在藥物使用的範疇中，如果想要讓藥物能夠完全的發揮出療效，藥物的控制釋放一向是研究的重點，並且在過去的研究文獻中發現，藥物載體的粒徑越均一，則在應用於藥物的控制與釋放上就越有優勢，但是在過去文獻中所提出的藥物載體的製作方式，均無法有效獲得均一粒徑的載體。因此，在本研究將利用微機電系統製程技術之灌注成形法，完成聚二甲基矽氧烷微流體晶片之製備，希望利用微流體晶片可以生成均一粒徑的藥物載體。在本研究中成功開發三種微流體晶片，包含可同時生成四種不同濃度微乳化球之微流體晶片，可調整流速比(sample phase 1/sample phase 2)來生成十一種不同濃度微乳化球之微流體晶片，與電噴灑之微流體晶片。首先，可同時生成四種不同濃度微乳化球之微流體晶片的研究策略為利用計算流體力學軟體來模擬微流道晶片內四個微流管道的流速分佈情形，並改變樹狀分流管道寬度設計，以達到微流體晶片於後端產生四管一樣的流速分佈。實驗上，在微流體晶片前端分別注入台盼藍水溶液和去離子水，利用微混合器與樹狀分流的設計，均勻混合出四種不同的濃度，並在微流體晶片後端利用鞘流原理來產出四管均一粒徑且具有不同濃度的微乳化球，粒徑分佈範圍介於50到100 m之間。之後，將此微流體晶片應用於生成均一粒徑且包覆不同牛血清蛋白濃度之褐藻酸鈣微膠囊的生成上，實驗結果在粒徑分佈範圍可介於60到105 m之間。將微流體晶片所生成四種不同牛血清蛋白濃度的微膠囊置於磷酸鹽緩衝溶液中進行牛血清蛋白濃度釋放，在經過長時間的紫外光-可見光吸收光譜儀量測，發現此微流體晶片所生成的褐藻酸鈣微膠囊，可成功釋放出具有不同濃度分佈的牛血清蛋白濃度，證明本研究所設計的微流體晶片可應用於同時生成均一粒徑且不同濃度的微膠囊。
可調整流速比來生成十一種不同濃度微乳化球之微流體晶片在研究策略上將利用兩相流體交會流道結合混合器在不同的注入流量比(w1/w2)下，產生不同的濃度分佈，並利用後端的流體聚焦區生成微乳化球。在實驗中，在微流體晶片前端分別注入台盼藍水溶液和去離子水，利用微混合器與不同的流速比，混合出多種不同的台盼藍濃度，並在微流體晶片後端利用鞘流原理來產出均一粒徑且具有不同台盼藍濃度的微乳化球。之後，將此微流體晶片應用於生成均一粒徑且包覆不同磁奈米粒子濃度之幾丁聚糖微膠囊的生成，實驗結果在粒徑分佈範圍可介於44 m到83 m之間。將微流體晶片所生成十一種不同磁奈米粒子濃度的幾丁聚糖微膠囊經由超導量子干涉震動磁量儀的量測下，可以發現此微流體晶片所生成的幾丁聚糖微膠囊具有十一種磁力分佈，證明本研究中所設計的微流體晶片可應用於生成多種濃度且均一粒徑的微膠囊
最後，為了讓微乳化球的粒徑大小在改變微流體管道幾何形狀、縮小管道尺寸與改變流體特性的限制下，能再繼續將微乳化球粒徑持續縮小，本研究將應用質譜儀分析之電噴灑現象，製作出電噴灑微流體晶片。在微流體晶片的設計上，利用管道之幾何形狀造成鞘流現象，以製備出均一粒徑的微乳化球，同樣藉由微機電製程技術在銦錫氧化物玻璃基板上製作所需之電極晶片，並與微流道晶片接合，目的為提供電場於微流道之鞘流區，使鞘流現象與電噴灑現象結合。在實驗中，操控連續相乳化劑之濃度、施加之驅動電壓與分離相與連續相之流量比，在鞘流區讓分離相產生穩定的泰勒錐與電噴灑現象並生成粒徑小於5 m的微水滴，之後將電噴灑微流體晶片應用於生成聚乳酸-聚甘醇酸共聚合物微乳化球，結果在製備之微乳化球粒徑範圍可介於70到7 m之間。利用電噴灑微流體晶片確實可以縮小微乳化球在微流體晶片製備上所產生的粒徑分佈限制，由於微乳化球粒徑的縮小，對於藥物載體的療效之應用將可更廣泛。

Conventional drug release models include the dump system, oral intake, and injection, etc. These models cause drugs to be quickly absorbed by the human body and cause the drug concentration to be higher in the blood. Patients might not get the optimal efficacy and get side effects. So, the drug control release technique is very important. The objective of the drug controlled release research was to increase the drug efficacy, decrease the medication frequency, and reduce side effects. Because the microcapsule size and distribution have an influence on the clearance rate from the body and ultimately determine the drug dosage, it is important to control the size of the uniform biomaterial microspheres and narrow the size distribution. So, in this study, the developed microfluidic chips were used to generate the uniform emulsions. The gradient-microfluidic droplet generator, the adjustable-microfluidic droplet generator, and the electro-spraying microfluidic chip were successfully developed in this study. First, the gradient-microfluidic droplet generator uses the micro-mixers and flow-focusing devices to generate the different sizes of the droplets with different concentrations simultaneously and applies these microcapsules for drug release. The sizes of these four types of droplet with different concentrations are uniform and can be precisely controlled by adjusting the aqueous phase flow rate and oil phase flow rate. Moreover, Ca-alginate microcapsules with different concentrations of the bovine serum albumin (BSA) are used for drug release, and the Ca-alginate microcapsule size is from 60 to 105 µm in diameter. The gradient-microfluidic droplet generator has the advantages of actively controlling the droplet diameter, simultaneously generating uniform size droplets with different concentrations, and having a simple process and a high throughput. Second, the adjustable-microfluidic droplet generator uses the micro-mixer and flow-focusing device to produce the aqueous droplets with different trypan blue concentrations under the various flow rate ratios of the trypan blue solution (sample phase 1, w1) and the D.I. water (sample phase 2, w2) and applies these microparticles for encapsulating the magnetic nanoparticles. The chitosan emulsions with eleven different concentrations are very uniform, and the chitosan emulsion size can be precisely controlled by adjusting the flow rate of the sample phase sum (w1+w2) and oil phase flow rate. Moreover, chitosan microparticles with different concentrations of the magnetic nanoparticles are used for uniform size, and the chitosan microparticles size is from 44 to 83 µm in diameter. The adjustable-microfluidic droplet generator has the advantages of actively controlling the droplet diameter, generating uniform size droplets with different concentrations, and having a simple process. Third, an electro-spraying microfluidic chip was integrated with a parallel electrode and flow-focusing device to successfully generate uniform emulsions with an electric field. This approach utilizes a high electric field driven by a direct-current voltage to form a stable Taylor cone in the flow-focusing position. The Taylor cone can then generate stable and uniform emulsions that are less than 5 µm in diameter. The emulsion size is controlled by the surfactant concentration, the ratio of the aqueous and oil phase flow rates and the strength of the electric field. When the strength of the electric field increases at a high surfactant concentration and low ratio of flow rates, the Taylor angle decreases, which causes the emulsion size to decrease. In this study, the aqueous emulsion diameter ranged from 1 µm to 98 µm, and the poly(lactic-co-glycolic acid) (PLGA) emulsion size ranged from 7 to 70 µm. The microfluidic chip developed in this work has the advantages of actively controlling the emulsion size and generating uniform emulsions (the relative standard deviation was less than 10%) and represents a new emulsion generation process. These preparation approaches for generating the biomaterial microcapsules of different concentrations and for generating the smaller biomaterial microcapsules size will provide many potential applications for drug delivery and pharmaceutical area.

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