共查询到20条相似文献，搜索用时 390 毫秒
1.
L. Yu S. M. Grist S. S. Nasseri E. Cheng Y.-C. E. Hwang C. Ni K. C. Cheung 《Biomicrofluidics》2015,9(2)
Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since they may provide a better model of the tumor than conventional monolayer culture. Moreover, tumor cell interaction with the extracellular matrix can determine cell organization and behavior. In this work, a microfluidic system was used to form cell-laden core-shell beads which incorporate elements of the extracellular matrix and support the formation of multicellular spheroids. The bead core (comprising a mixture of alginate, collagen, and reconstituted basement membrane, with gelation by temperature control) and shell (comprising alginate hydrogel, with gelation by ionic crosslinking) were simultaneously formed through flow focusing using a cooled flow path into the microfluidic chip. During droplet gelation, the alginate acts as a fast-gelling shell which aids in preventing droplet coalescence and in maintaining spherical droplet geometry during the slower gelation of the collagen and reconstituted basement membrane components as the beads warm up. After droplet gelation, the encapsulated MCF-7 cells proliferated to form uniform spheroids when the beads contained all three components: alginate, collagen, and reconstituted basement membrane. The dose-dependent response of the MCF-7 cell tumor spheroids to two anticancer drugs, docetaxel and tamoxifen, was compared to conventional monolayer culture. 相似文献
2.
Myat Noe Hsu Rongcong Luo Kerwin Zeming Kwek Yong Chen Por Yong Zhang Chia-Hung Chen 《Biomicrofluidics》2015,9(5)
The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules. 相似文献
3.
Shape controllable microgel particles prepared by microfluidic combining external ionic crosslinking
Alginate microgels with varied shapes, such as mushroom-like, hemi-spherical, red blood cell-like, and others, were generated by combining microfluidic and external ionic crosslinking methods. This novel method allows a continuous fine tuning of the microgel particles shape by simply varying the gelation conditions, e.g., viscosity of the gelation bath, collecting height, interfacial tension. The release behavior of iopamidol-loaded alginate microgel particles with varied morphologies shows significant differences. Our technique can also be extended to microgels formation from different anionic biopolymers, providing new opportunities to produce microgels with various anisotropic dimensions for the applications in drug delivery, optical devices, and in advanced materials formation. 相似文献
4.
Computational fluid dynamic (CFD) simulation is a powerful tool in the design and implementation of microfluidic systems, especially for systems that involve hydrodynamic behavior of objects such as functionalized microspheres, biological cells, or biopolymers in complex structures. In this work, we investigate hydrodynamic trapping of microspheres in a novel microfluidic particle-trap array device by finite element simulations. The accuracy of the time-dependent simulation of a microsphere''s motion towards the traps is validated by our experimental results. Based on the simulation, we study the fluid velocity field, pressure field, and force and stress on the microsphere in the device. We further explore the trap array''s geometric parameters and critical fluid velocity, which affect the microsphere''s hydrodynamic trapping. The information is valuable for designing microfluidic devices and guiding experimental operation. Besides, we provide guidelines on the simulation set-up and release an openly available implementation of our simulation in one of the popular FEM softwares, COMSOL Multiphysics. Researchers may tailor the model to simulate similar microfluidic systems that may accommodate a variety of structured particles. Therefore, the simulation will be of particular interest to biomedical research involving cell or bead transport and migration, blood flow within microvessels, and drug delivery. 相似文献
5.
Precise temporal control of microfluidic droplets such as synchronization and combinatorial pairing of droplets is required to achieve a variety range of chemical and biochemical reactions inside microfluidic networks. Here, we present a facile and robust microfluidic platform enabling uniform interval control of flowing droplets for the precise temporal synchronization and pairing of picoliter droplets with a reagent. By incorporating microbridge structures interconnecting the droplet-carrying channel and the flow control channel, a fluidic pressure drop was derived between the two fluidic channels via the microbridge structures, reordering flowing droplets with a defined uniform interval. Through the adjustment of the control oil flow rate, the droplet intervals were flexibly and precisely adjustable. With this mechanism of droplet spacing, the gelation of the alginate droplets as well as control of the droplet interval was simultaneously achieved by additional control oil flow including calcified oleic acid. In addition, by parallel linking identical microfluidic modules with distinct sample inlet, controlled synchronization and pairing of two distinct droplets were demonstrated. This method is applicable to facilitate and develop many droplet-based microfluidic applications, including biological assay, combinatorial synthesis, and high-throughput screening. 相似文献
6.
Tiantian Kong Jun Wu Michael To Kelvin Wai Kwok Yeung Ho Cheung Shum Liqiu Wang 《Biomicrofluidics》2012,6(3)
Developing carriers of active ingredients with pre-determined release kinetics is a main challenge in the field of controlled release. In this work, we fabricate designer microparticles as carriers of active ingredients using droplet microfluidics. We show that monodisperse droplet templates do not necessarily produce monodisperse particles. Magnetic stirring, which is often used to enhance the droplet solidification rate, can promote breakup of the resultant microparticles into fragments; with an increase in the stirring time, microparticles become smaller in average size and more irregular in shape. Thus, the droplet solidification conditions affect the size, size distribution and morphology of the fabricated particles, and these attributes of the microparticles strongly influence their release kinetics. The smaller the average size of the microparticles is, the higher the initial release rate is. The release kinetics of drug carriers is strongly related to their characteristics. The understanding of this relationship enables the fabrication of tailor-designed carriers with a specified release rate, and even programmed release to meet the needs of applications that require a complex release profile of the active ingredients. 相似文献
7.
Integration of microfluidic devices with pressure-driven, self-powered fluid flow propulsion methods has provided a very effective solution for on-chip, droplet blood testing applications. However, precise understanding of the physical process governing fluid dynamics in polydimethylsiloxane (PDMS)-based microfluidic devices remains unclear. Here, we propose a pressure-driven diffusion model using Fick''s law and the ideal gas law, the results of which agree well with the experimental fluid dynamics observed in our vacuum pocket-assisted, self-powered microfluidic devices. Notably, this model enables us to precisely tune the flow rate by adjusting two geometrical parameters of the vacuum pocket. By linking the self-powered fluid flow propulsion method to the sedimentation, we also show that direct plasma separation from a drop of whole blood can be achieved using only a simple construction without the need for external power sources, connectors, or a complex operational procedure. Finally, the potential of the vacuum pocket, along with a removable vacuum battery to be integrated with non-PDMS microfluidic devices to drive and control the fluid flow, is demonstrated. 相似文献
8.
Microfluidic devices have been established as useful platforms for cell culture for a broad range of applications, but challenges associated with controlling gradients of oxygen and other soluble factors and hemodynamic shear forces in small, confined channels have emerged. For instance, simple microfluidic constructs comprising a single cell culture compartment in a dynamic flow condition must handle tradeoffs between sustaining oxygen delivery and limiting hemodynamic shear forces imparted to the cells. These tradeoffs present significant difficulties in the culture of mesenchymal stem cells (MSCs), where shear is known to regulate signaling, proliferation, and expression. Several approaches designed to shield cells in microfluidic devices from excessive shear while maintaining sufficient oxygen concentrations and transport have been reported. Here we present the relationship between oxygen transport and shear in a "membrane bilayer" microfluidic device, in which soluble factors are delivered to a cell population by means of flow through a proximate channel separated from the culture channel by a membrane. We present an analytical model that describes the characteristics of this device and its ability to independently modulate oxygen delivery and hemodynamic shear imparted to the cultured cells. This bilayer configuration provides a more uniform oxygen concentration profile that is possible in a single-channel system, and it enables independent tuning of oxygen transport and shear parameters to meet requirements for MSCs and other cells known to be sensitive to hemodynamic shear stresses. 相似文献
9.
We demonstrate a valve-less microfluidic peristaltic pumping method which enables the delivery of continuous nanoliter-scale flow with high precision. The fluid is driven by squeezing the microchannels embedded in a poly(dimethylsiloxane) device with rolling cams or bearings. We achieve continuous and uniform flow with velocity range from 1 to 500 nl/s, with outflow volume error within 3 nl. The devices show enhanced backpressure resistance up to 340 kPa. This method also shows great flexibility. By altering the channels'' layout, emulsions and plugs can be generated easily. These low-cost and easy-to-fabricate micro-pumps offer novel approaches for liquid actuation in various microfluidic applications. 相似文献
10.
In this article, the authors present the fabrication of an enzyme-entrapped alginate hollow fiber using a microfluidic device. Further use of enzyme-entrapped alginate hollow fibers as a biocatalytic microchemical reactor for chemical synthesis is also deliberated in this article. To ensure that there is no enzyme leaching from the fiber, fiber surfaces were coated with chitosan. To confine the mobility of reactants and products within the porous hollow fibers the entire fibers were embedded into a transparent polydimethylsiloxane (PDMS) matrix which also works as a support matrix. A vanadium-containing bromoperoxidase enzyme isolated from Corallina confusa was used as a model enzyme to demonstrate the use of these alginate hollow-fiber reactors in bromo-oxidation of phenol red to bromophenol blue at different dye flow rates. Stability of the entrapped enzyme at different temperatures and the effect of the chitosan coating on the reaction conversion were also studied. It was observed that molecules as big as 27 kDa can be retained in the matrix after coating with chitosan while molecules with molecular-weight of around 378 Da can still diffuse in and out of the matrix. The kinetic conversion rate in this microfluidic bioreactor was more than 41-fold faster when compared with the standard test-tube procedure. 相似文献
11.
Ikram Khan Anil Prabhakar Chloe Delepine Hayley Tsang Vincent Pham Mriganka Sur 《Biomicrofluidics》2021,15(2)
Organoids are biological systems grown in vitro and are observed to self-organize into 3D cellular tissues of specific organs. Brain organoids have emerged as valuable models for the study of human brain development in health and disease. Researchers are now in need of improved culturing and imaging tools to capture the in vitro dynamics of development processes in the brain. Here, we describe the design of a microfluidic chip and bioreactor, to enable in situ tracking and imaging of brain organoids on-chip. The low-cost 3D printed microfluidic bioreactor supports organoid growth and provides an optimal imaging chamber for live-organoid imaging, with drug delivery support. This fully isolated design of a live-cell imaging and culturing platform enables long-term live-imaging of the intact live brain organoids as it grows. We can thus analyze their self-organization in a controlled environment with high temporal and spatial resolution. 相似文献
12.
Duilia N. du Chatinier Kianti P. Figler Prajwal Agrawal Wanjun Liu Yu Shrike Zhang 《Biomicrofluidics》2021,15(4)
Microfluidics-enhanced bioprinting holds great promise in the field of biofabrication as it enables the fabrication of complex constructs with high shape fidelity and utilization of a broad range of bioinks with varying viscosities. Microfluidic systems contain channels on the micrometer-scale, causing a change in fluid behaviors, enabling unconventional bioprinting applications such as facilitating the precise spatial positioning and switching between bioinks with higher accuracy compared to traditional approaches. These systems can roughly be divided into three groups: microfluidic chips, co- and triaxial printheads, and printheads combining both. Although several aspects and parameters remain to be improved, this technology is promising as it is a step toward recapitulating the complex native histoarchitecture of human tissues more precisely. In this Perspective, key research on these different systems will be discussed before moving onto the limitations and outlook of microfluidics-enhanced bioprinting as a whole. 相似文献
13.
Heidi Stoll Heiko Kiessling Martin Stelzle Hans Peter Wendel Julia Schütte Britta Hagmeyer Meltem Avci-Adali 《Biomicrofluidics》2015,9(3)
Aptamers are promising cell targeting ligands for several applications such as for the diagnosis, therapy, and drug delivery. Especially, in the field of regenerative medicine, stem cell specific aptamers have an enormous potential. Using the combinatorial chemistry process SELEX (Systematic Evolution of Ligands by Exponential enrichment), aptamers are selected from a huge oligonucleotide library consisting of approximately 1015 different oligonucleotides. Here, we developed a microfluidic chip system that can be used for the selection of cell specific aptamers. The major drawbacks of common cell-SELEX methods are the inefficient elimination of the unspecifically bound oligonucleotides from the cell surface and the unspecific binding/uptake of oligonucleotides by dead cells. To overcome these obstacles, a microfluidic device, which enables the simultaneous performance of dielectrophoresis and electrophoresis in the same device, was designed. Using this system, viable cells can be selectively assembled by dielectrophoresis between the electrodes and then incubated with the oligonucleotides. To reduce the rate of unspecifically bound sequences, electrophoretic fields can be applied in order to draw loosely bound oligonucleotides away from the cells. Furthermore, by increasing the flow rate in the chip during the iterative rounds of SELEX, the selection pressure can be improved and aptamers with higher affinities and specificities can be obtained. This new microfluidic device has a tremendous capability to improve the cell-SELEX procedure and to select highly specific aptamers. 相似文献
14.
This paper reports the use of microfluidic approaches for the fabrication of yeastosomes (yeast-celloidosomes) based on self-assembly of yeast cells onto liquid-solid or liquid-gas interfaces. Precise control over fluidic flows in droplet- and bubble-forming microfluidic devices allows production of monodispersed, size-selected templates. The general strategy to organize and assemble living cells is to tune electrostatic attractions between the template (gel or gas core) and the cells via surface charging. Layer-by-Layer (LbL) polyelectrolyte deposition was employed to invert or enhance charges of solid surfaces. We demonstrated the ability to produce high-quality, monolayer-shelled yeastosome structures under proper conditions when sufficient electrostatic driving forces are present. The combination of microfluidic fabrication with cell self-assembly enables a versatile platform for designing synthetic hierarchy bio-structures. 相似文献
15.
A method for monitoring the biological exocytotic phenomena on a microfluidic system was proposed. A microfluidic device coupled with functionalities of fluorescence imaging and amperometric detection has been developed to enable the real-time monitoring of the exocytotic events. Exocytotic release of single SH-SY5Y neuroblastoma cells was studied. By staining the cells located on integrated microelectrodes with naphthalene-2,3-dicarboxaldehyde, punctuate fluorescence consistent with localization of neurotransmitters stored in vesicles was obtained. The stimulated exocytotic release was successfully observed at the surface of SH-SY5Y cells without refitting the commercial inverted fluorescence microscope. Spatially and temporally resolved exocytotic events from single cells on a microfluidic device were visualized in real time using fluorescence microscopy and were amperometrically recorded by the electrochemical system simultaneously. This coupled technique is simple and is hoped to provide new insights into the mechanisms responsible for the kinetics of exocytosis. 相似文献
16.
David W. Inglis 《Biomicrofluidics》2010,4(2)
Poly(dimethylsiloxane) or PDMS is an excellent material for replica molding, widely used in microfluidics research. Its low elastic modulus, or high deformability, assists its release from challenging molds, such as those with high feature density, high aspect ratios, and even negative sidewalls. However, owing to the same properties, PDMS-based microfluidic devices stretch and change shape when fluid is pushed or pulled through them. This paper shows how severe this change can be and gives a simple method for limiting this change that sacrifices few of the desirable characteristics of PDMS. A thin layer of PDMS between two rigid glass substrates is shown to drastically reduce pressure-induced shape changes while preserving deformability during mold separation and gas permeability. 相似文献
17.
We report the design and implementation of capacitive detection and control of microfluidic droplets in microfluidic devices. Integrated microfluidic chip(s) with detection∕control circuit enables us to monitor in situ the individual volume of droplets, ranging from nanoliter to picoliter, velocity and even composition, with an operation frequency of several kilohertz. Through electronic feedback, we are able to easily count, sort, and direct the microfluidic droplets. Potential applications of this approach can be employed in the areas of biomicrofluidic processing, microchemical reactions as well as digital microfluidics. 相似文献
18.
Unwanted sedimentation and attachment of a number of cells onto the bottom channel often occur on relatively large-scale inlets of conventional microfluidic channels as a result of gravity and fluid shear. Phenomena such as sedimentation have become recognized problems that can be overcome by performing microfluidic experiments properly, such as by calculating a meaningful output efficiency with respect to real input. Here, we present a dual-inlet design method for reducing cell loss at the inlet of channels by adding a new “ upstream inlet ” to a single main inlet design. The simple addition of an upstream inlet can create a vertically layered sheath flow prior to the main inlet for cell loading. The bottom layer flow plays a critical role in preventing the cells from attaching to the bottom of the channel entrance, resulting in a low possibility of cell sedimentation at the main channel entrance. To provide proof-of-concept validation, we applied our design to a microfabricated flow cytometer system (μFCS) and compared the cell counting efficiency of the proposed μFCS with that of the previous single-inlet μFCS and conventional FCS. We used human white blood cells and fluorescent microspheres to quantitatively evaluate the rate of cell sedimentation in the main inlet and to measure fluorescence sensitivity at the detection zone of the flow cytometer microchip. Generating a sheath flow as the bottom layer was meaningfully used to reduce the depth of field as well as the relative deviation of targets in the z-direction (compared to the x-y flow plane), leading to an increased counting sensitivity of fluorescent detection signals. Counting results using fluorescent microspheres showed both a 40% reduction in the rate of sedimentation and a 2-fold higher sensitivity in comparison with the single-inlet μFCS. The results of CD4+ T-cell counting also showed that the proposed design results in a 25% decrease in the rate of cell sedimentation and a 28% increase in sensitivity when compared to the single-inlet μFCS. This method is simple and easy to use in design, yet requires no additional time or cost in fabrication. Furthermore, we expect that this approach could potentially be helpful for calculating exact cell loading and counting efficiency for a small input number of cells, such as primary cells and rare cells, in microfluidic channel applications. 相似文献
19.
Cell encapsulation technology is a promising strategy applicable to tissue engineering and cell therapy. Many advanced microencapsulation chips that function via multiple syringe pumps have been developed to generate mono-disperse hydrogel beads encapsulating cells. However, their operation is difficult and only trained microfluidic engineers can use them with dexterity. Hence, we propose a microfluidic manifold system, driven by a single syringe pump, which can enable the setup of automated flow sequences and generate highly mono-disperse alginate beads by minimizing disturbances to the pump pressure. The encapsulation of P19 mouse embryonic carcinoma cells and embryonic body formation are demonstrated to prove the efficiency of the proposed system. 相似文献
20.
This paper presents integrated microfluidic lab-on-a-chip technology combining surface acoustic wave (SAW) and electro-wetting on dielectric (EWOD). This combination has been designed to provide enhanced microfluidic functionality and the integrated devices have been fabricated using a single mask lithographic process. The integrated technology uses EWOD to guide and precisely position microdroplets which can then be actuated by SAW devices for particle concentration, acoustic streaming, mixing and ejection, as well as for sensing using a shear-horizontal wave SAW device. A SAW induced force has also been employed to enhance the EWOD droplet splitting function. 相似文献