間接加熱式微幫浦與微流體平台之研製及其應用

Development of an Indirect-heating Thermo-pneumatic Micropump and a Microfluidic Platform with Application Demonstration

賈婷婷(Bonnie Tingting Chia)

指導教授 ： 楊燿州

國立臺灣大學/工學院/機械工程學研究所/博士(2011年)

https://doi.org/10.6342/NTU.2011.02708

摘要

本研究開發了間接加熱式熱氣致動之蠕動式微幫浦(indirect-heating thermo-pneumatic peristaltic micropump)，並將相同原理之間接加熱式微閥(indirect-heating thermo-pneumatic valve, IH-TPV)整合於一可於單一拋棄式晶片上完成多項連續實驗操作的微流體平台上，以此展示間接加熱式微流體元件於生醫晶片上之應用。間接加熱式的驅動模式擁有熱氣致動的優點，如元件結構簡單、驅動方式簡單、驅動電壓相對小、系統體積小等，卻同時改善了因熱氣致動造成元件與流體溫度上升的現象。間接加熱式微閥在多功能微流體平台中扮演著連結不同獨立反應區域間的介面。藉此微流體平台可成功進行去氧核醣核酸(DNA)的樣品製備(sample preparation)與放大(amplification)反應，驗證了多項連續實驗操作可於單一晶片上完成的目的。除了間接加熱式熱氣致動之蠕動式微幫浦以及整合間接加熱式微閥之多功能微流體平台，本論文研究尚包含了對於使用雙穩態電磁致動器驅動之微幫浦的特性研究。

間接加熱式熱氣致動之蠕動式微幫浦的特色在於其驅動腔體由不同的區域達成加熱空氣與運送流體的功能。由於流體經過的流體運送區(fluid-squeezing zone, FS-zone)與熱氣致動的空氣加熱區(air-heating zone, AH-zone)相距一段距離，因熱氣致動產生之元件溫度上升現象對於流道內的流體影響甚低。因此，此間接加熱模式具備十足的潛能整合於生醫晶片。又由於間接加熱的驅動模式可大幅降低流道內流體的溫度上升量，因此，在合理的溫度上升範圍內，可藉由提高操作電壓的方式，達成更高的間接加熱式微幫浦之流率與背壓。

基於對間接加熱式熱氣致動之蠕動式微幫浦的間接加熱驅動模式的開發，相同驅動原理之間接加熱式微閥亦於本研究中整合於一可於單一晶片上完成一系列連續實驗操作的微流體平台上。微流體平台採用電磁線圈陣列操控表面附著目標生物樣品的磁性顆粒於反應區域內的液體溶液中移動，而間接加熱式微閥則負責調控不同反應區域間的連結，作為晶片上獨立的反應區域之間的介面。此自足式微流體平台包含微流體反應晶片(microfluidic reaction chip, MFR chip)以及流體驅動/感測模組(fluidic driving/sensing module, FDS module)兩大部分。微流體反應晶片上具備多個獨立的反應區域，供不同實驗操作的功能整合。間接加熱式微閥則以一體成形的方式整合於微流體反應晶片上不同的反應區域之間。流體驅動/感測模組上包含了操控磁性顆粒的電磁線圈陣列、加熱並控制溫度的加熱器與溫度感測器晶片、促進溶液混合之壓電片等進行實驗操作的元件。本論文研究利用此微流體平台的架構設計了一DNA樣品製備與放大反應的微系統。DNA由原始生物樣品之萃取(extraction)、純化(purification)、至放大(amplification)反應皆可在單一拋棄式晶片上完成。由於完成核酸樣品製備與放大反應功能的所有元件，如電磁線圈、間接加熱式微閥、加熱器等，皆可由簡單的控制電路運作，此整合式微流體平台可透過一直流電源完成自足式的操作。

最後，本論文研究尚針對一整合於聚合酶連鎖反應(polymerase chain reaction, PCR)微系統中的電磁致動微幫浦進行特性研究。此電磁致動微幫浦由一微流道晶片與一外部式的雙穩態電磁致動器組成，於PCR微系統中負責來回運送PCR溶液於微流道晶片上的反應區域之間。使用的雙穩態電磁致動器僅需5 V的直流電源驅動，成為整個PCR微系統自足運作的關鍵。微流道晶片之驅動薄膜受電磁致動器驅動的反作用力反應由CoventorWare®軟體進行模擬與分析。此電磁致動微幫浦的流率亦被量測。

關鍵字

微流體 ； 熱氣致動 ； 蠕動式 ； 微幫浦 ； 微閥 ； 磁性顆粒 ； 樣品製備 ； 聚合酶連鎖反應 ； 電磁式

並列摘要

In this work, the development of an indirect-heating thermo-pneumatic micropump and a microfluidic platform integrated with indirect-heating thermo-pneumatic valves (IH-TPVs) are presented. The proposed indirect-heating thermo-pneumatic mechanism possesses the advantages of simple device structure, simple actuation scheme, relatively low actuation voltage, and small system size, while temperature elevation on working fluid caused by thermo-pneumatic actuation can be significantly reduced. The indirect-heating thermo-pneumatic valves integrated in a microfluidic platform serve as the interfaces between reaction zones for sequential laboratorial operations. Also, DNA sample preparation and amplification are demonstrated using the microfluidic platform.

The indirect-heating thermo-pneumatic mechanism consists of two separate zones for air-heating and fluid-squeezing. Temperature elevation on working fluid can be significantly reduced since the fluidic channel surface is away from the actuation heater. Furthermore, the flow rate performance of the indirect-heating micropump can be improved by increasing the applied voltage, while relatively low temperature elevation on working fluid is induced.

Based on the proposed actuation scheme, indirect-heating thermo-pneumatic valves are designed and integrated into a microfluidic platform, which is capable of carrying out a series of laboratorial operations on a disposable chip. The platform employs coil arrays to transport biological samples attached on magnetic beads through different reaction zones in aqueous solutions. Indirect-heating thermo-pneumatic valves are adopted as the interfaces between sequential reactions. The self-contained system is composed of a disposable microfluidic reaction (MFR) chip and a fluidic driving/sensing (FDS) module. On the MFR chip, various reaction zones with different functionalities are implemented. Also, indirect-heating thermo-pneumatic valves, which are monolithically integrated into the disposable MFR chip, are proposed for interfacing adjacent reaction zones. On the FDS module, arrays of coils are implemented for electromagnetically transporting sample-carried magnetic beads through different reaction zones in aqueous solutions. In addition, micromachined chips with heating and sensing capabilities are integrated on the FDS module for actuating the valves and controlling the temperature of the reaction zones. A series of laboratorial operations, including DNA extraction, purification and amplification (polymerase chain reaction, PCR), is performed by using the proposed microfluidic system. Since the driving circuits for the coil arrays, the thermally-driven valves, and the heaters are very simple, the proposed system is self-contained and can be fully operated with a simple DC power supply.

並列關鍵字

Microfluidic ； Thermo-pneumatic ； Peristaltic ； Micropump ； Microvalve ； Magnetic particle ； Sample preparation ； PCR ； Electromagnetic

參考文獻

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