微通道與固體表面增強拉曼光譜 (SERS) 基底的整合用於從全血中分離和檢測癌細胞

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吉里基(Kiran Giri) 查詢紙本館藏

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機械工程學系

論文名稱

微通道與固體表面增強拉曼光譜 (SERS) 基底的整合用於從全血中分離和檢測癌細胞
(Integration of Microchannel with Solid Surface-Enhanced Raman Spectroscopy (SERS) Substrate for Isolation and Detection of Cancer Cells from Whole Blood)

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至系統瀏覽論文 (2026-1-1以後開放)

摘要(中)

循環腫瘤細胞（CTCs）作為液體活檢的可靠生物標誌物顯示出顯著的潛力，提供了一種微創的方法來檢測癌症並監測治療進展。然而，循環腫瘤細胞的分離和檢測仍然是一個主要挑戰。本論文將提出一種利用微通道集成表面增強拉曼散射（SERS）基板來分離和檢測癌細胞的新方法。使用微流體器件中的微柱和不同微通道內部間隙的基於大小的方法來從全血中分離癌細胞。HT-29細胞系被加入血樣中以觀察癌細胞的分離。微通道中的微流體濾波器能夠根據癌細胞與血細胞之間的大小差異從血液中分離出癌細胞。然而，微柱在微通道中導致血液顆粒與血漿分離的流動導致微通道堵塞。使用數值和實驗方法研究了微通道中微柱直徑、形狀和間隙等不同參數對血流中堵塞現象的影響。採用電化學無電鍍方法開發的固態SERS基板用於檢測細胞。集成在微通道中的SERS基板將為快速而敏感地檢測癌細胞提供可能，以用於監測癌症進展和研究對治療的反應。

摘要(英)

Circulating tumor cells (CTCs) shows significant promise as reliable biomarkers through liquid biopsies, offering a minimally invasive approach for detecting cancer and monitoring therapeutic progress. However, isolation and detection of circulating tumor cells remains one of the major challenge. This thesis will present a novel method to isolate and detect cancer cells using a microchannel integrated with SERS substrate. A size-based isolation of cancer cells from whole blood using micro pillars and varying gap spacing within the microchannel of microfluidic device is developed. HT-29 cell line was spiked into the blood sample to observe isolation of cancer cells. The microfluidic filters in microchannel was able to isolate cancer cells from blood based on the size difference between cancer cells and blood cells. However, the flow of blood in microchannel with micropillar cause the separation of blood particles from the blood plasma resulting in clogging of the microchannel. The effect of different parameters such as diameter, shape and gap between micropillar in clogging phenomenon during the blood flow in the microchannel was studied using numerical and experimental method. Solid state SERS substrates developed by electroless droplet deposition method was used for detection of the cells. The SERS substrate integrated with the microchannel will provide a fast and sensitive detection of cancer cells for monitoring of cancer progression and studying the response to treatment.

關鍵字(中)

★ 循環腫瘤細胞
★ 表面增強拉曼光譜
★ 細胞分離
★ 阻塞現象

關鍵字(英)

★ Circulating tumor cells
★ Surface-enhanced Raman spectroscopy
★ Isolation of cells
★ Clogging phenomenon

論文目次

中文摘要 i
Abstract ii
Acknowledgement iii
List of Figures vi
List of Tables ix
Chapter I Introduction 1
1-1 Cancer Diagnosis 1
1-2 Circulating Tumor Cells (CTCs) 2
1-3 Microfluidics Based CTC Isolation method 3
1-4 Flow of blood through the micropillar 9
1-5 Fabrication of micropillar 10
1-6 CTC detection methods 11
1-7 SERS based CTC detection 13
1-8 SERS substrates 16
1-9 Motivation 19
Chapter II Materials and Methods 22
2-1 Modeling and Simulations 22
2-1-1 Geometry and Computational domain 22
2-1-2 Meshes Parameter 23
2-1-3 Simulation Method 24
2-2 Device design and fabrication 25
2-2-1 Design of microchannel 25
2-2-2 CNC Milling 26
2-2-3 Photolithography 27
2-2-4 Soft Lithography 28
2-3 Fabrication of SERS substrate 29
2-4 Assembly of microfluidic device 30
2-5 Experimental Setup 31
2-6 SERS Measurement 31
2-7 Blood Sample Preparation 32
2-8 HT-29 (adherent) cells preparation 32
Chapter III Results and Discussion 33
3-1 Flow Analysis of Blood in Micropillar 33
3-1-1 Flow in microchannel 33
3-1-2 Effect of diameter 37
3-1-3 Effect of shapes 39
3-1-4 Effect of gap between micropillar 41
3-1-5 Effect of Pattern 43
3-1-6 Experimental Results 44
3-2 Cancer cell isolation using microfluidic device 47
3-2-1 Characteristics of HT-29 cells 48
3-2-2 Isolation of cancer cells 49
3-2-3 Clogging of microchannel due to blood flow 51
3-2-4 Comparison of isolation results 53
3-3 Micromilling for fabrication of micropillar 54
3-4 SERS based detection of CTC cells 55
3-4-1 Fabrication of SERS substrate 55
3-4-2 Testing of SERS substrate 56
3-4-3 Detection of Cancer cells using SERS substrate 57
3-4-4 Aptamer-based sensing of cancer cells 58
Chapter IV Conclusion 61
References 64

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指導教授

曹嘉文(Chia-Wen Tsao)

審核日期

2023-12-27

推文