在疾病的早期，人體內可能會產生具有疾病指標性的物質(Biomarker)，但往往這些指標性物質的濃度都非常得低，導致診斷的困難度大幅的提升。 因此，如何去提升生物訊號是現今一個重要的議題，目前有很多研究以微粒子來做為訊號載體，可以有效的提升生物訊號，但目前的研究在微粒子收集的部分無法達到很好的效果且常需要複雜的製程。有鑑於此本研究提出了一項光電整合的微粒子操控技術來濃縮訊號載體達到提升訊訊號的效果，由於光電動技術是以雷射光及交流電的交互作用下達到微粒子的操控，因此光電動技術會受雷射光強度、電壓及頻率影響。 在本研究中發現，粒子濃縮的效率會隨著雷射光及電壓的強度增強而有所提升，隨著頻率的改變也會有不同的情形產生。而透過改變微粒子的大小、雷射光的位置及電場的頻率可以達到許多不同的微粒子操控，像是濃縮、移動、分類、排列及單一粒子的操控，因此，此光電晶片可期望發展成一個多功能的檢測平台。
在模擬低濃度樣本檢測的部分，我們分別以修飾有軟白素(streptavidin)的微粒子及生物素(biotin)來模擬訊號載體及生物樣本，結果顯示微量的生物素(3.87 nM)訊號透過濃縮在單一粒子上的方式能夠成功量測，相較於傳統儀器―螢光酵素免疫分析儀，以微珠作為訊號載體的檢測至少可以提升兩個數量級，再藉由光電晶片將訊號載體聚集，結果顯示訊號隨著時間的增長而有顯著的提升。因此以微粒子作為訊號載體及光電晶片都可以有效的提升生物訊號。
本研究最終目的是要去偵測糖尿病視網膜病變的指標性蛋白(LCN1)，糖尿病視網膜病變為全球人口中失明的主要原因之一，有許多研究指出及早發現糖尿病視網膜病並且給予適當的治療可以降低失明的風險。在實際檢測樣本的部分，為了避免額外的樣本處理，我們藉由螢光共振的方式來去做實際的檢測，此檢測系統將標記有螢光物質的抗體連接在微粒子表面的方式來去捕捉抗原，同時抗原也會與修飾有量子點(Quantum dot)的抗體鍵結，因此產生螢光共振的效果，再藉由光電晶片將產生螢光共振的複合物濃縮，結果顯示在40秒的濃縮過程中訊號有顯著的提升，此外在有待測物及沒有待測物的情況下，螢光共振的訊號強度有明顯的差異，這表示此方法是可以成功偵測到指標性蛋白的。目前我們研究的方向著重在糖尿病視網膜病變的檢測，未來藉由改變修飾抗體和不同抗原接合，就能夠去偵測不同疾病的指標性蛋白。使得同一種技術，能夠延伸應用在多種疾病的快速檢測上。

In the early stage of diseases, biomarkers may be hard to detect due to low concentration. As a result, improving the bio-signal is an important issue. A considerable number of research studies have proven particles to be useful carriers in many bead-based bioassays. However, most of them require complex fabrication to achieve efficient collection of beads. To solve this problem, this thesis presents a simple optoelectrokinetic method for bead-based sensing carrier concentration. Since the optoelectrokinetic method combines the laser and AC electric field, laser intensity, voltage, and frequency were investigated for the optoelectrokinetic manipulation. The result shows that concentration efficiency increases as the light intensity or voltage is elevated. Our study shows that carefully tuning of frequency, path of irradiation, and voltage, several manipulation capabilities, such as particle concentration, translation, single particle trapping, sorting, and patterning can be achieve. Accordingly, this optoelectrokinetic method can be developed to a versatile examination platform.
For assessment of low-dose sample detection, streptavidin functionalized particles (6 μm) and FITC tagged biotin were used. The biotin-FITC represents a biomarker in a biological fluid while the streptavidin functionalized particles represent a platform of an immunoassay. The results showed that trace amounts of biotin (3.87 nM) signals were detected by confined the biotins in a micro scale domain. As compared with the conventional instrument, ELISA Reader, the signal was improved by at least two orders of magnitude. To assess the effect of signal enhancement by the optoelectrokinetic method, the mixture of sensing carrier and analyte is concentrated by optoelectrokinetic method. The results show that bio-signals make noticeable enhancement over time. These results indicated that both bead-based bioassay and optoelectrokinetic method can effectively improve the bio-signal.
The final goal of this thesis is to detect the diabetic retinopathy. Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness in many countries. To achieve simple examination, FRET-based immunoassay was used to detect the LCN1, which is known as one of the diabetic retinopathy biomarker. This sensing system uses dye (acceptor) labeled antibody linked to polystyrene bead to capture antigen. The antigen binds to a quantum dot (donor) functionalized antibody thus forming a FRET donor–acceptor ensemble. Subsequently, FRET-based immunecomplexes were concentrated by optoelectrokinetic method. The result reveals that the signal improves noticeably within 40 seconds and the FRET-induced dye s
ignal intensity is higher with the target protein than in its absence. This result indicates that biomarker LCN1 can be detected by FRET-based immunoassay. In the future, the others biomarker of disease can be detected with the different identify antibody in the same fashion.

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