Acoustofluidic lysis of cancer cells and Raman spectrum profiling.

The lysis of cancer cells inside a sessile droplet was performed using traveling surface acoustic waves (SAWs) without any chemical reagents. Raman spectrum profiling was then carried out to explore detailed cell-derived data. The Rayleigh waves formed by an interdigital transducer were made to propagate along the surface of an LiNbO3 substrate. Polystyrene microparticles (PSMPs) were used to establish mechanical cell lysis effectively, and gold nanoparticles (AuNPs) were added to enhance the Raman signals from the lysed cells by SAWs. The lysis efficiency was evaluated according to the size and concentration of the PSMPs in experiments where the frequency was varied. Lysis occurred mainly by mechanical collision using PSMPs in a high-frequency domain, and the lysis efficiency was improved by increasing the application time and the energy density of the SAWs. Raman signals from the lysed cells were greatly enhanced by nanogaps formed by the AuNPs, which were evenly distributed irrespective of the SAWs through the frequency-independent behavior of the AuNPs. Finally, detailed Raman spectra of MDA-MB-231, malignant breast cancer cells, were acquired, and various organic matter-derived peaks were observed. The 95% confidence region for cells subjected to lysis was more widely distributed than that of cells not subjected to lysis. The proposed SAW platform is expected to facilitate the detection of small quantities and to be applied in biomedical applications.

Dielectrophoresis-field flow fractionation for separation of particles: A critical review.

Dielectrophoresis-field flow fractionation (DEP-FFF) has emerged as an efficient in-vitro, non-invasive, and label-free mechanism to manipulate a variety of nano- and micro-scaled particles in a continuous-flow manner. The technique is mainly used to fractionate particles/cells based on differences in their sizes and/or dielectric properties by employing dielectrophoretic force as an external force field applied perpendicular to the flow direction. The dielectrophoretic force is the result of a spatially non-uniform electric field in the microchannel that can be generated either by exploiting microchannel geometry or using special arrangements of microelectrode arrays. Several two-dimensional (e.g., coplanar interdigitated, castellated) and three-dimensional (e.g., top-bottom, side-wall) microelectrode designs have been successfully utilized to perform fractionation of heterogeneous samples. Although originally introduced as a separation technique, DEP-FFF has attracted increasing interest in performing other important operations such as switching, focusing, dipping, and surface functionalization of target particles. Nonetheless, the technique still suffers from limitations such as low throughput and joule heating. By comparatively analyzing recent developments that address these shortcomings, this work is a step forward towards realizing the full potential of DEP-FFF as an ideal candidate for point-of-care (POC) devices with diverse applications in the fields of biomedical, chemical, and environmental engineering.

Lateral fluid flow fractionation using dielectrophoresis (LFFF-DEP) for size-independent, label-free isolation of circulating tumor cells.

This short communication introduces a continuous-flow, dielectrophoresis-based lateral fluid flow fractionation microdevice for detection/isolation of circulating tumor cells in the presence of other haematological cells. The device utilizes two sets of planar interdigitated transducer electrodes micropatterned on top of a glass wafer using standard microfabrication techniques. A microchannel with a single inlet and two outlets, realized in polydimethylsiloxane, is bonded on the glass substrate. The two sets of electrodes slightly protrude into the microchannel. Both of the electrode sets are energized with signals at different frequencies and different operating voltages ensuring that the cancer cells experience positive dielectrophoretic force from one set of the electrodes and negative dielectrophoretic force from the other array. Normal cells experience unequal negative dielectrophoretic forces from opposing sets of electrodes. The resultant dielectrophoretic forces on cancer and normal cells push them to flow towards their designed outlets. Successful isolation of green fluorescent protein-labelled MDA-MB-231 breast cancer cells from regular blood cells, both suspended in a sucrose/dextrose medium, is reported in this work.