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PR Hightlights(Vol. 9, Iss. 3): 皮秒光脉冲与纳秒电脉冲协同作用开辟将药物、疫苗输送到细胞和组织的新方法

2021-04-07

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皮秒光脉冲与纳秒电脉冲协同作用开辟将药物、疫苗输送到细胞和组织的新方法

 

自20世纪50年代以来光击穿和电击穿一直受到研究人员的广泛关注,其描述了在极端光场或电场作用下材料的变性。然而此前从未有人研究过光场和电场相结合,特别是其在生物相关系统中的应用。得克萨斯A&M大学的Vladislav V. Yakovlev教授提出,通过研究电脉冲和光脉冲的协同作用,研究人员能够更好地实现高局域击穿,同时降低击穿阈值。

这种新发现的协同效应,在以高局域方式选择性破坏细胞膜方面尤其重要。此前常用的是电穿孔技术,即对细胞施加电场,以增加细胞膜通透性;还有一种常用的方法是光穿孔,即用超短激光脉冲在细胞膜上钻一个小孔。将两种方法结合起来,取二者之长,将能开辟一种将药物、疫苗输送到细胞和组织的新方法。

近日,Vladislav V. Yakovlev教授等在Photonics Research2021年第3期发表的文章(Zachary N. Coker, Xiao-Xuan Liang, Allen S. Kiester, Gary D. Noojin, Joel N. Bixler, Bennett L. Ibey, Alfred Vogel, Vladislav V. Yakovlev. Synergistic effect of picosecond optical and nanosecond electrical pulses on dielectric breakdown in aqueous solutions[J]. Photonics Research, 2021, 9(3): 03000416)中表明在纳秒电脉冲和皮秒光脉冲同时激励下,可产生一种协同效应,进而降低击穿的阈值。

图1 (a)用于预测电脉冲和光脉冲对介电击穿阈值协同效应的理论模型;(b)用于触发、监测介质中介电击穿的实验装置示意图;(c)图中实验结果显示了击穿概率与输入激光能量的关系

该研究是在三个不同研究团队的共同努力下完成的,生物材料光学击穿研究领域的领军专家——Alfred Vogel教授领导的德国团队提出了一个理论模型(如图1(a)),该理论模型为得克萨斯A&M大学和美国空军研究实验室的研究人员提供了实验上实现协同作用的指导。实验装置包括纳秒电脉冲发生器,以及聚焦皮秒光脉冲激励源 (如图1(b))。并且通过在一些生物相关介质上进行实验,验证了协同效应理论(如图1(c))。

图2 细胞实验的初步结果。荧光图像所示的是YO-PRO-1染料在(a)控制、(b)纳秒电脉冲单独作用、(c)皮秒光脉冲单独作用以及(d)皮秒光脉冲和纳秒电脉冲同时作用条件下的吸收情况。图(c)中的黄色虚线圈中为培养层细胞被击穿移除的位置培养层细胞。(d)中的橙色虚线圈表示,与周围暴露在纳秒电脉冲下的细胞相比,皮秒光脉冲聚焦处目标细胞中YO-PRO染料的吸收减少。

从目前的全球形势来看,这种协同效应与普罗大众最息息相关的作用是其可以提高COVID-19疫苗接种的准确性。在初步实验中,合作团队使用电脉冲和光脉冲照射细胞(如图2),并使用一种沿用已久的染料YO-PRO-1来监测细胞膜的完整性;一旦细胞膜被破坏,这种染料就会渗入细胞。

尽管此项技术目前并不存在于实验室已有的技术范畴内,但该合作团队指出,产生协同效应无需复杂的设备,因此可以在大多数实验设施中使用。而且认为,这类把新型基础科学研究与高影响力技术(比如极端光-物质相互作用,纳米生物技术等)结合起来的研究,必将会得到广泛关注。

 

Synergistic effect of picosecond optical and nanosecond electrical pulses on dielectric breakdown in aqueous solutions

 

Optical and electrical breakdown of materials, which describe material modification in the presence of extreme optical or electrical fields, have been studied since the 1950s. However, simultaneous application of optical and electrical fields, especially, to biologically relevant systems hasn't been explored before. Prof. Vladislav V. Yakovlev from Texas A&M University said by investigating the synergistic action of electrical and optical pulses, they were able to promote highly localized breakdown, while reducing the threshold for such breakdown.

The newly discovered synergistic effect is particularly important if there is a need to selectively disrupt cellular membrane in a highly localized manner. Typically, an electroporation, a technique that applies an electrical field to cells to increase the permeability of the cell membrane, is used. Alternatively, an optoporation, which uses ultrashort laser pulses to form a small hole in the cell membrane, can be employed. A powerful combination of electroporation and optoporation can provide the benefits of both of approaches, leading to new ways drugs and vaccines can be delivered to cells and tissues.

The cooperative team's recent publication in Photonics Research vol. 9 No. 3 (Zachary N. Coker, Xiao-Xuan Liang, Allen S. Kiester, Gary D. Noojin, Joel N. Bixler, Bennett L. Ibey, Alfred Vogel, Vladislav V. Yakovlev. Synergistic effect of picosecond optical and nanosecond electrical pulses on dielectric breakdown in aqueous solutions[J]. Photonics Research, 2021, 9(3): 03000416) demonstrated that upon simultaneous excitation by nanosecond electrical pulse and picosecond optical pulse, a synergetic effect occurs, leading to reduced threshold for such breakdown.

Figure 1. (a) A theoretical model, which predicts the synergistic effect of electrical and optical pulses on the threshold of dielectric breakdown; (b) a schematic of experimental setup which used for initiating and monitoring dielectric breakdown in a medium; (c) experimental results demonstrating the probability of breakdown on the input laser energy.

The research was completed with the joint efforts of three different teams. The German team led by Prof. Alfred Vogel, the leading expert in the optical breakdown studies of biological materials, developed a theoretical model (Fig. 1a) which provided Texas A&M University and Air Force Research Laboratory researchers with guidelines for experimental realization of the proposed synergistic interactions. An experimental setup, which included both the nanosecond electrical pulser and a focused beam picosecond optical pulse excitation, was constructed (Fig. 1b), and the proposed effect was experimentally demonstrated for a number of biologically relevant media (Fig. 1c).

Figure 2. Preliminary results for cell-based studies. Fluorescent images showing YO-PRO-1 dye uptake under (a) control, (b) nanosecond electrical pulse alone, (c) picosecond optical pulses alone, and (d) combined picosecond optical and nanosecond electrical exposure conditions. Yellow dashed circle in c indicates where cells were removed from culture layer by breakdown event. Orange dashed circle in d indicates where picosecond optical pulse was focused and the reduced YO-PRO dye uptake in targeted cells, compared to surrounding cells exposed to nanosecond electrical pulse.

One of the impacts of paramount significance of this effect, which can be of great interest to a general audience, is improved accuracy of vaccine delivery for COVID-19. In preliminary data, the team performed cellular exposure to both electrical and optical pulses (Fig. 2) monitoring the integrity of the cellular membrane using a well-established dye, YO-PRO-1, which upon membrane disruption penetrates the cell.

While this technology would be a new addition to a laboratory, the research team noted that creating the effect doesn't require sophisticated equipment, allowing it to be used in a broad range of facilities.

As the research team states, a unique combination of a new fundamental science and a broad range of high-impact applications ranging from extreme light-matter interactions to nano- and biotechnology would be of great interest for a broad audience.