Single-Cell-Level Cancer Therapy Using a Hollow Optical Fiber-Based Microplasma
Single-Cell-Level Cancer Therapy Using a Hollow Optical Fiber-Based Microplasma
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DOI：
10.1002/smll.201000480
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发表时间：
2010-07-19
期刊：
影响因子：
13.3
通讯作者：
Kim, Sung-O
中科院分区：
文献类型：
--
作者：
Kim, Jae Young;Ballato, John;Kim, Sung-O
常压等离子体已用于癌症治疗，但输送系统的尺寸阻碍了单细胞治疗。[1-5] 等离子体是电离粒子的气态集合，其中包括自由电子和自由基，它们是短暂但具有强反应性的物质。[6-13] 基于在常压下运行的等离子体的癌症治疗已经开发出来，它将这些自由基暴露于肿瘤细胞，导致其随后快速凋亡。[1, 2] 定义等离子体诱导的肿瘤细胞凋亡，优选具有可以在单细胞水平上治疗肿瘤细胞的等离子体装置。因此，挑战在于产生等离子体并将其输送到单个细胞。由带有电极的管组成的微等离子体喷射装置已被证明是产生尺寸约为数百微米的非热常压等离子体的来源[10-22]。 [23-27] 减小等离子体尺寸的主要方法有两种。第一种方法使用内径较小的玻璃毛细管。第二种方法采用细金属线作为电极。由于微等离子体射流最初是为表面工作（即仅处理物体的表面）而开发的，因此两种传统方法都使用刚性玻璃管。由此产生的不灵活性使得这种方法几乎不可能用于内部肿瘤的等离子体治疗。因此，高度灵活的微等离子体喷射装置可以将等离子体精确地靶向肿瘤细胞，无论它们位于体内或体表上。在这项工作中，采用空心光纤作为玻璃毛细管。由此产生的微等离子体喷射装置具有两个显着优点：1）它的内径比传统毛细管小得多； 2) 由于光纤制造工艺的成熟，这些光纤非常坚固，并且可以以非常低的成本制造很长的长度（>公里）。与传统内窥镜检查相比，这种灵活的微米级等离子喷射装置可以治疗较小的肿瘤细胞集合，并且切口较小。图 1a 显示了空心玻璃光纤横截面的扫描电子显微镜 (SEM) 图像。所使用的光纤内径为 55 毫米，外径为 125 毫米，并具有额外的塑料保护涂层，使得光纤的全直径为 240 毫米（参见支持信息）。等离子体羽流被限制在中央空心核心中，该核心仅比包括肿瘤细胞在内的常规细胞大一到两倍。因此，来自这种高度灵活的微等离子体喷射装置的等离子体羽流将能够精确地处理单个细胞。铜带（6 毫米宽）用作单个电极，放置在距光纤末端 5 毫米处。使用高纯度氦气作为放电气体。氦气流速保持恒定在约35标准立方厘米每分钟(sccm)。与其他具有毫米级管（2000–40000sccm）的等离子射流装置相比，这里使用的气体流量极低。[10–13, 16–22]
Atmospheric-pressure plasmas have been used in cancer therapies, but the size of the delivery systems precludes single-cell treatments.[1–5] Plasmas are gaseous collections of ionized particles that include free electrons and radicals that are short-lived but strongly reactive species.[6–13] Cancer therapies based on plasmas that operate at atmospheric pressure have been developed, which expose these free radicals to tumor cells causing their subsequent apoptosis at a rapid pace.[1, 2] To define the mechanism of plasma-induced tumor cell apoptosis, it would be preferred to have a plasma device that can treat tumor cells at the single-cell level. Thus, the challenge is to generate and deliver plasmas to a single cell. A microplasma jet device consisting of a tube with electrodes has been demonstrated as a source for creating nonthermal atmospheric-pressure plasmas [10–22] with dimensions on the order of several hundred micrometers.[23–27] There are two principal methods for reducing the size of the plasma. The first method utilizes a glass capillary tube with a small inner diameter. The second approach employs a thin metal wire as an electrode. Because microplasma jets were originally developed for superficial work (ie, treating only the surface of objects), both conventional methods utilize rigid glass tubes. The resultant inffexibility makes such methods almost impossible to use in plasma treatments of interior tumors. Thus, a highly ffexible microplasma jet device could result in the precise targeting of plasmas onto tumor cells regardless of their location in or on the body. In this work, a hollow-core optical fiber is employed as a glass capillary tube. The resulting microplasma jet device has two significant advantages: 1) it has a considerably smaller inner diameter than the conventional capillary tubes; and 2) these fibers are exceedingly strong and can be made in very long lengths (> km) at a very low cost due to the maturity of the optical-fiber fabrication process. This ffexible and micrometer-scale plasma jet device can permit the treatment of smaller collections of tumor cells and with smaller incisions in comparison to conventional endoscopy. Figure 1a shows a scanning electron microscopy (SEM) image of the cross section of the hollow-core glass optical fiber. The fiber employed had an inner diameter of 55 mm, an outer diameter of 125mm, and an additional protective plastic coating such that the full diameter of the fiber was 240 mm (see Supporting Information). The plasma plume is confined in the central hollow core, which is only one or two times larger than conventional cells including tumor cells. Thus, the plasma plume from this highly ffexible microplasma jet device would be able to precisely treat a single cell. Copper tape (6 mm wide) was used as a single electrode that was placed 5 mm from the end of the optical fiber. High-purity helium gas was used as the discharge gas. The helium gas ffow rate was held constant at approximately 35 standard cubic centimeters per minute (sccm). Compared to other plasma jet devices with millimetersized tubes (2000–40000sccm), the gas ffow used here is extremely low.[10–13, 16–22]