We report here a 3D cell culture microgel-based system containing carbon dots capable of sensing the pH changes in the cellular microenvironment. We have utilized a simple droplet-based microfluidics methodology for encapsulating cells and fluorescent pH sensitive carbon dots in polyethylene glycol microgels. Since the microfluidics assembly is developed from simple components that can be modified easily to yield microgels of different size, composition, and architecture, it can be utilized to develop complex 3D cell culture scaffolds of desired composition along with spatial control on the polymer composition. The synthesized pH sensitive carbon dots possess green fluorescence emission, which increases as the pH is lowered from neutral to acidic. Since the probe sensitivity to pH change is well within the physiologically relevant range (pH 5.8–7.7), the probe can be used for detecting a lowering of pH as the cells proliferate or undergo various biological processes. We demonstrate that the nanoprobes as well as the process of forming the microgel beads with nanoprobes and mammalian cells is biocompatible, and the cells easily proliferate inside the microgels. The changes in pH as the mammalian cells grow in the microgels is easily monitored via fluorescence microscopy, suggesting that the platform can be used to study time dependent changes in cellular microenvironment pH and can be easily utilized to monitor cellular growth, disease progression, etc.

中文翻译：

---

使用荧光碳点的3D微凝胶中的细胞微环境pH传感

我们在这里报告一个基于3D细胞培养基于微凝胶的系统，该系统包含能够感应细胞微环境中pH值变化的碳点。我们已经利用了基于液滴的简单微流控方法，将细胞和荧光pH敏感的碳点封装在聚乙二醇微凝胶中。由于微流体组件是由简单的组件开发而成的，可以轻松地对其进行修饰以产生具有不同大小，组成和结构的微凝胶，因此可以将其用于开发具有所需组成的复杂3D细胞培养支架以及对聚合物组成进行空间控制。合成的pH敏感碳点具有绿色荧光发射，随着pH从中性降低到酸性而增加。由于探针对pH变化的敏感度完全在生理相关范围内（pH 5.8–7）。7），该探针可用于检测细胞增殖或经历各种生物学过程时pH的降低。我们证明纳米探针以及与纳米探针和哺乳动物细胞形成微凝胶珠的过程是生物相容的，并且细胞容易在微凝胶内增殖。通过荧光显微镜可以轻松监测随着哺乳动物细胞在微凝胶中生长而产生的pH值变化，这表明该平台可用于研究细胞微环境pH值随时间的变化，并可轻松用于监测细胞生长，疾病进展等。我们证明纳米探针以及与纳米探针和哺乳动物细胞形成微凝胶珠的过程是生物相容的，并且细胞容易在微凝胶内增殖。通过荧光显微镜可以轻松监测随着哺乳动物细胞在微凝胶中生长而产生的pH值变化，这表明该平台可用于研究细胞微环境pH值随时间的变化，并可轻松用于监测细胞生长，疾病进展等。我们证明纳米探针以及与纳米探针和哺乳动物细胞形成微凝胶珠的过程是生物相容的，并且细胞容易在微凝胶内增殖。通过荧光显微镜可以轻松监测随着哺乳动物细胞在微凝胶中生长而产生的pH值变化，这表明该平台可用于研究细胞微环境pH值随时间的变化，并可轻松用于监测细胞生长，疾病进展等。