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1.
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2.
We demonstrate monolithic integration of fine cylindrical glass microcapillaries (diameter ∼1 μm) on silicon and evaluate their performance for electrophoretic separation of biomolecules. Such microcapillaries are achieved through thermal reflow of a glass layer on microstructured silicon whereby slender voids are moulded into cylindrical tubes. The process allows self-enclosed microcapillaries with a uniform profile. A simplified method is also described to integrate the microcapillaries with a sample-injection cross without the requirement of glass etching. The 10-mm-long microcapillaries sustain field intensities up to 90 kV/m and limit the temperature excursions due to Joule heating to a few degrees Celsius only.  相似文献   

3.
The majority of cancer deaths are linked to tumor spread, or metastasis, but 3D in vitro metastasis models relevant to the tumor microenvironment (including interstitial fluid flow) remain an area of unmet need. Microfluidics allows us to introduce controlled flow to an in vitro cancer model to better understand the relationship between flow and metastasis. Here, we report new hybrid spheroid-on-chip in vitro models for the impact of interstitial fluid flow on cancer spread. We designed a series of reusable glass microfluidic devices to contain one spheroid in a microwell under continuous perfusion culture. Spheroids derived from established cancer cell lines were perfused with complete media at a flow rate relevant to tumor interstitial fluid flow. Spheroid viability and migratory/invasive capabilities were maintained on-chip when compared to off-chip static conditions. Importantly, using flow conditions modeled in vitro, we are the first to report flow-induced secretion of pro-metastatic factors, in this case cytokines vascular endothelial growth factor and interleukin 6. In summary, we have developed a new, streamlined spheroid-on-chip in vitro model that represents a feasible in vitro alternative to conventional murine in vivo metastasis assays, including complex tumor environmental factors, such as interstitial fluid flow, extracellular matrices, and using 3D models to model nutrient and oxygen gradients. Our device, therefore, constitutes a robust alternative to in vivo early-metastasis models for determination of novel metastasis biomarkers as well as evaluation of therapeutically relevant molecular targets not possible in in vivo murine models.  相似文献   

4.
We have performed microfluidic experiments with erythrocytes passing through a network of microchannels of 20–25 μm width and 5 μm of height. Red blood cells (RBCs) were flowing in countercurrent directions through microchannels connected by μm pores. Thereby, we have observed interesting flow dynamics. All pores were blocked by erythrocytes. Some erythrocytes have passed through pores, depending on the channel size and cell elasticity. Many RBCs split into two or more smaller parts. Two types of splits were observed. In one type, the lipid bilayer and spectrin network were cut at the same time. In the second type, the lipid bilayer reconnected, but the part of spectrin network stayed outside the cell forming a rope like structure, which could eventually break. The microporous membrane results in multiple breakups of the cells, which can have various clinical implications, e.g., glomerulus hematuria and anemia of patients undergoing dialysis. The cell breakup procedure is similar to the one observed in the droplet breakage of viscoelastic liquids in confinement.  相似文献   

5.
Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs.  相似文献   

6.
We describe design and miniaturization of a polymeric optical interface for flow monitoring in biomicrofluidics applications based on polydimethylsiloxane technology, providing optical transparency and compatibility with biological tissues. Design and ray tracing simulation are presented as well as device realization and optical analysis of flow dynamics in microscopic blood vessels. Optics characterization of this polymeric microinterface in dynamic experimental conditions provides a proof of concept for the application of the device to two-phase flow monitoring in both in vitro experiments and in vivo microcirculation investigations. This technology supports the study of in vitro and in vivo microfluidic systems. It yields simultaneous optical measurements, allowing for continuous monitoring of flow. This development, integrating a well-known and widely used optical flow monitoring systems, provides a disposable interface between live mammalian tissues and microfluidic devices making them accessible to detection∕processing technology, in support or replacing standard intravital microscopy.  相似文献   

7.
We have developed a coaxial flow focusing geometry that can be fabricated using soft lithography in poly(dimethylsiloxane) (PDMS). Like coaxial flow focusing in glass capillary microfluidics, our geometry can form double emulsions in channels with uniform wettability and of a size much smaller than the channel dimensions. However, In contrast to glass capillary coaxial flow focusing, our geometry can be fabricated using lithographic techniques, allowing it to be integrated as the drop making unit in parallel drop maker arrays. Our geometry enables scalable formation of emulsions down 7 μm in diameter, in large channels that are robust against fouling and clogging.  相似文献   

8.
We show, via three-dimensional immersed-boundary-finite-element-lattice-Boltzmann simulations, that deformability-based red blood cell (RBC) separation in deterministic lateral displacement (DLD) devices is possible. This is due to the deformability-dependent lateral extension of RBCs and enables us to predict a priori which RBCs will be displaced in a given DLD geometry. Several diseases affect the deformability of human cells. Malaria-infected RBCs, for example, tend to become stiffer than their healthy counterparts. It is therefore desirable to design microfluidic devices which can detect diseases based on the cells'' deformability fingerprint, rather than preparing samples using expensive and time-consuming biochemical preparation steps. Our findings should be helpful in the development of new methods for sorting cells and particles by deformability.  相似文献   

9.
Red blood cell (RBC) aggregation is a multifaceted phenomenon, and whether it is generally beneficial or deleterious remains unclear. In order to better understand its effect on microvascular blood flow, the phenomenon must be studied in complex geometries, as it is strongly dependent on time, flow, and geometry. The cell-depleted layer (CDL) which forms at the walls of microvessels has been observed to be enhanced by aggregation; however, details of the characteristics of the CDL in complex regions, such as bifurcations, require further investigation. In the present study, a microchannel with a T-junction was used to analyze the influence of aggregation on the flow field and the CDL. Micro-PIV using RBCs as tracers provided high resolution cell velocity data. CDL characteristics were measured from the same data using a newly developed technique based on motion detection. Skewed and sharpened velocity profiles in the daughter branches were observed, contrary to the behavior of a continuous Newtonian fluid. RBC aggregation was observed to increase the skewness, but decrease the sharpening, of the velocity profiles in the daughter branches. The CDL width was found to be significantly greater, with a wider distribution, in the presence of aggregation and the mean width increased proportionally with the reciprocal of the fraction of flow entering the daughter branch. Aggregation also significantly increased the roughness of the interface between the CDL and the RBC core. The present results provide further insight into how RBC aggregation may affect the flow in complex geometries, which is of importance in both understanding its functions invivo, and utilizing it as a tool in microfluidic devices.  相似文献   

10.
The way in which bacterial communities colonize flow in porous media is of importance, but basic knowledge on the dynamic of these phenomena is still missing. The aim of this work is to develop microfluidic experiments in order to progress in the understanding of bacteria capture in filters and membranes. PDMS microfluidic devices mimicking filtration processes have been developed to allow a direct dynamic observation of bacteria across 10 or 20 μm width microchannels. When filtered in such devices, bacteria behave surprisingly: Escherichia coli, Pseudomonas aeruginosa or Staphylococcus aureus accumulate in the downstream zone of the filter and form large streamers which oscillate in the flow. In this study, streamer formation is put in evidence for bacteria suspension in non nutritive conditions in less than 1 h. This result is totally different from the one observed in same system with “inert” particles or dead bacteria which are captured in the bottleneck zone and are accumulated in the upstream zone. Observations within different flow geometries (straight channels, connected channels, and staggered row pillars) show that the bacteria streamer development is influenced by the flow configuration and, particularly by the presence of tortuosity within the microchannels zone. These results are discussed at the light of 3D flow simulations. In confined systems and in laminar flow, there is secondary flow (z-velocities) superimposed to the streamwise motion (in xy plane). The presence of the secondary flow in the microsystems has an effect on the bacterial adhesion. A scenario in three steps is established to describe the formation of the streamers and to explain the positive effect of tortuous flow on the development kinetics.  相似文献   

11.
Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two non-toxic species Ru-N3 and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N3 and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>83%) and showed high anti-tumor efficacy in vitro. This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models. It is interesting that the combination of metal-arene complexes with rhein via CuAAC reaction could transform two non-toxic species into a targeting anti-cancer metallodrug both in vitro and in vivo, while the product Ru-rhein was non-toxic towards normal cells. This is the first example that exclusive endogenous copper was used to generate metal-based anti-cancer drugs for cancer treatment. The anti-cancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage. The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes. Compared with the traditional methods for cancer treatment, this work presented a new approach to generating targeting metallodrugs in vivo via the BCL strategy from non-toxic species in metal-based chemotherapy.  相似文献   

12.
Alternating current (AC) dielectrophoresis (DEP) experiments for biological particles in microdevices are typically done at a fixed frequency. Reconstructing the DEP response curve from static frequency experiments is laborious, but essential to ascertain differences in dielectric properties of biological particles. Our lab explored the concept of sweeping the frequency as a function of time to rapidly determine the DEP response curve from fewer experiments. For the purpose of determining an ideal sweep rate, homogeneous 6.08 μm polystyrene (PS) beads were used as a model system. Translatability of the sweep rate approach to ∼7 μm red blood cells (RBC) was then verified. An Au/Ti quadrapole electrode microfluidic device was used to separately subject particles and cells to 10Vpp AC electric fields at frequencies ranging from 0.010 to 2.0 MHz over sweep rates from 0.00080 to 0.17 MHz/s. PS beads exhibited negative DEP assembly over the frequencies explored due to Maxwell-Wagner interfacial polarizations. Results demonstrate that frequency sweep rates must be slower than particle polarization timescales to achieve reliable incremental polarizations; sweep rates near 0.00080 MHz/s yielded DEP behaviors very consistent with static frequency DEP responses for both PS beads and RBCs.  相似文献   

13.
In this special topic of Biomicrofluidics, the importance of microfluidics in the field of drug delivery is highlighted. Different aspects from cell-drug carrier interactions, delivery vehicle assembly to novel drug delivery devices are considered. The contributing reviews and original articles illustrate the synergistic outcomes between these two areas of research with the aim to have a positive impact on biomedical applications.Microfluidics is certainly one of the huge success stories when it comes to anticipated impact and fulfilled promises in academic research environments. Microfluidic approaches are game changers in many disciplines in natural science, including (bio)medical science. In the latter case, the fields of biosensing/diagnostics, tissue engineering, and drug discovery/delivery have benefited from concepts which allow for the fast throughput manipulation of fluids at the submillimeter length scale.A key aim in microfluidic-assisted drug discovery is the development of strategies which will facilitate the identification of potential “hits”—new drugs with the anticipated therapeutic benefit. In this context, “organ(disease)-on-chips” are considered as highly sophisticated in vitro models with lower cost and less ethical issues compared to extensive testing in animals. This technology is still very young with countless research challenges to be addressed and eventually overcome, but the few current reports are promising, and include “gut-on-chip,” “cancer-on-chip,” or “blood vessel-on-chip.” Additionally, intravenously injected drug delivery vehicles are exposed to the blood stream and the induced mechanical forces which are likely to affect their interaction with cells and tissue. Therefore, understanding the diffusion phenomena of biomolecules in microfluidic devices as reviewed by Yesil-Celiktas and coworkers in the current special content is crucial.1 What is more, the contribution by Hosta-Rigau and colleagues provides a comprehensive overview over the interaction of drug carriers and cells in microfluidic-based systems which deliver a simple, but yet more realistic model of the dynamic in vivo situation.2 Further, to illustrate the relevance of shear stress when assessing the potential of nanocarriers for drug delivery applications, we assembled novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) as the hydrophilic extensions together with lipids into vesicles using the evaporation-rehydration method.3 Following on, we biologically evaluated the assemblies with applied shear stress using macrophages. In a related report by the Chakraborty group, a biocompatible acoustic microfluidic system was outlined including the effect of microbubbles with the applied acoustic field on biological cells.4From a different perspective, droplet microfluidics has become a popular method to assemble a huge diversity of particles of different size, shape, and morphology equipped with options for active or passive drug release. Microfluidics provides unique opportunities and flexibility to fabricate decent amounts of mono-disperse drug carriers using monomers, polymers, lipids, or inorganic precursor materials as building blocks. The assembly of size-tunable polymer/lipid particles by Sun et al.,5 and the fabrication of poly (lactic-co-glycolic acid) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels by the Chen group,6 provide interesting examples in this context. Further, artefacts associated with this technique have to be addressed and understood to avoid inaccurate and misleading data as reported by Litten et al.7 Microfluidic techniques can also be employed for cell encapsulation. Fan et al. demonstrated the trapping of human colon cancer cells in hydrogel particles with preserved viability and response to inflammatory stimuli.8Novel drug delivery devices which consider microfluidic concepts and set-ups are an interesting addition to traditional approaches. Implantable drug delivery systems provide an alternative to ensure constant drug level in blood without relying on the compliance of the patient while circumventing challenges involved in oral drug delivery coming from drug instability or limited absorbance among others. Yi and coworkers propose a reservoir approach in combination with a heat responsive valve towards the long term delivery of solid drugs.9 What is more, nebulizers, as alternative to inhalers for pulmonary drug delivery, suffer from miniaturization and drug degradation issues. Cortez-Jugo et al. report on a novel portable acoustomicrofluidic device, which successfully nebulized monoclonal antibodies into a fine aerosol mist including the first positive biological evaluation.10Further, combining microfluidics with sensing concepts as illustrated by Knoll and coworker11 is of importance, since the design of drug delivery vehicles strongly relies on the fundamental understanding of the interaction between biomolecules, cells, and tissue.Taken together, these articles give an overview over the use of microfluidics in the area of drug delivery, which goes beyond the assembly of drug carries, but also provides a platform for their biological evaluation or the design of entirely new drug delivery devices. I hope that this collection of articles will stimulate new ideas and future collaborations between engineers/chemists/physicist and biologists towards the common goal to provide solutions for biomedical challenges. Finally, I would like to thank Professor Leslie Yeo for the invitation to be the guest editor for this special topic, and Christine Urso and other editorial and production staffs of Biomicrofluidics for making it a reality.  相似文献   

14.
A variety of methods have been used to introduce chemicals into a stream or to mix two or more streams of different compositions using microfluidic devices. In the following paper, the introduction of cryoprotective agents (CPAs) used during cryopreservation of cells in order to protect them from freezing injuries and increase viability post thaw is described. Dimethylsulphoxide (DMSO) is the most commonly used CPA. We aim to optimize the operating conditions of a two-stream microfluidic device to introduce a 10% vol/vol solution of DMSO into a cell suspension. Transport behavior of DMSO between two streams in the device has been experimentally characterized for a spectrum of flow conditions (0.7 < Re < 10), varying initial donor stream concentrations, (1% vol/vol < Co < 15% vol/vol) and different flow rate fractions (0.23 < fq < 0.77). The outlet cell stream concentration is analyzed for two different flow configurations: one with the cell stream flowing on top of the DMSO-rich donor stream, and the other with the cell stream flowing beneath the heavy DMSO-laden stream. We establish a transition from a diffusive mode of mass transfer to gravity-influenced convective currents for Atwood numbers (At) in the range of (1.7 × 10−3 < At < 3.1 × 10−3) for the latter configuration. Flow visualization with cells further our understanding of the effect of At on the nature of mass transport. Cell motion studies performed with Jurkat cells confirm a high cell recovery from the device while underscoring the need to collect both the streams at the outlet of the device and suggesting flow conditions that will help us achieve the target DMSO outlet concentration for clinical scale flow rates of the cell suspension.  相似文献   

15.
2D nanomaterials generally exhibit enhanced physiochemical and biological functions in biomedical applications due to their high surface-to-volume ratio and surface charge. Conventional cancer chemotherapy based on nanomaterials has been hindered by their low drug loading and poor penetration in tumor tissue. To overcome these difficulties, novel materials systems are urgently needed. Hereby, the lanthanide-based porphyrin metal–organic framework (MOF) nanosheets (NSs) with promising cancer imaging/chemotherapy capacities are fabricated, which display superior performance in the drug loading and tumor tissue penetration. The biodegradable PPF-Gd NSs deliver an ultrahigh drug loading (>1500%) and demonstrate the stable and highly sensitive stimuli-responsive degradation/release for multimodal tumor imaging and cancer chemotherapy. Meanwhile, PPF-Gd NSs also exhibit excellent fluorescence and magnetic resonance imaging capability in vitro and in vivo. Compared to the traditional doxorubicin (DOX) chemotherapy, the in vivo results confirm the evident suppression of the tumor growth by the PPF-Gd/DOX drug delivery system with negligible side effects. This work further supports the potential of lanthanide-based MOF nanomaterials as biodegradable systems to promote the cancer theranostics technology development in the future.  相似文献   

16.
Intestinal enteroids are ex vivo primary cultured single-layer epithelial cell spheroids of average diameter ∼150 μm with luminal surface facing inward. Measurement of enteroid swelling in response to secretagogues has been applied to genetic testing in cystic fibrosis and evaluation of drug candidates for cystic fibrosis and secretory diarrheas. The current measurement method involves manual addition of drugs and solutions to enteroids embedded in a Matrigel matrix and estimation of volume changes from confocal images of fluorescently stained enteroids. We developed a microfluidics platform for efficient trapping and immobilization of enteroids for quantitative measurement of volume changes. Multiple enteroids are trapped in a “pinball machine-like” array of polydimethylsiloxane posts for measurement of volume changes in unlabeled enteroids by imaging of an extracellular, high-molecular weight fluorescent dye. Measurement accuracy was validated using slowly expanding air bubbles. The method was applied to measure swelling of mouse jejunal enteroids in response to an osmotic challenge and cholera toxin-induced chloride secretion. The microfluidics platform allows for parallel measurement of volume changes on multiple enteroids during continuous superfusion, without an immobilizing matrix, and for quantitative volume determination without chemical labeling or assumptions about enteroid shape changes during swelling.  相似文献   

17.
Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μBlood/μPBS) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (QPBSSS/QBloodL). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (ABlood (t) = Aα + Aβ exp [−(t − t0)/λBlood]) is selected based on the pressure difference (ΔP = PA − PB) at each junction (A, B) of both side channels. The characteristic time of blood (λBlood) is measured by analyzing the area (ABlood) filled with blood in the bridge channel by selecting an appropriate detection window in the microscopic images captured by a high-speed camera (frame rate = 200 Hz, total measurement time = 7 s). The elasticity of blood (GBlood) is identified using the relationship between the characteristic time and the viscosity of blood. For practical demonstrations, the proposed method is successfully applied to evaluate the variations in viscosity and elasticity of various blood samples: (a) various hematocrits form 20% to 50%, (b) thermal-induced treatment (50 °C for 30 min), (c) flow-induced shear stress (53 ± 0.5 mL/h for 120 min), and (d) normal rat versus spontaneously hypertensive rat. Based on these experimental demonstrations, the proposed method can be effectively used to monitor variations in viscosity and elasticity of bloods, even with the absence of fully integrated sensors, tedious labeling and calibrations.  相似文献   

18.
Red blood cells (RBCs) are important to dictate hemorheological properties of blood. The shear-thinning effect of blood is mainly attributed to the characteristics of the RBCs. Variations in hemorheological properties alter flow resistance and wall shear stress in blood vessels. Therefore, detailed understanding of the relationship between the hemorheological and hemodynamic properties is of great importance. In this study, blood viscosity and blood flow were simultaneously measured in the same microfluidic device by monitoring the flow-switching phenomenon. To investigate blood flows according to hemorheological variations, the flow rate of blood samples (RBCs suspended in autologous plasma, dextran-treated plasma, and in phosphate buffered saline solution) was precisely controlled with a syringe pump. Velocity profiles of blood flows were measured by using a micro-particle image velocimetry technique. The shape of velocity profiles was quantified by using a curve-fitting equation. It is found that the shape of the velocity profiles is highly correlated with blood viscosity. To demonstrate the relationship under ex vivo conditions, biophysical properties and velocity profiles were measured in an extracorporeal rat bypass loop. Experimental results show that increased blood viscosity seems to induce blunt velocity profile with high velocity component at the wall of the microchannel. Simultaneous measurement of blood viscosity and velocity profile would be useful for understanding the effects of hemorheological features on the hemodynamic characteristics in capillary blood vessels.  相似文献   

19.
Bacterial aggregation and patchiness play an important role in a variety of ecological processes such as competition, adaptation, epidemics, and succession. Here, we demonstrate that hydrodynamics of their environment can lead to their aggregation. This is specially important since microbial habitats are rarely at rest (e.g., ocean, blood stream, flow in porous media, and flow through membrane filtration processes). In order to study the dynamics of bacterial collection in a vortical flow, we utilize a microfluidic system to mimic some of the important microbial conditions at ecologically relevant spatiotemporal scales. We experimentally demonstrate the formation of “ring”-shaped bacterial collection patterns and subsequently the formation of biofilm streamers in a microfluidic system. Acoustic streaming of a microbubble is used to generate a vortical flow in a microchannel. Due to bacteria''s finite-size, the microorganisms are directed to closed streamlines and trapped in the vortical flow. The collection of bacteria in the vortices occurs in a matter of seconds, and unexpectedly, triggers the formation of biofilm streamers within minutes. Swimming bacteria have a competitive advantage to respond to their environmental conditions. In order to investigate the role of bacterial motility on the rate of collection, two strains of Escherichia coli bacteria with different motilities are used. We show that the bacterial collection in a vortical flow is strongly pronounced for high motile bacteria.  相似文献   

20.
In this study, we demonstrate a new perspective on in vitro assessment method for evaluating quantum dot (QD) toxicity by using microfluidics technology. A new biomimetic approach, based on the flow exposure condition, was applied in order to characterize the cytotoxic potential of QD. In addition, the outcomes obtained from the flow exposure condition were compared to those of the static exposure condition. An in vitro cell array system was established that used an integrated multicompartmented microfluidic device to develop a sensitive flow exposure condition. QDs modified with cetyltrimethyl ammonium bromide∕trioctylphosphine oxide were used for the cytotoxicity assessment. The results suggested noticeable differences in the number of detached and deformed cells and the viability percentages between two different exposure conditions. The intracellular production of reactive oxygen species and release of cadmium were found to be the possible causes of QD-induced cytotoxicity, irrespective of the types of exposure condition. In contrast to the static exposure, the flow exposure apparently avoided the gravitational settling of particles and probably assisted in the homogeneous distribution of nanoparticles in the culture medium during exposure time. Moreover, the flow exposure condition resembled in vivo physiological conditions very closely, and thus, the flow exposure condition can offer potential advantages for nanotoxicity research.  相似文献   

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