Universal diagnostic platforms based on oligonucleotide codified nanoparticles and DNA microarray devices

[eng] Personalized therapy has become a crucial issue lately. It should be based on the simultaneous monitoring of different biomarkers which might include molecules of different chemical nature. This fact, calls for developing universal technological diagnostic approaches, able to determine these b...

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Detalles Bibliográficos
Autor: Broto Avilés, Marta
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120766
Acceso en línea:https://hdl.handle.net/2445/120766
http://hdl.handle.net/10803/462828
Access Level:acceso abierto
Palabra clave:Oligonucleòtids
Marcadors bioquímics
ADN
Nanopartícules
Oligonucleotides
Biochemical markers
DNA
Nanoparticles
Descripción
Sumario:[eng] Personalized therapy has become a crucial issue lately. It should be based on the simultaneous monitoring of different biomarkers which might include molecules of different chemical nature. This fact, calls for developing universal technological diagnostic approaches, able to determine these biomarkers, independently from their chemical nature, while modulating the necessary amplification factor. In this context, the aim of the project is to develop of a universal, multiplexed (for several biomarkers) and multimodal (biomarkers of different chemical nature) in vitro diagnostic bioanalytical platform. The proposed approach (Figure 1) pretends to translate any type of biomolecular interaction (bioreceptor-biomarker) into a PCR-less DNA amplification process that is finally detected on a DNA-microarray biosensor platform. This strategy is called biobarcode assay. As proof-of-concept of the proposed approach, we have focused on the detection of biomarkers related to cardiovascular diseases (CVDs) and, also, drugs related to cancer disease. CVDs are the main cause of death in the world and include a group of disorders of the heart and blood vessels, multimodal and multiplexed detection of CVDs-related biomarkers would help the monitoring of patient status. Otherwise, the second cause of death worldwide is cancer; drugs used to treat cancer are called cytostatics. Closely levels of therapeutic and toxic doses of cytostatics make therapeutic drug monitoring the milestone for the optimization of cancer treatment. It can be assumed that monitoring of drug concentration jointly with main metabolites should improve efficacy and tolerability and reduce toxicity. The main objective of the project will consist on demonstrating that it is possible to analyze targets of different chemical nature, and that the amplification can be modulated by varying the charge of oligonucleotides covalently attached to the nanoparticles.