Microflow photochemistry—a reactor comparison study using the photochemical synthesis of terebic acid as a model reaction

The continuous-microflow photochemical synthesis of terebic acid from maleic acid was investigated in two different microreactor set-ups. The results were subsequently compared to analogue experiments in a conventional chamber reactor. Based on conversion rates, reactor design and energy efficiency calculations, the simple microcapillary reactor showed the best overall performance.     

A cleaner and simple spectrophotometric micro-fluidic procedure for copper determination using nitroso-R salt as chromogenic agent

A cleaner and simple spectrophotometric method using microflow analysis (muFA) was performed. It consisted of a T-junction with microcoil on a polymethyl methacrylate (PMMA) chip which was fabricated by laser ablation and a molded polydimethylsiloxane (PDMS) as top plate. The fabricated PMMA chip was integrated with light emitting diode (LED) as light source and spectrometer as detector. The proposed device was applied to determining copper in water samples using nitroso-R salt as chromogenic reagent at 495nm. It was found that the proposed muFA system was with less reagents and samples consumption with tiny waste generation. The relative standard deviation (R.S.D.) was less than 2% (n=11) with the percentage recovery of 98.0+/-1.7% (n=7). The linear range for determination of copper in water samples was over the range of 0.05-3.0mugmL(-1) with a correlation coefficient (r(2)) of 0.999. The limit of detection (3sigma) was 47ngmL(-1) with a sample throughput of 30h(-1).     

Current State of Microflow Trifluoromethylation Reactions

The trifluoromethyl group is a powerful structural motif in drugs and polymers; thus, developing trifluoromethylation reactions is an important area of research in organic chemistry. Over the past few decades, significant progress has been made in developing new methods for the trifluoromethylation of organic molecules, ranging from nucleophilic and electrophilic approaches to transition-metal catalysis, photocatalysis, and electrolytic reactions. While these reactions were initially developed in batch systems, more recent microflow versions are highly attractive for industrial applications owing to their scalability, safety, and time efficiency. In this review, we discuss the current state of microflow trifluoromethylation. Approaches for microflow trifluoromethylation based on different trifluoromethylation reagents are described, including continuous flow, flow photochemical, microfluidic electrochemical reactions, and large-scale microflow reactions.     

Quantitative evaluation of radiation dose by γ-H2AX on a microfluidic chip in a miniature fluorescence cytometer

Evaluation of radiation dose is very important for the detection of radiation damage. γ-H2AX is a popular biological dosimeter to evaluate the radiation effect. Typically, bulky and expensive commercial flow cytometers are used to detect γ-H2AX. This paper presents a miniaturized and high sensitive cytometer using a microfluidic chip for evaluating the radiation dose by detecting the mean immunofluorescence intensity of γ-H2AX. A compact optical focusing system and a shift-phase differential amplifier are designed to improve the detection sensitivity. Sample lymphocyte cells are stained by FITC fluorescent dye after being irradiated by UVC. Comparison experiments between the developed miniature cytometer and a commercial flow cytometer were conducted under different radiation doses. The developed microfluidic cytometer also demonstrates a good linear correlation between the measured fluorescence intensity and the irradiation dose with a detection limit similar to that of the commercial flow cytometer. The developed cytometer can evaluate quantitatively the radiation dose by the mean fluorescence intensity of γ-H2AX with a significantly smaller amount of blood samples than a commercial flow cytometer.     

Multiplex bio-assay with inductively coupled plasma mass spectrometry: Towards a massively multivariate single-cell technology

Recent progress in the development of massively multiplexed bioanalytical assays using element tags with inductively coupled plasma mass spectrometry detection is reviewed. Feasibility results using commercially available secondary immunolabeling reagents for leukemic cell lines are presented. Multiplex analysis of higher order is shown with first generation tag reagents based on functionalized carriers that bind lanthanide ions. DNA quantification using metallointercalation allows for cell enumeration or mitotic state differentiation. In situ hybridization permits the determination of cellular RNA. The results provide a feasibility basis for the development of a multivariate assay tool for individual cell analysis based on inductively coupled plasma mass spectrometry in a cytometer configuration.     

Modeling Large-deformation-induced Microflow in Soft Biological Tissues

The homogenization approach to multiscale modeling of soft biological tissues is presented. The homogenized model describes the relationship between the macroscopic hereditary creep behavior and the microflow in a fluid-saturated dual-porous medium at the microscopic level. The micromodel is based on Biot’s system for quasistatic deformation processes, modified for the updated Lagrangian formulation to account for coupling the fluid diffusion through a porous solid undergoing large deformation. Its microstructure is constituted by fluid-filled inclusions embedded in the porous matrix. The tangential stiffness coefficients and the retardation stress for the macromodel are derived for a time-stepping algorithm. Numerical examples are discussed, showing the strong potential of the model for simulations of deformation-driven physiological processes at the microscopic scale.     

Counting of Escherichia coli by a microflow cytometer based on a photonic–microfluidic integrated device

Counting of Escherichia coli DH5α‐cell suspensions in PBS is performed using a microflow cytometer based on a photonic–microfluidic integrated device. Side‐scattered light signals are used to count the E. coli cells. A detection efficiency of 92% is achieved when compared with the expected count from a hemocytometer. The detection efficiency is correlated to the ratio of sample to sheath flow rates. It is demonstrated that E. coli can be easily distinguished from beads of similar sizes (2–4 μm) as their scattering intensities are different.     

Synergetic Effect of Tumor Treating Fields and Zinc Oxide Nanoparticles on Cell Apoptosis and Genotoxicity of Three Different Human Cancer Cell Lines

Cancer remains a leading cause of death worldwide, despite extraordinary progress. So, new cancer treatment modalities are needed. Tumor-treating fields (TTFs) use low-intensity, intermediate-frequency alternating electric fields with reported cancer anti-mitotic properties. Moreover, nanomedicine is a promising therapy option for cancer. Numerous cancer types have been treated with nanoparticles, but zinc oxide nanoparticles (ZnO NPs) exhibit biocompatibility. Here, we investigate the activity of TTFs, a sub-lethal dose of ZnO NPs, and their combination on hepatocellular carcinoma (HepG2), the colorectal cancer cell line (HT-29), and breast cancer cell lines (MCF-7). The lethal effect of different ZnO NPs concentrations was assessed by sulforhodamine B sodium salt assay (SRB). The cell death percent was determined by flow cytometer, the genotoxicity was evaluated by comet assay, and the total antioxidant capacity was chemically measured. Our results show that TTFs alone cause cell death of 14, 8, and 17% of HepG2, HT-29, and MCF-7, respectively; 10 µg/mL ZnO NPs was the sub-lethal dose according to SRB results. The combination between TTFs and sub-lethal ZnO NPs increased the cell death to 29, 20, and 33% for HepG2, HT-29, and MCF-7, respectively, without reactive oxygen species increase. Increasing NPs potency using TTFs can be a novel technique in many biomedical applications.     

Size-resolved counting of circulating tumor cells on pinched flow-based microfluidic cytometry

Precise cell detecting and counting is meaningful in circulating tumor cells (CTCs) analysis. In this work, a simple cyclic olefin copolymer (COC) microflow cytometer device was developed for size-resolved CTCs counting. The proposed device is constructed by a counting channel and a pinched injection unit having three channels. Through injection flow rate control, microspheres/cells can be focused into the centerline of the counting channel. Polystyrene microspheres of 3, 9, 15, and 20 µm were used for the microspheres focusing characterization. After coupling to laser-induced fluorescence detection technique, the proposed device was used for polystyrene microspheres counting and sizing. A count accuracy up to 97.6% was obtained for microspheres. Moreover, the proposed microflow cytometer was applied to CTCs detecting and counting. To mimic blood sample containing CTCs and CTCs mixture with different subtypes, an MDA-MB-231 (human breast cell line) spiked red blood cells sample and a mixture of MDA-MB-231 and MCF-7 (human breast cell line) sample were prepared, respectively, and then analyzed by the developed pinched flow-based microfluidic cytometry. The simple fabricated and easy operating COC microflow cytometer exhibits the potential in the point-of-care clinical application.     

Asymmetric nozzle structure for particles converging into a highly confined region

Asymmetric nozzle inlet was suggested for particles to converge into a highly confined region. The physical properties from the nano-scaled volumetric difference at nozzle inlet were investigated using computational fluid dynamics and particle motion measurement with fluorescence beads and erythrocytes. The asymmetric nozzle structure made particles converge efficiently without clogging at nozzle inlet. It could be used as a micro/nanofluidic unit for cell based assay in a microchip such as chip-based flow cytometer.