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2010 IEEE International Conference on Nano/Molecular Medicine and Engineering最新文献

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High-throughput screening of xanthine oxidase inhibitory properties of drug analogs using photodiode array microchip 利用光电二极管阵列芯片高通量筛选药物类似物黄嘌呤氧化酶抑制特性
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749839
Jae Hyung Lee, Jae Ah Kim, J. Song
We have developed a high-throughput chip-based assay that uses a photodiode array (PDA) microchip system to explore the inhibitory effects of drug analogs on Xanthine oxidase (XO). Inhibitory effects of dithranol (anthracene derivative), aminoglutethimide (anti-steroid), cyclosporine A (immunosuppressant) and naringenin (flavonoid) on XO were elucidated using the chip-based assay in the presence or absence of a free radical scavenging enzyme (SOD, superoxide dismutase). Drug analogs were assessed for their ability to inhibit XO, which loads to a reduction in the conversion of nitroblue tetrazolium (NBT) to NBT diformazan. The reduction of NBT to NBT formazan in the presence of XO and drug analog can be seen. The PDA microchip system employed in this study consists of an array of red light-emitting diodes (LEDs) focused precisely onto the photodetectors of the PDA chip. The ability of drugs to inhibit XO was assessed based on NBT reduction. Free radicals produced due to the oxidation of xanthine by XO resulted in the reduction of NBT to insoluble NBT formazan. We report a new high-throughput chip-based xanthine assay to explore the XO inhibitory properties of drug analogs, along with their modes of action. The work presented here has important implications with regard to rapid and automated drug discovery screening processes in the pharmaceutical industry.
我们开发了一种基于芯片的高通量检测方法,该方法使用光电二极管阵列(PDA)微芯片系统来探索药物类似物对黄嘌呤氧化酶(XO)的抑制作用。利用芯片法研究了在自由基清除酶(SOD,超氧化物歧化酶)存在或不存在的情况下,二thranol(蒽衍生物)、氨基酰硫胺(抗类固醇)、环孢素A(免疫抑制剂)和柚皮素(类黄酮)对XO的抑制作用。药物类似物被评估为其抑制XO的能力,其负荷减少硝基蓝四氮唑(NBT)转化为NBT双双胍。在XO和药物类似物存在的情况下,可以看到NBT还原为NBT formazan。本研究采用的PDA微芯片系统由一组红色发光二极管(led)组成,它们精确地聚焦在PDA芯片的光电探测器上。根据NBT的减少来评估药物抑制XO的能力。由XO氧化黄嘌呤产生的自由基导致NBT还原为不溶性NBT甲酸。我们报告了一种新的高通量基于芯片的黄嘌呤检测,以探索药物类似物的XO抑制特性,以及它们的作用模式。这里提出的工作具有重要的意义,关于快速和自动化的药物发现筛选过程在制药工业。
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引用次数: 0
Characterizing the micromechanical properties of myeloblasts from cancer patients with optical tweezers 用光学镊子表征癌症患者骨髓母细胞的微力学特性
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749800
Youhua Tan, A. Y. Leung, Kaiqun Wang, T. Fung, Dong Sun
Cell mechanics, in particular mechanical properties, has been suggested as a new biomarker indicative of cell state and phenotype. Acute myeloid leukemia (AML) is characterized by the abnormal increase of myeloblasts in blood and bone marrow. While AML has been extensively studied from the perspectives of biochemical and genetic aspects, little is known about its cellular biophysical properties. In this study, optical tweezer technology was used to examine the micromechanical properties of myeloblasts from bone marrow of AML patients at single cell level. The myeloblasts were separately analyzed according to their expression of CD34+, a marker of primitive hematopoietic cells. To extract the intrinsic properties from the relationship between the stretching force and the induced deformation, a theoretical approach was developed to model the mechanical responses of cells and further characterize their mechanical properties. The preliminary results show that the area compressibility modulus of CD34+ myeloblasts was significantly less than that of CD34− cells, which indicate that micromechanical properties are unique features of myeloblasts and provide us with an insight into the cell mechanics of primitive AML cells.
细胞力学,特别是力学性能,已被认为是一种新的指示细胞状态和表型的生物标志物。急性髓性白血病(Acute myeloid leukemia, AML)以血液和骨髓中成髓细胞异常增加为特征。AML已经从生物化学和遗传学的角度进行了广泛的研究,但对其细胞生物物理特性知之甚少。本研究采用光镊技术在单细胞水平上检测AML患者骨髓成髓细胞的微力学特性。根据原始造血细胞标志物CD34+的表达分别分析成髓细胞。为了从拉伸力和诱导变形之间的关系中提取固有特性,建立了一种理论方法来模拟单元的力学响应,并进一步表征其力学特性。初步结果表明,CD34+成髓细胞的面积压缩模量明显小于CD34−细胞,这表明微力学特性是成髓细胞的独特特征,并为我们了解原始AML细胞的细胞力学提供了新的思路。
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引用次数: 0
Multicolor single cell imaging cytometry: A new drug screening platform for monitoring intracellular caspases as potential therapeutic targets 多色单细胞成像细胞术:监测细胞内半胱天冬酶作为潜在治疗靶点的新药物筛选平台
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749843
Min Jung Kim, J. Song
SH-03 is a rotenoid-containing deguelin analog. In this study, the anticancer activity and the dynamics of the caspase-mediated apoptotic cascade induced by SH-03 was simultaneously monitored in myeloid leukemia cells using multicolor single cell imaging cytometry as a new drug-screening platform. The constructed single cell imaging cytometer consists of an Ar-ion laser beam, a microscope objective lens, an acousto-optic tunable filter (AOTF), a charged coupled device (CCD) camera, and commercially available image processing software (MetaMorph). PI3K/AKT activation and phosphorylation assays were carried out to clarify the mechanistic details of the SH-03-induced intrinsic apoptotic pathway in HL-60 cells. SH-03 inhibited the PI3K/AKT signal transduction pathway in HL-60 cells. Given the fact that PI3K/AKT signaling pathway plays an important role in the proliferation, the inhibition of phosphorylation of PI3K/AKT by SH-03 can be assumed to trigger apoptosis. SH-03-induced caspase cascade was also investigated. Our results suggest that SH-03 induces apoptosis in HL-60 cells via a caspase-9-mediated intrinsic apoptotic pathway. Cellular imaging cytometry revealed that SH-03 triggers apoptosis via a caspase-mediated intrinsic pathway.
SH-03是一种含鱼素的脱胶类似物。本研究采用多色单细胞成像细胞术作为新的药物筛选平台,同时监测SH-03诱导的caspase介导的凋亡级联的抗癌活性和动力学。所构建的单细胞成像细胞仪由ar离子激光束、显微镜物镜、声光可调滤光片(AOTF)、电荷耦合器件(CCD)相机和市售图像处理软件(MetaMorph)组成。通过PI3K/AKT活化和磷酸化实验,阐明sh -03诱导HL-60细胞内在凋亡通路的机制细节。SH-03抑制HL-60细胞中PI3K/AKT信号转导通路。考虑到PI3K/AKT信号通路在细胞增殖中起重要作用,SH-03抑制PI3K/AKT磷酸化可以被认为是触发细胞凋亡的机制。sh -03诱导的caspase级联也进行了研究。我们的研究结果表明SH-03通过caspase-9介导的内在凋亡途径诱导HL-60细胞凋亡。细胞成像细胞检测显示SH-03通过caspase介导的内在通路触发细胞凋亡。
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引用次数: 0
Depth of Anaesthesia: Measuring or guessing? 麻醉深度:测量还是猜测?
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749809
Richard Landers, P. Wen, S. Pather
This paper is a comprehensive literature review on the Depth of Anaesthesia (DoA) monitoring problem. We first investigate the current clinical practice, then briefly introduce the DoA monitors, finally we analyse and discuss the reliability and accuracy of current DoA assessment practice. In this study we find that most of the responses suppressed by anaestheic agents are not of the central nervous system (CNS) but are responses from the peripheral nervous systems (PNS). The responses generated for drug combinations across the therapeutic ranges show considerable variations in drug concentrations that constitute adequate anaesthesia for a particular stimulus. We propose to capture the decision process of anaesthetist using neural networks as neural networks are good at finding patterns in non linear, non stationary signals.
本文对麻醉深度(DoA)监测问题进行了全面的文献综述。本文首先调查了目前临床实践,然后简要介绍了DoA监测仪,最后对目前DoA评估实践的可靠性和准确性进行了分析和讨论。在本研究中,我们发现麻醉剂抑制的大多数反应不是中枢神经系统的,而是来自周围神经系统的反应。在不同的治疗范围内,药物组合所产生的反应显示出药物浓度的相当大的变化,这些变化构成了对特定刺激的充分麻醉。我们建议使用神经网络来捕捉麻醉师的决策过程,因为神经网络擅长在非线性、非平稳信号中发现模式。
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引用次数: 5
Luminescent rhenium(I) polypyridine fluorous complexes as new biological probes 发光多吡啶芴配合物作为新型生物探针
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749806
Man-Wai Louie, Tommy Tsz-Him Fong, K. K. Lo
We present the synthesis and characterization of luminescent biological probes derived from rhenium(I) polypyridine fluorous complexes [Re(Me2 bpy)(CO)3(py-Rf-R)](PF6) (R = NH2 (1), NCS (2), TU-C2H5 (3)). The photophysical properties of these complexes have been studied. The fluorous complex 2 has been used to label glutathione (GSH) and bovine serum albumin (BSA). The photophysical properties of the resultant bioconjugates have been studied. The isolation of the luminescent fluorous rhenium-GSH conjugate from a mixture of twenty amino acids has been demonstrated using fluorous solidphase extraction (FSPE). Additionally, the cytotoxicity of complexes 1 and 3 toward HeLa cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular uptake properties of complex 3 have been investigated by laser-scanning confocal microscopy.
本文合成并表征了铼(I)多吡啶芴配合物[Re(Me2 bpy)(CO)3(py-Rf-R)](PF6) (R = NH2 (1), NCS (2), TU-C2H5(3))的发光生物探针。研究了这些配合物的光物理性质。含氟络合物2已被用于标记谷胱甘肽(GSH)和牛血清白蛋白(BSA)。研究了合成的生物偶联物的光物理性质。用氟固相萃取法(FSPE)从20种氨基酸的混合物中分离荧光铼-谷胱甘肽偶联物。此外,复合物1和3对HeLa细胞的细胞毒性已通过3-(4,5-二甲基-2-噻唑)-2,5-二苯基溴化四唑(MTT)试验进行了检测。用激光扫描共聚焦显微镜研究了配合物3的细胞摄取特性。
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引用次数: 2
Laminar stream-based microfluidic chip with high efficiency for human sperm motility sorting 基于层流的高效人类精子活力分选微流控芯片
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749808
Hui-Ting Fu, D. Yao, Hung-Ju Huang, Chin-Jung Li, Hong-Yuan Huang
A novel laminar stream-based microfluidic chip that can serve as the high efficient technique for human sperm motility sorting through the use of flow cytometry was proposed in this study. Recently, the selection of good sperms in semen plays an important role in the reproductive medicine. However, the traditional sorting methods are normally expensive and time consuming. This modified microfluidic chip provided a new selection, which had advantages of low-cost, high-precision, and disposable. This paper was proposed and tested the interactions between laminar flow and sperm activity. Due to the laminar flow in a different direction, the semen samples were loaded into a curve laminar flow through straight-curve stream and it would offer a y component force for dead sperms to be selected. In addition, the semen samples were loaded into a straight laminar flow and the results showed that most of the proportion of motile sperms with lateral activity can swim across the two fluid boundaries to be sorted. From the results of flow cytometry analysis, the injected semen sample from a straight inlet with the counted percentage of living sperms was 92.68% by the observation in outlet reservoir. Therefore, the microfluidic chip with remarkable sperm motility sorting has the potential for reproductive medicine.
本研究提出了一种新型的层流微流控芯片,该芯片可作为流式细胞术对人类精子活力进行高效分选的技术。近年来,精液中优质精子的选择在生殖医学中发挥着重要作用。然而,传统的分拣方法通常既昂贵又耗时。这种改进的微流控芯片具有成本低、精度高、可一次性使用等优点,提供了一种新的选择。本文提出并验证了层流与精子活性之间的相互作用。由于层流方向不同,通过直曲线流将精液样本装入曲线层流,为选择死精子提供y分力。此外,将精液样本装入一个直层流中,结果表明,大部分具有横向活动的运动精子比例可以游过两个流体边界进行分类。流式细胞术分析结果显示,经出口库观察,直进口注射的精液标本活精子计数率为92.68%。因此,精子运动分选效果显著的微流控芯片在生殖医学方面具有潜力。
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引用次数: 2
Observation of angiotensin II-induced changes in tubular epithelial cells utilizing AFM: Angiotensin II-induced changes in tubular cells 利用AFM观察血管紧张素ii诱导的小管上皮细胞的变化:血管紧张素ii诱导的小管细胞的变化
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749834
Gi-Ja Lee, Ji-Hye Kim, Hun-Kuk Park, K. Jeong, Hyun-jung Kang, T. Lee
Atomic force microscopy (AFM) has become an important device to visualize various cells and biological materials for non-invasive imaging. The major advantage of AFM compared to the conventional optical and electron microscopes is its convenience. Sample preparation for AFM does not need special coating or vacuum as a procedure. AFM can detect samples even under the aqueous condition. Although the AFM is originally used to obtain surface topography of sample, it can measure precisely the interactions between its probe tip and the sample surface from force-distance measurements. Epithelial-to-mesenchymal transformation of tubular cells into myofibroblastic phenotype is an important mediator of renal injury in chronic nephropathy. It is generally known that angiotensin II (Ang II) plays a direct profibrotic role in the kidney, but the mechanism is unclear. In this study, we observed structural and mechanical changes in tubular epithelial cell after Ang II treatment using AFM.
原子力显微镜(Atomic force microscopy, AFM)已成为对各种细胞和生物材料进行无创成像的重要手段。与传统的光学显微镜和电子显微镜相比,AFM的主要优点是方便。AFM的样品制备不需要特殊的涂层或真空作为一个过程。AFM可以在水溶液条件下检测样品。虽然AFM最初是用于获取样品表面形貌,但它可以通过力距测量来精确测量其探针尖端与样品表面之间的相互作用。小管细胞上皮向间质转化为肌成纤维细胞表型是慢性肾病肾损伤的重要中介。众所周知,血管紧张素II (angii)在肾脏中起直接促纤维化作用,但其机制尚不清楚。在这项研究中,我们用AFM观察了Ang II处理后小管上皮细胞的结构和力学变化。
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引用次数: 1
Silver as antibacterial agent: Metal nanoparticles to nanometallopharmaceuticals: (Silver based antibacterial nanometallopharmaceuticals) 银作为抗菌剂:金属纳米颗粒到纳米金属药物:(银基抗菌纳米金属药物)
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749812
J. Song
Because of increase in bacterial resistance to common antibiotics, antibacterial nanometallopharmaceuticals have been drawing increasing interest. Recent literature reports encouraging results about the bactericidal activity of silver nanoparticles of either a simple or composite nature. We, for the first time, demonstrated that silver nanoparticles (AgNP) undergo a shape dependant interaction with bacteria. We also developed highly antibacterial porous carbon matrices supporting nano-silver by simple and cost effective way. The antibacterial mechanism of the developed composite under prolonged incubation conditions was investigated against Escherichia coli. The application of silver in the treatment of burn wounds is of special interest, and has prompted an upsurge in research on the synthesis of antibacterial silver(I) complexes. However, the antibacterial performance of silver ion is correlated to its valence form and it has been found that the high valence silver ion exhibits stronger and more effective antibacterial action than low valence ion. Recently, we reported the synthesis of highly monodispersed nanoparticles of a trivalent silver polydiguanide complex in reverse microemulsion, demonstrating its flexibility for complexation reaction and the fabrication of essentially monodispersed nanoparticles of higher valent metal complex. The synthesized material showed strong antibacterial activity against the tested Gram (+)/(−) and methicillin-resistant Stahylococcus aureus strains. Interaction of polydiguanide ligands with silver at different oxidation states was also investigated. The in vitro pharmacodynamics of these complexes revealed that silver polydiguanide complexes provide faster killing kinetics compared to silver nitrate or polydiguanide ligands.
由于细菌对普通抗生素的耐药性增加,抗菌纳米金属药物已引起越来越多的兴趣。最近的文献报道了简单或复合性质的银纳米颗粒杀菌活性的令人鼓舞的结果。我们首次证明了银纳米颗粒(AgNP)与细菌发生形状依赖的相互作用。我们还通过简单、经济的方法开发了高抗菌的纳米银多孔碳基质。研究了复合材料在长时间培养条件下对大肠杆菌的抑菌机理。银在烧伤创面治疗中的应用引起了人们的特别关注,并促进了抗菌银(I)配合物的合成研究。然而,银离子的抗菌性能与其价态有关,研究发现,高价银离子比低价银离子表现出更强、更有效的抗菌作用。最近,我们报道了在反相微乳液中合成高度单分散的三价银聚双胍配合物纳米颗粒,证明了其配合反应的灵活性和高价金属配合物的基本单分散纳米颗粒的制备。合成的材料对革兰氏(+)/(−)和耐甲氧西林金黄色葡萄球菌具有较强的抗菌活性。研究了不同氧化态的聚二胍配体与银的相互作用。这些配合物的体外药效学表明,与硝酸银或聚二胍配体相比,聚二胍银配合物具有更快的杀伤动力学。
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引用次数: 2
Measurement of interchain binding affinity of nucleic acid duplex using atomic force microscopy 用原子力显微镜测定核酸双链间结合亲和力
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.5749818
Tianbiao Zhang, Changlin Zhang, Zai-li Dong, Y. Guan
Atomic force microscope (AFM), as its high resolution and precision, was employed to directly probe intermolecular hydrogen bonds between self-assembled purines and pyrimidines. In the experiment, we directly stretch the DNA double strands that are attached to the planar modified glass surfaces and AFM tip respectively. However, distinguishing from previous literatures we focus on the NaCl density and holding time influencing the rupture force of DNA double helix and monitor the probing process under three different densities of sodium chloride (NaCl): 0mM, 50mM, and 100mM. The result shows complementary DNA strands are easier to bond as the density of NaCl increases. At the same time we test the probing process considering three holding durations: 0S, 10S, and 40S. We find the complementary DNA strands bond forming well under the situation of 40S. Then we separately do experiments with three lengths of strands: 10bp, 14bp, 20bp. Using cluster analysis method we find that the clustering center intervals are about 0.21nN, 0.29nN, and 0.39nN, and we can calculate the hydrogen bond of the single G-C is about 20pN.
原子力显微镜(Atomic force microscope, AFM)以其高分辨率和高精度,直接探测自组装嘌呤和嘧啶之间的分子间氢键。在实验中,我们直接拉伸了分别附着在平面修饰玻璃表面和AFM尖端的DNA双链。然而,与以往文献不同的是,我们重点研究了NaCl浓度和保持时间对DNA双螺旋破裂力的影响,并监测了0mM、50mM和100mM三种不同NaCl浓度下DNA双螺旋破裂力的探测过程。结果表明,随着NaCl浓度的增加,互补DNA链更容易结合。同时,我们测试了探测过程,考虑了三个保持持续时间:0S、10S和40S。我们发现,在40S的情况下,互补DNA链形成良好。然后分别用10bp、14bp、20bp三种长度的链进行实验。利用聚类分析方法,我们发现聚类中心间隔约为0.21nN, 0.29nN和0.39nN,我们可以计算出单个G-C的氢键约为20pN。
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引用次数: 1
Low-cost portable respiration monitor based on micro hot-film flow sensor 基于微热膜流量传感器的低成本便携式呼吸监测仪
Pub Date : 2010-12-01 DOI: 10.1109/NANOMED.2010.6107964
Zhe Cao, R. Zhu, R. Que
We present a portable, low cost, sensitive respiration monitoring system based on a micro hot-film flow sensor. The sensitive component of the flow sensor is a patterned thin-film with nanometer thickness fabricated on a flexible polyimide substrate by incorporating printed circuit technique with micromachining technique. The respiratory flow measurement is under a constanttemperature mode, and the measured signals are sampled and processed using SCM and transferred to PC through USB data communication. Virtual instruments technology is applied to achieve the real-time display of respiratory flow waveform and related respiratory parameters on PC. Finally, the system is experimentally calibrated, static and dynamic characteristics of the system are acquired and the effectiveness of the system is verified.
我们提出了一种便携式、低成本、灵敏的呼吸监测系统,该系统基于微热膜流量传感器。该流量传感器的敏感元件是结合印刷电路技术和微加工技术在柔性聚酰亚胺基板上制作的纳米厚度的图像化薄膜。呼吸流量测量在恒温模式下,通过单片机对测量信号进行采样和处理,并通过USB数据通信传输到PC机。应用虚拟仪器技术实现了呼吸流量波形及相关呼吸参数在PC机上的实时显示。最后,对系统进行了实验标定,获得了系统的静态和动态特性,验证了系统的有效性。
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引用次数: 3
期刊
2010 IEEE International Conference on Nano/Molecular Medicine and Engineering
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