Evaluation and validation of a point-of-care type biosensor for the measurement of S100B in plasma as a potential predictor of neurological impairment in traumatic brain injury

Traumatic brain injury (TBI) represents at least half of the trauma-related deaths, with a reported mortality rate of 37% in severe TBI. It is considered one of the significant causes of disability globally, producing high annual costs to the healthcare system. A crucial aspect in managing these patients is to predict their evolution immediately after the trauma, which allows an adequate classification of the TBI severity before the appearance of clinical or imaging indicators. The above has stimulated the search for other early indicators of brain injury, such as plasma biomarkers, among which the S100B protein, released from damaged nerve cells into the bloodstream, is one of the most extensively studied, with solid evidence reported associating its blood levels with the probability of intracranial injuries. Currently, the standard tests for S100B detection require either immunoassay or other complex/expensive laboratory techniques, which are also not available in primary trauma care areas, requiring prior sample processing. The little availability of cost-effective, easy-to-use, and rapid methods for the timely measurement of S100B justify the development of a point-of-care device to detect and quantify this biomarker. This work aims to fill this gap, focusing on the manufacture, evaluation, and validation of an electrochemical biosensor for the label-free detection of S100B in plasma. Disposable electrodes based on low-cost materials were used to manufacture two different platforms of detection: DropSens carbon-polyaniline and thin gold film three-contact electrodes. The first biosensor, based on the C-Pani, was fabricated using the covalent binding of the antibody to cysteamine-single assembled monolayer via EDC-NHS cross-linking. This biosensor was able to identify the S100B biomarker in spiked plasma through impedance measurements with a limit of detection of 34.13pg/ml in a range of 10-316pg/ml. In addition, a +0.2V DC set potential instead of open circuit potential (OCP) before the EIS runs was proposed as a novel strategy to counteract the undesirable effects on the electrical properties of pH on the Pani protonation and conductivity. The second developed biosensor used the same chemistry of functionalization, this time onto Au electrodes. The Au/Cys/anti-S100B biosensor showed selectivity to identify S100B in plasma in the 10pg-316pg/ml clinically relevant range and a limit of detection of 18pg/ml. Better overall results were obtained when a strategy based on Au electrodes instead C-Pani electrodes was implemented to construct the biosensor, supporting this approach as a promising strategy for the manufacture of an S100B-point-of-care-type biosensor. Furthermore, this strategy also could be a valuable framework for designing immunosensors for other biomarkers. Further studies are necessary to assess the developed biosensor using samples from multiple individuals, compared to the gold standard technique in clinical trials to evaluate the sensibility and specificity of the medical device and to identify nuisance factors affecting the measurement, such as temperature, humidity, electrical noise in real settings beyond the laboratory Future works are proposed to evaluate a point-of-care device in a predictive model that integrates S100B tests to clinical/tomographic data to support initial TBI classification, prognosis, and follow-up, becoming a guide for the therapeutic level of intensity.

• Autores: Rodríguez Sanjuán, Alexander
• Tipo de recurso: Doctoral thesis
• Fecha de publicación: 2021
• Institución: Universidad del Norte
• Repositorio: Repositorio Uninorte
• Idioma: eng
• OAI Identifier: oai:manglar.uninorte.edu.co:10584/12056
• Acceso en línea: http://hdl.handle.net/10584/12056
• Palabra clave: Biosensores; Electroquímica; Plasma sanguíneo; Lesiones cerebrales; Neurología
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/