High throughput of cell irradiation with microfluidics in single ion microbeam system
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摘要: 辐照通量是指单位时间里离子辐照的细胞数量，是单离子束细胞辐照系统的重要性能指标。为提高单离子定位辐照通量，将微流控技术应用于单离子束细胞辐照系统，实现了单离子-单细胞精确定位自动辐照技术。微流控芯片上建立细胞储液池、O2和CO2注入通道、恒温加热、pH检测、细胞检测等功能机构。细胞微流受驱动在通道中保持运动，离子经微流控芯片辐照点射入微通道，对动态细胞进行辐照。基于CAS-LIBB装置，建立离子定位微流细胞的计算模型，研究离子精确瞄准微流细胞的基本方法和规律，获得微流细胞速度、最大辐照通量、辐照剂量、细胞间距等多个参量之间的相互约束关系，成为系统运行的理论指导。提出“即测即打”运行模式，以加快辐照速度，提高离子定位准确性。结果表明，细胞速度和辐照通量均存在上限值，提高微流细胞数密度和离子发射密度，是提高辐照通量的可选方法。采用微流控技术后，辐照通量达到
10000 细胞/h，相比之前提高10倍以上。计算数据和实验结果基本吻合。Abstract: The irradiation throughout means the amount of the cells irradiated per unit time, which is the important performance indicator of a single ion microbeam system. To improve the single ion localization irradiation throughout, microfluidic chip technology is applied to the single ion beam cell irradiation system with single ion to single cell auto-irradiation. A cell storage pool, O2 and CO2 injection channels, constant temperature control, pH detection and cell inspection are built on the chip. Ions irradiate the moving cells through the irradiation point on the microfluidic chip. Based CAS-LIBB system, this article establishes a computational model for ion targeting microfluidic cells. The basic methods and laws of ion targeting microfluidic cells are studied, therefore it has obtained the multi-relationships among cell velocity, irradiation throughout, irradiation dose, and cell separation, which are the theoretical guidance for system operation. A mode of “Promptly Irradiate with Inspected” is proposed to improve the irradiating effectivity and accuracy. The results show that there is an upper limit for cell speed as well as for irradiation throughout, and increasing cell number density and ion emission density are the most feasible ways to raise the irradiation throughout. With the microfluidic technology, the irradiation throughout now reaches10000 cells/h, more than 10 times higher than before. The calculated data is basically consistent with the experimental results. -
图 4 两个离子相继辐照一个运动细胞，准直器固定不动，细胞上两击中点的间距须小于a，a为细胞尺度， b为束斑直径
Figure 4. Two ions irradiate a cell successively, separation of the two hit points on cell is a, collimator is fixed, b is the beam spot diameter
图 5 微流通道中单列细胞数密度
Figure 5. Number density of the single-row cells in the microfluidic channel
表 1 设计实例数据
Table 1. Data of a design example
k d/mm n/s−1 m/μL−1 vm/(mm·s−1) Qmax /h−1 Q/h−1 relative error/% 2 1.0 1000 2500 8.5 30600 − − 2 1.0 2000 2500 17.0 61200 invalid − 5 1.0 1000 2500 3.4 12240 11861 −3.1 5 1.0 2000 2500 6.8 24480 23427 −4.3 10 1.0 1000 2500 1.7 6120 5954 −2.7 10 1.0 2000 2500 3.4 12240 11775 −3.8 
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