Direct Infusion ICP-qMS of Lined-up Single-Cell Using an Oil-Free Passive Microfluidic System
Direct Infusion ICP-qMS of Lined-up Single-Cell Using an Oil-Free Passive Microfluidic System
复制标题
使用无油被动微流体系统直接输注排列单细胞的 ICP-qMS
DOI：
10.1021/acs.analchem.9b05838
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发表时间：
2020
影响因子：
7.4
通讯作者：
Qiuquan Wang
中科院分区：
文献类型：
--
作者：
Yang Zhou;Zhangqian Chen;Juxing Zeng;Jiaxuan Zhang;Danxia Yu;Bo Zhang;Xiaowen Yan;Limin Yang;Qiuquan Wang
当在线与质谱仪(MS)联用时，广泛应用的油包水微流控单细胞分析遇到了问题。例如，油相影响了MS的稳定性、效率和准确度，MS与微流控芯片之间的传统接口存在进样效率低的问题，传输速率有时与瞬时信号采集的读出停留时间不匹配。考虑到细胞已经是具有亲水表面和弹性疏水膜的液滴，我们开发了一种无油被动微流控系统(OFPMS)，该系统由交替的直-弯-直微通道和直接输注(Di)微雾化器组成，用于列阵单细胞的电感耦合等离子体四极杆质谱(ICPQMS)。OFPMS只需使用可热分解的NH4HCO3缓冲液即可确保精确的单细胞分离，无需使用任何油和不相容的聚合物载体。由于具有400-25000个电池/分钟的可调吞吐量，以及相邻排列的单个电池之间至少20ms的可控间隔时间，因此可以更加灵活和方便地适应电感耦合等离子体质谱仪的驻留时间。以OFPMS-Di-ICPQMS为例，实现了单细胞的定量传输和70%以上的高检测效率。因此，细胞间的异质性可以通过测定单个细胞中的金属来简单地揭示出来。
When coupled online with mass spectrometry (MS), widely applied water-in-oil droplet-based microfluidics for single cell analysis met problems. For example, the oil phase rumpled the stability, efficiency, and accuracy of MS, the conventional interface between MS and the microfluidic chip suffered the low sample introduction efficiency, and the transportation rates sometimes unmatched the readout dwell times for transient signal acquisition. Considering cells are already droplets with hydrophilic surface and elastic hydrophobic membrane, we developed an oil-free passive microfluidic system (OFPMS) that consists of alternating straight-curved-straight microchannels and a direct infusion (dI) micronebulizer for inductively coupled plasma quadrupole-based mass spectrometry (ICP-qMS) of lined-up single-cell. OFPMS guarantees exact single cell isolation one by one just using a thermo-decomposable NH4HCO3 buffer, eliminating the use of any oil and incompatible polymer carriers. It is more flexible and facile to adapt to the dwell time of ICP-qMS owing to the adjustable throughput of 400 to 25000 cells/min and the controllable interval time of at least 20 ms between the lined-up adjacent single cells. Quantitative single-cell transportation and high detection efficiency of more than 70% was realized using OFPMS-dI-ICP-qMS exemplified here. Thus, cell-to-cell heterogeneity can be simply uncovered via the determination of metals in the individual cells.