Disposable immunoplatforms for the simultaneous determination of biomarkers for neurodegenerative disorders using poly(amidoamine) dendrimer/gold nanoparticle nanocomposite

Abstract

Early diagnosis in primary care settings can increase access to therapies and their efficiency as well as reduce health care costs. In this context, we report in this paper the development of a disposable immunoplatform for the rapid and simultaneous determination of two protein biomarkers recently reported to be involved in the pathological process of neurodegenerative disorders (NDD), tau protein (tau), and TAR DNA-binding protein 43 (TDP-43). The methodology involves implementation of a sandwich-type immunoassay on the surface of dual screen-printed carbon electrodes (dSPCEs) electrochemically grafted with p-aminobenzoic acid (p-ABA), which allows the covalent immobilization of a gold nanoparticle-poly(amidoamine) (PAMAM) dendrimer nanocomposite (3D-Au-PAMAM). This scaffold was employed for the immobilization of the capture antibodies (CAbs). Detector antibodies labeled with horseradish peroxidase (HRP) and amperometric detection at − 0.20 V (vs. Ag pseudo-reference electrode) using the H2O2/hydroquinone (HQ) system were used. The developed methodology exhibits high sensitivity and selectivity for determining the target proteins, with detection limits of 2.3 and 12.8 pg mL−1 for tau and TDP-43, respectively. The simultaneous determination of tau and TDP-43 was accomplished in raw plasma samples and brain tissue extracts from healthy individuals and NDD-diagnosed patients. The analysis can be performed in just 1 h using a simple one-step assay protocol and small sample amounts (5 μL plasma and 2.5 μg brain tissue extracts).

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Forman MS, Trojanowski JQ, Lee VM. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med. 2004;10:1055–63.

    CAS  PubMed  Google Scholar 

  2. 2.

    Gleerup HS, Hasselbalch SG, Simonsen AH. Biomarkers for Alzheimer’s disease in saliva: a systematic review. Dis Markers. 2019;4761054. https://doi.org/10.1155/2019/4761054.

  3. 3.

    Irwin DJ, Trojanowski JQ, Grossman M. Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer’s disease. Front Aging Neurosci. 2013;5:6. https://doi.org/10.3389/fnagi.2013.00006.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Schneider P, Hampel H, Buerger K. Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci Ther. 2009;15:358–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Laske C, Sohrabi HR, Frost SM, Lopez-de-Ipiña K, Garrard P, Buscema M, et al. Innovative diagnostic tools for early detection of Alzheimer’s disease. Alzheimers Dement. 2015;11:561–78.

    PubMed  Google Scholar 

  6. 6.

    O’Bryant SE, Xiao G, Barber R, Huebinger R, Wilhelmsen K, Edwards M, et al. A blood-based screening tool for Alzheimer’s disease that spans serum and plasma: findings from TARC and ADNI. PLoS One. 2011;6:e28092. https://doi.org/10.1371/journal.pone.0028092.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    O’Bryant SE, Edwards M, Johnson L, Hall J, Villarreal AE, Britton GB, et al. A blood screening test for Alzheimer’s disease. Alzheimers Dement. 2016;3:83–90.

    Google Scholar 

  8. 8.

    Shi L, Baird AL, Westwood S, Hye A, Dobson R, Thambisetty M, et al. A decade of blood biomarkers for Alzheimer’s disease research: an evolving field, improving study designs, and the challenge of replication. J Alzheimers Dis. 2018;62:1181–98.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, et al. Microvascular injury and blood-brain barrier leakage in Alzheimer’s disease. Neurobiol Aging. 2007;28:977–86.

    CAS  PubMed  Google Scholar 

  10. 10.

    Zetterberg H, Burnham SC. Blood-based molecular biomarkers for Alzheimer’s disease. Mol Brain. 2019;12:26. https://doi.org/10.1186/s13041-019-0448-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    McAvoy T, Lassman ME, Spellman DS, Ke Z, Howell BJ, Wong O, et al. Quantification of tau in cerebrospinal fluid by immunoaffinity enrichment and tandem mass spectrometry. Clin Chem. 2014;60:e683–9.

    Google Scholar 

  12. 12.

    Kametani F, Obi T, Shishido T, Akatsu H, Murayama S, Saito Y, et al. Mass spectrometric analysis of accumulated TDP-43 in amyotrophic lateral sclerosis brains. Sci Rep. 2016;6:23281. https://doi.org/10.1038/srep23281.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Meeter LH, Kaat LD, Rohrer JD, van Swieten JC. Imaging and fluid biomarkers in frontotemporal dementia. Nat Rev Neurol. 2017;13:406–19.

    CAS  PubMed  Google Scholar 

  14. 14.

    Hye A, Riddoch-Contreras J, Baird AL, Ashton NJ, Bazenet C, Leung R, et al. Plasma proteins predict conversion to dementia from prodromal disease. Alzheimers Dement. 2014;10:799–807.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Law WP, Wang WY, Moore PT, Mollee PN, Ng AC. Cardiac amyloid imaging with 18F-florbetaben PET: a pilot study. J Nucl Med. 2016;57:1733–9.

    CAS  PubMed  Google Scholar 

  16. 16.

    Foulds PG, Davidson Y, Mishra M, Hobson DJ, Humphreys KM, Taylor M, et al. Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration. Acta Neuropathol. 2009;118:647–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Hosokawa M, Arai T, Yamashita M, Tsuji H, Nonaka T, Masuda-Suzukake M, et al. Differential diagnosis of amyotrophic lateral sclerosis from Guillain–Barre´ syndrome by quantitative determination of TDP-43 in cerebrospinal fluid. Int J Neurosci. 2014;124:344–9.

    CAS  PubMed  Google Scholar 

  18. 18.

    Junttila A, Kuvaja M, Hartikainen P, Siloaho M, Helisalmi S, Moilanen V, et al. Cerebrospinal fluid TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis patients with and without the C9ORF72 hexanucleotide expansion. Dement Geriatr Cogn Dis Extra. 2016;6:142–9.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Guntert A, Campbell J, Saleem M, O’Brien DP, Thompson AJ, Byers HL, et al. Plasma gelsolin is decreased and correlates with rate of decline in Alzheimer’s disease. J Alzheimers Dis. 2010;21:585–96.

    PubMed  Google Scholar 

  20. 20.

    Steinacker P, Hendrich C, Sperfeld AD, Jesse S, von Arnim CA, Lehnert S, et al. TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch Neurol. 2008;65:1481–7.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Arai T, Mackenzie IRA, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, et al. Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol. 2009;117:125–36.

    CAS  PubMed  Google Scholar 

  22. 22.

    Shui B, Tao D, Florea A, Cheng J, Zhao Q, Gu Y, et al. Biosensors for Alzheimer's disease biomarker detection: a review. Biochimica. 2018;147:13–24.

    CAS  Google Scholar 

  23. 23.

    Saleem M. Biosensors a promising future in measurements. IOP Conf Ser Mater Sci Eng. 2013;51. https://doi.org/10.1088/1757-899X/51/1/012012.

  24. 24.

    Scarano S, Lisi S, Ravelet C, Peyrin E, Minunni M. Detecting Alzheimer’s disease biomarkers: from antibodies to new biomimetic receptors and their application to established and emerging bioanalytical platforms – a critical review. Anal Chim Acta. 2016;940:21–37.

    CAS  PubMed  Google Scholar 

  25. 25.

    Marín S, Merkoçi A. Nanomaterials based electrochemical sensing applications for safety and security. Electroanalysis. 2012;24:459–69.

    Google Scholar 

  26. 26.

    Luo X, Morrin A, Killard AJ, Smyth MR. Application of nanoparticles in electrochemical sensors and biosensors. Electroanalysis. 2006;18:319–26.

    CAS  Google Scholar 

  27. 27.

    Mutali SA, Anwar RE, Radji M, Pujiyanto A, Purnamasari P, Joshita D, et al. Synthesis of gold nanoparticles with polyamidoamine (PAMAM) generation 4 dendrimer as stabilizing agent for CT scan contrast agent. Macromol Symp. 2015;353:96–101.

    Google Scholar 

  28. 28.

    Razzino CA, Serafín V, Gamella M, Pedrero M, Montero-Calle A, Barderas R, et al. An electrochemical immunosensor using gold nanoparticles-PAMAM-nanostructured screen-printed carbon electrodes for tau protein determination in plasma and brain tissues from Alzheimer patients. Biosens Bioelectron. 2020; in press. https://doi.org/10.1016/j.bios.2020.112238.

  29. 29.

    Umeda Y, Kojima C, Horinaka H, Kono K. PEG-attached PAMAM dendrimers encapsulating gold nanoparticles: growing gold nanoparticles in the dendrimers for improvement of their photothermal properties. Bioconjug Chem. 2010;21:1559–64.

    CAS  PubMed  Google Scholar 

  30. 30.

    Vasile E, Serafim A, Petre D, Giol D, Dubruel P, Iovu H, et al. Direct synthesis and morphological characterization of gold-dendrimer nanocomposites prepared using PAMAM succinamic acid dendrimers: preliminary study of the calcification potential. Sci World J. 2014. https://doi.org/10.1155/2014/103462.

  31. 31.

    Luo J, Dong M, Lin F, Liu M, Tang H, Li H, et al. Three-dimensional network polyamidoamine dendrimer-Au nanocomposite for the construction of a mediator-free horseradish peroxidase biosensor. Analyst. 2011;136:4500–6.

    CAS  PubMed  Google Scholar 

  32. 32.

    Araque E, Arenas CB, Gamella M, Reviejo J, Villalonga R, Pingarrón JM. Graphene–polyamidoamine dendrimer–Pt nanoparticles hybrid nanomaterial for the preparation of mediatorless enzyme biosensor. J Electroanal Chem. 2014;717:96–102.

    Google Scholar 

  33. 33.

    Borisova B, Sánchez A, Jiménez-Falcao S, Martín M, Salazar P, Parrado C, et al. Reduced graphene oxide-carboxymethylcellulose layered with platinum nanoparticles/PAMAM dendrimer/magnetic nanoparticles hybrids. Application to the preparation of enzyme electrochemical biosensors. Sensors Actuators B Chem. 2016;232:84–90.

    CAS  Google Scholar 

  34. 34.

    Zhang X, Shen J, Ma H, Jiang Y, Huang C, Han E, et al. Optimized dendrimer-encapsulated gold nanoparticles and enhanced carbon nanotube nanoprobes for amplified electrochemical immunoassay of E. coli in dairy product based on enzymatically induced deposition of polyaniline. Biosens Bioelectron. 2016;80:666–73.

    CAS  PubMed  Google Scholar 

  35. 35.

    Singal S, Srivastava AK, Kotnala, Rajesh RK. Single-frequency impedance analysis of biofunctionalized dendrimer-encapsulated Pt nanoparticles-modified screen-printed electrode for biomolecular detection. J Solid State Electrochem. 2018;22:2649–57.

    CAS  Google Scholar 

  36. 36.

    Liu B, Li M, Zhao Y, Pan M, Gu Y, Sheng W, et al. A sensitive electrochemical immunosensor based on PAMAM dendrimer-encapsulated Au for detection of norfloxacin in animal-derived foods. Sensors. 2018;18:1946. https://doi.org/10.3390/s18061946.

    CAS  Article  Google Scholar 

  37. 37.

    Niu X, Huang L, Zhao J, Yin M, Luo D, Yang Y. An ultrasensitive aptamer biosensor for the detection of codeine based on a Au nanoparticle/polyamidoamine dendrimer-modified screen printed carbon electrode. Anal Methods. 2016;8:1091–5.

    CAS  Google Scholar 

  38. 38.

    An Y, Jiang X, Bi W, Chen H, Jin L, Zhang S, et al. Sensitive electrochemical immunosensor for α-synuclein based on dual signal amplification using PAMAM dendrimer-encapsulated Au and enhanced gold nanoparticle labels. Biosens Bioelectron. 2012;32:224–30.

    CAS  PubMed  Google Scholar 

  39. 39.

    Pei X, Xu Z, Zhang J, Liu Z, Tian J. Electroactive dendrimer-encapsulated silver nanoparticles for sensing low-abundance proteins with signal amplification. Anal Methods. 2013;5:3235–41.

    CAS  Google Scholar 

  40. 40.

    Hu L, Dong T, Zhao K, Deng A, Li J. Ultrasensitive electrochemiluminescent brombuterol immunoassay by applying a multiple signal amplification strategy based on a PAMAM-gold nanoparticle conjugate as the bioprobe and Ag@Au core shell nanoparticles as a substrate. Microchim Acta. 2017;184:3415–23.

    CAS  Google Scholar 

  41. 41.

    Fang J, Guo Y, Yang Y, Yu W, Tao Y, Dai T, et al. Portable and sensitive detection of DNA based on personal glucose meters and nanogold-functionalized PAMAM dendrimer. Sensors Actuators B Chem. 2018;272:118–26.

    CAS  Google Scholar 

  42. 42.

    Sierks M, Williams S, Venkataraman L. Antibody based reagents that other publications specifically recognize neurodegenerative disease related forms of the protein TPD-43. (2019) Patent No.: US 10, 191, 068 B2: United States of America.

  43. 43.

    Baird AL, Westwood S, Lovestone S. Blood-based proteomic biomarkers of Alzheimer’s disease pathology. Front Neurol. 2015;6:236. https://doi.org/10.3389/fneur.2015.00236.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J. 1997;323:577–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Lee VM-Y, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24:1121–59.

    CAS  PubMed  Google Scholar 

  46. 46.

    Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, et al. TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol. 2007;61:435–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K, et al. Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer’s disease and dementia with Lewy bodies. Brain Res. 2007;1184:284–94.

    CAS  PubMed  Google Scholar 

  48. 48.

    Freeman SH, Spires-Jones T, Hyman BT, Growdon JH, Frosch MP. TAR-DNA binding protein 43 in Pick disease. J Neuropathol Exp Neurol. 2008;67:62–7.

    CAS  PubMed  Google Scholar 

  49. 49.

    Schwab C, Arai T, Hasegawa M, Yu S, McGeer PL. Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol. 2008;67:1159–65.

    PubMed  Google Scholar 

  50. 50.

    Kim YG, Oh SK, Crooks RM. Preparation and characterization of 1-2 nm dendrimer-encapsulated gold nanoparticles having very narrow size distributions. Chem Mater. 2004;16:167–72.

    CAS  Google Scholar 

  51. 51.

    Moreno-Guzmán M, Ojeda I, Villalonga R, González-Cortés A, Yáñez-Sedeño P, Pingarrón JM. Ultrasensitive detection of adrenocorticotropin hormone (ACTH) using disposable phenylboronic-modified electrochemical immunosensors. Biosens Bioelectron. 2012;35:82–6.

    PubMed  Google Scholar 

  52. 52.

    Mirra SS, Hart MN, Terry RD. Making the diagnosis of Alzheimer’s disease. A primer for practicing pathologists. Arch Pathol Lab Med. 1993;117:132–44.

    CAS  PubMed  Google Scholar 

  53. 53.

    Thal DR, Rub U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58:1791–800.

    PubMed  Google Scholar 

  54. 54.

    Barderas R, Babel I, Díaz-Uriarte R, Moreno V, Suárez A, Bonilla F, et al. An optimized predictor panel for colorectal cancer diagnosis based on the combination of tumor-associated antigens obtained from protein and phage microarrays. J Proteome. 2012;75:4647–55.

    CAS  Google Scholar 

  55. 55.

    Barderas R, Villar-Vázquez R, Fernández-Aceñero MJ, Babel I, Peláez-García A, Torres S, et al. Sporadic colon cancer murine models demonstrate the value of autoantibody detection for preclinical cancer diagnosis. Sci Rep. 2013;3:2938. https://doi.org/10.1038/srep02938.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Garranzo-Asensio M, San Segundo-Acosta P, Martínez-Useros J, Montero-Calle A, Fernández-Aceñero MJ, Häggmark-Månberg A, et al. Identification of prefrontal cortex protein alterations in Alzheimer’s disease. Oncotarget. 2018;9:10847–67.

    PubMed  PubMed Central  Google Scholar 

  57. 57.

    Gamella M, Campuzano S, Conzuelo F, Reviejo AJ, Pingarrón JM. Amperometric magnetoimmunosensors for direct determination of D-dimer in human serum. Electroanalysis. 2012;24:2235–43.

    CAS  Google Scholar 

  58. 58.

    Esteves-Villanueva JO, Trzeciakiewicz H, Martic S. A protein-based electrochemical biosensor for detection of tau protein, a neurodegenerative disease biomarker. Analyst. 2014;139:2823–31.

    CAS  PubMed  Google Scholar 

  59. 59.

    Derkus B, Ozkan M, Emregul KC, Emregul E. Single frequency analysis for clinical immunosensor design. RCS Adv. 2016;6:281–9.

    CAS  Google Scholar 

  60. 60.

    Derkus B, Bozkurt PA, Tulu M, Emregul KC, Yucesan C, Emregul E. Simultaneous quantification of myelin basic protein and tau proteins in cerebrospinal fluid and serum of multiple sclerosis patients using nanoimmunosensor. Biosens Bioelectron. 2017;89:781–8.

    CAS  PubMed  Google Scholar 

  61. 61.

    Dai Y, Molazemhosseini A, Liu CC. A single-use, in vitro biosensor for the detection of T-tau protein, a biomarker of neuro-degenerative disorders, in PBS and human serum using differential pulse voltammetry (DPV). Biosensors. 2017;7:10. https://doi.org/10.3390/bios7010010.

    CAS  Article  PubMed Central  Google Scholar 

  62. 62.

    Wang SX, Acha D, Shah AJ, Hills F, Roitt I, Demosthenous A, et al. Detection of the tau protein in human serum by a sensitive four-electrode electrochemical biosensor. Biosens Bioelectron. 2017;92:82–488.

    CAS  Google Scholar 

  63. 63.

    Shui B, Tao D, Cheng J, Mei Y, Jaffrezic-Renault N, Guo Z. A novel electrochemical aptamer–antibody sandwich assay for the detection of tau-381 in human serum. Analyst. 2018;143:3549–54.

    CAS  PubMed  Google Scholar 

  64. 64.

    Carlin N, Martic-Milne S. Anti-tau antibodies based electrochemical sensor for detection of tau protein biomarker. J Electrochem Soc. 2018;165:G3018–25.

    CAS  Google Scholar 

  65. 65.

    Tao D, Shui B, Gu Y, Cheng J, Zhang W, Jaffrezic-Renault N, et al. Development of a label-free electrochemical aptasensor for the detection of Tau381 and its preliminary application in AD and non-AD patients’ sera. Biosensors. 2019;9:84. https://doi.org/10.3390/bios9030084.

    CAS  Article  PubMed Central  Google Scholar 

  66. 66.

    Ye M, Jiang M, Cheng J, Li X, Liu Z, Zhang W, et al. Single-layer exfoliated reduced graphene oxide-antibody tau sensor for detection in human serum. Sensors Actuators B Chem. 2020;308:127692. https://doi.org/10.1016/j.snb.2020.127692.

    CAS  Article  Google Scholar 

  67. 67.

    Dai Y, Wang C, Chiu LY, Abbasi K, Tolbert BS, Sauvé G, et al. Application of bioconjugation chemistry on biosensor fabrication for detection of TAR-DNA binding protein 43. Biosens Bioelectron. 2018;117:60–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Grigorieva DV, Gorudko IV, Sokolov AV, Kosmachevskaya OV, Topunov AF, et al. Measurement of plasma hemoglobin peroxidase activity. Bull Exp Biol Med. 2013;155:118–21.

    CAS  PubMed  Google Scholar 

  69. 69.

    Zhao RN, Feng Z, Zhao YN, Jia LP, Ma RN, Zhang W, et al. A sensitive electrochemical aptasensor for Mucin1 detection based on catalytic hairpin assembly coupled with PtPdNPs peroxidase-like activity. Talanta. 2019;200:503–10.

    CAS  PubMed  Google Scholar 

  70. 70.

    Foulds PG, McAuley E, Gibbons L, Davidson Y, Pickering-Brown SM, Neary D, et al. TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer’s disease and frontotemporal lobar degeneration. Acta Neuropathol. 2008;116:141–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Müller S, Preische O, Göpfert JC, Carcamo Yañez VA, Joos TO, Boecker H, et al. Tau plasma levels in subjective cognitive decline: results from the DELCODE study. Sci Rep. 2017;7:9529. https://doi.org/10.1038/s41598-017-08779-0.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Wilson AC, Dugger BN, Dickson DW, Wang DS. TDP-43 in aging and Alzheimer’s disease – a review. Int J Clin Exp Pathol. 2011;4:147–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Steinacker P, Barschke P, Otto M. Biomarkers for diseases with TDP-43 pathology. Mol Cell Neurosci. 2019;97:43–59.

    CAS  PubMed  Google Scholar 

Download references

Funding

The financial support of the CTQ2015-64402-C2-1-R (Spanish Ministerio de Economía y Competitividad) and RTI2018-096135-B-I00 (Ministerio de Ciencia, Innovación y Universidades) Research Projects and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (Grant S2018/NMT-4349) are gratefully acknowledged. C.A.R. thanks FAPESP (Grant # 2018/14130-7, Sao Paulo Research Foundation (FAPESP)) for the support granted. R.B. acknowledges the financial support of the PI17CIII/00045 grant from the AES-ISCIII program. A.M-C. was supported by a predoctoral contract of the Fundación Tatiana Perez de Guzman el Bueno and now by an FPU predoctoral contract supported by the Spanish Ministerio de Educación, Cultura y Deporte. E.P. acknowledges a predoctoral contract from the Spanish Ministerio de Economía y Competitividad (BES-2016-076606). 

Author information

Affiliations

Authors

Corresponding authors

Correspondence to María Pedrero or Susana Campuzano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Disclaimer

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Published in the topical collection 2D Nanomaterials for Electroanalysis with guest editor Sabine Szunerits.

Electronic supplementary material

ESM 1

(PDF 459 kb).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Serafín, V., Razzino, C.A., Gamella, M. et al. Disposable immunoplatforms for the simultaneous determination of biomarkers for neurodegenerative disorders using poly(amidoamine) dendrimer/gold nanoparticle nanocomposite. Anal Bioanal Chem 413, 799–811 (2021). https://doi.org/10.1007/s00216-020-02724-3

Download citation

Keywords

  • Dual immunosensing platform
  • Tau
  • TDP-43
  • Amperometric detection
  • Plasma
  • Brain tissue extracts