Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing

In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.

The development of an inhomogeneous damage field in an elastic-plastic model

By making use of the evolution equation of the damage field as derived from the statistical mesoscopic damage theory, we have preliminarily examined the inhomogeneous damage field in an elastic-plastic model under constant-velocity tension. Three types of deformation and damage field evolution are presented. The influence of the plastic matrix is examined. It seems that matrix plasticity may defer the failure due to damage evolution. A criterion for damage localization is consistent with the numerical results.

Influence of Obstacle-Produced Turbulence on Development of Premixed Flames

An investigation into influence of obstructions on premixed flame propagation has been carried out in a semi-open tube. It is found that there exists flame acceleration and rising overpressure along the path of flame due to obstacles. According to the magnitude of flame speeds, the propagation of flame in the tube can be classified into three regimes: the quenching, the choking and the detonation regimes. In premixed flames near the flammability limits, the flame is observed first to accelerate and then to quench itself after propagating past a certain number of obstacles. In the choking regime, the maximum flame speeds are somewhat below the combustion product sound speeds, and insensitive to the blockage ratio. In the more sensitive mixtures, the transition to detonation (DDT) occurs when the equivalence ratio increases. The transition is not observed for the less sensitive mixtures. The dependence of overpressure on blockage ratio is not monotonous. Furthermore, a numerical study of flame acceleration and overpressure with the unsteady compressible flow model is performed, and the agreement between the simulation and measurements is good.

Development Of Biosensor Based On Imaging Ellipsometry

The concept of biosensor based on imaging ellipsometry was proposed ten years ago. Its principle and the methodology as well as some solutions to problems which have to be faced during the development are mentioned. Its properties of phase sensitive, high throughput and fast sampling, as well as label-free, sensitivity better than 1 ng/ml for Immunoglobulin G, and real-time analysis for protein interaction process, etc. provide a potential for applications in biomedicine field. The recent biosensing development with total internal reflection imaging ellipsometry is presented also. [GRAPHICS] An example of 48 protein arrays in matrix. (C) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formation, microstructure and development of the localized shear deformation in low-carbon steels

An investigation has been made into the effect of microstructural parameters on the propensity for forming shear localization produced during high speed torsional testing by split Hopkinson bar with different average rates of 610, 650 and 1500 s(-1) in low carbon steels. These steels received the quenched, quenched and tempered as well as normalized treatments that provide wide microstructural parameters and mechanical properties. The results indicate that the occurrence of the shear localization is susceptible to the strength of the steels. In other words, the tendency of the quenched steel to form a shear band is higher than that of the other two steels. It is also found that there is a critical strain at which the shear localization occurs in the steels. The critical strain value is strongly dependent on the strength of the steels. Before arriving at this point, the material undergoes a slow work-hardening. After this point, the material suffers work-softening, corresponding to a process during which the deformation is gradually localized and eventually becomes spatially correlated to form a macroscopic shear band. Examinations by SEM reveal that the shear localization within the band involves a series of sequential crystallographic and non-crystallographic events including the change in crystal orientation, misorientation, generation and even perhaps damage in microstructures such as the initiation, growth and coalescence of the microcracks. It is expected that the sharp drop in the load-carrying capacity is associated with the growth and coalescence of the microcracks rather than the occurrence of the shear localization, but the shear localization is seen to accelerate the growth and coalescence of the microcracks. The thin foil observations by TEM reveal that the density of dislocations in the band is extremely high and the tangled arrangement and cell structure of dislocations tends to align along the shear direction. The multiplication and interaction of dislocations seems to be responsible for work-hardening of the steels. The avalanche of the dislocation cells corresponds to the sharp drop in shear stress at which the deformed specimen is broken. Double shear bands and kink bands are also observed in the present study. The principal band develops first and its width is narrower than that of the secondary band.

Initial development of microdamage under impact loading

In this paper, the initial development of microdamage in material subjected to impulsive loading was investigated experimentally and analytically with controllable short-load duration. Based on a general solution to the statistical evolution of a one-dimensional system of ideal microcracks, a prerequisite to experimental investigation of nucleation of microcracks was derived. By counting the number of microcracks, the distribution of nucleation of microcracks was studied. The law of the nucleation rate of microcracks can be expressed as a separable function of stress and cracksize. It is roughly linear dependence on loading stress. The normalized number density of microcracks is in agreement with that of a second-phase particle.

Development of Mini Space Bioreactor System

微重力对空间细胞培养的影响规律一直是国际空间生物学的重点研究领域。而空间细胞培养技术和方法作为空间细胞生物学研究的基础，其概念性和原理性设计是正确区分重力对细胞的直接作用和间接作用的前提。另外，空间实验成本高昂，空间细胞培养装置的体积、重量、功耗是首要的制约因素。为保证充分物质交换，满足细胞代谢需求，同时尽可能降低由细胞供液形式产生的力学环境对细胞的影响，区分重力对细胞的直接作用和间接作用，我们研制了逆流片层式微型细胞培养装置。实验表明为使培养液流动对细胞生长影响最小，流动剪切应变率应小于1s-1。通过理论计算分析的逆流片层式微型细胞培养装培养室内流场及流动剪切范围表明，该装置可以满足要求。通过实验检测细胞培养时的氧耗、糖耗等，可以确定不同种类细胞的培养液流量范围。培养室内采用经表面改性的聚合物网架作为细胞载体，使得培养空间得到充分利用，并利于操作。从而为空间细胞培养研究提供了一种新的技术手段。

The Development of Biosensor with Imaging Ellipsometry

The concept of biosensor with imaging ellipsometry was proposed about ten years ago. It has become an automatic analysis technique for protein detection with merits of label-free, multi-protein analysis, and real-time analysis for protein interaction process, etc. Its principle, andrelated technique units, such as micro-array, micro-fluidic and bio-molecule interaction cell, sampling unit and calibration for quantitative detection as well as its applications in biomedicine field are presented here.

Development of a Cell Size Relaxed Scheme for the Direct Simulation Monte Carlo Method

The conventional direct simulation Monte Carlo (DSMC) method has a strong restriction on the cell size because simulated particles are selected randomly within the cell for collisions. Cells with size larger than the molecular mean free path are generally not allowed in correct DSMC simulations. However, the cell-size induced numerical error can be controlled if the gradients of flow properties are properly involved during collisions. In this study, a large cell DSMC scheme is proposed to relax the cell size restriction. The scheme is applied to simulate several test problems and promising results are obtained even when the cell size is greater than 10 mean free paths of gas molecules. However, it is still necessary, of course, that the cell size be small with respect to the flow field structures that must be resolved.

Development of an efficient particle approach for micro-scale gas flow simulations

The micro-scale gas flows are usually low-speed flows and exhibit rarefied gas effects. It is challenging to simulate these flows because traditional CFD method is unable to capture the rarefied gas effects and the direct simulation Monte Carlo (DSMC) method is very inefficient for low-speed flows. In this study we combine two techniques to improve the efficiency of the DSMC method. The information preservation technique is used to reduce the statistical noise and the cell-size relaxed technique is employed to increase the effective cell size. The new cell-size relaxed IP method is found capable of simulating micro-scale gas flows as shown by the 2D lid-driven cavity flows.

Development of arc root attachment in the nozzle of 1 kW N2 and H2-N2 arcjet thrusters

Arc root behavior affects the energy transfer and nozzle erosion in an arcjet thruster. To investigate the development of arc root attachment in 1 kW class N2 and H2-N2 arcjet thrusters from the time of ignition to the stably working condition, a kinetic series of end-on view images of the nozzle obtained by a high-speed video camera was analyzed. The addition of hydrogen leads to higher arc voltage levels and the determining factor for the mode of arc root attachment was found to be the nozzle temperature. At lower nozzle temperatures, constricted type attachment with unstable motions of the arc root was observed, while a fully diffused and stable arc root was observed at elevated nozzle temperatures.

Development of high-power OPCPA laser at 1064 and 780 nm

A compact 10-TW/100-fs level ultrashort-pulse and ultra-intense laser system at 1064 nm based on optical parametric chirped pulse amplification (OPCPA) scheme is described, at which the pump and seed for the optical parametric amplification (OPA) process is optically synchronized. We investigated the output stability and the conversion efficiency of the system. Moreover, a design toward higher peak power output is given and an optically synchronized amplifier based on the concept of OPCPA at 800 nm is preliminarily explored.