本研究聚焦於探討聲學渦流技術 (acoustic vortex, AVX) 在清除生物膜方面的應用可行性，並驗證其潛在的臨床價值。由於生物膜具有獨特的結構與抗藥性，長期以來成為人工植入物感染及慢性細菌感染治療中的主要挑戰。隨著人口老齡化，人工關節等植入物的需求不斷增加，對於更高效且安全的感染治療技術需求愈加迫切。然而，傳統物理或化學方法在清除生物膜時效果有限，且通常伴隨高侵入性、手術複雜性與高成本。聚焦式超音波 (focused ultrasound, FUS) 作為一種新興技術，在清除生物膜方面雖已受到關注，但仍存在明顯限制。例如，低強度聚焦超音波需結合微氣泡或特殊粒子才能提升清除效果，但這些外來物可能帶來生物相容性風險，且微氣泡產生的慣性穴蝕效應可能損傷周圍健康組織。高強度聚焦超音波能產生較強的聲流，也可能產生慣性穴蝕效應，雖具有較強的清除能力，但其高聲壓( > 3.5 MPa)、高機械指數也伴隨更高的生物安全風險。AVX是一種具有螺旋相位結構的聲波，透過特定相位調控或螺旋形狀透鏡的設計，使聲波攜帶角動量，進而導致聲波波前產生干涉，並在橫向聲場中呈現環狀能量分佈，此類聲場的特性可於液體中誘導環狀流動，進一步施加旋轉力於懸浮的微粒或細胞。與FUS相比，相同聲學參數之AVX理論上應能產生更強的旋轉聲流與剪切力。本研究旨在利用AVX技術，以相較於FUS更低的聲學參數，實現高效清除生物膜的效果並深入了解其清除生物膜的作用機制。同時，我們進一步探討其結合抗生素後的增效作用與潛在影響。
本研究首先使用實驗室自行製作的FUS與AVX兩用式超音波探頭，測試其性能與工作能力。接著，以 E. coli ATCC13706 作為生物膜培養的模型菌株，建立體外生物膜疾病模型，並利用超音波探頭進行生物膜清除實驗。結果顯示，在AVX模式下能在聚焦區產生沿中軸直進並快速旋轉的向心聲流，旋轉的速度可透過調整AVX之聲壓及工作週期控制，然而FUS組僅觀察到由中軸直進並向外散開的聲流，且在相同聲學參數下其流速僅有達到AVX的 0.4倍。生物膜清除實驗中，本研究發現調整聲壓比調整工作週期可以更顯著提升清除效果。當聲壓達 1.75 MPa、工作週期為 10%，且治療時間為 3 分鐘時，在SYTO9染色下之生物膜清除面積可達90.5 ± 20%。而在相同參數下，FUS模式僅能清除7 ± 6.2%之生物膜，需將聲壓提高至 4 MPa 才能產生明顯效果(91.3 ± 10.5%)。本研究排除了熱效應的影響，並進一步分析其物理機制發現慣性穴蝕效應強度與生物膜清除的相關性僅有0.36，聲流則高達0.97，說明聲流為關鍵影響因素。此外，我們最後結合AVX與抗生素進行協同生物膜清除實驗，結果顯示，此偕同清除技術能抑制生物膜的生長達12小時，增加生物膜上的5.2倍死菌比例，並降低培養液中84%的細菌濃度。未來將進一步AVX技術應用於動物體內生物膜模型中，驗證其可行性與有效性，同時評估綜合治療的效果及其安全性，以期推動此技術在臨床上的應用。

This study focuses on the feasibility of applying acoustic vortex (AVX) technology for biofilm removal and evaluates its potential clinical value. Biofilms, with their unique structure and drug resistance, have long posed major challenges in the treatment of implant-associated and chronic bacterial infections. With the aging population driving the demand for implants such as artificial joints, there is an increasing need for more efficient and safe infection treatment technologies. However, conventional physical and chemical methods are limited in their effectiveness against biofilms and are often associated with high invasiveness, surgical complexity, and high costs. Focused ultrasound (FUS) has emerged as a novel technique for biofilm removal but still faces significant limitations. For instance, low-intensity FUS requires the addition of microbubbles (MBs) or special particles to enhance its biofilm removal effects. However, these foreign agents may pose biocompatibility risks, and the inertial cavitation effects generated by MBs could damage surrounding healthy tissues. High-intensity FUS can produce strong acoustic streaming and inertial cavitation effects, offering better removal capabilities, but its high acoustic pressure (>3.5 MPa) and mechanical index carry higher bio-safety risks. AVX, characterized by its helical phase structure, imparts angular momentum to sound waves through specific phase modulation or spiral-shaped lens designs. This creates interference in the wavefront and generates a ring-shaped energy distribution in the transverse acoustic field. These characteristics can induce circular fluid flow in liquids, exerting rotational forces on suspended particles or cells. Compared to FUS, AVX is theoretically capable of producing stronger rotational acoustic streaming and shear forces under the same acoustic parameters.
This study aims to utilize AVX technology to achieve efficient biofilm removal with lower acoustic parameters compared to FUS and to explore the mechanisms underlying biofilm removal. Furthermore, we investigate its synergistic effects and potential impacts when combined with antibiotics. First, a custom-designed dual-mode ultrasound probe for FUS and AVX was tested for performance and operational capability. Using E. coli ATCC13706 as a model strain, an in vitro biofilm model was established for biofilm removal experiments. Results showed that under AVX mode, centripetal acoustic streaming was generated along the axial direction with rapid rotation, and the rotational speed could be controlled by adjusting the acoustic pressure (AP) and duty cycle (DC). In contrast, the FUS group exhibited only outward-dispersing axial acoustic streaming, with a flow rate reaching only 0.4 times that of AVX under the same acoustic parameters. In biofilm removal experiments, we observed that adjusting the AP had a more significant impact on removal efficacy than adjusting the DC. At an AP of 1.75 MPa, DC of 10%, and treatment duration of 3 minutes, biofilm removal area reached 90.5 ± 20% as stained by SYTO9. Under the same parameters, the FUS mode could only remove 7 ± 6.2% of the biofilm, requiring an AP increase to 4 MPa to achieve a significant effect (91.3 ± 10.5%). This study excluded thermal effects and further analyzed the physical mechanisms, revealing that inertial cavitation correlated only weakly (0.36) with biofilm removal, while acoustic streaming showed a strong correlation (0.97), identifying it as the key influencing factor. Lastly, synergistic experiments combining AVX with antibiotics demonstrated that this combined technique inhibited biofilm growth for up to 12 hours, increased the proportion of dead bacteria within the biofilm by 5.2-fold, and reduced bacterial concentration in the culture medium by 84%.
Future work will focus on applying AVX technology to in vivo biofilm models to verify its feasibility and efficacy. Additionally, we will assess the outcomes and safety of combined treatments, aiming to advance the clinical application of this technology.

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