Single-cell phenotypic profiling of circulating tumor cells (CTCs) in the blood of cancer patients can reveal vital tumor biology information. Even though various approaches have been provided to enrich and detect CTCs, it remains challenging for consecutive CTC sorting, enumeration, and single-cell characterizations. Here, we report an integrated microfluidic device (IMD) for single-cell phenotypic profiling of CTCs that enables automated CTCs sorting from whole blood following continuous single-cell phenotypic analysis while satisfying the requirements of both high purity (92 ± 3%) of cell sorting and high-throughput processing capacity (5 mL whole blood/3 h). Using this new technique we test the phenotypes of individual CTCs collected from xenograft tumor-bearing mice and colorectal (CRC) patients at different tumor stages. We obtained a correlation between CTC characterization and clinical tumor stage and treatment response. The developed IMD offers a high-throughput, convenient, and rapid strategy to study individual CTCs toward minimally invasive cancer therapy prediction and disease monitoring and has the potential to be translated to clinic for liquid biopsy.
The phase behavior of a kind of pseudogemini surfactant in aqueous solutions, formed by the mixture of sodium dodecyl benzene sulfonate (SDBS) and butane-1,4-bis (methylimidazolium bromide) ([mim-C4-mim]Br2) or butane-1,4-bis(methylpyrrolidinium bromide) ([mpy-C4-mpy]Br2) in a molar ratio of 2 : 1, is reported in the present work. When [mim-C4-mim]Br2 or [mpy-C4-mpy]Br2 is mixed with SDBS in aqueous solutions, one cationic [mim-C4-mim]Br2 or [mpy-C4-mpy]Br2 molecule "bridges" two SDBS molecules by noncovalent interactions (e.g. electrostatic, π-π stacking, and σ-π interactions), behaving like a pseudogemini surfactant. Vesicles can be formed by this kind of pseudogemini surfactant, determined by freeze-fracture transmission electron microscopy (FF-TEM) or cryogenic-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). The mixed system of sodium dodecyl sulfate (SDS) with [mim-C4-mim]Br2 or [mpy-C4-mpy]Br2 was also constructed, and only micelles were observed. We infer that a pseudogemini surfactant is formed under the synergic effect of electrostatic, π-π stacking, and σ-π interactions in the SDBS/[mim-C4-mim]Br2/H2O system, while electrostatic attraction and hydrophobic interactions may provide the directional force for vesicle formation in the SDBS/[mpy-C4-mpy]Br2/H2O system.
Water-in-water (w/w) emulsions are particularly advantageous for biomedical-related applications, such as cell encapsulation, bioreactors, biocompatible storage, and processing of biomacromolecules. However, due to ultralow interfacial tension, generation and stabilization of uniform w/w droplets are challenging. In this work, we report a strategy of creating stable and size-controllable w/w droplets that can quickly form polyelectrolyte microcapsules (PEMCs) in a microfluidic device. A three-phase (inner, middle, outer) aqueous system was applied to create a stream of inner phase, which could be broken into droplets via a mechanical perturbation frequency, with size determined by the stream diameter and vibration frequency. The interfacial complexation i s f o r m e d v i a e l e c t r o s t a t i c i n t e r a c t i o n o f p o l y c a t i o n s o f p o l y -(diallyldimethylammoniumchloride) with polyanions of polystyrene sodium sulfate in the inner and outer phases. With addition of negatively charged silica nanoparticles, the stability, permeability, and mechanical strength of the PEMC shell could be well manipulated. Prepared PEMCs were verified by encapsulating fluorescein isothiocyanate-labeled dextran molecules and stimuli-triggered release by varying the pH value or osmotic pressure. A model enzyme, trypsin, was successfully encapsulated into PEMCs and released without impairing their catalytic activity. These results highlight its potential applications for efficient encapsulation, storage, delivery, and release of chemical, biological, pharmaceutical, and therapeutic agents.
We report an easily-established capillary-based open microfluidic device (COMD) as a simple and robust method for size on-demand generation of monodisperse droplets of various fluidic materials with controllable volume. A device is set up in which a capillary is positioned with its tip close to a flat surface with a precise gap distance in a container. The continuous phase remains static in the container, and the dispersed phase is pumped through the capillary and forms droplets at the exit of the gap. Monodisperse droplets, bubbles and microcapsules of various fluids with diameters of 10-300 μm (picoliter to nanoliter) and generation frequency of 1-1000 Hz are obtained by controlling the gap distance in the range of 5-500 μm. The droplet formation is caused by capillarity-induced narrowing of the dispersed phase at the capillary exit, with droplet size being determined by the gap volume and fluid flow. We find that, at low flow rate, using the same COMD, the generated droplet size is constant, being determined by the gap size; however, at higher flow rate, droplet size increases with the flow rate. Droplet types can be managed by fluids and surface modification of the capillary and bottom surfaces. High throughput droplet generation is achieved by in-parallel integration of multiple capillaries in one device. Such a COMD is simple and easy-to-build without complex microfabrication requirements; however, it is highly robust, flexible and easy-to-operate for size on-demand droplet generation. It offers an opportunity for common laboratories to perform droplet-based assays, and has high potential for high throughput industrial emulsification applications as well.
Ionic liquid crystals (ILCs) with hexagonal and lamellar phases were successfully fabricated by the self-assembly of a polymerizable amphiphilic zwitterion, which is formed by 3-(1-vinyl-3-imidazolio)propanesulfonate (VIPS) and 4-dodecyl benzenesulfonic acid (DBSA) based on intermolecular electrostatic interactions. The microstructures and phase behaviors of ILCs were studied by polarized microscope (POM) and small-angle X-ray scattering (SAXS). The ILC topological structures can be considered as proton pathways and further fixed by photopolymerization to prepare nanostructured proton-conductive films. The introduction of highly ordered and well-defined ILC structures into these polymeric films radically improves the ionic conductivities.
We report on a simple approach for in-channel functionalization of a polydimethylsiloxane (PDMS) surface to obtain a switchable and reversible wettability change between hydrophilic and hydrophobic states. The thermally responsive polymer, poly(N-Isopropylacrylamide) (PNIPAAm), was grafted on the surface of PDMS channels by UV-induced surface grafting. PNIPAAm-grafted PDMS (PNIPAAm-g-PDMS) surface wettability can be thermally tuned to obtain water contact angles varying in the range of 24.3 to 106.1°by varying temperature at 25−38°C. By selectively modifying the functionalized area in the microfluidic channels, multiform emulsion droplets of oil-in-water (O/W), water-in-oil (W/O), oil-in-water-in-oil (O/W/O), and water-in-oil-inwater (W/O/W) could be created on-demand. Combining solid surface wettability and liquid−liquid interfacial properties, tunable generation of O/W and W/O droplet and stratified flows were enabled in the same microfluidic device with either different or the same two-phase fluidic systems, by properly heating/cooling thermal-responsive microfluidic channels and choosing suitable surfactants. Controllable creation of O/W/O and W/O/W droplets was also achieved in the same microfluidic device, by locally heating or cooling the droplet generation areas with integrated electric heaters to achieve opposite surface wettability. Hollow microcapsules were prepared using double emulsion droplets as templates in the microfluidic device with sequential hydrophobic and hydrophilic channel segments, demonstrating the strength of the proposed approach in practical applications.
Janus particles (JNPs) with controlled anisotropies are regarded as promising materials for sophisticated building blocks and assembly. Herein a straightforward method was proposed for the synthesis of uniformly distributed JNPs with controllable anisotropies, showing two compartmental bulbs with different surface wettability. The synthetic strategy is based on the phase separation-induced styrene liquid protrusion on seed poly(styrene-co-acrylic acid) (CPSAA) nanoparticles via controlled swelling, with the formed polystyrene (PS) and CPSAA compartments corresponding to the amount of monomers. The size (lateral length) ratio of formed PS and CPSAA bulbs, D PS /D CPSAA , defined as "Janusity", has been precisely tuned in the range of 0−0.91 by controlling the mass ratio of two monomers. Obtained JNPs with tunable amphiphilicity are utilized as colloid surfactants to prepare Pickering-emulsions of both water-in-oil (W/O) and oil-in-water (O/W) with proper Janusity. The stability of achieved W/O and O/W Pickering-emulsions is dependent on the adhesion energy of a JNP at the water−oil interfaces. Prepared JNPs have also being utilized to prepare and stabilize monodisperse droplets in microfluidic devices, demonstrating their high potential for fundamental research and practical applications.
Electrowetting display technology is realized by tuning the surface energy of a hydrophobic surface by applying a voltage based on electrowetting mechanism. Electrowetting displays have favorable optical properties combined with reflective paper‐like performance. It has been successfully demonstrated in reflective mode with high switching speed. In this paper, we propose a portable driving scheme that can display 4‐bit gray scale dynamic video using an active matrix electrowetting display. The proposed driving scheme includes an electronic system and a dynamic driving waveform design. High‐performance multi‐gray video playing and quick response were obtained for a Quarter Video Graphics Array electrowetting display cell fabricated by our team.
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