This report covers advances in capillary electrophoresis (CE) from January 2018 through September 2019. A summary of the literature during this time period is insightful. A search performed using the SciFinder Scholar® database for journal reports (limited to English) using the term capillary electrophoresis returned approximately 1,800 publications. Further analysis of this list, depicted in Figure 1, provided a snapshot of activity in biomolecular research. Classes of biomolecules most frequently associated with CE publications were proteins, drugs, DNA and metabolites. Another measure of the impact of CE is the translation of this technology into society. A search of patent activity illustrating this process of CE technology transfer returned 346 patents published in all languages, with a substantial contribution reported only in Chinese (198 patents) or English (98 patents). The versatility of CE for biological systems is exemplified by the rise of the technique in several areas. Metabolomics research involving measurements of large sets of molecules with subtle structural differences benefits from rapid separations achieved with high peak capacity and automated instruments. Single cell and sub-cellular analyses continue to progress in CE because of the size compatibility of the technique with the sample. Other examples of areas utilizing CE that are accelerating include portable and printable instrumentation, affinity interaction, as well as proteomics. As an established analytical tool, CE instrumentation and methods have been designed to be accessible and easily adopted by researchers with expertise in areas beyond the field of separations. Generally, publications including CE measurements either outline innovations in the technique or they are compelling applications of a mature analytical approach. The goal of this review, which is limited to 180 citations, is
We introduce a new method to construct microfluidic devices especially useful for bulk acoustic wave (BAW)-based manipulation of cells and microparticles. To obtain efficient acoustic focusing, BAW devices require materials that have high acoustic impedance mismatch relative to the medium in which the cells/microparticles are suspended and materials with a high-quality factor. To date, silicon and glass have been the materials of choice for BAW-based acoustofluidic channel fabrication. Silicon- and glass-based fabrication is typically performed in clean room facilities, generates hazardous waste, and can take several hours to complete the microfabrication. To address some of the drawbacks in fabricating conventional BAW devices, we explored a new approach by micromachining microfluidic channels in aluminum substrates. Additionally, we demonstrate plasma bonding of poly(dimethylsiloxane) (PDMS) onto micromachined aluminum substrates. Our goal was to achieve an approach that is both low cost and effective in BAW applications. To this end, we micromachined aluminum 6061 plates and enclosed the systems with a thin PDMS cover layer. These aluminum/PDMS hybrid microfluidic devices use inexpensive materials and are simply constructed outside a clean room environment. Moreover, these devices demonstrate effectiveness in BAW applications as demonstrated by efficient acoustic focusing of polystyrene microspheres, bovine red blood cells, and Jurkat cells and the generation of multiple focused streams in flow-through systems. Graphical abstract The aluminum acoustofluidic device and the generation of multinode focusing of particles.
Acoustophoresis has gained increasing attention as a gentle, non-contact, and high-throughput cell and particle separation technique. It is conveniently used to isolate and enrich particles that are greater than 2 μm; however, its use in manipulating particles smaller than 2 μm is limited. In this work, we present an alternative way of using acoustic forces to manipulate sub-micrometer particles in continuous flow fashion. It has been shown that acoustic forces can be employed to relocate parallel laminar flow streams of two impedance-mismatched fluids. We demonstrate the separation of sub-micron particles from micron particles by the combination of acoustophoresis and acoustic fluid relocation. The micron particles are focused into the middle of the flow channel via primary acoustic forces while sub-micron particles are moved to the side via drag forces created by the relocating fluid. We demonstrate the proof of the concept using binary mixtures of particles comprised of sub-micron/micron particles, micron/micron particles, and bovine red blood cells with E. coli. The efficiency of the particle enrichment is determined via flow cytometry analysis of the collected streams. This study demonstrates that by combining acoustic fluid relocation with acoustophoresis, sub-micron particles can be effectively separated from micron particles at high flow rates and it can be further implemented to separate binary mixtures of micron particles if the volumetric ratio of two particles is greater than 10 and the larger particle diameter is about 10 μm. The combined method is more appropriate to use than acoustophoresis in situations where acoustic streaming and differences in acoustic impedance of fluids can be of concern. Graphical abstract In the presence of a resonance acoustic field, the clean high-density fluid (dark gray) and the low-density sample fluid are relocated. During this process, E. coli are separated from the red blood cells (RBCs).
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