Publicação
Development of an automated microfluidics-based device for simulating human gastrointestinal digestion
| Resumo: | Understanding the fate of bioactive compounds under digestive conditions is critical for early-stage drug development. In vitro digestion methods offer an alternative to human and animal studies to reduce costs and complexity and avoid ethical concerns. Current in vitro digestion methods can be generally divided into the designations of static and dynamic models. While static models are typically simplified and lack the ability to fully reproduce the complexity of human digestion, dynamic models make use of large and complex equipment and require relatively large amounts of sample and reagents, making them unsuitable to study the digestion of valuable compounds, such as nano-delivery systems. In this work, a microfluidic-based method was developed to bridge the current gap between dynamic and static digestion models. The device was semi-automated and miniaturized to allow reducing sample and reagent usage, operator inputs, and downsize lab occupation. Di-gestion-chips were fabricated following a layer-by-layer approach from micro-milled and laser cut poly methyl methacrylate (PMMA) layers. Temperature and pH sensors were integrated to monitor key digestion parame-ters and worked in direct feedback with resistors for heating and syringe pumps injecting HCl or NaOH for real-time pH adjustments. Using this device, gastric and intestinal digestions were successfully replicated and validated using a casein reporter molecule against the gold standard static digestion protocol defined within the INFOGEST Cost action. In addition, the peristaltic pump developed within this work will allow to include important features of digestion such as gastric emptying, thus increasing the physiological relevance of the model. Overall, this work achieved a semi-automated and miniaturized device for human digestive simula-tions. The device was validated against gold standard protocols and showed the potential to be used in labor-atory settings for in vitro testing of compounds aiming for oral administration using reduced volumes and with minimal operator input. |
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| Autores principais: | Dias, Tiago Nuno Gomes |
| Assunto: | In vitro digestion models Semi-dynamic digestion Microfluidics Sensors automation |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Understanding the fate of bioactive compounds under digestive conditions is critical for early-stage drug development. In vitro digestion methods offer an alternative to human and animal studies to reduce costs and complexity and avoid ethical concerns. Current in vitro digestion methods can be generally divided into the designations of static and dynamic models. While static models are typically simplified and lack the ability to fully reproduce the complexity of human digestion, dynamic models make use of large and complex equipment and require relatively large amounts of sample and reagents, making them unsuitable to study the digestion of valuable compounds, such as nano-delivery systems. In this work, a microfluidic-based method was developed to bridge the current gap between dynamic and static digestion models. The device was semi-automated and miniaturized to allow reducing sample and reagent usage, operator inputs, and downsize lab occupation. Di-gestion-chips were fabricated following a layer-by-layer approach from micro-milled and laser cut poly methyl methacrylate (PMMA) layers. Temperature and pH sensors were integrated to monitor key digestion parame-ters and worked in direct feedback with resistors for heating and syringe pumps injecting HCl or NaOH for real-time pH adjustments. Using this device, gastric and intestinal digestions were successfully replicated and validated using a casein reporter molecule against the gold standard static digestion protocol defined within the INFOGEST Cost action. In addition, the peristaltic pump developed within this work will allow to include important features of digestion such as gastric emptying, thus increasing the physiological relevance of the model. Overall, this work achieved a semi-automated and miniaturized device for human digestive simula-tions. The device was validated against gold standard protocols and showed the potential to be used in labor-atory settings for in vitro testing of compounds aiming for oral administration using reduced volumes and with minimal operator input. |
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