超音波彈性成像應用於微流道內細胞外基質彈性測量

Ultrasound Elastography for Measuring Extracellular Matrix Elasticity in Microchannels

蔡宜珊(Yi-Shan Tsai)

指導教授 ： 李百祺

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/碩士(2024年)

https://doi.org/10.6342/NTU202500034

摘要

相比於宏觀尺度，微觀環境下培養細胞具有更多優勢，其體積小且尺度接近體內微環境，更能真實模擬細胞在體內的生理狀態。細胞外基質的機械性質對細胞的黏附、遷移及分化等行為有重要影響，因此在微流道內進行細胞培養時，實時監測細胞外基質的彈性對於維持適合的培養環境至關重要。然而，目前主要的細胞外基質彈性量測技術多需與樣本直接接觸，增加了操作上的限制。為了解決這一問題，本研究嘗試利用超音波彈性影像技術實現微流道內基質彈性的非接觸式量測。由於隨著流道尺寸的縮小，臨床常用的大型探頭難以適應小型仿體的量測需求，本研究採用了更小型的探頭進行研究，並使用兩種不同的超音波系統進行實驗，第一種系統使用一維陣列式探頭，其探頭尺寸較大、能量輸出較高，能有效引起較大的粒子位移。第二種系統則採用三單一探頭的設置，具備更高的軸向解析度，能更精確地對應微流道結構的細微特性。此外，本研究考量了微流道材質與厚度對超音波傳遞特性可能造成的影響，自製了不同大小的PDMS微流道以進行實驗，並利用k-Wave軟體模擬超音波探頭的聲場，進一步分析聲波在流道內的傳遞行為並與實驗結果比較，檢驗實驗的準確性。由於邊界效應的影響，波速與楊氏模數之間無法簡單以一個公式轉換，因此，本研究建立了針對特定流道尺寸的波速對應表，總體而言越小的流道會有越快的波速，為後續研究提供參考依據。實驗結果顯示，在大仿體與較寬流道中，三單一探頭系統可有效使用；而在波速較快或衰減較大的仿體中，一維陣列式探頭更適合進行準確量測。未來，隨著流道尺寸進一步縮小，一維陣列式探頭可能因對位困難而受到限制，此時可透過縮小並固定三單一探頭的間距來提高其精度和穩定性。整體而言，三單一探頭系統在微流道應用中具備改進潛力，未來可成為精準測量波速的有效工具。

關鍵字

超音波彈性影像 ； 細胞外基質彈性 ； 微流道內彈性量測 ； 導波彈性 ； 邊界效應

並列摘要

Compared to macroscale environments, microenvironments offer significant advantages for cell culture, closely mimicking the small-scale and physiological conditions of the in vivo environment. The mechanical properties of the extracellular matrix (ECM) significantly influence cell behaviors such as adhesion, migration, and differentiation. Therefore, real-time monitoring of the ECM's elasticity in microchannels is crucial for maintaining a suitable cultivation environment. However, most current ECM elasticity measurement techniques require direct contact with the sample, which imposes operational limitations. This study explores using ultrasound elastography for non-contact measurement of ECM elasticity within microchannels. As the size of the channels decreases, conventional large-scale clinical ultrasound transducers become unsuitable for measuring small-scale phantoms. Hence, this research employs more miniature transducers and conducts experiments with two ultrasound systems: one for higher energy and the other for higher resolution. Polydimethylsiloxane (PDMS) microchannels of various sizes were fabricated for experiments. Additionally, k-Wave software was employed to simulate the acoustic field of the ultrasound transducers, analyzing the wave propagation within the channels and comparing the results with experimental data. Due to boundary effects, the relationship between wave speed and Young's modulus cannot be simplified into a single equation. Therefore, a wave speed correspondence table specific to particular channel dimensions was established. Generally, smaller channels exhibit faster wave speeds, providing a reference for future research. Experimental results indicate that in larger phantoms and wider channels, the three-element transducer system is effective. Conversely, in phantoms with faster wave speeds or higher attenuation, the linear array transducer is more suitable for accurate measurements. In the future, as the channel size further decreases, the linear array transducer may face limitations due to alignment difficulties. In such cases, reducing and fixing the spacing between the three-element transducer can enhance precision and stability. Overall, the three-element transducer system has the potential for improvement in microchannel applications and could become an effective tool for accurately measuring wave speeds.

並列關鍵字

Ultrasound Elastography ； ECM Elasticity ； Elasticity Measurement in Microchannels ； Guided Wave Elastography ； Boundary Effect

參考文獻

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