Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry , Wuhan University , Wuhan 430072 , China.
Anal Chem. 2018 Aug 21;90(16):10078-10086. doi: 10.1021/acs.analchem.8b03078. Epub 2018 Aug 3.
The issue of quantifying trace metals in cells has drawn widespread attention but is threatened with insufficient sensitivity of the instruments, complex cellular matrix and limited cell consumption. In this study, microfluidic droplet-based liquid phase microextraction (LPME), as a miniaturized platform, was developed and combined with electrothermal vaporization (ETV)-inductively coupled plasma mass spectrometry (ICPMS) for the analysis of trace Cd, Hg, Pb, and Bi in cells. A novel and facile design of phase separation region was proposed, which made the phase separation very easily for subsequent ETV-ICPMS detection. Mechanism of the phase separation was carefully discussed using the incompressible formulation of the Navier-Stokes equations. The developed microfluidic droplet-based LPME system exhibited much higher extraction efficiency to target metals than microfluidic stratified flow-based LPME. Under the optimized conditions, the limits of detection of the proposed microfluidic droplet-based LPME-ETV-ICPMS system were 2.5, 3.9, 5.5, and 3.4 ng L for Cd, Hg, Pb, and Bi, respectively. The accuracy of the developed method was well validated by analyzing the target metals in Certified Reference Materials of GBW07601a human hair. Finally, the proposed method was successfully applied to the analysis of target metals in HeLa and HepG2 cells with the recoveries for the spiked samples ranging from 83.5 to 112.3%. Overall, the proposed design is a simple and reliable solution for the phase separation on droplet-chip and the microfluidic droplet-based LPME-ETV-ICPMS combination strategy shows great promise for trace elements analysis in cells.
量化细胞中痕量金属的问题引起了广泛关注，但仪器的灵敏度不足、复杂的细胞基质和有限的细胞消耗等问题仍然存在。在这项研究中，我们开发了一种基于微流控液滴的液相微萃取（LPME）微型化平台，并将其与电热蒸发（ETV）-电感耦合等离子体质谱（ICPMS）相结合，用于分析细胞中的痕量 Cd、Hg、Pb 和 Bi。我们提出了一种新颖且简便的相分离区域设计，使得相分离非常容易，便于后续进行 ETV-ICPMS 检测。我们使用不可压缩 Navier-Stokes 方程的公式仔细讨论了相分离的机制。与基于微流控分层流的 LPME 相比，所开发的基于微流控液滴的 LPME 系统对目标金属具有更高的萃取效率。在优化条件下，所提出的基于微流控液滴的 LPME-ETV-ICPMS 系统对 Cd、Hg、Pb 和 Bi 的检出限分别为 2.5、3.9、5.5 和 3.4 ng L。通过分析 GBW07601a 人发标准物质中的目标金属，验证了所开发方法的准确性。最后，该方法成功应用于 HeLa 和 HepG2 细胞中目标金属的分析，加标样品的回收率在 83.5%至 112.3%之间。总的来说，所提出的设计是一种简单可靠的液滴芯片相分离解决方案，基于微流控液滴的 LPME-ETV-ICPMS 组合策略有望用于细胞中痕量元素的分析。
