Search

Centrifugal microfluidics allows for miniaturization, automation and parallelization of laboratory workflows. The fact that centrifugal forces are always directed radially outwards has been considered a main drawback for the implementation of complex workflows leading to the requirement of additional actuation forces for pumping, valving and switching. In this work, we review and discuss the combination of centrifugal with pneumatic forces which enables transport of even complex liquids in any direction on centrifugal systems, provides actuation for valving and switching, offers alternatives for mixing and enables accurate and precise metering and aliquoting. In addition, pneumatics can be employed for timing to carry out any of the above listed unit operations in a sequential and cascaded manner. Firstly, different methods to generate pneumatic pressures are discussed. Then, unit operations and applications that employ pneumatics are reviewed. Finally, a tutorial section discusses two examples to provide insight into the design process. The first tutorial explains a comparatively simple implementation of a pneumatic siphon valve and provides a workflow to derive optimum design parameters. The second tutorial discusses cascaded pneumatic operations consisting of temperature change rate actuated valving and subsequent pneumatic pumping. In conclusion, combining pneumatic actuation with centrifugal microfluidics allows for the design of robust fluidic networks with simple fluidic structures that are implemented in a monolithic fashion. No coatings are required and the overall demands on manufacturing are comparatively low. We see the combination of centrifugal forces with pneumatic actuation as a key enabling technology to facilitate compact and robust automation of biochemical analysis. [ABSTRACT FROM AUTHOR]

Paper has unique advantages over other materials, including low cost, flexibility, porosity, and self-driven liquid pumping, thus making it widely used in various fields in biology, chemistry, physics and materials science. Recently, many multifunctional and highly integrated membrane-based devices have been achieved with the rapid development of membrane-building materials such as paper and pseudo-paper. Therefore, the rigid boundary between paper and other membranes has become blurred; paper can be considered a flexible membrane, and membranes with appropriately flexible or porous structures can also be defined as paper. Paper can manipulate liquids and respond photoelectrically to external objects to be measured, making it suitable for (bio)chemical sensing (chromatographic analysis, electrochemical analysis and wearable sensing). This review focuses on the development of microfluidic devices built with both traditional paper and other flexible membranes, including fabrication, (bio)chemical sensing, microfluidics manipulation and multiple applications. [ABSTRACT FROM AUTHOR]

The ability to thoroughly mix two fluids is a fundamental need in microfluidics. While a variety of different microfluidic mixers have been designed by researchers, it remains unknown which (if any) of these mixers are optimal (that is, which designs provide the most thorough mixing with the smallest possible fluidic resistance across the mixer). In this work, we automatically designed and rationally optimized a microfluidic mixer. We accomplished this by first generating a library of thousands of different randomly designed mixers, then using the non-dominated sorting genetic algorithm II (NSGA-II) to optimize the random chips in order to achieve Pareto efficiency. Pareto efficiency is a state of allocation of resources (e.g. driving force) from which it is impossible to reallocate so as to make any one individual criterion better off (e.g. pressure drop) without making at least one individual criterion (e.g. mixing performance) worse off. After 200 generations of evolution, Pareto efficiency was achieved and the Pareto-optimal front was found. We examined designs at the Pareto-optimal front and found several design criteria that enhance the mixing performance of a mixer while minimizing its fluidic resistance; these observations provide new criteria on how to design optimal microfluidic mixers. Additionally, we compared the designs from NSGA-II with some popular microfluidic mixer designs from the literature and found that designs from NSGA-II have lower fluidic resistance with similar mixing performance. As a proof of concept, we fabricated three mixer designs from 200 generations of evolution and one conventional popular mixer design and tested the performance of these four mixers. Using this approach, an optimal design of a passive microfluidic mixer is found and the criteria of designing a passive microfluidic mixer are established. [ABSTRACT FROM AUTHOR]

The selection of improved producers among the huge number of variants in mutant libraries is a key issue in filamentous fungi of industrial biotechnology. Here, we developed a droplet-based microfluidic high-throughput screening platform for selection of high-cellulase producers from filamentous fungus Trichoderma reesei. The screening system used a fluorogenic assay to measure amount of cellulase and its activity. The key effectors such as cellulase-inducing medium, spore germination, droplet cultivation time, droplet fluorescence signal detection, and droplet cell sorting were studied. An artificial pre-mixed library of high- and low-cellulase-producing T. reesei strains was screened successfully to verify the feasibility of our method. Finally, two cellulase hyperproducers exhibiting improvements in cellulase activity of 27% and 46% were isolated from an atmospheric and room-temperature plasma (ARTP)-mutated library. This high-throughput screening system could be applied to the engineering of T. reesei strains and other industrially valuable protein-producing filamentous fungi. [ABSTRACT FROM AUTHOR]

• Drug development and disease modeling for rare diseases remains a challenge. • Advances in in vitro modeling has led to development of human-on-a-chip technology. • PK and PD mathematical modeling is a powerful tool for orphan drug development. • HoaC systems have potential for facilitating rare disease and orphan drug research. Drug development for rare diseases, classified as diseases with a prevalence of < 200 000 patients, is limited by the high cost of research and low target population. Owing to a lack of representative disease models, research has been challenging for orphan drugs. Human-on-a-chip (HoaC) technology, which models human tissues in interconnected in vitro microfluidic devices, has the potential to lower the cost of preclinical studies and increase the rate of drug approval by introducing human phenotypic models early in the drug discovery process. Advances in HoaC technology can drive a new approach to rare disease research and orphan drug development. After more than three decades of the Orphan Drug Act, drug development for rare diseases remains a challenge. Human-on-a-chip technology holds the promise to drive orphan drug development to the next level. [ABSTRACT FROM AUTHOR]

Zebrafish or Danio rerio is an established model organism for studying the genetic, neuronal and behavioral bases of diseases and for toxicology and drug screening. The embryonic and larval stages of zebrafish have been used extensively in fundamental and applied research due to advantages offered such as body transparency, small size, low cost of cultivation and high genetic homology with humans. However, the manual experimental methods used for handling and investigating this organism are limited due to their low throughput, labor intensiveness and inaccuracy in delivering external stimuli to the zebrafish while quantifying various neuronal and behavioral responses. Microfluidic and lab-on-a-chip devices have emerged as ideal technologies to overcome these challenges. In this review paper, the current microfluidic approaches for investigation of behavior and neurobiology of zebrafish at embryonic and larval stages will be reviewed. Our focus will be to provide an overview of the microfluidic methods used to manipulate (deliver and orient), immobilize and expose or inject zebrafish embryos or larvae, followed by quantification of their responses in terms of neuron activities and movement. We will also provide our opinion in terms of the direction that the field of zebrafish microfluidics is heading toward in the area of biomedical engineering. [ABSTRACT FROM AUTHOR]

With ever increasing drug resistance and emergence of new diseases, demand for new drug development is at an unprecedented urgency. This fact has led to extensive recent efforts to develop new drugs and novel techniques for efficient drug screening. However, new drug development is commonly hindered by cost and time span. Thus, developing more accessible, cost-effective methods for drug screening is necessary. Compared with conventional drug screening methods, a microfluidic-based system has superior advantages in sample consumption, reaction time, and cost of the operation. In this paper, the advantages of microfluidic technology in drug screening as well as the critical factors for device design are described. The strategies and applications of microfluidics for drug screening are reviewed. Moreover, current limitations and future prospects for a drug screening microdevice are also discussed. [ABSTRACT FROM AUTHOR]

Inertial microfluidic systems have been arousing interest in medical applications due to their simple and cost-efficient use. However, comparably small sample volumes in the microliter and milliliter ranges have so far prevented efficient applications in continuous bioprocesses. Nevertheless, recent studies suggest that these systems are well suited for cell separation in bioprocesses because of their facile adaptability to various reactor sizes and cell types. This review will discuss potential applications of inertial microfluidic cell separation systems in downstream bioprocesses and depict recent advances in inertial microfluidics for bioprocess intensification. This review thereby focusses on spiral microchannels that separate particles at a moderate Reynolds number in a laminar flow (Re < 2300) according to their size by applying lateral hydrodynamic forces. Spiral microchannels have already been shown to be capable of replacing microfilters, extracting dead cells and debris in perfusion processes, and removing contaminant microalgae species. Recent advances in parallelization made it possible to process media on a liter-scale, which might pave the way toward industrial applications. [ABSTRACT FROM AUTHOR]

We have simulated bipolar nanopore fluidic diodes for different values of surface charge densities, electrolyte concentrations, and thickness of transition zone. Nanopore enrichment leads to increased nanopore conductivity with the surface charge density at low electrolyte concentrations. Potential drop across the nanopore and electric field inside the nanopore decreases. Forward current and ionic current rectification peaks for a specific value of surface charge density. Even though the electro-osmotic current component remains small as compared to other components, its non-inclusion in the modeling leads to serious errors in the solutions. Significant ion current rectification can be obtained even if transition zone between oppositely charged zones is not narrow. The effect of the surface charge is screened by counterions at higher electrolyte concentrations, which leads to reduced electrolyte polarization and a decrease in the ion current rectification. [ABSTRACT FROM AUTHOR]

If a gas volume is distributed into many microbubbles of a sub-millimetre size, the total gas/liquid surface becomes very large. This increases overall heat and/or mass transport across the sum of surfaces. The paper discusses several applications in which the use of microbubbles increases efficiency of various processes, especially in wastewater treatment and in growing microorganisms such as algae, yeast, bacteria, or primitive fungi. The problem of microbubble generation by percolation in aerator is their coalescence into larger bubbles, whatever small are the pores in the aerator in which the microbubbles are generated. The solution of this size discrepancy question was found in agitating the gas flow by a fluidic oscillator prior to its injection through the aerator. The oscillator is a no-moving-part device, simple, inexpensive, resistant to external effects like acceleration or heat, and with long maintenance-free working life.

Functional surfaces with reversible wettability transition between superhydrophobicity and superhydrophilicity have attracted much attention due to their potential applications in self-cleaning, anti-icing, anti-fogging, anti-biofouling, and oil-water separation, along with smart membranes, sensors, and microfluidic devices. In order to achieve such transition, the surface wettability or intrinsic Young contact angle must be able to reversibly change upon being stimulated by external factors. Meanwhile, the surface structure must have sufficient ability to magnify this change in the surface wettability. For metals, metallic oxides and some other materials, the surface wettability can be changed by controlling adsorption and decomposition of airborne organic compounds on these surfaces via different methods such as ultraviolet irradiation, long-term storage at room temperature and heating treatments and their combinations. In this study, we reported for the first time that such transition can be realized on a laser-ablated brass surface by using alternate heating-reheating cycles. Our study demonstrated that the reversible change in the Young contact angle of the substrate material caused by the adsorption and decomposition of airborne organic compounds and a great reduction in the width of the Wenzel region separating the Cassie-Baxter region and the full wetting region caused by the micro/nano-scale hierarchical structure are responsible for the observed transition. Unlabelled Image • Reversible wetting transition between superhydrophobicity and superhydrophilicity was realized by heating-reheating cycle. • Heat treatments lead to reversible change in substrate wettability via adsorption of airborne organic compounds. • Hierarchical structure greatly magnifies substrate wettability by reducing the width of Wenzel region. • Reversible change in substrate wettability and magnifying effect of surface structure are responsible for the transition. [ABSTRACT FROM AUTHOR]

Microfluidic devices have been increasingly used for low-volume liquid handling operations. However, laboratory automation of such delicate devices has lagged behind due to the lack of world-to-chip (macro-to-micro) interfaces. In this paper, we have presented the first pipette-free robotic–microfluidic interface using a microfluidic-embedded container cap, referred to as a microfluidic cap-to-dispense (μCD), to achieve a seamless integration of liquid handling and robotic automation without any traditional pipetting steps. The μCD liquid handling platform offers a generic and modular way to connect the robotic device to standard liquid containers. It utilizes the high accuracy and high flexibility of the robotic system to recognize, capture and position; and then using microfluidic adaptive printing it can achieve high-precision on-demand volume distribution. With its modular connectivity, nanoliter processability, high adaptability, and multitask capacity, μCD shows great potential as a generic robotic–microfluidic interface for complete pipette-free liquid handling automation. [ABSTRACT FROM AUTHOR]

Fluorescence microscopy is one of the workhorses of biomedical research and laboratory diagnosis; however, their cost, size, maintenance, and fragility has prevented their adoption in developing countries or low-resource settings. Although significant advances have decreased their size, cost and accessibility, their designs and assembly remain rather complex. Here, inspired on the simple mechanism from a nut and a bolt, we report the construction of a portable fluorescence microscope that operates in bright-field mode and in three fluorescence channels: UV, green, and red. It is assembled in under 10 min from only six 3D printed parts, basic electronic components, a microcomputer (Raspberry Pi) and a camera, all of which can be readily purchased in most locations or online for US $122. The microcomputer was programmed in Python language to capture time-lapse images and videos. Resolution and illumination conditions of the microscope were characterized, and its performance was compared with a high-end fluorescence microscope in bright-field and fluorescence mode. We demonstrate that our miniature microscope can resolve and track single cells in both modes. The instructions on how to assemble the microscope are shown in a video, and the software to control it and the design files of the 3D-printed parts are freely available online. Our portable microscope is ideal in applications where space is at a premium, such as lab-on-a-chips or space missions, and can find applications in basic and clinical research, diagnostics, telemedicine and in educational settings. [ABSTRACT FROM AUTHOR]

Background: Pancreatic islets are heavily vascularized in vivo yet lose this vasculature after only a few days in culture. Determining how to maintain islet vascularity in culture could lead to better outcomes in transplanting this tissue for the treatment of type 1 diabetes as well as provide insight into the complex communication between beta-cells and endothelial cells (ECs). We previously showed that islet ECs die in part due to limited diffusion of serum albumin into the tissue. We now aim to determine the impact of hypoxia on islet vascularization. Methods: We induced hypoxia in cultured mouse islets using the hypoxia mimetic cobalt chloride (100 μM CoCl2). We measured the impact on islet metabolism (two-photon NAD(P)H and Rh123 imaging) and function (insulin secretion and survival). We also measured the impact on hypoxia related transcripts (HIF-1α, VEGF-A, PDK-1, LDHA, COX4) and confirmed increased VEGF-A expression and secretion. Finally, we measured the vascularization of islets in static and flowing culture using PECAM-1 immunofluorescence. Results: CoCl2 did not induce significant changes in beta cell metabolism (NAD(P)H and Rh123), insulin secretion, and survival. Consistent with hypoxia induction, CoCl2 stimulated HIF-1α, PDK-1, and LDHA transcripts and also stimulated VEGF expression and secretion. We observed a modest switch to the less oxidative isoform of COX4 (isoform 1 to 2) and this switch was noted in the glucose-stimulated cytoplasmic NAD(P)H responses. EC morphology and survival were greater in CoCl2 treated islets compared to exogenous VEGF-A in both static (dish) and microfluidic flow culture. Conclusions: Hypoxia induction using CoCl2 had a positive effect on islet EC morphology and survival with limited impact on beta-cell metabolism, function, and survival. The EC response appears to be due to endogenous production and secretion of angiogenic factors (e.g. VEGF-A), and mechanistically independent from survival induced by serum albumin. [ABSTRACT FROM AUTHOR]

A fully enclosed paper microfluidic device has been fabricated using pentafluoroethane (PFE) plasma deposition followed by O2 plasma etching. Structures with one and two non-interacting, fully enclosed hydrophilic channels were generated in a single paper sheet using metal masks. Furthermore, by performing an additional O2 plasma step with a secondary mask, pinholes were created at the reaction zones for reagent loading. Finally, to demonstrate the functionality of the device, a glucose assay was performed. Quantitative analysis of glucose assays showed that the device can be used for the clinically relevant range of glucose. To our knowledge, this is the first time that such structures have been fabricated without paper stacking. Multi-layer devices have enhanced functionality relative to a single channel device, because the design space for creating networks of channels within the paper substrate is greatly expanded. The fluid-filled channels in the fabricated device are isolated, thereby preventing contamination due to handling and environmental exposure. Fluid evaporation can be inhibited by sealing the device with adhesive tape without contaminating the enclosed channels. The method described is a dry process and compatible with roll-to-roll technology, thus facilitating large scale production. The novel method to fabricate enclosed μ-PADs overcomes many of the limitations experienced with current approaches and thus offers an alternative means to develop low-cost point-of-care diagnostics for resource-limited settings. [ABSTRACT FROM AUTHOR]

In nature, protozoa play a major role in controlling bacterial populations. This paper proposes a microfluidic device for the study of protozoa behaviors change due to their chemotactic response in the presence of bacterial cells. A three-channel microfluidic device was designed using a nitrocellulose membrane into which channels were cut using a laser cutter. The membrane was sandwiched between two glass slides; a Euglena suspension was then allowed to flow through the central channel. The two side channels were filled with either, 0.1% peptone as a negative control, or a Listeria suspension respectively. The membrane design prevented direct interaction but allowed Euglena cells to detect Listeria cells as secretions diffused through the nitrocellulose membrane. A significant number of Euglena cells migrated toward the chambers near the bacterial cells, indicating a positive chemotactic response of Euglena toward chemical cues released from Listeria cells. Filtrates collected from Listeria suspension with a series of molecular weight cutoffs (3k, 10k and 100k) were examined in Euglena chemotaxis tests. Euglena cells were attracted to all filtrates collected from the membrane filtration with different molecular weight cutoffs, suggesting small molecules from Listeria might be the chemical cues to attract protozoa. Headspace volatile organic compounds (VOC) released from Listeria were collected, spiked to 0.1% peptone and tested as the chemotactic effectors. It was discovered that the Euglena cells responded quickly to Listeria VOCs including decanal, 3,5- dimethylbenzaldehyde, ethyl acetate, indicating bacterial VOCs were used by Euglena to track the location of bacteria. [ABSTRACT FROM AUTHOR]

The challenges for high-strength adhesive-free sealing of thermoplastic microfluidics have impeded commercialization. We present the technique of gas-assisted thermal bonding (GATB) for joining thermoplastic surfaces at elevated temperatures to produce microfluidic devices with low distortion. In this technique a pressurized gas is used to supply the force to bond the two substrates rather than relying on direct contact of thermoplastics with a rigid press. Mechanical characterization tests were performed to analyze and optimize the effect of GATB pressure and temperature on the bonding strength of laminated polymethyl-methacrylate (PMMA) membranes. Tensile tests on PMMA membranes subjected to GATB process conditions examined the effects of these conditions on the single membrane's characteristics. Adhesive strength was assessed on thin PMMA strips bonded together by GATB in lap shear and T-peel test configurations. The maximum lap shear and peel strength were found to occur at the lowest tested pressure of 1.17 MPa based on bonding experiments at 160 °C and 180 °C, respectively. Thereafter, the GATB is compared with the conventional plate-to-plate method to bond a capping sheet on pre-fabricated microchannels. Channel deformation is quantified by cross-section imaging before and after the sealing experiments. It was found that GATB enables low-distortion microchannels with higher uniformity at elevated temperatures, providing a solution for adhesive-free manufacturing of thermoplastic-based microfluidic systems. [ABSTRACT FROM AUTHOR]

In this work, we report on the design and implementation of a new method for the two dimensional (2D) simulation of rigid spherical particles trajectory which are to be separated in a microfluidics device based on their sizes. The advantages of efficient particle trajectory simulation method (EPTSM) include drastically smaller runtimes as compared with other methods as well as the ability to include particle collisions with channel's walls and its ability to be extended to 3D simulations. Numerically simulated results were verified using a specifically designed and fabricated deterministic lateral displacement microfluidic device test structure. The method has provided realistic results for the study of multi-particles throughout the entire channel. [ABSTRACT FROM AUTHOR]

Recent connection methods to micro fluidic chips, such as gluing tubes and hoses into orifices or pressing a gasket on them have been studied to improve the common problem to establish a connection of the macroscopic world to a fluidic micro system. In this study, micro fluidic chips from polycarbonate plates with screwed connections have been fabricated by ultrasonic hot embossing and welding, both as in plain and out of plain arrangements. To fabricate threads in the polymer plates, an M3 screw was ultrasonically welded into a hole in the chip and the screw was turned out after the process. The tightness of micro channels and fittings was proven by pumping ink and yeast cells through the micro channels and by applying air pressure of up to 700 kPa, respectively. The process introduced here is especially advantageous because sealing micro channels and welding in micro fluidic screwed connections is done in a single fabrication step. [ABSTRACT FROM AUTHOR]

This paper covers the modeling and testing of a helicopter tailboom integrated with a fluidic flexible matrix composite (F²MC) damped vibration absorber. In an advance over previous work, the F2MC absorber presented in this paper treats a combination of tailboom lateral, torsional, and vertical vibrations. A finite element structural model of a laboratory-scale tailboom is combined with a model of attached F2MC tubes and a tuned fluidic circuit. Vibration reductions of over 75% in a coupled 26.8-Hz lateral bending/torsion tailboom mode are predicted by the model and measured experimentally. These results demonstrate that F2MC vibration control is viable at higher frequencies and for more complex vibration modes than previous research had explored. A new absorber with a fluidic circuit that targets two tailboom vibration modes is designed and experimentally tested. On the lab-scale tailboom testbed, the absorber with this circuit is shown to provide vibration reductions of over 60% in both a 12.2-Hz vertical mode and a 26.8-Hz lateral bending/torsion mode. Using this new absorber, vertical and lateral/torsion mode damping are achieved with almost no added weight relative to a purely vertical absorber. [ABSTRACT FROM AUTHOR]

Resistance to targeted therapies is a major clinical challenge in cancer treatment. Despite technological advances, robust biomarkers or platforms predictive of treatment response are lacking owing to the inherent nature of complex genomic landscape of carcinoma. Nevertheless, recent efforts centred on performing direct drug screening on patient-derived cells through their ex vivo expansion and maintenance have enabled personalized stratification of treatment modalities. Microfluidics is one such technology that allows high-throughput drug screening through parallelization and automation using small-volume sample. In this review, we present recent microfluidic platforms that have been successfully applied for the maintenance and expansion of patient-derived tumor cells spanning diverse cancer types and sources (solid tumors or liquid biopsies (circulating tumor cells)) for personalized drug screening applications. [ABSTRACT FROM AUTHOR]

Copyright of Synthesis of Theoretical & Applied Mechanics / Sinteze de Mecanică Teoretică și Aplicată is the property of Matrix Rom and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We identified two poplar (Populus sp.)-associated microbes, the fungus, Mortierella elongata strain AG77, and the bacterium, Burkholderia strain BT03, that mutually promote each other's growth. Using culture assays in concert with a novel microfluidic device to generate time-lapse videos, we found growth specific media differing in pH and pre-conditioned by microbial growth led to increased fungal and bacterial growth rates. Coupling microfluidics and comparative metabolomics data results indicated that observed microbial growth stimulation involves metabolic exchange during two ordered events. The first is an emission of fungal metabolites, including organic acids used or modified by bacteria. A second signal of unknown nature is produced by bacteria which increases fungal growth rates. We find this symbiosis is initiated in part by metabolic exchange involving fungal organic acids. [ABSTRACT FROM AUTHOR]

No matter how sophisticated the structures are and on what length scale the pore sizes are, fluid displacement in porous media can be visualized, captured, mimicked and optimized using microfluidics. Visualizing transport processes is fundamental to our understanding of complex hydrogeological systems, petroleum production, medical science applications and other engineering applications. Microfluidics is an ideal tool for visual observation of flow at high temporal and spatial resolution. Experiments are typically fast, as sample volume is substantially low with the use of miniaturized devices. This review first discusses the fabrication techniques for generating microfluidics devices, experimental setups and new advances in microfluidic fabrication using three-dimensional printing, geomaterials and biomaterials. We then address multiphase transport in subsurface porous media, with an emphasis on hydrology and petroleum engineering applications in the past few decades. We also cover the application of microfluidics to study membrane systems in biomedical science and particle sorting. Lastly, we explore how synergies across different disciplines can lead to innovations in this field. A number of problems that have been resolved, topics that are under investigation and cutting-edge applications that are emerging are highlighted. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC). Materials and methods: Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment (“baseline”), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses. Results: The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS. Conclusions: This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform. [ABSTRACT FROM AUTHOR]

Here, we present a straightforward technique to create bio-functional microfluidic channels using CO2 plasma to induce both carboxylic and hydroxyl groups onto the channel surface. Consequently, not only does the surface allow for irreversible covalent bonding to an oxygen plasma treated PDMS for microfluidic device fabrication, but it also provides functionality for biomolecular immobilization. Furthermore, we demonstrate integration of this technique with microcontact printing to covalently micropattern functional biomolecules inside microfluidic channels. The bio-functionality and efficacy of the microcontact printed antibodies is demonstrated for both bioassays as well as patterning and culturing different cell lines. Results show that the introduced method can be an excellent candidate for cell culture studies in microfluidics. With the new printing method, full cell confluency (∼400 cells per mm2) was achieved after incubation for only 1 day, which is significantly greater than other conventional cell culture techniques inside microfluidic devices. As a proof of concept, we demonstrated the endothelial cells functionality by stimulating von Willebrand Factor secretion under shear stress. This is done via perfusion of histamine through the channel and performing immunofluorescence labeling to observe the inflammatory response of the cells. The developed method eliminates the need for wet chemistry and significantly simplifies producing bio-functional chips which can be used for biosensing, organs-on-chips and tissue engineering applications. [ABSTRACT FROM AUTHOR]

We report a wearable electrofluidic actuation system, which exploits the alternating current electrothermal (ACET) effects to engineer biofluid flow profiles on the body. The wearable ACET flow is induced with the aid of corrosion-resistant electrode configurations (fabricated on a flexible substrate) and custom-developed, wirelessly programmable high frequency (MHz) excitation circuitry. Various tunable flow profiles are demonstrated with the aid of the devised flexible ACET electrode configurations, where the induced profiles are in agreement with the ACET theory and simulation. The demonstrated capabilities rendered by the presented system create new degrees of freedom for implementing advanced bioanalytical operations for future lab-on-the-body platforms. [ABSTRACT FROM AUTHOR]

The majority of microfluidic devices nowadays are built on rigid or bulky substrates such as glass slides and polydimethylsiloxane (PDMS) slabs, and heavily rely on external equipment such as syringe pumps. Although a variety of micropumps have been developed in the past, few of them are suitable for flexible microfluidics or lab-on-a-foil systems. In this paper, stick-and-play acoustic micropump is built on thin and flexible plastic film by printing microstructures termed defended oscillating membrane equipped structures (DOMES) using two-photon polymerization. Specifically, this new micropump induces rectified flow upon the actuation of acoustic waves, and the flow patterns agree with simulation results very well. More importantly, the developed micropump has the capabilities to generate adjustable flow rates as high as 420 nL min−1, and does not suffer from problems such as bubble instability, gas dissolution, and undesired bubble-trapping that commonly occur in other forms of acoustic micropumps. Since the micropump works in stick-and-play mode, it is reusable after cleaning thanks to the easy separation of covers and substrates. Lastly, the developed micropump is applied for creating a self-pumped single-cell trapping device. The excellent trapping capability of the integrated device proves its potential for long-term studies of biological behaviors of individual cells for biomedical applications. [ABSTRACT FROM AUTHOR]

This paper presents a microfluidic chemical reaction using an electrowetting-on-dielectric (EWOD) digital microfluidic device. Despite a number of chemical/biological applications using EWOD digital microfluidic devices, their applications to organic reactions have been seriously limited because most of the common solvents used in synthetic organic chemistry are not compatible with EWOD devices. To address this unsolved issue, we first introduce a novel technique using an "engine-and-cargo" system that enables the use of non-movable fluids (e.g., organic solvents) on an EWOD device. With esterification as the model reaction, on-chip chemical reactions were successfully demonstrated. Conversion data obtained from on-chip reactions were used to characterize and optimize the reaction with regard to reaction kinetics, solvent screening, and catalyst loading. As the first step toward on-chip combinatorial synthesis, parallel esterification of three different alcohols was demonstrated. Results from this study clearly show that an EWOD digital microfluidic platform is a promising candidate for microscale chemical reactions. [ABSTRACT FROM AUTHOR]

• Performance analysis of a reversible solid oxide cell system using multi-scale model. • Model directly links micro-scale to stack-scale and system-scale. • Effects of excess air ratio and fuel utilization were studied. • Acquisition of 3-D stack temperature distributions and electrode/cell/stack/system performance. The increasing penetration of intermittent renewable energy into power grids calls for energy storage means to balance the electricity production and consumption. The reversible solid oxide cell is a promising technology for distributed renewable energy storage. A system-level model is a useful tool for system design and efficiency optimization. In this study, a reversible solid oxide cell system model was developed in gPROMS ModelBuilder for distributed energy storage applications by integrating a multi-scale hierarchical three-dimensional solid oxide cell stack model with zero-dimensional balance of plant components models. The hierarchical rSOC stack model considers the electrochemical reactions at the electrodes, the one-dimensional + one-dimensional thermo-fluidic transport along the thickness and the flow direction at repeating unit level, and the three-dimensional heat transfer at stack level. The proposed system model enables the simultaneous investigations on both the total system performance and detailed stack temperature distributions. The roundtrip stack efficiency and roundtrip system efficiency reached 72.3% and 58.3% respectively at base case operation conditions. The effects of excess air ratio and fuel utilization on the system efficiency as well as the temperature uniformity of the reversible solid oxide cell stack were investigated. While increasing the excess air ratio decreases stack temperature gradients, it also decreases both the stack and system roundtrip efficiency. However, improved fuel utilization decreases stack temperature gradients without affecting the stack and system roundtrip efficiency. [ABSTRACT FROM AUTHOR]

Using an antimicrobial susceptibility test (AST) as an example, this work demonstrates a practical method to fabricate microfluidic chips entirely from polypropylene (PP) and the benefits for potential commercial use. Primarily caused by the misuse and abuse of antibiotics, antimicrobial resistance (AMR) is a major threat to modern medicine. The AST is a promising technique to help with the optimal use of antibiotics for reducing AMR. However, current phenotypic ASTs suffer from long turnaround time, while genotypic ASTs suffer from low reliability, and both are unaffordable for routine use. New microfluidics based AST methods are rapid but still unreliable as well as costly due to the PDMS chip material. Herein, we demonstrate a convenient method to fabricate whole PP microfluidic chips with high resolution and fidelity. Unlike PDMS chips, the whole PP chips showed better reliability due to their inertness; they are solvent-compatible and can be conveniently reused and recycled, which largely decreases the cost, and are environmentally friendly. We specially designed 3D chambers that allow for quick cell loading without valving/liquid exchange; this new hydrodynamic design satisfies the shear stress requirement for on-chip bacterial culture, which, compared to reported designs for similar purposes, allows for a simpler, more rapid, and high-throughput operation. Our system allows for reliable tracking of individual cells and acquisition of AST results within 1–3 hours, which is among the group of fastest phenotypic methods. The PP chips are more reliable and affordable than PDMS chips, providing a practical solution to improve current culture-based AST and benefiting the fight against AMR through helping doctors prescribe effective, narrow-spectrum antibiotics; they will also be broadly useful for other applications wherein a reliable, solvent-resistant, anti-fouling, and affordable microfluidic chip is needed. [ABSTRACT FROM AUTHOR]

Aim. Few haematopoietic stem cells (HSCs) injected systemically for therapeutic purposes actually reach sites of injury as the vast majority become entrapped within pulmonary capillaries. One promising approach to maintain circulating HSC numbers would be to separate subpopulations with smaller size and/or greater deformability from a heterogeneous population. This study tested whether this could be achieved using label-free microfluidic devices. Methods. 2 straight (A-B) and 3 spiral (C-E) devices were fabricated with different dimensions. Cell sorting was performed at different flow rates after which cell diameter and stiffness were determined using micromanipulation. Cells isolated using the most efficient device were tested intravitally for their ability to home to the mouse injured gut. Results. Only straight Device B at a high flow rate separated HSCs with different mechanical properties. Side outlets collected mostly deformable cells (nominal rupture stress/σR=6.81 kPa; coefficient of variation/CV=0.31) at a throughput of 2.3×105 cells/min. All spiral devices at high flow rates separated HSCs with different stiffness and size. Inner outlets collected mostly deformable cells in Devices C (σR=25.06 kPa; CV=0.26), D (σR=22.21 kPa; CV=0.41), and E (σR=29.26 kPa; CV=0.27) at throughputs of 2.3×105 cells/min, 1.5×105 cells/min, and 1.6×105 cells/min, respectively. Since Device C separated cells with higher efficiency and throughput, it was utilized to test the homing ability of separated cells in vivo. Significantly more deformable cells were observed trafficking through the injured gut—interestingly, increased retention was not observed. Conclusion. This study applied microfluidics to separate subpopulations from one stem cell type based on their intrinsic mechanical heterogeneity. Fluid dynamics within curved devices most effectively separated HSCs. Such devices may benefit cellular therapy. [ABSTRACT FROM AUTHOR]

This work describes a novel sequential injection chromatography (SIC) method combined with linear gradient elution for the separation and determination of three main methylxanthines (theobromine, theophylline and caffeine) using a short C18 monolithic column. The method utilizes a hybrid manifold which exploits zone fluidics for solution manipulation and programmable fluidics for the implementation of a two-solvent linear gradient elution protocol. This approach offers a high degree of automation and enables faster separation of the three target methylxanthines with respect to isocratic elution as well as better chromatographic efficiency. The limits of detection of the three methylxanthines ranged from 0.18 to 0.45 μmol L−1, the instrumental repeatability (at the 10 μmol L−1 level of the target compounds, n = 6) was ≤2% and the separation time was 3.3 min. The SIC method was validated and applied to the analysis of coffee, chocolate and tea samples. Image 1 • A linear gradient sequential injection chromatography approach was developed. • Linear gradient elution was implemented using programmable fluidics. • The method was applied to the determination of three methylxanthines. • The methodology presents distinct advantages over the isocratic elution mode. • The method proved accurate, precise, robust and fit-for-purpose. [ABSTRACT FROM AUTHOR]