A Microfluidic Device for Measuring the Oxygen Consumption Rate of a Single Zebrafish Embryo in Applications of Toxicants and Anti-Cancer Drugs Screening

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Project title

Code/計畫編號

NSC101-2221-E019-014

Translated Name/計畫中文名

可量測胚胎耗氧代謝之微流體裝置應用於斑馬魚模式動物對致癌毒物與抗癌藥物之快速篩選

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=2645035

Year

2012

Start date/計畫起

01-08-2012

Expected Completion/計畫迄

01-07-2013

Bugetid/研究經費

723千元

ResearchField/研究領域

醫學工程
藥學

"近年來斑馬魚已成為研究脊椎動物胚胎發育的重要模式動物，用斑馬魚來探討藥物作用的機制，如一些心血管及抗癌症等藥物，都已經發現在斑馬魚胚胎及哺乳類系統皆能產生相似的生理及形態的反應。傳統上，斑馬魚用來從事化學藥物庫的篩選、藥物毒性預測…等研究，主要是利用96 盤培養皿將斑馬魚胚胎浸泡於藥物或毒物的溶液中，觀察其對胚胎發育的影響，然而，此方式觀察胚胎發育的定性觀測，缺乏一量測方式可針對藥物或毒物對胚胎發育造成的影響進行定量的檢測，同時，亦缺乏一高輸出快速檢測與篩選平台，可整合自動化操作平台加速篩選過程，進行來大量藥物的篩選。因此，本計劃將建立一個胚胎耗氧磷光相位感測微流體裝置應用於斑馬魚模式動物對致癌毒物與抗癌藥物之快速篩選，結合斑馬魚胚胎培養微流體裝置、氣動密閉作動裝置、與磷光相位差光學檢測系統，製作出具有多重藥物或毒物注入功能之光學掃瞄式胚胎耗氧代謝感測裝置，可針對藥物或毒物對胚胎發育造成的影響進行定量的檢測。藉由微流體晶片可大量平行檢測的特性，可探討各種毒物或藥物對斑馬魚胚胎發育的干擾機制：針對單一斑馬魚胚胎於不同毒物濃度或多種毒物…等作用下，進行在不同發育時期下胚胎耗氧代謝之定量感測。本計畫以胚胎耗氧代謝感測藥物對胚胎發育的定量的檢測，將整合自動化操作平台加速篩選過程，進行大量藥物的篩選，快速得知藥物對斑馬魚胚胎之影響，加速藥物開發的時程。" "Small size and optical transparency of complex organs make the zebrafish (Danio rerio) larva an ideal organism for large-scale in vivo genetic and chemical studies of many processes. Zebrafish models of several human diseases have been developed. Current methods for toxicity assessment on zebrafish eggs were qualitatively observed via teratological effects. There is no effective measuring method to evaluate the toxicity of zebrafish eggs. Therefore, we proposed a device and system which has ability of automatic drug injection and optical scanning of zebrafish embryonic oxygen consumption with a miniaturization and real-time detection. The device consists of three main components including: (1) A microwell array for a single embryo culture. A single embryo was loaded onto the oxygen-sensitive dye inside a microwell. (2) Pneumatically-driven lid to hermetically seal the microwell. This component also contains microfluidic channels to generation concentration gradient for automatic drug injection. (3) A optical measuring system for a single embryo oxygen consumption rates based on phase-based lifetime detection. This system includes a digital micromirror device (DMD) to project an illumination pattern, which excites the oxygen-sensitive dye for measurement of OCR. Through our proposed device, we hope to develop the effective and quick bioassay platforms for screening the anti-cancer drugs."

Keyword(s)

斑馬魚胚胎
微流體晶片
磷光相位感測
藥物篩選
zebrafish embryo
oxygen consumption rate
phase-based lifetime detection
drug screening

DSpace CRIS

A Microfluidic Device for Measuring the Oxygen Consumption Rate of a Single Zebrafish Embryo in Applications of Toxicants and Anti-Cancer Drugs Screening

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