Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

中文翻译：

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通过声流技术对白血病细胞进行片上快速药物筛选

快速和个性化的单细胞药物筛选测试在急性髓系白血病药物联合化疗中起着至关重要的作用。由于细胞膜对药物的天然抗性，传统的化疗药物筛选是一个耗时的过程，并且在高通量和精确的单细胞药物筛选中使用改变膜通透性的技术（如声孔）仍然存在巨大挑战。最小的损坏。在这项研究中，我们提出了一种基于声流的非侵入性单细胞药物筛选加速方法，在浓度梯度微流体装置中使用高频声波 (>10 MHz)。高频声学导致诱导空化的难度增加，并在每个单个细胞周围产生声流。所以，单细胞膜通透性通过声压和声流诱导的剪切力非侵入性地增加，这显着改善了药物摄取过程。在实验中，单个人髓系白血病单核（THP-1）细胞被三角形细胞陷阱捕获在具有不同阿糖胞苷（Ara-C）药物浓度的浓度梯度芯片中。由于这种双重声学效应，药物在不到 30 分钟内影响细胞活力，这比传统方法（通常超过 24 小时）更快。当与微流体技术相结合进行多浓度药物筛选时，这种基于双声学效应的药物输送策略有可能节省时间并降低药物筛选成本。