Silver Nanoparticles-Based Substrate for Blood Serum Analysis under 785 nm Laser Excitation

Sahar Z. Al-Sammarraie (Login required)
Samara University, Russian Federation

Lyudmila A. Bratchenko
Samara University, Russian Federation

Elena N. Typikova
Samara University, Russian Federation

Peter A. Lebedev
Samara State Medical University

Valery P. Zakharov
Samara University, Russian Federation

Ivan A. Bratchenko
Samara University, Russian Federation

Paper #3461 received 1 Nov 2021; revised manuscript received 24 Jan 2022; accepted for publication 24 Jan 2022; published online 3 Feb 2022.

DOI: 10.18287/JBPE22.08.010301


Individuals who have different diseases need a routine assessment of their body metabolism, and the methods that used are practically difficult, inconvenient or expensive. The objective of this study was to develop a technique of human blood serum analysis that is simple, reliable and fast, and based on a surface-enhanced Raman spectroscopy (SERS). In this study, serum samples were examined using conventional Raman (CR) and SERS. The observed CR and SERS bands were analyzed. Several of these bands (724, 813, 890, 961, and 1132 cm−1) clearly stand out by the impact of the SERS technique, as the intensities of these bands in CR measurements are weaker than the intensity of the autofluorescence and noise. The Enhancement Factor (EF) was up to 4 × 105. Stability of the proposed SERS technique was confirmed by the measurements of signal standard deviation. The observed standard deviation does not exceed 19% for different SERS substrates and does not exceed 8% in case of a single SERS substrate measurements. The obtained results demonstrate that the proposed SERS technique is stable and has significant potential in clinical diagnosis applications.


surface-enhanced Raman spectroscopy; Enhancement Factor; blood serum; silver nanoparticles; Raman band shift

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1. “Mortality Data”, World Health Organization, (accessed 02.02.2022) [].

2. O. J. Wouters, D. J. O’donoghue, J. Ritchie, P. G. Kanavos, and A. S. Narva, “Early chronic kidney disease: diagnosis, management and models of care,” Nature Reviews Nephrology 11(8), 491–502 (2015).

3. S. K. Elwia, S. M. Abo El Wafa, and Y. M. Marei, “The Metabolic Mechanism Underlying the Enhancing Effects of Glycine and Tryptophan on Kidney Function: How to Reduce EGFR Inhibitory Effect on AAs,” Egyptian Academic Journal of Biological Sciences, F. Toxicology & Pest Control 13(2), 37–48 (2021).

4. S. Luis-Lima, E. Porrini, “An overview of errors and flaws of estimated GFR versus true GFR in patients with diabetes mellitus,” Nephron 136, 287–291 (2017).

5. R. Moynihan, R. Glassock, and J. Doust, “Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling many people as diseased,” BMJ 347, f4298 (2013).

6. D.-Q. Chen, G. Cao, H. Chen, D. Liu, W. Su, X.-Y. Yu, N. D. Vaziri, X.-H. Liu, X. Bai, L. Zhang, and Y.-Y. Zhao, “Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease,” Redox biology 12, 505–521 (2017).

7. C. H. Johnson, J. Ivanisevic, and G. Siuzdak, “Metabolomics: beyond biomarkers and towards mechanisms,” Nature Reviews Molecular Cell Biology 17(7), 451–459 (2016).

8. P. F. Mulders, “From genes to metabolomics in renal cell carcinoma translational research,” European Urology, 2(63), 252–253 (2013).

9. S. Kalim, E. P. Rhee, “An overview of renal metabolomics,” Kidney International 91(1), 61–69 (2017).

10. Y. Y. Zhao, “Metabolomics in chronic kidney disease,” Clinica Chimica Acta 422, 59–69 (2013).

11. R. H. Weiss, K. Kim, “Metabolomics in the study of kidney diseases,” Nature Reviews Nephrology 8(1), 22–33 (2012).

12. L. A. Bratchenko, I. A. Bratchenko, A. A. Lykina, M. V. Komarova, D. N. Artemyev, O. O. Myakinin, A. A. Moryatov, I. L. Davydkin, S. V. Kozlov, and V. P. Zakharov, “Comparative study of multivariative analysis methods of blood Raman spectra classification,” Journal of Raman Spectroscopy 51(2), 279–292 (2020).

13. L. A. Bratchenko, I. A. Bratchenko, Y. A. Khristoforova, D. N. Artemyev, D. Y. Konovalova, P. A. Lebedev, and V. P. Zakharov, “Raman spectroscopy of human skin for kidney failure detection,” Journal of Biophotonics 14(2), e202000360 (2021).

14. I. A. Bratchenko, L. A. Bratchenko, A. A. Moryatov, Y. A. Khristoforova, D. N. Artemyev, O. O. Myakinin, A. E. Orlov, S. V. Kozlov, and V. P. Zakharov, “In vivo diagnosis of skin cancer with a portable Raman spectroscopic device,” Experimental Dermatology 30(5), 652–663 (2021).

15. P. A. Mosier-Boss, “Review of SERS substrates for chemical sensing,” Nanomaterials 7(6), 142 (2017).

16. E. Critselis, H. L. Heerspink, “Utility of the CKD273 peptide classifier in predicting chronic kidney disease progression,” Nephrology Dialysis Transplantation 31(2), 249–254 (2016).

17. C. Pontillo, L. Jacobs, J. A. Staessen, J. P. Schanstra, P. Rossing, H. J. Heerspink, J. Siwy, W. Mullen, A. Vlahou, H. Mischak, and R. Vanholder, “A urinary proteome-based classifier for the early detection of decline in glomerular filtration,” Nephrology Dialysis Transplantation 32(9), 1510–1516 (2017).

18. A. C. Webster, E. V. Nagler, R. L. Morton, and P. Masson, “Chronic kidney disease,” The Lancet 389(10075), 1238–1252 (2017).

19. P. Ruggenenti, A. Fassi, A. P. Ilieva, S. Bruno, I. P. Iliev, V. Brusegan, N. Rubis, G. Gherardi, F. Arnoldi, M. Ganeva, and B. Ene-Iordache, “Preventing microalbuminuria in type 2 diabetes,” New England Journal of Medicine 351(19), 1941–1951 (2004).

20. E. J. Want, I. D. Wilson, H. Gika, G. Theodoridis, R. S. Plumb, J. Shockcor, E. Holmes, and J. K. Nicholson, “Global metabolic profiling procedures for urine using UPLC–MS,” Nature Protocols 5(6), 1005–1018 (2010).

21. A. Bonifacio, S. Dalla Marta, R. Spizzo, S. Cervo, A. Steffan, A. Colombatti, and V. Sergo, “Surface-enhanced Raman spectroscopy of blood plasma and serum using Ag and Au nanoparticles: a systematic study,” Analytical and Bioanalytical Chemistry 406(9), 2355–2365 (2014).

22. X. Cao, Z. Wang, L. Bi, and J. Zheng, “Label-free detection of human serum using surface-enhanced raman spectroscopy based on highly branched gold nanoparticle substrates for discrimination of non-small cell lung cancer,” Journal of Chemistry 2018, 9012645 (2018).

23. A. Pérez, Y. A. Prada, R. Cabanzo, C. I. González, and E. Mejía-Ospino, “Diagnosis of chagas disease from human blood serum using surface-enhanced Raman scattering (SERS) spectroscopy and chemometric methods,” Sensing and Bio-Sensing Research 21, 40–45 (2018).

24. S. Madhuri, N. Vengadesan, P. Aruna, D. Koteeswaran, P. Venkatesan, and S. Ganesan, “Native Fluorescence Spectroscopy of Blood Plasma in the Characterization of Oral Malignancy,” Photochemistry and Photobiology 78(2), 197–204 (2003).

25. R. Kalaivani, V. Masilamani, K. Sivaji, M. Elangovan, V. Selvaraj, S. G. Balamurugan, and M. S. Al-Salhi, “Fluorescence spectra of blood components for breast cancer diagnosis,” Photomedicine and Laser Surgery 26(3), 251–256 (2008).

26. B. Sharma, R. R. Frontiera, A. I. Henry, E. Ringe, and R. P. Van Duyne, “SERS: Materials, applications, and the future,” Materials Today 15(1–2), 16–25 (2012).

27. B. Sardari, M. Özcan, “Real-time and tunable substrate for surface enhanced Raman spectroscopy by synthesis of copper oxide nanoparticles via electrolysis,” Scientific Reports 7(1), 7730 (2017).

28. G. M. Herrera, A. C. Padilla, and S. P. Hernandez-Rivera, “Surface enhanced Raman scattering (SERS) studies of gold and silver nanoparticles prepared by laser ablation,” Nanomaterials 3(1), 158–172 (2013).

29. A. Subaihi, L. Almanqur, H. Muhamadali, N. AlMasoud, D. I. Ellis, D. K. Trivedi, K. A. Hollywood, Y. Xu, and R. Goodacre, “Rapid, accurate, and quantitative detection of propranolol in multiple human biofluids via surface-enhanced Raman scattering,” Analytical Chemistry 88(22), 10884–10892 (2016).

30. E. Witkowska, T. Jagielski, A. Kamińska, A. Kowalska, A. Hryncewicz-Gwóźdź, and J. Waluk, “Detection and identification of human fungal pathogens using surface-enhanced Raman spectroscopy and principal component analysis,” Analytical Methods 8(48), 8427–8434 (2016).

31. R. Liu, X. Zi, Y. Kang, M. Si, and Y. Wu, “Surface-enhanced Raman scattering study of human serum on PVA–Ag nanofilm prepared by using electrostatic self-assembly,” Journal of Raman Spectroscopy 42(2), 137–144 (2011).

32. J. L. Pichardo-Molina, C. Frausto-Reyes, O. Barbosa-García, R. Huerta-Franco, J. L. González-Trujillo, C. A. Ramírez-Alvarado, G. Gutiérrez-Juárez, and C. Medina-Gutiérrez, “Raman spectroscopy and multivariate analysis of serum samples from breast cancer patients,” Lasers in Medical Science 22(4), 229–236 (2007).

33. Q. Liao, M. Y. Li, R. Hao, X. C. Ai, J. P. Zhang, and Y. Wang, “Surface-enhanced Raman scattering and DFT computational studies of a cyanuric chloride derivative,” Vibrational Spectroscopy 44(2), 351–356 (2007).

34. H. Ma, S. Liu, N. Zheng, Y. Liu, X. X. Han, C. He, H. Lu, and B. Zhao, “Frequency shifts in surface-enhanced Raman spectroscopy-based immunoassays: mechanistic insights and application in protein carbonylation detection,” Analytical Chemistry 91(15), 9376–9381 (2019).

35. Z. Huang, S. Feng, Q. Guan, T. Lin, J. Zhao, C. Y. Nguan, H. Zeng, D. Harriman, H. Li, and C. Du, “Correlation of surface-enhanced Raman spectroscopic fingerprints of kidney transplant recipient urine with kidney function parameters,” Scientific Reports 11(1), 2463 (2021).

36. S. Feng, L. Zhou, D. Lin, J. Zhao, Q. Guan, B. Zheng, K. Wang, H. Li, R. Chen, H. Zeng, and C. Du, “Assessment of treatment efficacy using surface-enhanced Raman spectroscopy analysis of urine in rats with kidney transplantation or kidney disease,” Clinical and Experimental Nephrology 23(7), 880–889 (2019).

37. N. Stone, C. Kendall, J. Smith, P. Crow, and H. Barr, “Raman spectroscopy for identification of epithelial cancers,” Faraday Discussions 126, 141–157 (2004).

38. N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, “Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers,” Journal of Raman spectroscopy 33(7), 564–573 (2002).

39. J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, “Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells,” Biophysical Journal 90(2), 648–656 (2006).

40. S. Feng, R. Chen, J. Lin, J. Pan, Y. Wu, Y. Li, J. Chen, and H. Zeng, “Gastric cancer detection based on blood plasma surface-enhanced Raman spectroscopy excited by polarized laser light,” Biosensors and Bioelectronics 26(7), 3167–3174 (2011).

41. J. Lin, R. Chen, S. Feng, J. Pan, Y. Li, G. Chen, M. Cheng, Z. Huang, Y. Yu, and H. Zeng, “A novel blood plasma analysis technique combining membrane electrophoresis with silver nanoparticle-based SERS spectroscopy for potential applications in noninvasive cancer detection,” Nanomedicine: Nanotechnology, Biology and Medicine 7(5), 655–663 (2011).

42. J. De Gelder, K. De Gussem, P. Vandenabeele, and L. Moens, “Reference database of Raman spectra of biological molecules,” Journal of Raman Spectroscopy: An International Journal for Original Work in all Aspects of Raman Spectroscopy, Including Higher Order Processes, and also Brillouin and Rayleigh Scattering 38(9), 1133–1147 (2007).

43. Z. Movasaghi, S. Rehman, and D. I. ur Rehman, “Fourier transform infrared (FTIR) spectroscopy of biological tissues,” Applied Spectroscopy Reviews 43(2), 134–179 (2008).

44. G. Shetty, C. Kendall, N. Shepherd, N. Stone, and H. Barr, “Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus,” British Journal of Cancer 94(10), 1460–1464 (2006).

45. D. Naumann, “Infrared and NIR Raman spectroscopy in medical microbiology,” Proceedings of SPIE 3257, 245–257 (1998).

46. R. J. Lakshmi, V. B. Kartha, C. R. Murali Krishna, J. G. Solomon, G. Ullas, and P. Uma Devi, “Tissue Raman spectroscopy for the study of radiation damage: brain irradiation of mice,” Radiation Research 157(2), 175–182 (2002).

47. W. T. Cheng, M. T. Liu, H. N. Liu, and S. Y. Lin, “Micro-Raman spectroscopy used to identify and grade human skin pilomatrixoma,” Microscopy Research and Technique 68(2), 75–79 (2005).

48. D. P. Lau, Z. Huang, H. Lui, D. W. Anderson, K. Berean, M. D. Morrison, L. Shen, and H. Zeng, “Raman spectroscopy for optical diagnosis in the larynx: preliminary findings,” Lasers in Surgery and Medicine 37(3), 192–200 (2005).

49. M. V. Canamares, J. V. Garcia-Ramos, S. Sanchez-Cortes, M. Castillejo, and M. Oujja, “Comparative SERS effectiveness of silver nanoparticles prepared by different methods: A study of the enhancement factor and the interfacial properties,” Journal of Colloid and Interface Science 326(1), 103–109.

50. Z. H. Lin, I. C. Chen, and H. T. Chang, “Detection of human serum albumin through surface-enhanced Raman scattering using gold “pearl necklace” nanomaterials as substrates,” Chemical Communications 47(25), 7116–7118 (2011).

51. Z. Y. Wang, W. Li, Z. Gong, P. R. Sun, T. Zhou, and X. W. Cao, “Detection of IL-8 in human serum using surface-enhanced Raman scattering coupled with highly-branched gold nanoparticles and gold nanocages,” New Journal of Chemistry 43(4), 1733–1742 (2019).

52. H. Wang, N. Malvadkar, S. Koytek, J. Bylander, W. B. Reeves, and M. C. Demirel, “Quantitative analysis of creatinine in urine by metalized nanostructured parylene,” Journal of Biomedical Optics 15(2), 027004 (2010).

53. C. Popa, M. Petrus, and A. M. Bratu, “Ammonia and ethylene biomarkers in the respiration of the people with schizophrenia using photoacoustic spectroscopy,” Journal of Biomedical Optics 20(5), 057006 (2015).

54. Y. Kitahama, “Observation and analysis of blinking surface-enhanced Raman scattering,” Journal of Visualized Experiments 131, e56729 (2018).

55. Y. Zhu, C. S. Choe, S. Ahlberg, M. C. Meinke, A. Ulrike, J. M. Lademann, and M. E. Darvin, “Penetration of silver nanoparticles into porcine skin ex vivo using fluorescence lifetime imaging microscopy, Raman microscopy, and surface-enhanced Raman scattering microscopy,” Journal of Biomedical Optics, 20(5), 051006 (2014).

56. Y. S. Huh, A. J. Chung, and D. Erickson, “Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis,” Microfluidics and Nanofluidics 6(3), 285–297 (2009).

57. M. Sharifi, S. H. Hosseinali, R. H. Alizadeh, A. Hasan, F. Attar, A. Salihi, M. S. Shekha, K. M. Amen, F. M. Aziz, A. A. Saboury, and K. Akhtari, “Plasmonic and chiroplasmonic nanobiosensors based on gold nanoparticles,” Talanta 212, 120782 (2020).

58. Y. L. Liu, J. Zhu, G. J. Weng, J. J. Li, and J. W. Zhao, “Gold nanotubes: synthesis, properties and biomedical applications,” Microchimica Acta 187(11), 612 (2020).

59. F. Chu, S. Yan, J. Zheng, L. Zhang, H. Zhang, K. Yu, X. Sun, A. Liu, and Y. Huang, “A simple laser ablation-assisted method for fabrication of superhydrophobic SERS substrate on Teflon film,” Nanoscale Research Letters 13(1), 244 (2018).

60. J. Chi, T. Zaw, I. Cardona, M. Hosnain, N. Garg, H. R. Lefkowitz, P. Tolias, and H. Du, “Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection,” Biomedical Optics Express 6(3), 761–769 (2015).

61. M. Zong, L. Zhou, Q. Guan, D. Lin, J. Zhao, H. Qi, D. Harriman, L. Fan, H. Zeng, and C. Du, “Comparison of Surface-Enhanced Raman Scattering Properties of Serum and Urine for the Detection of Chronic Kidney Disease in Patients,” Applied Spectroscopy 75(4), 412–421 (2021).

62. J. Guo, Z. Rong, Y. Li, S. Wang, W. Zhang, and R. Xiao, “Diagnosis of chronic kidney diseases based on surface-enhanced Raman spectroscopy and multivariate analysis,” Laser Physics 28(7), 075603 (2018).

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