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

Abstract

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.

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One drop at a time: toward droplet microfluidics as a versatile tool for single-cell analysis

“…One possibility is to use fluorescently labeled cells for encapsulation and subsequently perform fluorescence-activated droplet sorting. 25,28 Additionally, discrimination between empty and cell-containing droplets can also be achieved One drop at a time A Rakszewska et al by electrical impedance measurements 53,54 or by sorting cells in microfluidic channels based on the Clausius-Mossotti effect, which has been demonstrated for both continuous-phase 55 and droplet microfluidics. 56 Although the active sorting of cells requires a relatively complex setup, the number of recently published studies in this field indicates the feasibility of this approach for single-cell droplet experiments.…”

Droplet microfluidics: A tool for biology, chemistry and nanotechnology

“…The latter has been recently achieved using real-time image-based droplet classification [35]. Electrical impedance measurements allow for fast (> 100 Hz), labelfree detection of cells within a droplet with single-cell sensitivity [36]. This approach also allows for discrimination between viable and non-viable cells.…”