The Development of a Microfluidic Device for the Investigation of Metabolic Profiles of Caenorhabditis Elegans Induced by High-Glucose Toxicity and the Protective Effect of Natural Anti-Glucose Toxicity Drugs

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簡歷

基本資料

Project title

Code/計畫編號

MOST106-2221-E019-054

Translated Name/計畫中文名

以秀麗隱桿線蟲為模式動物於微流體感測平台下探討受高糖毒性作用下之代謝型態與抗高糖毒性天然藥物評估之研究

Project Coordinator/計畫主持人

Shih-Hao Huang

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Mechanical and Mechatronic Engineering

Website

https://www.grb.gov.tw/search/planDetail?id=12226750

Year

2017

Start date/計畫起

01-08-2017

Expected Completion/計畫迄

01-07-2018

Bugetid/研究經費

880千元

ResearchField/研究領域

機械工程

Description

Abstract

"秀麗隱杆線蟲(Caenorhabditis elegans, C. elegans)與人類在基因上具有高度同源性，是研究衰老和代謝障礙的模式生物。近年研究指出：處於高濃度葡萄糖環境中產生的高糖毒性作用下的線蟲，發現其生命週期會有縮短的現象，然而，卻缺少一有效率的微流體裝置可探討單一線蟲在受高糖毒性作用下，分析其生物能量代謝型態與進行代謝健康指標的評估。白藜蘆醇（resveratrol）是近幾年發現的具有抗氧化能力的天然藥物，而白藜蘆醇苷是否對高糖毒性作用下造成的氧化壓力具有保護的效果，亦缺少代謝健康指標的評估。本計畫將建立一個微流體感測平臺結合單一線蟲培養微陣列晶片、氣動密閉作動裝置、與磷光相位差光學檢測系統，可即時同步感測單一線蟲在高糖毒性作用下之粒線體有氧呼吸的耗氧率、以及糖酵解作用下的酸化率進行量測，並配合粒腺體電子傳遞鏈抑制劑的作用下，量測其耗氧率與酸化率的型態變化得知其對高濃度葡萄糖的代謝轉換效率，並進而計算出在不同高糖毒性程度下之生物能量健康指數 (Bioenergetic Health Index, BHI)。藉由整合樹狀微流道濃度梯度裝置至線蟲培養微陣列晶片中，並加入陣列化光纖式光學檢測系統，可對不同濃度的高糖毒性以及抗氧化天然藥物作用下單一線蟲進行有系統的代謝型態分析與BHI 代謝指標的評估，篩選出抗氧化天然藥物有效抑制高糖毒性的劑量，可為治療糖尿病相關藥物提供一種新的感測裝置。" "Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with human at molecular or genomic level. In this project, we will develop a microfluidic system which enables to simultaneously monitor the oxygen consumption and acidification rates of a single C. elegans across lifespan under high-glucose condition. We will not only investigate the response of a single C. elegans including metabolic activities, lifespan and oxidative stress under high-glucose condition, but also evaluate the protective effect of resveratrol for C. elegans induced by high-glucose condition. The microfluidic device combines two components: PMMA microwells containing an oxygen and pH-sensitive luminescent layers and a microfluidic module with pneumatically actuated lids to seal the microwells. Sequentially adding inhibitors of bioenergetic pathways allows us to perform respiratory measurements of a single C. elegans under high-glucose condition across lifespan and monitor changes in mitochondrial function to calculate the bioenergetic health index (BHI). Our proposed approach is simple and useful for real-time detection of metabolic activities in parallel, providing a potential platform for drug evaluation/screening in a high throughput format at single animal resolution."

Keyword(s)

秀麗隱杆線蟲
白藜蘆醇
耗氧率
酸化率
微流體裝置
藥物篩選
Caenorhabditis elegans
resveratrol
oxygen consumption rate
acidification rates
microfluidic device
drug screening