Application of ionic liquids in the concentration of cancer biomarkers

• Autor(a) principal: Quental, Maria João Valente
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/13784
• topic: Bioquímica clínica; Cancro da próstata; Antigenes; Marcadores bioquímicos; Sistemas aquosos bifásicos; Soluções iónicas

Prostate cancer (CaP) is the third most common cancer-related cause of death in men. Currently, there are no effective therapeutic options for the treatment of advanced prostate cancer and its early detection is pivotal and can increase the curative successful rate. The quantification of prostate specific antigen (PSA) levels in serum remains the most commonly used screening approach. Nevertheless, most of the PSA assays currently applied present several drawbacks, namely a time-consuming sample processing, the identification and characterization of specific antibodies and the need of highly trained technical operators. Therefore, in order to develop an efficient method to extract and concentrate PSA from human fluids and also to overcome the limitations of traditional analytical equipment, in this work, aqueous biphasic systems (ABS) composed of ionic liquids (ILs) were employed as an extraction and concentration liquid-liquid technique. Since the commercially available cancer biomarkers are highly cost products, bovine serum albumin (BSA) was selected as a model protein to infer on the best ABS and their further application on the extraction/concentration of PSA. In this work, two types of ABS were studied: ILs + organic salts and ILs + polymers. First, ABS constituted by a biodegradable organic salt (K3C6H5O7) and a new type of ILs composed of anions with buffer capacity (Good’s buffers) combined with the tetrabutylammonium ([N4444]+) and tetrabutylphosphonium ([P4444]+) cations were studied. ABS formed by polypropylene glycol with a molecular weight of 400 g·mol-1 (PPG4 00) and several cholinium-based ILs, including the Good’s buffers anions, were also evaluated The selected ILs allowed the study of the effect of the anion and cation nature on the phase diagrams behaviour, and thus on their ability to form two-phase systems, as well as the investigation on their potential to extract and concentrate BSA (and thus PSA) from aqueous solutions. According to the obtained results, the complete extraction of BSA was achieved in a single step in various systems. Amongst the several ABS evaluated, those composed of K3C6H5O7 + [N4444][Tricine] and PPG 400 + [Ch][Tricine] were considered the most effective for the extraction (allowing complete extractions). However, ABS composed of polymers did not allow to achieve the concentrations factors initially expected and, therefore, ABS constituted by ILs and K3C6H5O7 are the best alternative and proved to be a promising concentration and extraction technique that may, in the near future, be implemented previously to the clinical analysis of PSA. Finally, in order to support this statement, the ABS formed by K3C6H5O7 and [N4444][Tricine] was used in the extraction of PSA and where it was confirmed the complete extraction of the cancer biomarker for the IL-rich phase.