Abstract：
Photodynamic therapy (PDT) is a medical radio chemotherapeutic method that uses light, photosensitizing agents, and oxygen to produce cytotoxic compounds, which eliminate malignant cells. Recently, Microfluidic systems have been used to analyse photosensitizers (PSs) due to their potential to replicate in vivo environments. While prior studies have established a strong correlation between reacted singlet oxygen concentration and PDT-induced cellular death, the effects that the ambient fluid flow might have on the concentration of oxygen and PS have been disregarded in many, which limits the reliability of the results. Herein, we coupled the transport of oxygen and PS throughout the ambient medium and within the spheroidal multicellular aggregate to initially study the profiles of oxygen and PS concentration alongside PDT-induced cellular death throughout the spheroid before and after radiation. The attained results indicate that the PDT-induced cellular death initiates on the surface of the spheroids and subsequently spreads to the neighbouring regions, which is in great accordance with experimental results. Afterward, the effects that drug-light interval (DLI), fluence rate, PS composition, microchannel height, and inlet flow rate have on the therapeutic outcomes are studied. The findings show that adequate DLI is critical to ensure uniform distribution of PS throughout the medium, and a value of 5 h was found to be sufficient. The composition of PS is critical, as ALA-PpIX induces earlier cell death but accelerates oxygen consumption, especially in the outer layers, depriving the inner layers of oxygen necessary for PDT, which in turn disrupts and prolongs the exposure time compared to mTHPC and Photofrin. Despite the fluence rate directly influencing the singlet oxygen generation rate, increasing the fluence rate by 189 mW/cm2 would not significantly benefit us. Microwell height and inlet flow rate involve competing phenomena-increasing height or decreasing flow reduces oxygen supply and increases PS \"washout\" and its concentration.
摘要：
光动力疗法（PDT）是一种使用光，光敏剂，和氧气产生细胞毒性化合物，消除恶性细胞。最近,微流体系统已用于分析光敏剂（PS），因为它们具有在体内环境中复制的潜力。虽然先前的研究已经建立了反应的单线态氧浓度和PDT诱导的细胞死亡之间的强相关性，环境流体流动可能对氧气和PS浓度的影响在许多情况下都被忽视了，这限制了结果的可靠性。在这里，我们将氧气和PS在整个环境介质中以及球形多细胞聚集体内的运输相结合，以初步研究辐射前后整个球体中氧气和PS浓度以及PDT诱导的细胞死亡的分布。获得的结果表明，PDT诱导的细胞死亡始于球状体的表面，随后扩散到相邻区域，这与实验结果非常吻合。之后,药光间隔(DLI)的影响，通量率，PS组成,微通道高度,和入口流速对治疗结果的影响进行了研究。研究结果表明，充分的DLI对于确保PS在整个培养基中的均匀分布至关重要，发现5小时的值就足够了。PS的组成至关重要,ALA-PpIX诱导早期细胞死亡，但加速氧消耗，尤其是在外层，剥夺PDT所需的内层氧气，与mTHPC和Photofrin相比，这反过来又破坏并延长了曝光时间。尽管注量率直接影响单线态氧生成率，将注量率增加189mW/cm2不会显着受益。微孔高度和入口流量涉及竞争现象-增加高度或减少流量会减少氧气供应并增加PS“冲刷”及其浓度。
