新型非接觸式環形共振生物感測器應用於癌細胞無標籤判定與生長監測

Label-free discrimination and growth monitoring of cancer cell with novel non-contact ring resonator biosensor

岳士榕(Shih-Jung Yueh)

指導教授 ： 劉建豪

國立臺灣大學/工學院/機械工程學研究所/碩士(2022年)

https://doi.org/10.6342/NTU202201405

摘要

近年來，智慧生物反應器快速發展，其原理為新式仿活體細胞生長之裝置，透過培養與觀察細胞或生物組織之生長或對藥物的反應，當作臨床實驗或動物實驗之先期研究，相對於傳統使用之培養皿與平面生物反應器，其主要觀察平面細胞生長情形，新式2.5D與3D生物反應器可觀測實際細胞或組織於三維空間中的生長體積變化。
本研究所提出之新型非接觸式微波阻抗式生物感測器，利用數值解搭配電路模擬軟體設計共平面波導傳輸結構及共振環之等效電路模型，再透過電磁有限元素模擬軟體(Computer Simulation Technology, CST)進行三維結構設計與模擬。其優點包含運用共平面波導作為饋入傳輸線結構，降低損耗之影響及提升傳輸效能，另外透過延伸開口面積及加入曲折線結構於並聯共振電路中，達到降低電感值與增加電容值來提升平均電磁能與品質因子，增加感測器之靈敏度。所提出之結構具備最大電場能量達 ，電場集中密度最高達 ，品質因子達550，插入損耗為-3.53 dB。
透過PCB標準製程製作感測器，並針對不同濃度之癌細胞進行實驗，包含MCF-7乳癌細胞、SW-480原發性大腸癌細胞及SW-620淋巴道轉移性大腸癌細胞。根據頻率飄移與振幅變化，感測器監測癌細胞於培養皿內濃度變化與生長的情形，實驗結果證明以共振器為基底並且選用微波頻段中設計之生物感測器，不只具備癌細胞量測尺度之波長，再運用共振環的特性使電場集中於待測空間進行量測。實驗數據展示感測器能監測三種癌細胞於不同濃度之變化，並具備高靈敏性，同時能分辨不同細胞，具備無標籤判定能力。此研究結果有助於監測細胞於空間中生長與對藥物反應。

關鍵字

開口共振環 ； 無標籤判定 ； 非接觸式生物感測器 ； 高品質因子 ； 高靈敏度

並列摘要

In recent years, smart bioreactors have developed rapidly for in vitro-test of living cancer cells. By culturing cells or biological tissues and observing their responses to drugs, the main application is used for clinical experiments or early stage of animal experiments. In contrast to traditional petri dishes and planar bioreactors, which mainly observe the growth of planar cells, the new 2.5D and 3D bioreactors can observe the change of occupied volume living cells or tissues in three-dimensional space during growing.
The novel non-contact ring resonant biosensor proposed in this research is designed via numerical analysis and circuit simulations to develop the coplanar waveguide and the equivalent circuit model of the resonant ring. Then, the full wave EM simulation software is utilized for final 3D design. Coplanar Waveguide is used as the feed transmission line structure to reduce the influence of loss and improve transmission performance. To increase the average electromagnetic energy and quality factor within the desired space, the open area is extended and meander lines are added in the structure, where the inductance value is reduced and the capacitance value is increased. The figure of merit of the device include maximum electric field energy reach , the electric field concentration density is up to , the quality factor is up to 550, and the insertion loss is -3.53 dB.
Then, the device is fabricated via the standard PCB fabrication and examined with three cancer cells including MCF-7, SW-480, SW-620 carried in the petri dish. One advantage of the device is that operating wavelength math the size of cells and the microwave ring can concentrate electric field near the device. The experiment demonstrates average sensitivity of 34.329%, and the maximum insertion loss within -15dB. In addition, the opposite frequency shift of similar cells are useful for label-free determination of cancer cells. The research results are expected to be beneficial for real-time monitoring of growth of cancer cells and their responses to drugs.

並列關鍵字

Split-RIng Resonator ； label-free discrimination ； non-contact biosensor ； high Q-factor ； high sensitivity

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