Analysis of the Inhibitory Effect of Tirofiban on Shear-Induced Platelet Aggregation by Microfluidic Technique / 医用生物力学

Objective To observe the inhibitory effect of Tirofiban on different shear-induced platelet aggregation, and to provide medication suggestions for the treatment of thrombosis in different hemodynamic environment. Methods Polydimethylsiloxane ( PDMS)-glass microchannel chips were fabricated by soft lithography. The whole blood of healthy volunteers anticoagulated with sodium citrate was collected and incubated with different concentrations of Tirofiban in vitro. The blood flowed through the straight microchannel or channel with 80% narrow for 150 seconds at the speed of 11 μL/ min and 52 μL/ min, respectively. The wall shear stress rates in straight channel at 11 μL/ min and 52 μL/ min were 300 s-1 and 1 500 s-1, respectively. The maximum wall shear rates in the channel with 80% occlusion at 11 μL/ min and 52 μL/ min were 1 600 s-1 and 7 500 s-1, respectively. The adhesion and aggregation images of fluorescent labeled platelets on glass surface were photographed with the microscope, and the fluorescent images were analyzed with Image J. The platelet surface coverage ratio was used as a quantitative index of platelet aggregation behavior, and the IC50 of Tirofiban for platelet inhibition was calculated under different shear rates. Flow cytometry was used to detect the platelet activation index (CD62P, PAC-1) in the whole blood at 52 μL/ min in channel with 80% occlusion. Results Tirofiban inhibited platelet aggregation in a dose-dependent manner, and the inhibitory effect was related to the shear rate. Under the shear rates of 11 μL/ min and 52 μL/ min, the aggregation was almost completely inhibited when the concentration in straight channel reached 100 nmol / L. When the concentration in channels with 80% occlusion reached 1 μmol / L, the aggregation was almost completely inhibited. IC50 values at 11 μL/ min and 52 μL/ min in straight channel were 2. 3 nmol / L and 0. 5 nmol / L, respectively. IC50 values at 11 μL/ min and 52 μL/ min in channels with 80% occlusion were 20. 73 nmol / L and 4. 5 nmol / L. Pathologically high shearforce induced an increase in platelet activation, which could be inhibited by Tirofiban. Conclusions Tirofiban can effectively inhibit shear-induced platelet aggregation, and different concentrations of Tirofiban should be given according to the thrombus formed in different shear force environment in clinic practice

Application of Microfluidic Technology for Preparation of Nanoparticle Drug Carriers / 中国药学杂志

Microfluidic technology is a scientific technology that precisely controls and manipulates fluids in micro-nano-scale space, and has become one of the research hotspots in the field of nanomedicine. It has the ability to scale the basic functions of biological and chemical laboratories, including sample preparation, reaction, separation and detection, to a few square centimeters of chip. Compared with traditional approaches, microfluidic technology is equipped with many advantages in the development of nanomedicine carriers, such as controlling quality precisely, high reproducibility, fast and effective. Herein, this paper provides the brief introduction about the microfluidic technology and its application in the preparation of nanoparticulate drug carriers, which including polymer nanoparticles, lipid nanoparticles and hybrid nanoparticles. This review will provide ideas and references in utilization of microfluidic technology accurately and reasonably and also bring some prospects for its future development and challenges.

Research status of dynamic three-dimensional tissue culture driving methods / 中国组织工程研究

BACKGROUND: In vitro models are widely used in toxicology, pathology, and pharmaceutical research due to their short experimental cycles, low cost, and small species differences compared with animal models. Dynamic three-dimensional tissue culture mode is an important trend in the development of in vitro models. Dynamic three-dimensional culture in vitro models can be achieved by means of driving fluids in microfluidic systems. OBJECTIVE: To describe the microfluidic driving methods in the field of microfluidics, their respective advantages and disadvantages, and the application of different driving methods to different tissue culture requirements. METHODS: A computed-based retrieval of CNKI and Web of Science databases was performed for the articles concerning dynamic three-dimensional tissue culture and microfluidic driving methods to achieve dynamic culture of cells or tissues. The search terms were “microfluidic; micropump; organ-on-chip; three-dimensional tissue culture” in English and Chinese, respectively. RESULTS AND CONCLUSION: The microfluidic driving methods include passive driving and active driving. Whereas passive driving includes surface tension pump, osmotic pump and gravity pump. Active driving includes syringe pump and peristaltic pump. Each driving method has its advantages and disadvantages. To achieve accurate control of the medium flow rate in a dynamic three-dimensional tissue culture system, the best choice is to use syringe pumps or valve-type peristaltic pumps. To achieve closed-loop flow of culture medium in a dynamic three-dimensional tissue culture system, the best choice is to use gravity pumps or peristaltic pumps. To fulfill the need for a sterile environment in the experimental process in a dynamic three-dimensional tissue culture system, the best choices are surface tension pumps, gravity pumps, and pneumatic peristaltic pumps. To achieve high-throughput culture in dynamic three-dimensional tissue culture systems, the best choices are surface tension pumps, gravity pumps and pneumatic peristaltic pumps.

The Research Progress of Microfluidic Organ-on-Chips / 医用生物力学

Microfluidic technology refers to the technique of precise fluid control by manipulating submillimeter-scale fluids. In recent years, the use of microfluidic technology has realized the construction of organ-on-chips. The organ-on-chip refers to a micro-model with physiological functions, and cultivating living cells in a continuously perfused micro-chamber to simulate the physiological functions of tissues and organs. As the physiological function of the organ-on-chip has many advantages such as definite function, controllable microenvironment, rich measurement information, low chemical consumption, low cost, promising automation and high throughput, it has a huge application prospect in the field of drug development to solve the bottleneck problems in cellular and animal experiments, which has caused a great concern in the academic community. Although the organ-on-chip is still a very young research field, some microfluidic organ-on-chips have been developed and their potential applications are explored, including drug target optimization, drug screening and toxicity tests, and biomarker identification. In this review, the progress made in microfluidic organ microchips and their potential significance in clinical research were analyzed.

Application and prospect of microfluidic chip in central nervous system diseases / 生物工程学报

In recent years, many human central nervous systems (CNS) of microfluidic platforms and related disease models in vitro have been built with the continuous development of the microfluidic technology and biological microelectronics mechanical systems technology. Microplatforms have emerged to provide a better approximation of the in vivo scenario with better control of the structure, microenvironment and stimuli. This review summarized the basic technology of microfluidic chips in CNS and the application in CNS diseases. In addition, the research of microfluidic chip in CNS diseases has been also prospected. We also highlight challenges that can be addressed with interdisciplinary efforts to achieve more biomimicry.