中風是全球第二大死亡原因，其中缺血性中風佔70%，全球負擔也持續增加。目前的急性缺血性中風治療方法主要是靜脈內溶栓治療，但僅能適用於少數患者，且存在多重風險。並且在針對中風後的功能恢復的方面仍需要更有效的治療策略，幹細胞療法具有自我更新能力和多向分化潛力，被認為是治療多種疾病的重要再生方法。然而，現今的幹細胞遞送法，仍面臨高侵入性和低輸送效率(1-10%)的挑戰。而高血流速度會進一步降低幹細胞在目標部位的濃度與附著力，限制了其臨床應用和治療效果。此外，仍缺乏一種具備良好空間/時間分辨率的非侵入性策略來操縱血液循環中的幹細胞。為了解決這個問題，我們提出了一種基於聲學漩渦鑷子的技術，聲學漩渦鑷子的聲波因為相位差而沿波束方向產生破壞性干涉，形成螺旋傳播並生成環狀橫向聲場。該設備能夠產生淨力以非侵入性的方式捕獲幹細胞。通過顯微成像技術，可以實時定位在生理相關流速下累積的臍帶血間質幹細胞。我們成功使用5 MHz聲學漩渦鑷子在微流控裝置中捕獲了1和10 μm的微球及幹細胞，並確定了最佳的聲學參數為聲壓為700 kPa和60%的duty cycle。在靜場實驗中，微球在聲場中迅速旋轉，逐漸聚集並形成團簇。隨著捕獲時間增加，團簇尺寸不斷增大並最終穩定。在流場實驗中，流速越大，微球或是幹細胞的捕捉面積越小。我們的結果也顯示聲學漩渦鑷子可以在流場中累積幹細胞並進行操控，局部濃度可以提昇至少2倍左右。此外，我們監測了聲學漩渦鑷子對捕獲的幹細胞後短期和長期的活性，發現並沒有造成任何細胞損傷。我們提出的聲學漩渦鑷子不僅具備優異的生物相容性、具備良好空間解析度，並能在流場環境下捕捉和操控幹細胞，並提高其在目標部位的濃度，為幹細胞治療提供了一種創新的、具有潛在臨床應用價值的技術方案。

Stroke is the second leading cause of death worldwide, with ischemic stroke accounting for 70% of these cases, and the global burden continues to increase. Currently, the primary treatment for acute ischemic stroke is intravenous thrombolysis, but it is applicable only to a small percentage of patients and carries multiple risks. Furthermore, there is still an urgent need for more effective treatment strategies for functional restoration after a stroke. Stem cell therapy exhibits self-renewal capacity and multi-directional differentiation potential and is considered an important regenerative approach for treating several diseases. However, current stem cell delivery methods face challenges such as high invasiveness and low delivery efficiency (1-10%). Moreover, high blood flow velocities intrinsically caused lower stem cell concentration and adhesion at the targeted site, limiting their clinical application and treatment outcome. Besides, a non-invasive strategy with good spatial/ temporal resolutions capable of manipulating circulating stem cells remains lacking. To address this issue, we proposed a technology based on acoustic vortex tweezer (AVT). AVT generate destructive interference along the beam direction due to phase dislocations, resulting in spiral propagation and the formation of a ring-shaped lateral acoustic field. This device can generate net forces for noninvasive trapping of stem cells. The accumulated human umbilical cord blood mesenchymal stem cells in physiologically-relevant flow rates are located in real time by microscopic imaging. We have successfully utilized AVT to capture 1 μm and 10 μm microspheres and stem cells within a microfluidic device, optimizing the ultrasonic parameters to be acoustic pressure of 700 kPa and a 60% duty cycle. In static state experiments, microspheres rapidly rotated within the acoustic field, gradually clustered, and eventually stabilized as their cluster size increased with trapping time. In flow condition experiments, higher flow velocities reduced the trapping area for microspheres or stem cells. Our results demonstrate that AVT could effectively accumulate and manipulate stem cells under flow conditions, increasing the local concentration by at least 2-fold. Furthermore, we monitored the short-term and long-term viability of stem cells trapped by AVT and found no cell damage. Our proposed AVT is not only a biocompatible strategy with good spatial resolution, but also enables the trapping and manipulation of stem cells in flow environments, enhancing their concentration at the target site. This innovative technology offers a promising approach with potential clinical applications for stem cell therapy.

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