Microchimica Acta

, 186:838 | Cite as

Biosensors and nanobiosensors for rapid detection of autoimmune diseases: a review

  • Farzaneh Ghorbani
  • Hossein Abbaszadeh
  • Amir Mehdizadeh
  • Majid Ebrahimi-Warkiani
  • Mohammad-Reza Rashidi
  • Mehdi YousefiEmail author
Review Article


This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on amperometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities.

Graphical abstract

Schematic representation of various developed optical and electrochemical biosensors and nanobiosensors for rapid detection of autoimmune diseases nanobiosensors for rapid detection of autoimmune diseases which could significantly prevent irreversable tissue damages and increse the quality of life in these patients


Biosensor Nanomaterial Autoantibodies Sensing Biomarkers 



The authors acknowledge the Stem Cell Research Center at Tabriz University of Medical Sciences, Tabriz, Iran for their great help.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no competing interests.


  1. 1.
    Tozzoli R (2008) The diagnostic role of autoantibodies in the prediction of organ-specific autoimmune diseases. Clin Chem Lab Med 46(5):577–587CrossRefGoogle Scholar
  2. 2.
    Sinha AA, Lopez MT, McDevitt HO (1990) Autoimmune diseases: the failure of self tolerance. Science 248(4961):1380–1388CrossRefGoogle Scholar
  3. 3.
    Zhang X, Zambrano A, Lin Z-T, Xing Y, Rippy J, Wu T (2017) Immunosensors for biomarker detection in autoimmune diseases. Arch Immunol Ther Exp 65(2):111–121. CrossRefGoogle Scholar
  4. 4.
    Ahmadi M, Gharibi T, Dolati S, Rostamzadeh D, Aslani S, Baradaran B et al (2017) Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases. Biomed Pharmacother 87:596–608. CrossRefPubMedGoogle Scholar
  5. 5.
    Zharkova O, Celhar T, Cravens PD, Satterthwaite AB, Fairhurst AM, Davis LS (2017) Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology (Oxford) 56(suppl_1):i55–i66. CrossRefGoogle Scholar
  6. 6.
    Burbelo PD, O'Hanlon TP (2014) New autoantibody detection technologies yield novel insights into autoimmune disease. Curr Opin Rheumatol 26(6):717–723. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Conrad K, Roggenbuck D, Reinhold D, Sack U (2012) Autoantibody diagnostics in clinical practice. Autoimmun Rev 11(3):207–211. CrossRefPubMedGoogle Scholar
  8. 8.
    Rose NR (2008) Predictors of autoimmune disease: autoantibodies and beyond. Autoimmunity 41(6):419–428. CrossRefPubMedGoogle Scholar
  9. 9.
    Campuzano S, Pedrero M, González-Cortés A, Yáñez-Sedeño P, Pingarrón JM (2019) Electrochemical biosensors for autoantibodies in autoimmune and cancer diseases. Anal Methods 11(7):871–887. CrossRefGoogle Scholar
  10. 10.
    Thaler M, Buhl A, Welter H, Schreiegg A, Kehrel M, Alber B et al (2009) Biosensor analyses of serum autoantibodies: application to antiphospholipid syndrome and systemic lupus erythematosus. Anal Bioanal Chem 393(5):1417–1429. CrossRefPubMedGoogle Scholar
  11. 11.
    Nguyen HH, Park J, Kang S, Kim M (2015) Surface plasmon resonance: a versatile technique for biosensor applications. Sensors (Basel) 15(5):10481–10510. CrossRefGoogle Scholar
  12. 12.
    Turner APF (2013) Biosensors: sense and sensibility. Chem Soc Rev 42(8):3184–3196. CrossRefPubMedGoogle Scholar
  13. 13.
    Abolhasan R, Mehdizadeh A, Rashidi MR, Aghebati-Maleki L, Yousefi M (2019) Application of hairpin DNA-based biosensors with various signal amplification strategies in clinical diagnosis. Biosens Bioelectron 129:164–174. CrossRefPubMedGoogle Scholar
  14. 14.
    Damborský P, Švitel J, Katrlík J (2016) Optical biosensors. Essays Biochem 60(1):91–100. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Holzinger M, Le Goff A, Cosnier S (2014) Nanomaterials for biosensing applications: a review. Frontiers in chemistry 2:63–63. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zasonska BA, Hlidkova H, Petrovsky E, Myronovskij S, Nehrych T, Negrych N et al (2018) Monodisperse magnetic poly(glycidyl methacrylate) microspheres for isolation of autoantibodies with affinity for the 46 kDa form of unconventional Myo1C present in autoimmune patients. Microchim Acta 185(5):262. CrossRefGoogle Scholar
  17. 17.
    Derkus B, Acar Bozkurt P, Tulu M, Emregul KC, Yucesan C, Emregul E (2017) Simultaneous quantification of myelin basic protein and tau proteins in cerebrospinal fluid and serum of multiple sclerosis patients using nanoimmunosensor. Biosens Bioelectron 89(Pt 2):781–788. CrossRefPubMedGoogle Scholar
  18. 18.
    Vega B, Calle A, Sanchez A, Lechuga LM, Ortiz AM, Armelles G et al (2013) Real-time detection of the chemokine CXCL12 in urine samples by surface plasmon resonance. Talanta 109:209–215. CrossRefPubMedGoogle Scholar
  19. 19.
    La Belle JT, Bhavsar K, Fairchild A, Das A, Sweeney J, Alford TL et al (2007) A cytokine immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy. Biosens Bioelectron 23(3):428–431. CrossRefPubMedGoogle Scholar
  20. 20.
    Pang X, Zhang Y, Pan J, Zhao Y, Chen Y, Ren X et al (2016) A photoelectrochemical biosensor for fibroblast-like synoviocyte cell using visible light-activated NCQDs sensitized-ZnO/CH3NH3PbI3 heterojunction. Biosens Bioelectron 77:330–338. CrossRefPubMedGoogle Scholar
  21. 21.
    Tadi KK, Alshanski I, Mervinetsky E, Marx G, Petrou P, Dimitrios KM et al (2017) Oxytocin-monolayer-based Impedimetric biosensor for zinc and copper ions. ACS Omega 2(12):8770–8778. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Huang Y, Xu J, Liu J, Wang X, Chen B (2017) Disease-related detection with electrochemical biosensors: A review. Sensors (Basel) 17(10):2375. CrossRefGoogle Scholar
  23. 23.
    Fagúndez P, Brañas G, Cairoli E, Laíz J, Tosar JP (2018) An electrochemical biosensor for rapid detection of anti-dsDNA antibodies in absolute scale. Analyst 143(16):3874–3882. CrossRefPubMedGoogle Scholar
  24. 24.
    Giannetto M, Mattarozzi M, Umiltà E, Manfredi A, Quaglia S, Careri M (2014) An amperometric immunosensor for diagnosis of celiac disease based on covalent immobilization of open conformation tissue transglutaminase for determination of anti-tTG antibodies in human serum. Biosens Bioelectron 62:325–330. CrossRefPubMedGoogle Scholar
  25. 25.
    Dulay S, Lozano-Sanchez P, Iwuoha E, Katakis I, O'Sullivan CK (2011) Electrochemical detection of celiac disease-related anti-tissue transglutaminase antibodies using thiol based surface chemistry. Biosens Bioelectron 26(9):3852–3856. CrossRefPubMedGoogle Scholar
  26. 26.
    Rosales-Rivera LC, Dulay S, Lozano-Sanchez P, Katakis I, Acero-Sanchez JL, O'Sullivan CK (2017) Disulfide-modified antigen for detection of celiac disease-associated anti-tissue transglutaminase autoantibodies. Anal Bioanal Chem 409(15):3799–3806. CrossRefPubMedGoogle Scholar
  27. 27.
    Rosales-Rivera LC, Acero-Sánchez JL, Lozano-Sánchez P, Katakis I, O'Sullivan CK (2011) Electrochemical immunosensor detection of antigliadin antibodies from real human serum. Biosens Bioelectron 26(11):4471–4476. CrossRefPubMedGoogle Scholar
  28. 28.
    Ortiz M, Fragoso A, O'Sullivan CK (2011) Detection of Antigliadin autoantibodies in celiac patient samples using a Cyclodextrin-based supramolecular biosensor. Anal Chem 83(8):2931–2938. CrossRefPubMedGoogle Scholar
  29. 29.
    Wajs E, Fernández N, Fragoso A (2016) Supramolecular biosensors based on electropolymerised pyrrole–cyclodextrin modified surfaces for antibody detection. Analyst 141(11):3274–3279. CrossRefPubMedGoogle Scholar
  30. 30.
    Villa Mde G, Jimenez-Jorquera C, Haro I, Gomara MJ, Sanmarti R, Fernandez-Sanchez C, Mendoza E (2011) Carbon nanotube composite peptide-based biosensors as putative diagnostic tools for rheumatoid arthritis. Biosens Bioelectron 27(1):113–118. CrossRefPubMedGoogle Scholar
  31. 31.
    Li S, Zhang R, Li P, Yi W, Zhang Z, Chen S et al (2008) Development of a novel method to measure macrophage migration inhibitory factor (MIF) in sera of patients with rheumatoid arthritis by combined electrochemical immunosensor. Int Immunopharmacol 8(6):859–865. CrossRefPubMedGoogle Scholar
  32. 32.
    Yusoff N, Rameshkumar P, Mohamed Noor AA, Huang NM (2018) Amperometric determination of L-cysteine using a glassy carbon electrode modified with palladium nanoparticles grown on reduced graphene oxide in a Nafion matrix. Microchim Acta 185(4):246. CrossRefGoogle Scholar
  33. 33.
    Wilson L, Franke C, Ross N, Sunday CR, Makelane H, Bilibana M, . . ., Iwuoha IE (2015) Electrochemical Immunosensor Based on the Interactions Between Polypyrrole and Cobalt (II) Salicylaldiimine Dendrimer 10Google Scholar
  34. 34.
    West N, Baker P, Waryo T, Ngece FR, Iwuoha EI, O’Sullivan C, Katakis I (2013) Highly sensitive gold-overoxidized polypyrrole nanocomposite immunosensor for antitransglutaminase antibody. J Bioact Compat Polym 28(2):167–177. CrossRefGoogle Scholar
  35. 35.
    Singh KV, Bhura DK, Nandamuri G, Whited AM, Evans D, King J, Solanki R (2011) Nanoparticle-enhanced sensitivity of a nanogap-interdigitated electrode array impedimetric biosensor. Langmuir 27(22):13931–13939. CrossRefPubMedGoogle Scholar
  36. 36.
    Derkus B, Emregul E, Yucesan C, Cebesoy Emregul K (2013) Myelin basic protein immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy. Biosens Bioelectron 46:53–60. CrossRefPubMedGoogle Scholar
  37. 37.
    Bhavsar K, Fairchild A, Alonas E, Bishop DK, La Belle JT, Sweeney J et al (2009) A cytokine immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy using electroplated printed circuit board electrodes. Biosens Bioelectron 25(2):506–509. CrossRefPubMedGoogle Scholar
  38. 38.
    Biela A, Watkinson M, Meier UC, Baker D, Giovannoni G, Becer CR, Krause S (2015) Disposable MMP-9 sensor based on the degradation of peptide cross-linked hydrogel films using electrochemical impedance spectroscopy. Biosens Bioelectron 68:660–667. CrossRefPubMedGoogle Scholar
  39. 39.
    Neves MMPS, González-García MB, Nouws HPA, Costa-García A (2012) Celiac disease detection using a transglutaminase electrochemical immunosensor fabricated on nanohybrid screen-printed carbon electrodes. Biosens Bioelectron 31(1):95–100. CrossRefPubMedGoogle Scholar
  40. 40.
    Neves MMPS, González-García MB, Santos-Silva A, Costa-García A (2012) Voltammetric immunosensor for the diagnosis of celiac disease based on the quantification of anti-gliadin antibodies. Sensors Actuators B Chem 163(1):253–259. CrossRefGoogle Scholar
  41. 41.
    Neves M, González-García M, Nouws PAH, Costa-García A (2013) An electrochemical deamidated gliadin antibody immunosensor for celiac disease clinical diagnosis 138Google Scholar
  42. 42.
    Gupta S, Kaushal A, Kumar A, Kumar D (2017) Ultrasensitive transglutaminase based nanosensor for early detection of celiac disease in human. Int J Biol Macromol 105(Pt 1):905–911. CrossRefPubMedGoogle Scholar
  43. 43.
    Real-Fernandez F, Colson A, Bayardon J, Nuti F, Peroni E, Meunier-Prest R et al (2008) Ferrocenyl glycopeptides as electrochemical probes to detect autoantibodies in multiple sclerosis patients' sera. Biopolymers 90(4):488–495. CrossRefPubMedGoogle Scholar
  44. 44.
    Martin-Yerga D, Costa-Garcia A (2015) Towards a blocking-free electrochemical immunosensing strategy for anti-transglutaminase antibodies using screen-printed electrodes. Bioelectrochemistry 105:88–94. CrossRefPubMedGoogle Scholar
  45. 45.
    Martin-Yerga D, Fanjul-Bolado P, Hernandez-Santos D, Costa-Garcia A (2017) Enhanced detection of quantum dots by the magnetohydrodynamic effect for electrochemical biosensing. Analyst 142(9):1591–1600. CrossRefPubMedGoogle Scholar
  46. 46.
    Martin-Yerga D, Gonzalez-Garcia MB, Costa-Garcia A (2014) Electrochemical immunosensor for anti-tissue transglutaminase antibodies based on the in situ detection of quantum dots. Talanta 130:598–602. CrossRefPubMedGoogle Scholar
  47. 47.
    Ghalehno MH, Mirzaei M, Torkzadeh-Mahani M (2018) Aptamer-based determination of tumor necrosis factor alpha using a screen-printed graphite electrode modified with gold hexacyanoferrate. Microchim Acta 185(3):165. CrossRefGoogle Scholar
  48. 48.
    Wang H, Wu X, Dong P, Wang C, Wang J, Liu Y, Chen J (2014) Electrochemical biosensor based on interdigitated electrodes for determination of thyroid stimulating hormone. Int J Electrochem Sci 9:12–21Google Scholar
  49. 49.
    Singh V, Krishnan S (2015) Voltammetric immunosensor assembled on carbon-pyrenyl nanostructures for clinical diagnosis of type of diabetes. Anal Chem 87(5):2648–2654. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Kergaravat SV, Beltramino L, Garnero N, Trotta L, Wagener M, Isabel Pividori M, Hernandez SR (2013) Electrochemical magneto immunosensor for the detection of anti-TG2 antibody in celiac disease. Biosens Bioelectron 48:203–209. CrossRefPubMedGoogle Scholar
  51. 51.
    Hu H, Pan D, Xue H, Zhang M, Zhang Y, Shen Y (2018) A photoelectrochemical immunoassay for tumor necrosis factor-α using a GO-PTCNH2 nanohybrid as a probe. J Electroanal Chem 824:195–200. CrossRefGoogle Scholar
  52. 52.
    Liu X-P, Xie X-L, Wei Y-P, Mao C-J, Chen J-S, Niu H-L et al (2017) Photoelectrochemical immunoassay for human interleukin 6 based on the use of perovskite-type LaFeO3 nanoparticles on fluorine-doped tin oxide glass. Microchim Acta 185(1):52 CrossRefGoogle Scholar
  53. 53.
    Perumal V, Hashim UJJOAB (2014) Advances in biosensors. Principle Architect Appl 12(1):1–15Google Scholar
  54. 54.
    Brett C (2008) Electrochemical impedance spectroscopy for characterization of electrochemical sensors and biosensors 13Google Scholar
  55. 55.
    Xu R, Wei D, Du B, Cao W, Fan D, Zhang Y et al (2018) A photoelectrochemical sensor for highly sensitive detection of amyloid beta based on sensitization of Mn:CdSe to Bi2WO6/CdS. Biosens Bioelectron 122:37–42. CrossRefPubMedGoogle Scholar
  56. 56.
    Ghorbani F, Abbaszadeh H, Dolatabadi JEN, Aghebati-Maleki L, Yousefi M (2019) Application of various optical and electrochemical aptasensors for detection of human prostate specific antigen: A review. Biosens Bioelectron 142:111484. CrossRefPubMedGoogle Scholar
  57. 57.
    Bostan HB, Taghdisi SM, Bowen JL, Demertzis N, Rezaee R, Panahi Y et al (2018) Determination of microcystin-LR, employing aptasensors. Biosens Bioelectron 119:110–118. CrossRefPubMedGoogle Scholar
  58. 58.
    Habtamu HB, Sentic M, Silvestrini M, De Leo L, Not T, Arbault S et al (2015) A sensitive Electrochemiluminescence Immunosensor for celiac disease diagnosis based on Nanoelectrode ensembles. Anal Chem 87(24):12080–12087. CrossRefPubMedGoogle Scholar
  59. 59.
    Zhao Y, Liu Y, Li X, Wang H, Zhang Y, Ma H, Wei Q (2018) Label-free ECL immunosensor for the early diagnosis of rheumatoid arthritis based on asymmetric heterogeneous polyaniline-gold nanomaterial. Sensors Actuators B Chem 257:354–361. CrossRefGoogle Scholar
  60. 60.
    Ma X, Fang C, Yan J, Zhao Q, Tu Y (2018) A label-free electrochemiluminescent immunosensor for glutamate decarboxylase antibody detection on AuNPs supporting interface. Talanta 186:206–214. CrossRefPubMedGoogle Scholar
  61. 61.
    Mansourian N, Rahaie M, Hosseini M (2017) A Nanobiosensor based on fluorescent DNA-hosted silver nanocluster and HCR amplification for detection of MicroRNA involved in progression of multiple sclerosis. J Fluoresc 27(5):1679–1685. CrossRefPubMedGoogle Scholar
  62. 62.
    Ko H, Lee G-Y, Jeon B-J, Pyun J-C (2011) Fluorescence immunoassay of anti-cyclic citrulinated peptide (CCP) autoantibodies by using parylene-H film. BioChip J 5(3):242. CrossRefGoogle Scholar
  63. 63.
    Lee JW, Sim SJ, Cho SM, Lee J (2005) Characterization of a self-assembled monolayer of thiol on a gold surface and the fabrication of a biosensor chip based on surface plasmon resonance for detecting anti-GAD antibody. Biosens Bioelectron 20(7):1422–1427. CrossRefPubMedGoogle Scholar
  64. 64.
    Cao C, Sim SJ (2007) Signal enhancement of surface plasmon resonance immunoassay using enzyme precipitation-functionalized gold nanoparticles: A femto molar level measurement of anti-glutamic acid decarboxylase antibody. Biosens Bioelectron 22(9):1874–1880. CrossRefPubMedGoogle Scholar
  65. 65.
    Cennamo N, Varriale A, Pennacchio A, Staiano M, Massarotti D, Zeni L, D’Auria S (2013) An innovative plastic optical fiber-based biosensor for new bio/applications. The case of celiac disease. Sensors Actuators B Chem 176:1008–1014. CrossRefGoogle Scholar
  66. 66.
    Soler M, Estevez MC, Moreno Mde L, Cebolla A, Lechuga LM (2016) Label-free SPR detection of gluten peptides in urine for non-invasive celiac disease follow-up. Biosens Bioelectron 79:158–164. CrossRefPubMedGoogle Scholar
  67. 67.
    Real-Fernandez F, Rossi G, Lolli F, Papini AM, Rovero P (2015) Label-free method for anti-glucopeptide antibody detection in multiple sclerosis. MethodsX 2:141–144. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Bustos RH, Zapata C, Esteban E, Garcia JC, Jauregui E, Jaimes D (2018) Label-free quantification of anti-TNF-alpha in patients treated with adalimumab using an optical biosensor. Sensors (Basel), 18(3). doi: CrossRefGoogle Scholar
  69. 69.
    Beleoken E, Leh H, Arnoux A, Ducot B, Nogues C, De Martin E et al (2013) SPRi-based strategy to identify specific biomarkers in systemic lupus erythematosus, rheumatoid arthritis and autoimmune hepatitis. PLoS One 8(12):e84600. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Sguassero A, Artiga A, Morasso C, Jimenez RR, Rapun RM, Mancuso R et al (2019) A simple and universal enzyme-free approach for the detection of multiple microRNAs using a single nanostructured enhancer of surface plasmon resonance imaging. Anal Bioanal Chem 411(9):1873–1885. CrossRefPubMedGoogle Scholar
  71. 71.
    Liu S, Tong Z, Mu X, Liu B, Du B, Liu Z, Gao C (2018) Detection of Abrin by Electrochemiluminescence biosensor based on screen printed electrode. Sensors (Basel) 18(2):357. CrossRefGoogle Scholar
  72. 72.
    Khalilzadeh B, Shadjou N, Kanberoglu GS, Afsharan H, de la Guardia M, Charoudeh HN et al (2018) Advances in nanomaterial based optical biosensing and bioimaging of apoptosis via caspase-3 activity: a review. Microchim Acta 185(9):434. CrossRefGoogle Scholar
  73. 73.
    Dong H, Hao K, Tian Y, Jin S, Lu H, Zhou SF, Zhang X (2014) Label-free and ultrasensitive microRNA detection based on novel molecular beacon binding readout and target recycling amplification. Biosens Bioelectron 53:377–383. CrossRefPubMedGoogle Scholar
  74. 74.
    Leon SA, Green A, Ehrlich GE, Poland M, Shapiro B (1977) Avidity of antibodies in sle. Arthrit Rheumat 20(1):23–29. CrossRefGoogle Scholar
  75. 75.
    Saraux A, Bendaoud B, Dueymes M, Le Goff P, Youinou P (1997) The functional affinity of IgM rheumatoid factor is related to the disease duration in patients with rheumatoid arthritis. Ann Rheum Dis 56(2):126–129. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Yousefi M, Dehghani S, Nosrati R, Zare H, Evazalipour M, Mosafer J et al (2019) Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review. Biosens Bioelectron 130:1–19. CrossRefPubMedGoogle Scholar
  77. 77.
    Dehghani S, Nosrati R, Yousefi M, Nezami A, Soltani F, Taghdisi SM et al (2018) Aptamer-based biosensors and nanosensors for the detection of vascular endothelial growth factor (VEGF): A review. Biosens Bioelectron 110:23–37. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Student Research CommitteeTabriz University of Medical SciencesTabrizIran
  3. 3.Endocrine Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.School of Biomedical EngineeringUniversity Technology of SydneySydneyAustralia
  5. 5.Aging Research InstituteTabriz University of Medical SciencesTabrizIran
  6. 6.Department of Immunology, Faculty of MedicineTabriz University of Medical SciencesTabrizIran

Personalised recommendations