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1.
Paper-based microfluidics are an increasingly popular alternative to devices with conventional open channel geometries. The low cost of fabrication and the absence of external instrumentation needed to drive paper microchannels make them especially well suited for medical diagnostics in resource-limited settings. Despite the advantages of paper microfluidics, many assays performed using conventional open channel microfluidics are challenging to translate onto paper, such as bead, emulsion, and cell-based assays. To overcome this challenge, we have developed a hybrid open-channel/paper channel microfluidic device. In this design, wick-driven paper channels control the flow rates within conventional microfluidics. We fabricate these hybrid chips using laser-micromachined polymer sheets and filter paper. In contrast to previous efforts that utilized external, macroscopic paper-based pumps, we integrated micro-scale paper and open channels onto a single chip to control multiple open channels and control complex laminar flow-pattern within individual channels. We demonstrated that flow patterns within the open channels can be quantitatively controlled by modulating the geometry of the paper channels, and that these flow rates agree with Darcy''s law. The utility of these hybrid chips, for applications such as bead-, cell-, or emulsion-based assays, was demonstrated by constructing a hybrid chip that hydrodynamically focused micrometer-sized polystyrene beads stably for >10 min, as well as cells, without external instrumentation to drive fluid flow.  相似文献   

2.
We evaluate the feasibility of manipulating droplets in two dimensions by exploiting Coulombic forces acting on conductive droplets immersed in a dielectric fluid. When a droplet suspended in an immiscible fluid is located near an electrode under a dc voltage, the droplet can be charged by direct contact, by charge transfer along an electrically conducting path, or by both mechanisms. This process is called electrical charging of droplet (ECOD). This charged droplet may then be transported rapidly by exploiting Coulombic forces. We experimentally demonstrate electrical actuation of a charged droplet by applying voltage sequences. A charged droplet is two dimensionally actuated by following the direction of the electrical field signal. The droplet does not contact the surface of the microfluidic chip when it moves. This characteristic is very advantageous because treatments of the substrate surfaces of microfluidic chip become simpler. In order to test the feasibility of using ECOD in a droplet-based microreactor, electrocoalescence of two oppositely charged droplets is also studied. When two droplets approach each other due to Coulombic attraction, a liquid bridge is formed between them. We postulate that if the applied electric field is weaker than a certain critical level, the two droplets coalesce instantaneously when the charges are exchanged and redistributed through this liquid bridge.  相似文献   

3.
Cell migration is an essential process involved in the development and maintenance of multicellular organisms. Electric fields (EFs) are one of the many physical and chemical factors known to affect cell migration, a phenomenon termed electrotaxis or galvanotaxis. In this paper, a microfluidics chip was developed to study the migration of cells under different electrical and chemical stimuli. This chip is capable of providing four different strengths of EFs in combination with two different chemicals via one simple set of agar salt bridges and Ag/AgCl electrodes. NIH 3T3 fibroblasts were seeded inside this chip to study their migration and reactive oxygen species (ROS) production in response to different EF strengths and the presence of β-lapachone. We found that both the EF and β-lapachone level increased the cell migration rate and the production of ROS in an EF-strength-dependent manner. A strong linear correlation between the cell migration rate and the amount of intracellular ROS suggests that ROS are an intermediate product by which EF and β-lapachone enhance cell migration. Moreover, an anti-oxidant, α-tocopherol, was found to quench the production of ROS, resulting in a decrease in the migration rate.  相似文献   

4.
In past decades, a lot of studies have been carried out on complex networks and heat conduction in regular lattices. However, very little attention has been paid to the heat conduction in complex networks. In this work, we study (both thermal and electric) energy transport in physical networks rewired from 2D regular lattices. It is found that the network can be transferred from a good conductor to a poor conductor, depending on the rewired network structure and coupling scheme. Two interesting phenomena were discovered: (i) the thermal-siphon effect—namely the heat flux can go from a low-temperature node to a higher-temperature node and (ii) there exits an optimal network structure that displays small thermal conductance and large electrical conductance. These discoveries reveal that network-structured materials have great potential in applications in thermal-energy management and thermal-electric-energy conversion.  相似文献   

5.
Diffusion of autocrine and paracrine signaling molecules allows cells to communicate in the absence of physical contact. This chemical-based, long-range communication serves crucial roles in tissue function, activation of the immune system, and other physiological functions. Despite its importance, few in vitro methods to study cell-cell signaling through paracrine factors are available today. Here, we report the design and validation of a microfluidic platform that enables (i) soluble molecule-cell and/or (ii) cell-cell paracrine signaling. In the microfluidic platform, multiple cell populations can be introduced into parallel channels. The channels are separated by arrays of posts allowing diffusion of paracrine molecules between cell populations. A computational analysis was performed to aid design of the microfluidic platform. Specifically, it revealed that channel spacing affects both spatial and temporal distribution of signaling molecules, while the initial concentration of the signaling molecule mainly affects the concentration of the signaling molecules excreted by the cells. To validate the microfluidic platform, a model system composed of the signaling molecule lipopolysaccharide, mouse macrophages, and engineered human embryonic kidney cells was introduced into the platform. Upon diffusion from the first channel to the second channel, lipopolysaccharide activates the macrophages which begin to produce TNF-α. The TNF-α diffuses from the second channel to the third channel to stimulate the kidney cells, which express green fluorescent protein (GFP) in response. By increasing the initial lipopolysaccharide concentration an increase in fluorescent response was recorded, demonstrating the ability to quantify intercellular communication between 3D cellular constructs using the microfluidic platform reported here. Overall, these studies provide a detailed analysis on how concentration of the initial signaling molecules, spatiotemporal dynamics, and inter-channel spacing affect intercellular communication.  相似文献   

6.
Oxygen and glucose supply is one of the important factors for the growth and viability of the cells in cultivation of tissues, e.g., spheroid, multilayered cells, and three-dimensional tissue construct. In this study, we used finite element methods to simulate the flow profile as well as oxygen and glucose supply to the multilayered cells in a microwell array chip for static and perfusion cultures. The simulation results indicated that oxygen supply is more crucial than glucose supply in both static and perfusion cultures, and that the oxygen supply through the wall of the perfusion culture chip is important in perfusion cultures. Glucose concentrations decline with time in static cultures, whereas they can be maintained at a constant level over time in perfusion cultures. The simulation of perfusion cultures indicated that the important parameters for glucose supply are the flow rate of the perfusion medium and the length of the cell culture chamber. In a perfusion culture chip made of oxygen-permeable materials, e.g., polydimethylsiloxane, oxygen is hardly supplied via the perfusion medium, but mainly supplied through the walls of the perfusion culture chip. The simulation of perfusion cultures indicated that the important parameters for oxygen supply are the thickness of the flow channel and the oxygen permeability of the walls of the channel, i.e., the type of material and the thickness of the wall.  相似文献   

7.
The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.  相似文献   

8.
With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.  相似文献   

9.
This paper presents a microfluidic device for simultaneous mechanical and electrical characterization of single cells. The device performs two types of cellular characterization (impedance spectroscopy and micropipette aspiration) on a single chip to enable cell electrical and mechanical characterization. To investigate the performance of the device design, electrical and mechanical properties of MC-3T3 osteoblast cells were measured. Based on electrical models, membrane capacitance of MC-3T3 cells was determined to be 3.39±1.23 and 2.99±0.82 pF at the aspiration pressure of 50 and 100 Pa, respectively. Cytoplasm resistance values were 110.1±37.7 kΩ (50 Pa) and 145.2±44.3 kΩ (100 Pa). Aspiration length of cells was found to be 0.813±0.351 μm at 50 Pa and 1.771±0.623 μm at 100 Pa. Quantified Young's modulus values were 377±189 Pa at 50 Pa and 344±156 Pa at 100 Pa. Experimental results demonstrate the device's capability for characterizing both electrical and mechanical properties of single cells.  相似文献   

10.
《Research Policy》2023,52(9):104870
We posit that a communications gap exists between universities and commercial organizations, attributed to their idiosyncratic goals, interests, and incentives. To bridge this gap, universities need to recognize and leverage observable differences in the strength of signals and the width of channels used to disseminate their scientific knowledge externally. We explore these ideas by analyzing knowledge dissemination and academic engagement activities in 133 UK universities in the period 2011–2019. Our analysis shows that universities with a lower scientific impact have a higher intensity of collaborative research, contract research, and consultancy activities if they communicate that impact through more prominent scientific outlets. In turn, universities with a higher scientific impact have a lower intensity of interaction with commercial organizations if they communicate their scientific impact through less prominent scientific outlets. We further reveal that universities with a higher economic impact show a higher intensity of collaborative research. At the same time, we find no evidence that the social impact generated by universities is linked to the intensity of university-industry interaction, no matter the channels through which that impact is communicated. Using these findings, we draw implications for practice and policy.  相似文献   

11.
Cui S  Liu Y  Wang W  Sun Y  Fan Y 《Biomicrofluidics》2011,5(3):32003-320038
This paper examined the feasibility of a microfluidics chip for cell capturing and pairing with a high efficiency. The chip was fabricated by the polydimethylsiloxane-based soft-lithography technique and contained two suction duct arrays set in parallel on both sides of a main microchannel. Cells were captured and paired by activating two sets of suction ducts one by one with the help of syringe pumps along with switching the cell suspensions inside the main microchannel correspondingly. The effects of suction flow rate and the dimensions of suction channels on the cell capturing and pairing efficiency were characterized. The present chip was capable of creating 1024 pairs of two different cell populations in parallel. The preliminary experimental results showed that the cell capturing efficiency was 100% and the pairing one was 88% with an optimal suction rate of 5 μl/min in the chip in the 2 μm-sized suction duct chip. The cell viability after capture inside the microfluidic device was 90.0 ± 5.3%. With this cell capturing and pairing chip, interaction between cells in a single pair mode can be studied. The ability to create cell pairs has a number of biological applications for cell fusion, cell-cell interaction studies, and cell toxicity screening.  相似文献   

12.
Research on the diffusion of new technologies has centred on the study of the interfirm rate of diffusion, paying much less attention to intrafirm aspects. This paper attempts to overcome this gap in the literature by analysing the factors that influence the speed with which a new technology, the ATM, is fully adopted. The data over which the hypotheses are tested belongs to the Spanish savings banks market. The results show that the rate of intrafirm diffusion is explained by innovation, firm and market characteristics. In testing our hypotheses we make use of both traditional methods and survival analysis techniques.  相似文献   

13.
We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip’s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.  相似文献   

14.
The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy.  相似文献   

15.
Hepatoprotectant is critical for the treatment of liver disease. This study first reported the application of a liver chip in the hepatoprotective effect assessment. We first established a biomimetic sinusoid-on-a-chip by laminating four types of hepatic cell lines (HepG2, HUVEC, LX-2, and U937 cells) in a single microchannel with the help of laminar flow in the microchannel and some micro-fences. This chip was straightforward to fabricate and operate and was able to be long-term cultured. It also demonstrated better hepatic activity (cell viability, albumin synthesis, urea secretion, and cytochrome P450 enzyme activities) over the traditional planar cell culture model. Then, we loaded three hepatoprotectants (tiopronin, bifendatatum, and glycyrrhizinate) into the chip followed by the addition of acetaminophen as a toxin. We successfully observed the hepatoprotective effect of these hepatoprotectants in the chip, and we also found that bifendatatum predominantly reduced alanine transaminase secretion, tiopronin predominantly reduced lactate dehydrogenase secretion, and glycyrrhizinate predominantly reduced aspartate transaminase secretion, which revealed the different mechanisms of these hepatoprotectants and provided a clue for following molecular biological study of the protecting mechanism.  相似文献   

16.
Despite being invasive within surrounding brain tissues and the central nervous system, little is known about the mechanical properties of brain tumor cells in comparison with benign cells. Here, we present the first measurements of the peak pressure drop due to the passage of benign and cancerous brain cells through confined microchannels in a “microfluidic cell squeezer” device, as well as the elongation, speed, and entry time of the cells in confined channels. We find that cancerous and benign brain cells cannot be differentiated based on speeds or elongation. We have found that the entry time into a narrow constriction is a more sensitive indicator of the differences between malignant and healthy glial cells than pressure drops. Importantly, we also find that brain tumor cells take a longer time to squeeze through a constriction and migrate more slowly than benign cells in two dimensional wound healing assays. Based on these observations, we arrive at the surprising conclusion that the prevailing notion of extraneural cancer cells being more mechanically compliant than benign cells may not apply to brain cancer cells.  相似文献   

17.
Understanding the mechanism behind cancer metastasis is a major challenge in cancer biology. Several in vitro models have been developed to mimic a cancer microenvironment by engineering cancer–endothelial cell (EC) and cancer-stromal cell interactions. It has been challenging to realistically mimic angiogenesis, intravasation, and extravasation using macro-scale approaches but recent progress in microfluidics technology has begun to yield promising results. We present a metastasis chip that produce microvessels, where EC and stromal cells can be patterned in close proximity to tumor cells. The vessels are formed following a natural morphogenic process and have smooth boundaries with proper cell-cell junctions. The engineered microvessels are perfusable and have well-defined openings toward inlet and outlet channels. The ability to introduce cancer cells into different locations bordering to the microvessel wall allowed generation and maintenance of appropriate spatial gradients of growth factors and attractants. Cancer angiogenesis and its inhibition by anti-vascular endothelial growth factor (bevacizumab) treatment were successfully reproduced in the metastasis chip. Cancer intravasation and its modulation by treatment of tumor necrosis factor-α were also modeled. Compared to other models, the unique design of the metastasis chip that engineers a clear EC-cancer interface allows precise imaging and quantification of angiogenic response as well as tumor cell trans-endothelial migration. The metastasis chip presented here has potential applications in the investigation of fundamental cancer biology as well as in drug screening.  相似文献   

18.
We present a novel cell culture chip, namely, “inverting microwell array chip,” for cultivation of human induced pluripotent stem cells. The chip comprises a lower hydrogel microwell array and an upper polystyrene culture surface. We demonstrate the formation of uniform cellular aggregates in the microwell array, and after inversion, a culture with controlled aggregate size and geometrical arrangement on the polystyrene surface. Here, we report effects of cell concentrations on a cultivation sequence in the chip.  相似文献   

19.
Robust bubble-free priming of complex microfluidic chips represents a critical, yet often unmet prerequisite to enable their practical and widespread application. Towards this end, the usage of a network of capillary stop valves as a generic design feature is proposed. Design principles, numerical simulations, and their application in the development of a microfluidic cell culture device are presented. This chip comprises eight parallel chambers for the assembly and cultivation of human hepatocytes and endothelial cells. The inlet channel divides into cell chambers, after which the flows are reunited to a single chip outlet. Dimensions and geometry of channels and cell chambers are designed to yield capillary burst pressures sequentially increasing towards the chip outlet. Thus, progress of liquid flow through the device is predefined by design and enclosure of air bubbles inside the microfluidic structures is efficiently avoided. Capillary stop valves were designed using numerical simulations. Devices were fabricated in cyclic olefin polymer. Pressure during filling was determined experimentally and is in good agreement with data obtained from simulation.  相似文献   

20.
基于nRF2401的高压交流信号数据采集系统的设计   总被引：1，自引：0，他引：1  
文章从工程实际需要出发,在介绍无线收发一体芯片nRF2401的基础上,采用微处理器芯片PIC18F6621、交流采样技术和带有串行接口的功率/电能芯片CS5460,给出了基于nRF2401的高压交流信号无线数据采集系统的整体设计,并通过整个系统的仿真测试,其结果完全符合设计要求。  相似文献   

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