Rapid determination of erythrocyte sedimentation rate (ESR) by an electrically driven blood droplet biosensor

In healthcare practice, the sedimentation rate of red blood cells (erythrocytes) is a widely used clinical parameter for screening of several ailments such as stroke, infectious diseases, and malignancy. In a traditional pathological setting, the total time taken for evaluating this parameter varies typically from 1 to 2 h. Furthermore, the volume of human blood to be drawn for each test, following a gold standard laboratory technique (alternatively known as the Westergren method), varies from 4 to 5 ml. Circumventing the above constraints, here we propose a rapid (∼1 min) and highly energy efficient method for the simultaneous determination of hematocrit and erythrocyte sedimentation rate (ESR) on a microfluidic chip, deploying electrically driven spreading of a tiny drop of blood sample (∼8 μl). Our unique approach estimates these parameters by correlating the same with the time taken by the droplet to spread over a given radius, reproducing the results from more elaborate laboratory settings to a satisfactory extent. Our novel methodology is equally applicable for determining higher ranges of ESR such as high concentration of bilirubin and samples corresponding to patients with anemia and patients with some severe inflammation. Furthermore, the minimal fabrication steps involved in the process, along with the rapidity and inexpensiveness of the test, render the suitability of the strategy in extreme point-of-care settings.     

Verification of automatic analysers Roller 20PN and iSED for measuring erythrocyte sedimentation rate

IntroductionAutomated erythrocyte sedimentation rate (ESR) analysers are based on different methodology than Westergren method. It is questionable whether ESR values obtained from those analysers are comparable with determined values with Westergren method. The aim was verification of the precision, method comparison and accuracy of automated ESR analysers: Roller 20PN (Alifax S.p.A., Polverara, Italy) and iSED (Alcor Scientific, Smithfield, USA).Materials and methodsBlood samples (N = 752 for Roller 20PN and N = 213 for iSED) were sampled into K₂EDTA (Kima, Italy) tubes for automated and 3.8% Na-citrate tubes (Kima, Italy) for Westergren method. The data was divided into three groups according to the ESR values obtained with the Westergren method: Group Low (L) (ESR ≤ 20 mm), Group Medium (M) (ESR 21-60 mm), and Group High (H) (ESR ≥ 61 mm). Method agreement was assessed by Bland-Altman analysis and Passing-Bablok regression.ResultsAnalyser iSED has shown better comparability with Westergren method (bias 0.0 (95%Cl -1.4 to 1.5) range than Roller 20 PN (bias = - 6.4 (95%Cl - 7.1 to -5.7) in the whole measuring. For Roller 20 PN, Passing-Bablok regression has shown constant and proportional difference for Groups L and M, and for iSED only for Group H. Roller 20 PN had lower sensitivity (0.51 (95%Cl: 0.45-0.57) than iSED (0.72 (95%Cl: 0.59-0.80) while they had comparable specificity (> 0.90) and accuracy (≥ 0.80) in comparison with the Westergren method.ConclusionBoth analysers are not comparable with the Westergren method and should not be used interchangeably.     

The effects of transport by pneumatic tube system on blood cell count,erythrocyte sedimentation and coagulation tests

Introduction:

Today, the pneumatic tube transport system (PTS) is used frequently because of its advantages related to timing and speed. However, the impact of various types of PTS on blood components is unknown. The aim of this study was to examine the influence of PTS on the quality of routine blood cell counts, erythrocyte sedimentation, and certain blood coagulation tests.

Materials and methods:

Paired blood samples were obtained from each of 45 human volunteers and evaluated by blood cell count, erythrocyte sedimentation, and several coagulation tests, including prothrombin time (PT) and activated partial thromboplastin time (aPTT). Blood samples were divided into 2 groups: Samples from group 1 were transported to the laboratory via the PTS, and samples from group 2 were transported to the laboratory manually. Both groups were evaluated immediately by the tests listed above.

Results:

The blood sample test results from groups 1 and 2 were evaluated and compared. No statistically significant differences were observed (P = 0.069–0.977).

Conclusion:

The PTS yielded no observable effects on blood cell counts, erythrocyte sedimentation, or PT and aPTT test results. We concluded that the PTS can be used to transport blood samples and yield reliable results for blood cell counts, erythrocyte sedimentation, and several coagulation tests.     

Simulation of malaria-infected red blood cells in microfluidic channels: Passage and blockage

Malaria-infected red blood cells (iRBCs) become less deformable with the progression of infection and tend to occlude microcapillaries. This process has been investigated in vitro using microfluidic channels. The objective of this paper is to provide a quantitative basis for interpreting the experimental observations of iRBC occlusion of microfluidic channels. Using a particle-based model for the iRBC, we simulate the traverse of iRBCs through a converging microfluidic channel and explore the progressive loss of cell deformability due to three factors: the stiffening of the membrane, the reduction of the cell''s surface-volume ratio, and the growing solid parasites inside the cell. When examined individually, each factor tends to hinder the passage of the iRBC and lengthen the transit time. Moreover, at sufficient magnitude, each may lead to obstruction of narrow microfluidic channels. We then integrate the three factors into a series of simulations that mimic the development of malaria infection through the ring, trophozoite, and schizont stages. These simulations successfully reproduce the experimental observation that with progression of infection, the iRBC transitions from passage to blockage in larger and larger channels. The numerical results suggest a scheme for quantifying iRBC rigidification through microfluidic measurements of the critical pressure required for passage.     

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis.     

Study of flow rate induced measurement error in flow-through nano-hole plasmonic sensor

Flow-through gold film perforated with periodically arrayed sub-wavelength nano-holes can cause extraordinary optical transmission (EOT), which has recently emerged as a label-free surface plasmon resonance sensor in biochemical detection by measuring the transmission spectral shift. This paper describes a systematic study of the effect of microfluidic field on the spectrum of EOT associated with the porous gold film. To detect biochemical molecules, the sub-micron-thick film is free-standing in a microfluidic field and thus subject to hydrodynamic deformation. The film deformation alone may cause spectral shift as measurement error, which is coupled with the spectral shift as real signal associated with the molecules. However, this microfluid-induced measurement error has long been overlooked in the field and needs to be identified in order to improve the measurement accuracy. Therefore, we have conducted simulation and analytic analysis to investigate how the microfluidic flow rate affects the EOT spectrum and verified the effect through experiment with a sandwiched device combining Au/Cr/Si₃N₄ nano-hole film and polydimethylsiloxane microchannels. We found significant spectral blue shift associated with even small flow rates, for example, 12.60 nm for 4.2 μl/min. This measurement error corresponds to 90 times the optical resolution of the current state-of-the-art commercially available spectrometer or 8400 times the limit of detection. This really severe measurement error suggests that we should pay attention to the microfluidic parameter setting for EOT-based flow-through nano-hole sensors and adopt right scheme to improve the measurement accuracy.     

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate cancer cells were mixed with mouse blood cells and the label-free isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.     

我国服务外包企业承接能力评估模型研究——基于北京的实证调查与分析

全球服务业转移与离岸外包为我国现代服务业发展带来重大契机,中国服务外包企业迫切需要提升离岸外包业务的承接能力,从而摆脱处于价值链底部的不利地位,并逐步成长为具有国际竞争力的解决方案提供商。结合已有研究文献,并针对我国特定国情及离岸外包实践,作者以资源/能力理论为分析基础,建立了中国服务外包企业承接能力模型及评估指标,并选择北京地区企业进行了实地调研与综合分析。实证结果初步验证了作者提出的研究模型、能力结构及评估指标等,同时结合实证分析探讨了目前我国服务外包企业的承接能力现状、面临问题及相应对策。     

Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

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 (μ_Blood/μ_PBS) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (Q_PBS^SS/Q_Blood^L). 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 (A_Blood (t) = A_α + A_β exp [−(t − t₀)/λ_Blood]) is selected based on the pressure difference (ΔP = P_A − P_B) at each junction (A, B) of both side channels. The characteristic time of blood (λ_Blood) is measured by analyzing the area (A_Blood) 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 (G_Blood) 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.     

The role of government in supporting measurement standards for high-technology industries

The role of voluntary standards in industrial growth is discussed by characterizing standards as a public good and identifying the consequent determinants of underinvestment by the private sector. Underinvestment results from the nature of both the standard itself and the underlying technology. Although this problem occurs in most types of standards, measurement-related standards are a particularly severe case. To primary reason is that the measurement technology which underlies the standard typically requires capital-intensive research facilities and specialized research equipment and labor. Once the technology is available, an additional problem frequently arises of reaching agreement among buyers and sellers on the content, form, and timing of the standard. Although common to most standards-setting processes, this latter problem is particularly severe in markets based on advanced technologies because of the typically intense levels of competition and the dynamics of the technological change process.The underinvestment phenomena in the area of measurement-related standards lead to a role for government. In many cases, the most efficient policy response is a centralized government laboratory. This proposition is exemplified by three cases in which support for measurement-related standards was provided by the U.S. National Bureau of Standards. The case studies demonstrate that both the content and the timing of government support are important, if this support is to be an effective element of an industrial growth policy. The content of standards is critical for increasing the options with respect to the direction of industrial innovation as well as increasing the rate of diffusion (which determines measured productivity growth). The timing issue is becoming increasingly important as international competition intensifies in most advanced technology markets. Standards should therefore be a conscious element of industrial growth policy and appropriate government support provide.     

Microfluidics platform for measurement of volume changes in immobilized intestinal enteroids

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.     

我国技术市场发展程度的测度

摘要：本文首先对技术市场的概念及其测度进行述评,然后考虑指标体系的完整性和现实性、测度指标的科学性和可操作性,从技术市场主体发展程度、技术市场运行的完善程度、技术市场法律政策环境的保障程度和技术市场的效益等四个角度出发,构建了我国技术市场发展程度的测度指标体系;并采用专家打分法,对1991-2006年我国技术市场发展程度进行定量测算。结果显示：我国技术市场发展的总体趋势是上升的;但与我国市场经济总体发展程度相比,技术市场的发展水平还很低;从技术市场发展的四个方面来看,还存在很大的不平衡性。     

The application of RFIDs in libraries: an assessment of technological, management and professional issues

This paper starts by outlining the technologies involved in RFIDs and reviews the issues raised by their general application. It then identifies their potential application areas within the library sector based on a generic process view of library activities. Finally it highlights the issues that are raised by their application in libraries and provides an assessment of which of these issues are likely to raise ethical concerns for library professionals. The purpose is to provide an overview of the technology within the context of the library process and to highlight issues which may raise ethical concerns for the profession. A second paper will focus specifically on these concerns within the context of the professional obligations of the librarian.     

Viscoelasticity of blood and viscoelastic blood analogues for use in polydymethylsiloxane in vitro models of the circulatory system

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.     

市级土地利用总体规划实施中心城区用地布局评估研究

为适应国家有关规划的编制和实施,全面掌握土地利用总体规划实施情况,提高土地利用总体规划实施管理科学化、规范化水平,开展土地利用总体规划实施中期评估工作迫不及待。在实际评估工作当中,市级土地利用总体规划实施中心城区用地布局评估是一个重点和难点,文章以崇左市为例,研究土地利用总体规划实施中心城区用地布局评估新思路,为同期类似评估提供切实可行的新模式。     

城市雨洪模拟与年径流总量控制目标评估——以北京市未来科技城为例

伴随城市化进程加快,硬化地表面积的增加,城市降雨径流过程已发生明显变化,导致洪涝问题突出。城市雨洪模拟是当前城市水文学研究热点和难点之一,也是城市洪涝防治、海绵城市建设评估的关键技术手段。本文选取北京市未来科技城为研究区,利用SWMM模型构建城市雨洪模型,模拟不同降雨条件下地表和管网径流过程;依据不同场次雨型设计年径流总量控制目标对应的降雨过程,并驱动已构建的雨洪模型,评估现状地块下年径流总量控制目标实现情况;据此,提出不同海绵措施的空间布局以实现年径流总量控制目标。结果表明：城市雨洪模型模拟精度较高,洪峰流量误差在8~26%之间,而峰现时间误差为-8%,-1%和0。现状地块条件未达到北京市年径流总量控制目标（80%）;采用在道路、建筑和绿地分别增设透水铺装、绿色屋顶和下沉式绿地,并分别按20%,40%和40%的方案比例分配时研究区90%的地块均可达到年径流总量控制目标,还增加1.79万m³可利用水量。本文既可为海绵城市年径流总量控制目标的评估提供参考借鉴,也可为城市海绵措施布局优化等提供决策依据。     

A method for the precise measurement of optical path-difference,especially in stressed glass

In connection with an investigation that involved the measurement of optical path-difference and thence birefringence it became necessary to have much higher accuracy than is ordinarily attained. After a careful study of the various methods available it appeared that the one which best meets the requirements of precision and simplicity is a method first elaborated by Friedel (1893), and based on an interesting property possessed by a fixed combination of (1) a polarizer, (2) the birefracting material, and (3) a quarter-wave plate, each placed in a definite orientation to the others. When plane parallel monochromatic light passes through the elements of this fixed combination in the order shown above, the emergent light is plane polarized and the azimuth is related in a simple manner to the path-difference of the specimen. Since this azimuth can be measured by means of an analyzer and graduated circle, the determination of path-difference thus reduces itself to the measurement of an angular displacement, which can be done easily and with high precision.The method was first made applicable to a petrographic microscope for the purpose of determining the path-difference at a given spot in small specimens. Later, there was constructed a separate polarimeter in which large specimens could be conveniently measured. This instrument has given all that was expected of it in facility and rapidity of taking readings, and for any path-difference has a sensitivity about one hundred times greater than that of the devices in common use.A resumé of the general relations for elliptically polarized light as applied to the present method is given, and the magnitude of the errors that may arise is discussed in detail.