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Label-free, high-throughput, electrical detection of cells in droplets

机译:无标签,高通量的液滴中细胞电检测

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摘要

Today, droplet based microfluidics has become a standard platform for high-throughput single cell experimentation and analysis. However, until now no label-free, integrated single cell detection and discrimination method in droplets is available. We present here a microfluidic chip for fast (>100 Hz) and label-free electrical impedance based detection of cells in droplets. The microfluidic glass-PDMS device consists of two main components, the droplet generator and the impedance sensor. The planar electrode pair in the main channel allows the detection of only cells and cell containing droplets passing the electrodes using electrical impedance measurements. At a measurement frequency of 100 kHz non-viable cells, in low-conducting (LC) buffer, show an increase in impedance, due to the resistive effect of the membrane. The opposite effect, an impedance decrease, was observed when a viable cell passed the electrode pair, caused by the presence of the conducting cytoplasm. Moreover, we found that the presence of a viable cell in a droplet also decreased the measured electrical impedance. This impedance change was not visible when a droplet containing a non-viable cell or an empty droplet passed the electrode pair. A non-viable cell in a droplet and an empty droplet were equally classified. Hence, droplets containing (viable) cells can be discriminated from empty droplets. In conclusion, these results provide us with a valuable method to label-free detect and select viable cells in droplets. Furthermore, the proposed method provides the first step towards additional information regarding the encapsulated cells (e.g., size, number, morphology). Moreover, this all-electric approach allows for all-integrated Lab on a Chip (LOC) devices for cell applications using droplet-based platforms.
机译:如今,基于液滴的微流体技术已成为高通量单细胞实验和分析的标准平台。但是,到目前为止,还没有可用的无标记的,集成的液滴单细胞检测和鉴别方法。我们在这里介绍一种微流控芯片,用于基于液滴的细胞快速(> 100 Hz)和无标记的电阻抗检测。微流体玻璃-PDMS设备由两个主要组件组成,液滴生成器和阻抗传感器。主通道中的平面电极对允许使用电阻抗测量仅检测通过电极的细胞和含有液滴的细胞。在低频率(LC)缓冲液中,在100 kHz的测量频率下,由于该膜的电阻作用,无活力的细胞显示出阻抗增加。当有活力的细胞通过电极对时,观察到相反的效果,即阻抗降低,这是由导电细胞质的存在引起的。此外,我们发现液滴中存在活细胞也降低了测得的电阻抗。当包含无效细胞的液滴或空液滴通过电极对时,此阻抗变化不可见。液滴中的无活力细胞和空液滴被均等分类。因此,可以将包含(活的)细胞的液滴与空液滴区分开。总之,这些结果为我们提供了一种有价值的方法,可以无标记地检测和选择液滴中的活细胞。此外,所提出的方法提供了迈向有关封装细胞的附加信息的第一步(例如,大小,数量,形态)。此外,这种全电动方法允许使用基于液滴的平台对电池应用进行全集成的芯片实验室(LOC)设备。

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