Flow Characteristics of Non-Polar Organic Liquids with Small Molecules in a Microchannel

用去离子水及有机液体在内径约为25μm的石英圆管内进行了流量特性实验.液体分子量范围为18～160,动力黏性系数的范围为0.5～1 mPa.s.实验雷诺数范围为Re<8.所用有机液体为:四氯化碳、乙基苯及环己烷都是非极性液体,其分子结构尺度小于1 nm.实验结果表明,在定常层流条件下,圆管内的液体流量与两端压力差成正比,其压力-流量关系仍符合经典的Hagen-Poiseuille流动.这说明非极性小分子有机液体在本实验所用微米尺度管道中其流动规律仍符合连续介质假设.鉴于微尺度流动实验的特殊性,文中还介绍了微流动实验装置,分析了微尺度流动测量误差来源及提高测量精度的措施.

Real-Time Study of Genomic DNA Structural Changes upon Interaction with Small Molecules Using Dual-Polarization Interferometry

The structural changes of genomic DNA upon interaction with small molecules have been studied in real time using dual-polarization interferometry (DPI). Native or thermally denatured DNA was immobilized on the silicon oxynitride surface via a preadsorbed poly(ethylenimine) (PEI) layer. The mass loading was similar for both types of DNA, however, native DNA formed a looser and thicker layer due to its rigidity, unlike the more flexible denatured DNA, which mixed with PEI to form a denser and thinner layer. Ethidium bromide (EtBr), a classical intercalator, induced the large thickness decrease and density increase of native DNA (double-stranded), but a slight increase in both the thickness and density of denatured DNA (partial single-stranded).

Adaptive recognition of small molecules by nucleic acid aptamers through a label-free approach

We report a novel label-free method for the investigation of the adaptive recognition of small molecules by nucleic acid aptamers using capillary electrophoresis analysis. Cocaine and argininamide were chosen as model molecules, and the two corresponding DNA aptamers were used. These single-strand DNAs folded into their specific secondary structures, which were mainly responsible for the binding of the target molecules with high affinity and specificity. For molecular recognition, the nucleic acid structures then underwent additional conformational changes, while keeping the target molecules stabilized by intermolecular hydrogen bonds. The intrinsic chemical and physical properties of the target molecules enabled them to act as indicators for adaptive binding. Thus any labeling or modification of the aptamers or target molecules were made obsolete. This label-free method for aptamer-based molecular recognition was also successfully applied to biological fluids and therefore indicates that this approach is a promising tool for bioanalysis.

Reusable, label-free electrochemical aptasensor for sensitive detection of small molecules

We report a sensitive electrochemical aptasensor for adenosine based on electrochemical impedance spectroscopy measurement, which gives not only a label-free but also a reusable platform to make the detection of small molecules simple and convenient.

Surface plasmon resonance and electrochemistry for detection of small molecules using catalyzed deposition of metal ions on gold substrate

Small molecules are difficult to detect by conventional surface plasmon resonance (SPR) spectroscopy due to the fact that the changes in the refractive index resulted from the binding process of small biomolecules are quite small. Here, we report a simple and effective method to detect small biomolecule using SPR spectroscopy and electrochemistry by catalyzed deposition of metal ions on SPR gold film. As an example, the ascorbic acid-mediated deposition of Ag on gold film was monitored by in situ SPR spectrum. The deposition of Ag atom on gold film resulted in an obvious decrease of depth in SPR angular scan curves of reflectance intensity and minimum reflectivity angle. The depth change of the SPR reflectance intensity and minimum reflectivity angle curves mainly relied on the amount of Ag atom deposited on gold film that can be controlled by the concentration of ascorbic acid. By monitoring the deposition of Ag atom on gold film, ascorbic acid was detected in the concentration range of 2 x 10(-5) M to 1 x 10(-3) M. After each of detections, the SPR sensor surface was completely regenerated by a potential step that stripped off the Ag atom. Furthermore, the regeneration process of the sensor surface provides the feasibility for detecting the concentration of ascorbic acid by electrochemical method.

Using oxidized carbon nanotubes as matrix for analysis of small molecules by MALDI-TOF MS

Oxidized carbon nanotubes are tested as a matrix for analysis of small molecules by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Compared with nonoxidized carbon nanotubes, oxidized carbon nanotubes facilitate sample preparation because of their higher solubility in water. The matrix layer of oxidized carbon nanotubes is much more homogeneous and compact than that of nonoxidized carbon nanotubes. The efficiency of desorption/ionization for analytes and the reproducibility of peak intensities within and between sample spots are greatly enhanced on the surface of oxidized carbon nanotubes. The advantage of the oxidized carbon nanotubes in comparison with alpha-cyano-4-hydroxycinnamic acid (CCA) and carbon nanotubes is demonstrated by MALDI-TOF-MS analysis of an amino acid mixture. The matrix is successfully used for analysis of synthetic hydroxypropyl P-cyclodextrin, suggesting a great potential for monitoring reactions and for product quality control. Reliable quantitative analysis of jatrorrhizine and palmatine with a wide linear range (1-100 ng/mL) and good reproducibility of relative peak areas (RSD less than 10 %) is achieved using this matrix. Concentrations of jatrorrhizine (8.65 mg/mL) and palmatine (10.4 mg/mL) in an extract of Coptis chinensis Franch are determined simultaneously using the matrix and a standard addition method. (c) 2005 American Society for Mass Spectrometry.

Small-molecule-directed assembly: A gold nanoparticle-based strategy for screening of homo-adenine DNA duplex binders

By using AuNP-modified homo-adenine DNA conjugate as a model system, simple colorimetric and resonance Rayleigh scattering assays have been developed for screening small molecules that trigger the formation of the non-Watson-Crick homo-adenine duplexes. The assay presented here is more simplified in format as it involves only one type of ssDNA modified Au-NP, and can be easily adapted to high-throughput screening.

Flow Characteristics of Liquids in Microtubes Driven by a High Pressure

The flow characteristics of liquids in microtubes driven by a high pressure ranging from 1 MPa to 30 MPa are studied in this paper. The diameter of the microtube is from 3 μm to 10 μm and liquids composed of simple small molecules are chosen as the working fluids. The Reynolds number ranges from 0. 1 to 24. The behavior of isopropanol and carbon tetrachloride under high pressure is found different from the prediction from conventional Hagen-Poiseuille (HP) equation. The normalized friction coefficient C* increases significantly with the pressure. From an analysis of the microtube deformation, liquid compressibility, viscous heating and wall slip, it may be seen that the viscosity at high pressure plays an important role here. An exponential function of viscosity vs pressure is introduced into the HP equation to counteract the difference between experimental and theoretical values. However, this difference is not so marked for di-water.

非极性小分子有机液体在微管道中的流量特性

用去离子水及有机液体在内径约为25μm的石英圆管内进行了流量特性实验。液体分子量范围为18～160，动力黏性系数的范围为0.5～1 mPa·s。实验雷诺数范围为Re < 8。所用有机液体为：四氯化碳、乙基苯及环乙烷都是非极性液体，其分子结构尺度小于1nm。实验结果表明，在定常层流条件下，圆管内的液体流量与两端压力差成正比，其压力-流量关系仍符合经典的Hagen-Poiseuille流动。这说明非极性小分子有机液体在本实验所用微米尺度管道中其流动规律仍符合连续介质假设。鉴于微尺度流动实验的特殊性，文中还介绍了微流动实验装置，分析了微尺度流动测量误差来源及提高测量精度的措施。

Experiments about Simple Liquid Flows in Microtubes

The behavior of micro-scale flow is significant for the performance of Micro-Electro-Mechanical- Systems (MEMS) devices. Some experiments about liquid flow through microtubes with diameters about 3similar to20mum are presented here. The liquids used in our experiments include some simple liquids with small molecules, such as non-ion water and several kinds of organic liquids (CCL4, C6H5C2H5 and Isopropanol etc.). The flow rate and the normalized friction cocfficients were measured in micro-flow experimental apparatus. The results show that when the driven pressure varies from 0 to 1Mpa, the flow behaviors in 20mum microtube for both polar and non-polar liquids are in agreement with Hagen-Poiseuille law of the classical theory. It means that N-S equation based on continuous medium still acts well in this case. For higher pressure drop from 1 to 30Mpa, in the microtubes with diameter of 3similar to10mum, the normalized friction coefficients of organic liquids can't keep constant with pressure increases. However the non-ion water reveals different trends.

双源共蒸法制备非均匀膜的模型分析

探讨了双源共蒸法制备非均匀薄膜的堆积模型，并给出了非均匀膜的沉积速率与两种膜料沉积速率的关系．当两种膜料的沉积单分子大小近似相等或者小分子沉积速率远大于大分子时，可以近似认为混合介质膜的沉积速率等于两种膜料的沉积速率之和；当两种膜料的沉积单分子大小不满足近似相等且两种膜料的沉积速率可比较时，非均匀膜的沉积速率不能简单地用两种膜料的沉积速率之和来近似，它将随两种膜料沉积单分子的大小不同和沉积速率比不同按照不同的规律变化，并在文中给出了不同情况下的非均匀膜的沉积速率变化规律。

基于核酸特殊结构的分子识别及核酸相关纳米结构的设计应用

核酸为生命的最基本物质之一，是生物体遗传信息的携带者，在生长、遗传、变异等一系列重大生命现象中起决定性的作用。以核酸作为新药设计的靶分子，越来越受到人们的广泛重视。然而，不像其它靶分子如蛋白质、受体等具有特定的结构和功能，核酸结构在很多情况下是同源的，而且联系到很多人体正常的生理功能；能够与核酸结合的药物又往往不具有序列选择性，这就带来明显的毒副作用。因此，寻找和发现一些与疾病相关的核酸的特殊结构，并筛选对其有特异性结合能力的小分子，是以核酸为靶的药物研究的一个重要课题。 近年来，随着纳米科学技术的兴起，以核酸作为纳米体系的结构材料开始受到人们的广泛关注。作为一类特殊的线性高分子，核酸具有化学性质稳定，结构丰富且可控，良好的刚性和柔性，精确识别，高度生物相容性，合成方便等诸多优点，是一类优良的结构材料。目前核酸相关的纳米组装结构和器件研究还处于起步阶段，但是已经呈现出良好的发展前景。 本论文主要针对核酸特殊结构的分子识别及核酸相关功能纳米结构的设计这两方面展开了研究，全文由以下两大部分组成： 第一部分通过光谱学和生物化学等手段，研究了小分子对不同核酸结构的识别作用。借助于竞争平衡透析技术，发现一类恶嗪染料(oxazine dyes)能够与多种结构核酸结合。热变性及光谱实验结果表明，oxazine染料能够诱导杂合体三链核酸poly(rA):2poly(dT)的形成，并强烈地稳定其结构，其中以cresyl violet作用最强，是迄今发现的化合物中最强的。进一步研究发现，此类化合物以嵌插方式与杂合体三链核酸结合。RNase H酶切实验表明，杂合体三链核酸的形成能够强烈地抑制RNase H核酸酶的活性。研究了oxazine-170与三链核酸poly(dA):2poly(dT)及poly(rA):2poly(rU)的相互作用，发现oxazine-170能够强烈稳定三链DNA poly(dA):2poly(dT)的结构，而对相应双链DNA不具稳定作用；对三链RNA poly(rA):2poly(rU)及相应的双链RNA都有一定稳定作用，但作用不强。进一步研究发现，oxazine-170能够以两种结合方式与核酸结合：嵌插方式和外部静电堆积作用。研究了oxazine-170及cresyl violet与单链核酸的相互作用。研究发现oxazine-170能够序列特异性地与单链核酸poly(rA) 结合，CD光谱及AFM研究发现oxazine-170诱导poly(rA)形成新的二级结构。UV光谱、FL光谱及RLS研究发现poly(rA)促使oxazine 170形成H-aggregate，并以poly(rA)为模板自组装。而cresyl violet能够与单链核酸poly(rA)及poly(dA)结合，且采用不同的结合方式： cresyl violet能够与oxazine-170 类似地以poly(rA)为模板自组装；以嵌插方式与poly(dA)结合，并诱导其单链碱基堆积方式的改变。通过以上实验结果，我们进一步揭示了oxazine染料作为肿瘤细胞染色及光动力学治疗试剂的结构基础，对进一步设计、合成更加高效的抗肿瘤药物具有一定的指导意义。 第二部分中，我们尝试设计了几种基于核酸的纳米结构功能体系，并讨论了其相关应用。利用有机小分子coralyne能够诱导聚腺嘌呤序列反平行双链结构的形成，实现了一类新型的小分子诱导的纳米金组装结构。并以(dA)16功能化的金纳米粒子作为新型纳米探针，发展了一种简单的筛选单链核酸聚腺嘌呤序列结合分子的筛选方法。利用核酸限制性内切酶酶切位点回文序列的结构特点，设计了一种以DNA功能化的金纳米粒子组装体为酶切底物的比较通用的核酸限制性内切酶活力检测方法，并进一步用于甲基化酶活性检测及其抑制剂的筛选。基于单链DNA富胞嘧啶i-motif结构在不同pH值条件下的形成与解离，设计了一类质子驱动的DNA分子镊子，与基于链交换反应的DNA分子镊子相比，该体系更加简单，工作效率更高。随后，我们又通过合理设计，得到了两种分别能够结合与释放DNA和蛋白的分子镊子，为其应用做了一些探索。