{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:02:02Z","timestamp":1768802522482,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Cerebrospinal fluid (CSF) analysis supports diagnosis of neurodegenerative diseases (NDs), however a number of issues limits its potentialities in clinical practice. Here, a newly developed technique for fluid voltammetry, relying on a simple sensor (BIOsensor-based multisensorial system for mimicking Nose, Tongue and Eyes, BIONOTE), was used to test the applicability for CSF analysis. BIONOTE was initially calibrated on an artificial CSF-like solution and then applied on human CSF, either immediately after collection or after refrigerated storage. Following optimization, it was used to evaluate 11 CSF samples correlating the electrochemical dataset with CSF routine parameters and biomarkers of neurodegeneration. Multivariate data analysis was performed for model elaboration and calibration using principal component analysis and partial least squares discriminant analysis. BIONOTE presented a high capacity to predict both physiological and pathological constituents of artificial CSF. It differentiated distinct fresh human CSF samples well but lost accuracy after refrigerated storage. The electrochemical analysis-derived data correlated with either CSF routine cytochemical indexes or a biomarker of neurodegeneration. BIONOTE resulted as being a reliable system for electrochemical analysis of CSF. The CSF fingerprint provided by the sensor has shown itself to be sensitive to CSF modification, thus it is potentially representative of CSF alteration. This result opens the way to its testing in further study addressed at assessing the clinical relevance of the methodology. Because of its advantages due to the ease and rapidity of the methodology, a validation study is now required to translate the technique into clinical practice and improve diagnostic workup of NDs.<\/jats:p>","DOI":"10.3390\/s21113767","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T03:45:29Z","timestamp":1622432729000},"page":"3767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design of an Innovative Methodology for Cerebrospinal Fluid Analysis: Preliminary Results"],"prefix":"10.3390","volume":"21","author":[{"given":"Tommaso","family":"Schirinzi","sequence":"first","affiliation":[{"name":"Department of Systems Medicine, University of Roma Tor Vergata, 00133 Rome, Italy"}]},{"given":"Alberto","family":"Cordella","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy"},{"name":"Department of Fundamental Neurosciences, University of Lausanne, 1015 Lausanne, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-7491","authenticated-orcid":false,"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Roma Tor Vergata, 00133 Rome, Italy"},{"name":"IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy"}]},{"given":"Arnaldo","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, University of Roma Tor Vergata, 00133 Rome, Italy"}]},{"given":"Andrea","family":"Palombi","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, University of Roma Tor Vergata, 00133 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-4426","authenticated-orcid":false,"given":"Alessandro","family":"Zompanti","sequence":"additional","affiliation":[{"name":"Department of Engineering, Campus Bio-Medico, University of Rome Italy, 00128 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-7966","authenticated-orcid":false,"given":"Simone","family":"Grasso","sequence":"additional","affiliation":[{"name":"Department of Science and Technology for Humans and the Environment, Campus Bio-Medico, University of Rome Italy, 00128 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-9445","authenticated-orcid":false,"given":"Giorgio","family":"Pennazza","sequence":"additional","affiliation":[{"name":"Department of Engineering, Campus Bio-Medico, University of Rome Italy, 00128 Rome, Italy"}]},{"given":"Marco","family":"Santonico","sequence":"additional","affiliation":[{"name":"Department of Science and Technology for Humans and the Environment, Campus Bio-Medico, University of Rome Italy, 00128 Rome, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schirinzi, T., Canevelli, M., Suppa, A., Bologna, M., and Marsili, L. (2020). The continuum between neurodegeneration, brain plasticity, and movement: A critical appraisal. Rev. Neurosci.","DOI":"10.1515\/revneuro-2020-0011"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/mds.27360","article-title":"Disease modification in Parkinson\u2019s disease: Current approaches, challenges, and future considerations","volume":"33","author":"Lang","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Schirinzi, T., Sancesario, G.M., Di Lazzaro, G., Biticchi, B., Colona, V.L., Mercuri, N.B., Bernardini, S., and Pisani, A. (2018). CSF \u03b1-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients. Parkinsonism Relat. Disord.","DOI":"10.1016\/j.parkreldis.2018.10.018"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.neurobiolaging.2020.02.012","article-title":"Young-onset and late-onset Parkinson\u2019s disease exhibit a different profile of fluid biomarkers and clinical features","volume":"90","author":"Schirinzi","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Schirinzi, T., Sancesario, G.M., Di Lazzaro, G., Scalise, S., Colona, V.L., Imbriani, P., Mercuri, N.B., Bernardini, S., Lang, A.E., and Pisani, A. (2018). Clinical value of CSF amyloid-beta-42 and tau proteins in progressive supranuclear palsy. J. Neural Transm.","DOI":"10.1007\/s00702-018-1893-1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13195-018-0359-x","article-title":"White paper by the society for CSF analysis and clinical neurochemistry: Overcoming barriers in biomarker development and clinical translation","volume":"10","author":"Teunissen","year":"2018","journal-title":"Alzheimers. Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pennazza, G., Santonico, M., Vollero, L., Zompanti, A., Sabatini, A., Kumar, N., Pini, I., Solano, W.F.Q., Sarro, L., and D\u2019Amico, A. (2018). Advances in the electronics for cyclic voltammetry: The case of gas detection by using microfabricated electrodes. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00327"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16625","DOI":"10.3390\/s131216625","article-title":"Design and test of a Biosensor-based multisensorial system: A proof of concept study","volume":"13","author":"Santonico","year":"2013","journal-title":"Sensors"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pipita, M.E., Santonico, M., Pennazza, G., Zompanti, A., Fazzina, S., Cavalieri, D., Bruno, F., Angeletti, S., Pedone, C., and Incalzi, R.A. (2020). Integration of voltammetric analysis, protein electrophoresis and pH measurement for diagnosis of pleural effusions: A non-conventional diagnostic approach. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-71542-5"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Muley, M., Vespasiani-Gentilucci, U., de Vincentis, A., Santonico, M., Pennazza, G., Sanguedolce, S., de Luca, C., Plotti, F., Picardi, A., and Antonelli-Incalzi, R. (2020). Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: A proof of concept study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0233350"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/wrr.12696","article-title":"Use of voltammetric analysis for fast and objective discrimination of the etiology, evolution, and bacterial infection of lower limb ulcers","volume":"27","author":"Lelli","year":"2019","journal-title":"Wound Repair Regen."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lelli, D., Pedone, C., Alemanno, P., Bertini, A., Di Gioia, C., Fazzina, S., Pennazza, G., Santonico, M., Grasso, S., and Zompanti, A. (2018). Voltammetric analysis for fast and inexpensive diagnosis of urinary tract infection: A diagnostic study. J. Transl. Med., 16.","DOI":"10.1186\/s12967-018-1393-y"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.7150\/thno.29232","article-title":"Highly sensitive quantification of Alzheimer\u2019s disease biomarkers by aptamer-assisted amplification","volume":"9","author":"Chan","year":"2019","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1016\/j.nano.2018.05.013","article-title":"Rapid multiplexed detection of beta-amyloid and total-tau as biomarkers for Alzheimer\u2019s disease in cerebrospinal fluid","volume":"14","author":"Song","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112129","DOI":"10.1016\/j.bios.2020.112129","article-title":"A transistor-based label-free immunosensor for rapid detection of tau protein","volume":"159","author":"Haustein","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11892","DOI":"10.1021\/ja052522q","article-title":"A rapid label-free electrochemical detection and kinetic study of alzheimer\u2019s amyloid beta aggregation","volume":"127","author":"Vestergaard","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.neuroscience.2007.12.008","article-title":"Hydrogen sulphide in the hypothalamus causes an ATP-sensitive K+ channel-dependent decrease in blood pressure in freely moving rats","volume":"152","author":"Dawe","year":"2008","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"B466","DOI":"10.1149\/2.1151810jes","article-title":"Communication\u2014Electrooxidation of dopamine at CoNP-pAHNSA modified electrode: A sensitive approach to its determination","volume":"165","author":"Thomas","year":"2018","journal-title":"J. Electrochem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/ana.24372","article-title":"Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis","volume":"77","author":"Davoli","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fneur.2015.00086","article-title":"A clinical and biochemical analysis in the differential diagnosis of idiopathic normal pressure hydrocephalus","volume":"6","author":"Schirinzi","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Di Natale, C., Martinelli, E., Pennazza, G., Orsini, A., and Santonico, M. (2006). Data analysis for chemical sensor arrays. NATO Secur. Sci. Ser. A Chem. Biol., 147\u2013169.","DOI":"10.1007\/1-4020-4295-7_07"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3233\/JAD-171166","article-title":"Amyloid-mediated cholinergic dysfunction in motor impairment related to Alzheimer\u2019s disease","volume":"64","author":"Schirinzi","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jns.2014.11.012","article-title":"Symptomatic nonconvulsive status epilepticus erroneously suggestive of sporadic Creutzfeldt-Jakob disease","volume":"348","author":"Albanese","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_25","first-page":"455","article-title":"Cerebrospinal fluid biomarkers in Alzheimer\u2019s disease: Diagnostic accuracy and prediction of dementia","volume":"1","author":"Forlenza","year":"2015","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Schirinzi, T., Di Lazzaro, G., Sancesario, G.M., Colona, V.L., Scaricamazza, E., Mercuri, N.B., Martorana, A., and Sancesario, G. (2017). Levels of amyloid-beta-42 and CSF pressure are directly related in patients with Alzheimer\u2019s disease. J. Neural Transm.","DOI":"10.1007\/s00702-017-1786-8"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/11\/3767\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:12Z","timestamp":1760163012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/11\/3767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["s21113767"],"URL":"https:\/\/doi.org\/10.3390\/s21113767","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]}}}