Hu Siyi, Zhang Butian, Zeng Shuwen, Liu Liwei, Yong Ken-Tye, Ma Hanbin, Tang Yuguo
CAS Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No.88 Keling Road, Suzhou, Jiangsu 215163, P.R. China.
MOE Key Laboratory of Fundamental Physical Quantities Measurement, PGMF and School of Physics, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Lab Chip. 2020 Aug 11;20(16):3001-3010. doi: 10.1039/d0lc00202j.
Biofunctionalized quantum dots (QDs) are effective target fluorescent labels for bioimaging. However, conventional synthesis of biofunctionalized I-III-VI core-shell CuInS2/ZnS QDs requires complex bench-top operations, resulting in limited product performance and variety, and is not amenable to a 'one-step' approach. In this work, we have successfully demonstrated a fully automated method for preparing denatured bovine serum albumin (dBSA)-CuInS2/ZnS QDs by introducing microfluidic (MF) chips to synthesize biofunctionalized QDs, hence establishing a 'one-step' procedure. We have also studied and optimized the reaction synthesis parameters. The emission wavelength of the dBSA-CuInS2/ZnS QDs is located in the near-infrared range and can be tuned from 650 to 750 nm by simply varying the reaction parameters. In addition, the 'one-step'-synthesized dBSA-CuInS2/ZnS QDs have a long average fluorescence lifetime of 153.76 ns and a small particle size of 5 ± 2 nm. To demonstrate the applicability of the 'one-step'-synthesized dBSA-CuInS2/ZnS QDs in bioimaging studies, we modified the QDs with folic acid and hyaluronic acid, and then performed target bioimaging and cytotoxicity tests on macrophages, liver cancer cells and pancreatic cancer cells. The cell images show that the red emission signals originate from the QDs, which indicates that the dBSA-CuInS2/ZnS QDs prepared by the MF approach are suitable optical contrast agents for target bioimaging. This 'one-step' MF-based QD synthesis approach could serve as a rapid, cost-effective, and small-scale nanocrystal production platform for complex QD formulations for a wide range of bioapplications.
生物功能化量子点(QDs)是用于生物成像的有效靶标荧光标记物。然而,传统的生物功能化I-III-VI核壳CuInS2/ZnS量子点的合成需要复杂的台式操作,导致产品性能和种类有限,并且不适合“一步法”。在这项工作中,我们通过引入微流控(MF)芯片来合成生物功能化量子点,成功展示了一种全自动制备变性牛血清白蛋白(dBSA)-CuInS2/ZnS量子点的方法,从而建立了“一步法”程序。我们还研究并优化了反应合成参数。dBSA-CuInS2/ZnS量子点的发射波长位于近红外范围内,通过简单改变反应参数可在650至750nm之间调节。此外,“一步法”合成的dBSA-CuInS2/ZnS量子点具有153.76ns的长平均荧光寿命和5±2nm的小粒径。为了证明“一步法”合成的dBSA-CuInS2/ZnS量子点在生物成像研究中的适用性,我们用叶酸和透明质酸修饰了量子点,然后对巨噬细胞、肝癌细胞和胰腺癌细胞进行了靶标生物成像和细胞毒性测试。细胞图像显示红色发射信号源自量子点,这表明通过MF方法制备的dBSA-CuInS2/ZnS量子点是适用于靶标生物成像的光学造影剂。这种基于“一步法”MF的量子点合成方法可以作为一个快速、经济高效且小规模的纳米晶生产平台,用于制备适用于广泛生物应用的复杂量子点制剂。