921040060

15. Bizina E. V., Farafonova O. V., Zolotareva N. I., et al. A piezoelectric immunosensor based on magnetic carbon nanocomposites for the determination of ciprofloxacin / J Anal. Chem. 2022. Vol. 77. N 4. P. 458 – 465 [in Russian]. DOI: 10.31857/S0044450222040041

16. Bizina E. V., Farafonova O. V., Zolotareva N. I., et al. The use of magnetic carbon nanocomposites in the formation of a recognition layer of a piezoelectric immunosensor for the determination of penicillin G. / J. Anal. Chem.. 2023. Vol. 78. N 4. P. 488 – 496. DOI: 10.1134/S1061934823040068

17. Sauerbrey G. Verwendung von Schwingquarzen zur Wigung dunner Schichten und zur Mikrowigung / Zeitschrift fiir Physik. 1959. Vol. 55. P. 206 – 222. DOI: 10.1007/BF01337937

18. Grazhulene S. S., Zolotareva N. I., Redkin A. N., et al. Magnetic sorbent based on magnetite and modified carbon nanotubes for the extraction of some toxic elements / Russ. J. Appl. Chem. 2018. Vol. 91. N 11. P. 1849 – 1855. DOI: 10.1134/S0044461818110154

19. Rana S., Barick K. C., Hassan P. A. Stimuli Responsive Carboxyl PEGylated Fe3O4 Nanoparticles for Therapeutic Applications / J. Nanofluids. 2015. Vol. 4. N 4. P. 421 – 427. DOI: 10.1166/jon.2015.1183

20. Wang J., Zheng S., Shao Y. Amino-functionalized Fe3O4@SiO2 core-shell magnetic nanomaterial as a novel adsorbent for aqueous heavy metals removal / J. Colloid Interface Sci. 2010. Vol. 349. N 1. P. 293 – 299. DOI: 10.1016/j.jcis.2010.05.010

21. Singh S., Barick K. C., Bahadur D. Surface engineered magnetic nanoparticles for removal of toxic metal ions and bacterial pathogens / J. Hazard. Mater. 2011. Vol. 192. P. 1539 – 1547. DOI: 10.1016/j.jhazmat.2011.06.074

22. Shinko E. I., Farafonova O. V., Shestopalov K. V., Ermolaeva T. N. Activation of carbon nanotubes for increasing the affinity interaction efficiency on the surface of a piezoelectric sensor for determining antibiotics / Sorption and chromatographic processes. 2019. Vol. 19. N 3. P. 334 – 343 [in Russian]. DOI: 10.17308/sorpchrom.2019.19/750

23. Netto C. G. C. M., Toma H. E., Andrade L. H. Superparamagnetic nanoparticles as versatile carriers and supporting materials for enzymes / J. Mol. Catal. B Enzym. 2013. Vol. 85. P. 71 – 92. DOI: 10.1016/j.molcatb.2012.08.010