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1.
The normal coagulation process is initiated by disruption and exposure of the subendothelial components of blood vessels. Platelets adhere to subendothelium-bound von Willebrand factor via glycoprotein (GP) Ib complex. This initial interaction per se and the release of platelet agonists transduce signals that leads to the rise in intracellular Ca2+ which induces shape change, prostaglandin synthesis, release of granular contents and conformational changes in platelet Gp IIb-IIIa. Gp IIb-IIIa in activated platelets binds fibrinogen and other adhesive proteins and mediates platelet cohesion the primary haemostatic plug. Furthermore, the activated platelets due to aggregation, result in the formation of fibrin (secondary hemostasis). Normally the haemostatic process plays a delicate balance between keeping the blood in the fluid state to maintain flow and rapidly forming an occluding plug following vessel injury. Thrombosis occurs because of alteration in this delicate balance. Arterial thrombosis occurs in the setting of previous vessel wall injury mostly because of atherosclerosis, while venous thrombosis occurs in areas of stasis. The recent advances in understanding of the haemostatic process have led to a better understanding of the mechanism of action of many antithrombotic drugs and identification of new targets for drug development. The molecular target of the ticlopidine has been identified. Large numbers of IIb-IIIa inhibitors have been developed. The mechanism of action of heparin has been defined at the molecular level. As a result, a synthetic pentasaccharide, based on antithrombin-binding domain of heparin, has been developed and tested successfully in clinical trials. New generation direct thrombin inhibitors are being developed. Factor Xa has a critical position at the convergence of intrinsic and extrinsic pathway. The clinical tolerability and the efficacy of low molecular weight heparins has established that inhibition of further thrombin generation, by blocking factor Xa alone can be an effective way of preventing thrombus growth without inactivating thrombin. A large number of specific factor Xa inhibitors are under development. Some of these are in preliminary clinical trials and appear to be promising. Future clinical trials will determine whether these new drugs will provide better risk-benefit ratio in treatment of thrombotic disorders. Similarly role of thrombolytics has been clearly established in many diseases including coronary artery disease.  相似文献   

2.
Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-activated platelets adhered to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. To measure platelet adhesion and aggregation, the migration distance (MD) of blood through the microchannel was monitored. As the microstirrer speed increased, MD initially decreased exponentially but then increased beyond a critical rpm. For platelet-excluded blood samples, there were no changes in MD with increasing stirrer speed. These findings imply that the stirrer provided sufficiently high shear to activate platelets and that blood MD is a potentially valuable index for measuring the shear-dependence of platelet activation. Our microfluidic system is quick and simple, while providing a precise assay to measure the effects of shear on platelet aggregation and adhesion.  相似文献   

3.
In vitro assays of platelet function and coagulation are typically performed in the presence of an anticoagulant. The divalent cation chelator sodium citrate is among the most common because its effect on coagulation is reversible upon reintroduction of divalent cations. Adding divalent cations into citrated blood by batch mixing leads to platelet activation and initiation of coagulation after several minutes, thus limiting the time blood can be used before spontaneously clotting. In this work, we describe a herringbone microfluidic mixer to continuously introduce divalent cations into citrated blood. The mixing ratio, defined as the ratio of the volumetric flow rates of citrated blood and recalcification buffer, can be adjusted by changing the relative inlet pressures of these two solutions. This feature is useful in whole blood assays in order to account for differences in hematocrit, and thus viscosity. The recalcification process in the herringbone mixer does not activate platelets. The advantage of this continuous mixing approach is demonstrated in microfluidic vascular injury model in which platelets and fibrin accumulate on a collagen-tissue factor surface under flow. Continuous recalcification with the herringbone mixer allowed for flow assay times of up to 30 min, more than three times longer than the time achieved by batch recalcification. This continuous mixer allows for measurements of thrombus formation, remodeling, and fibrinolysis in vitro over time scales that are relevant to these physiological processes.  相似文献   

4.
Accurately mimicking the complexity of microvascular systems calls for a technology which can accommodate particularly small sample volumes while retaining a large degree of freedom in channel geometry and keeping the price considerably low to allow for high throughput experiments. Here, we demonstrate that the use of surface acoustic wave driven microfluidics systems successfully allows the study of the interrelation between melanoma cell adhesion, the matrix protein collagen type I, the blood clotting factor von Willebrand factor (vWF), and microfluidic channel geometry. The versatility of the tool presented enables us to examine cell adhesion under flow in straight and bifurcated microfluidic channels in the presence of different protein coatings. We show that the addition of vWF tremendously increases (up to tenfold) the adhesion of melanoma cells even under fairly low shear flow conditions. This effect is altered in the presence of bifurcated channels demonstrating the importance of an elaborate hydrodynamic analysis to differentiate between physical and biological effects. Therefore, computer simulations have been performed along with the experiments to reveal the entire flow profile in the channel. We conclude that a combination of theory and experiment will lead to a consistent explanation of cell adhesion, and will optimize the potential of microfluidic experiments to further unravel the relation between blood clotting factors, cell adhesion molecules, cancer cell spreading, and the hydrodynamic conditions in our microcirculatory system.  相似文献   

5.
In microcirculation, red blood cells (RBCs) flowing through bifurcations may deform considerably due to combination of different phenomena that happen at the micro-scale level, such as: attraction effect, high shear, and extensional stress, all of which may influence the rheological properties and flow behavior of blood. Thus, it is important to investigate in detail the behavior of blood flow occurring at both bifurcations and confluences. In the present paper, by using a micro-PTV system, we investigated the variations of velocity profiles of two working fluids flowing through diverging and converging bifurcations, human red blood cells suspended in dextran 40 with about 14% of hematocrit level (14 Hct) and pure water seeded with fluorescent trace particles. All the measurements were performed in the center plane of rectangular microchannels using a constant flow rate of about 3.0 × 10−12 m3/s. Moreover, the experimental data was compared with numerical results obtained for Newtonian incompressible fluid. The behavior of RBCs was asymmetric at the divergent and convergent side of the geometry, whereas the velocities of tracer particles suspended in pure water were symmetric and well described by numerical simulation. The formation of a red cell-depleted zone immediately downstream of the apex of the converging bifurcation was observed and its effect on velocity profiles of RBCs flow has been investigated. Conversely, a cell-depleted region was not formed around the apex of the diverging bifurcation and as a result the adhesion of RBCs to the wall surface was enhanced in this region.  相似文献   

6.
We present a microfluidic device capable of separating platelets from other blood cells in continuous flow using dielectrophoresis field-flow-fractionation. The use of hydrodynamic focusing in combination with the application of a dielectrophoretic force allows the separation of platelets from red blood cells due to their size difference. The theoretical cell trajectory has been calculated by numerical simulations of the electrical field and flow speed, and is in agreement with the experimental results. The proposed device uses the so-called "liquid electrodes" design and can be used with low applied voltages, as low as 10 V(pp). The obtained separation is very efficient, the device being able to achieve a very high purity of platelets of 98.8% with less than 2% cell loss. Its low-voltage operation makes it particularly suitable for point-of-care applications. It could further be used for the separation of other cell types based on their size difference, as well as in combination with other sorting techniques to separate multiple cell populations from each other.  相似文献   

7.
Extravasation of circulating cells is an essential process that governs tissue inflammation and the body''s response to pathogenic infection. To initiate anti-inflammatory and phagocytic functions within tissues, immune cells must cross the vascular endothelial barrier from the vessel lumen to the subluminal extracellular matrix. In this work, we present a microfluidic approach that enables the recreation of a three-dimensional, perfused endothelial vessel formed by human endothelial cells embedded within a collagen-rich matrix. Monocytes are introduced into the vessel perfusate, and we investigate the role of luminal flow and collagen concentration on extravasation. In vessels conditioned with the flow, increased monocyte adhesion to the vascular wall was observed, though fewer monocytes extravasated to the collagen hydrogel. Our results suggest that the lower rates of extravasation are due to the increased vessel integrity and reduced permeability of the endothelial monolayer. We further demonstrate that vascular permeability is a function of collagen hydrogel mass concentration, with increased collagen concentrations leading to elevated vascular permeability and increased extravasation. Collectively, our results demonstrate that extravasation of monocytes is highly regulated by the structural integrity of the endothelial monolayer. The microfluidic approach developed here allows for the dissection of the relative contributions of these cues to further understand the key governing processes that regulate circulating cell extravasation and inflammation.  相似文献   

8.
为提高造影剂的颗粒度,减少血池造影剂透过血管壁向组织间质渗出,影响血池造影剂的造影效果,采用液中干燥法( in-liquid drying method)制备了三碘苯酚乙基纤维素微球，研究了三碘苯酚与乙基纤维素的比例对微球成球性，粒径以及载药量的影响，发现两者的比例为1：2时成球性最好，所得微球为规整的球形，微球粒径最小，平均粒径D50为3.68um, 载药量为41.4%。  相似文献   

9.
This study suggests a new erythrocyte sedimentation rate (ESR) measurement method for the biophysical assessment of blood by using a microfluidic device. For an effective ESR measurement, a disposable syringe filled with blood is turned upside down and aligned at 180° with respect to gravitational direction. When the blood sample is delivered into the microfluidic device from the top position of the syringe, the hematocrit of blood flowing in the microfluidic channel decreases because the red blood cell-depleted region is increased from the top region of the syringe. The variation of hematocrit is evaluated by consecutively capturing images and conducting digital image processing technique for 10 min. The dynamic variation of ESR is quantitatively evaluated using two representative parameters, namely, time constant (λ) and ESR-area (AESR). To check the performance of the proposed method, blood samples with various ESR values are prepared by adding different concentrations of dextran solution. λ and AESR are quantitatively evaluated by using the proposed method and a conventional method, respectively. The proposed method can be used to measure ESR with superior reliability, compared with the conventional method. The proposed method can also be used to quantify ESR of blood collected from malaria-infected mouse under in vivo condition. To indirectly compare with the results obtained by the proposed method, the viscosity and velocity of the blood are measured using the microfluidic device. As a result, the biophysical properties, including ESR and viscosity of blood, are significantly influenced by the parasitemia level. These experimental demonstrations support the notion that the proposed method is capable of effectively monitoring the biophysical properties of blood.  相似文献   

10.
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   

11.
We demonstrate the method of non-inertial lift induced cell sorting (NILICS), a continuous, passive, and label-free cell sorting approach in a simple single layer microfluidic device at low Reynolds number flow conditions. In the experiments, we exploit the non-inertial lift effect to sort circulating MV3-melanoma cells from red blood cell suspensions at different hematocrits as high as 9%. We analyze the separation process and the influence of hematocrit and volume flow rates. We achieve sorting efficiencies for MV3-cells up to EMV3 = 100% at Hct = 9% and demonstrate cell viability by recultivation of the sorted cells.  相似文献   

12.
The behavior of a droplet train in a microfluidic network with hydrodynamic traps in which the hydrodynamic resistive properties of the network are varied is investigated. The flow resistance of the network and the individual droplets guide the movement of droplets in the network. In general, the flow behavior transitions from the droplets being immobilized in the hydrodynamic traps at low flow rates to breaking up and squeezing of the droplets at higher flow rates. A state diagram characterizing these dynamics is presented. A simple hydrodynamic circuit model that treats droplets as fluidic resistors is discussed, which predicts the experimentally observed flow rates for droplet trapping in the network. This study should enable the rational design of microfuidic devices for passive storage of nanoliter-scale drops.  相似文献   

13.
孙玉伟 《情报科学》2012,(5):740-745,768
以Web of Science数据库(1975-2011年)信息行为主题的1303条文献为数据源,借助CitespaceⅡ软件对相关被引文献数据和主题词等数据进行分析和处理,以知识图谱的方式,对信息行为研究的跨学科属性、核心刊物、高影响力著者及代表性文献、研究热点和前沿进行分析,从而直观地揭示信息行为领域的研究现状和发展趋势。  相似文献   

14.
Wei Hou H  Gan HY  Bhagat AA  Li LD  Lim CT  Han J 《Biomicrofluidics》2012,6(2):24115-2411513
Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.  相似文献   

15.
The non-Newtonian properties of blood are of great importance since they are closely related with incident cardiovascular diseases. A good understanding of the hemodynamics through the main vessels of the human circulatory system is thus fundamental in the detection and especially in the treatment of these diseases. Very often such studies take place in vitro for convenience and better flow control and these generally require blood analogue solutions that not only adequately mimic the viscoelastic properties of blood but also minimize undesirable optical distortions arising from vessel curvature that could interfere in flow visualizations or particle image velocimetry measurements. In this work, we present the viscoelastic moduli of whole human blood obtained by means of passive microrheology experiments. These results and existing shear and extensional rheological data for whole human blood in the literature enabled us to develop solutions with rheological behavior analogous to real whole blood and with a refractive index suited for PDMS (polydymethylsiloxane) micro- and milli-channels. In addition, these blood analogues can be modified in order to obtain a larger range of refractive indices from 1.38 to 1.43 to match the refractive index of several materials other than PDMS.  相似文献   

16.
In certain arteries the flow rate of blood can now be quantified by a non-invasive technique based on a newly developed ultrasound velocity profile meter. Clinical applications of this technique indicate that a reliable mathematical model of the circulatory system would facilitate the identification of pathologic patterns of flow rate and the corresponding possible causes. A relatively simple law for the viscoelastic behavior of arterial conduits is hypothesized and its influence on the phasis variations of pressure and flow examined with the aid of the method of characteristics. To test the feasibility of this model, its predictions of the attenuation and dispersion of small sinusoidal pressure waves are compared with data obtained in animal experiments. The results show good agreement and verify the significance of taper in reducing the attenuation of waves propagating towards the periphery and conversely increasing the damping of waves moving towards the heart. Beside this the natural pressure and flow pulses generated by the heart appear to be attenuated in a realistic manner: they no longer exhibit the somewhat exaggerated peaking predicted by the theoretical model when the viscoelasticity of the vessel wall is neglected.  相似文献   

17.
Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer''s disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.  相似文献   

18.
杨靖  夏阳 《大众科技》2012,(9):94-96
高血压病是全身系统性疾病,其主要危害是血管病变所引起的并发症。目前对高血压血管病变的研究很多,但早些时候人们往往更注重研究高血压和血管的一些形态学指标的相关性,如颈动脉斑块、内-中膜厚度(IMT)等,但临床实际工作中发现,单纯从颈动脉结构变化来评价高血压病有其局限性,近年对血管功能方面的研究逐渐受到人们的重视。本文通过汇总并整理国内外对高血压病和颈动脉内膜功能相关性的研究文献,以利于其他学者研究参考。  相似文献   

19.
A prerequisite for single cell study is the capture and isolation of individual cells. In microfluidic devices, cell capture is often achieved by means of trapping. While many microfluidic trapping techniques exist, hydrodynamic methods are particularly attractive due to their simplicity and scalability. However, current design guidelines for single cell hydrodynamic traps predominantly rely on flow resistance manipulation or qualitative streamline analysis without considering the target particle size. This lack of quantitative design criteria from first principles often leads to non-optimal probabilistic trapping. In this work, we describe an analytical design guideline for deterministic single cell hydrodynamic trapping through the optimization of streamline distributions under laminar flow with cell size as a key parameter. Using this guideline, we demonstrate an example design which can achieve 100% capture efficiency for a given particle size. Finite element modelling was used to determine the design parameters necessary for optimal trapping. The simulation results were subsequently confirmed with on-chip microbead and white blood cell trapping experiments.  相似文献   

20.
吴楚绶 《科技通报》1996,12(3):176-179
为探讨力平脂对血液流变学的影响，选择了４６例高脂血症及／或各类心脏病患者，服力平脂胶囊０．１，ＴｉＤ，连服二月为一疗程（治疗组），选择２３例高脂血症及／或各类心脏病患者，服金水宝胶囊０．９９，Ｔｉｄ，连服二月为一疗程（对照组），对比观察对不同性别病人的红细胞压积、血沉、全血粘度（从高切到低切）的影响，发现两组男性患者治疗后的红细胞压积和血沉的改变差异不显著，全血比粘度治疗组明显优于对照组，女性患者  相似文献   

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