Integration of programmable microfluidics and on-chip fluorescence detection for biosensing applications

We describe the integration of an actively controlled programmable microfluidic sample processor with on-chip optical fluorescence detection to create a single, hybrid sensor system. An array of lifting gate microvalves (automaton) is fabricated with soft lithography, which is reconfigurably joined to a liquid-core, anti-resonant reflecting optical waveguide (ARROW) silicon chip fabricated with conventional microfabrication. In the automaton, various sample handling steps such as mixing, transporting, splitting, isolating, and storing are achieved rapidly and precisely to detect viral nucleic acid targets, while the optofluidic chip provides single particle detection sensitivity using integrated optics. Specifically, an assay for detection of viral nucleic acid targets is implemented. Labeled target nucleic acids are first captured and isolated on magnetic microbeads in the automaton, followed by optical detection of single beads on the ARROW chip. The combination of automated microfluidic sample preparation and highly sensitive optical detection opens possibilities for portable instruments for point-of-use analysis of minute, low concentration biological samples.     

Adsorption and isolation of nucleic acids on cellulose magnetic beads using a three-dimensional printed microfluidic chip

While advances in genomics have enabled sensitive and highly parallel detection of nucleic acid targets, the isolation and extraction of the nucleic acids remain a critical bottleneck in the workflow. We present here a simple 3D printed microfluidic chip that allows for the vortex and centrifugation free extraction of nucleic acids. This novel microfluidic chip utilizes the presence of a water and oil interface to filter out the lysate contaminants. The pure nucleic acids, while bound on cellulose particles, are magnetically moved across the oil layer. We demonstrated efficient and rapid extraction of spiked Human Papillomavirus (HPV) 18 plasmids in specimen transport medium, in under 15 min. An overall extraction efficiency of 61% is observed across a range of HPV plasmid concentrations (5 × 10¹ to 5 × 10⁶ copies/100 μl). The magnetic, interfacial, and viscous drag forces inside the microgeometries of the chip are modeled. We have also developed a kinetics model for the adsorption of nucleic acids on cellulose functionalized superparamagnetic beads. We also clarify here the role of carrier nucleic acids in the adsorption and isolation of nucleic acids. Based on the various mechanistic insights detailed here, customized microfluidic devices can be designed to meet the range of current and emerging point of care diagnostics needs.     

Effect of methyl mercury induced free radical stress on nucleic acids and protein: Implications on cognitive and motor functions

Mercury pollution and acute neurotoxicity of mercury is well known. The recent reports suggest the adverse effect of low dose mercury, though the available literature is still silent on its mechanism. This study was therefore undertaken to probe the effect of low dose methyl mercury induced heavy metal toxicity on free radical stress and its impact on behaviour of male albino rats. Male albino rats were exposed to 1 mg/kg body wt of methylmercury chloride for seven days, on day 8 they were tested for motor and memory functions. They were sacrificed later for biochemical estimations for rate of lipid peroxidation, nucleic acids, proteins in cerebrum, cerebellum and brain stem. There was an increase in the rate of lipid peroxidation showing methyl mercury induced free radical stress. The motor and memory functions demonstrated a clear decline, besides there was a lowering in the levels of nucleic acids and proteins as compared to controls. The results are important in view of recent reports that methyl mercury induced free radical stress results in early ageing and may serve as an initiating factor more specifically for neurodegenerative disorders like Alzeihemer's disease and dementias. The current findings support the notion that incorporating dietary antioxidants like curcumin, ascorbic acid and α-tocopherol in routine diet from early age may help combat the risk of developing such disorders in ensuing years.     

基于核酸的信息安全技术研究现状及发展建议

由于具有巨大并行计算能力、海量信息存储密度及超低能耗等优势,近年来,核酸分子在分子计算、数据存储以及信息安全等研究领域广受关注。特别作为基于数学难题的、传统的密码理论与技术的有益补充,以核酸为信息载体的数据隐藏、认证、加密等信息安全技术极富发展前景。文章在介绍基于核酸的加密、隐藏及认证技术原理的基础上,详细论述了该领域国内外的最新研究成果,并对我国如何发展基于核酸的信息安全技术的研究提出了建议。     

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Detection of proteins and nucleic acids is dominantly performed using optical fluorescence based techniques, which are more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging. In this paper, we discuss our study of the electrical properties of nucleic acids and proteins at the nanoscale using a nanoelectronic probe we have developed, which we refer to as the Nanoneedle biosensor. The nanoneedle consists of four thin film layers: a conductive layer at the bottom acting as an electrode, an oxide layer on top, and another conductive layer on top of that, with a protective oxide above. The presence of proteins and nucleic acids near the tip results in a decrease in impedance across the sensing electrodes. There are three basic mechanisms behind the electrical response of DNA and protein molecules in solution under an applied alternating electrical field. The first change stems from modulation of the relative permittivity at the interface. The second mechanism is the formation and relaxation of the induced dipole moment. The third mechanism is the tunneling of electrons through the biomolecules. The results presented in this paper can be extended to develop low cost point-of-care diagnostic assays for the clinical setting.     

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

Respiratory viral infections are leading causes of death worldwide. A number of human respiratory viruses circulate in all age groups and adapt to person-to-person transmission. It is vital to understand how these viruses infect the host and how the host responds to prevent infection and onset of disease. Although animal models have been widely used to study disease states, incisive arguments related to poor prediction of patient responses have led to the development of microfluidic organ-on-chip models, which aim to recapitulate organ-level physiology. Over the past decade, human lung chips have been shown to mimic many aspects of the lung function and its complex microenvironment. In this review, we address immunological responses to viral infections and elaborate on human lung airway and alveolus chips reported to model respiratory viral infections and therapeutic interventions. Advances in the field will expedite the development of therapeutics and vaccines for human welfare.     

DNA纳米技术与生物编程

DNA纳米技术是设计和构建具有一定用途的人工核酸纳米结构。DNA纳米技术中的一个重要挑战就是如何有效设计和构建具有明确功能的纳米尺度的结构和器件。计算机辅助工具是预测、设计、建模以及描绘DNA结构的最强有力的工具。计算机辅助设计DNA结构以及识别有效的自组装路径让DNA作为一种独特的材料在构建纳米结构领域中显露锋芒。文章总结了DNA纳米结构设计的原理,介绍了一些用于DNA结构设计的算法以及一些用户友好软件。同时,对DNA纳米技术中构建DNA逻辑门以及DNA计算方面的最新研究进展做了介绍。     

国际研发合作模式选择的主导权掌控机制研究

在纵向产品差异框架内利用博弈论方法分析了处于不同技术梯度区国家间的技术研发合作模式选择主导权归属问题。研究结果表明,处于技术资源劣势的合作厂商拥有一定水平的自主研发能力,有助于其掌握研发合作模式选择的主导权,进而增进双方的合作深度。     

A self-contained polymeric cartridge for automated biological sample preparation

Sample preparation is one of the most crucial processes for nucleic acids based disease diagnosis. Several steps are required for nucleic acids extraction, impurity washes, and DNA/RNA elution. Careful sample preparation is vital to the obtaining of reliable diagnosis, especially with low copies of pathogens and cells. This paper describes a low-cost, disposable lab cartridge for automatic sample preparation, which is capable of handling flexible sample volumes of 10 μl to 1 ml. This plastic cartridge contains all the necessary reagents for pathogen and cell lysis, DNA/RNA extraction, impurity washes, DNA/RNA elution and waste processing in a completely sealed cartridge. The entire sample preparation processes are automatically conducted within the cartridge on a desktop unit using a pneumatic fluid manipulation approach. Reagents transportation is achieved with a combination of push and pull forces (with compressed air and vacuum, respectively), which are connected to the pneumatic inlets at the bottom of the cartridge. These pneumatic forces are regulated by pinch valve manifold and two pneumatic syringe pumps within the desktop unit. The performance of this pneumatic reagent delivery method was examined. We have demonstrated the capability of the on-cartridge RNA extraction and cancer-specific gene amplification from 10 copies of MCF-7 breast cancer cells. The on-cartridge DNA recovery efficiency was 54-63%, which was comparable to or better than the conventional manual approach using silica spin column. The lab cartridge would be suitable for integration with lab-chip real-time polymerase chain reaction devices in providing a portable system for decentralized disease diagnosis.     

生物纳米材料的进展与前景

在过去几年中,生物纳米材料的理论与实验研究已成为人们关注的焦点,特别是核酸与蛋白质的生化、生物物理、生物力学、热力学与电磁学特征及其智能复合材料已成为生命科学与材料科学的交叉前沿。目前,纳米生物芯片材料、仿生材料、纳米马达、纳米复合材料、界面生物材料、纳米传感器与药物传递系统等方面已取得很大进展。本文主要对这些材料的研究、开发及应用情况进行了综述,并探讨了生物纳米材料的发展前景。     

瑶山吉冬诺酒主要营养成份分析研究

文章对瑶山吉冬诺酒进行了检测分析,发现其含有丰富的多糖、核酸、卵磷脂、低聚糖、超氧化物歧化酶、不饱和脂肪酸、氨基酸、维生素等营养成份,以及钙、镁、钾、钠、铜、铁、锌、硅、锶、硒等矿物质或微量元素。     

Knowledge sharing and team trustworthiness: it's all about social ties!

This paper empirically examines knowledge sharing within innovation teams and explores the relationship between knowledge sharing and trust. This relationship has generally been identified in the literature as an important aspect of knowledge management. However, its pertinence to knowledge transfer within and between teams is less obvious. The case study based on four information technology R&D teams in Taiwan suggests that trust between a knowledge holder and a receiver may not exist. In fact, it can be connected by a mediator, although the use of social relationship in which trust is rooted in both host and visitor's trust of the mediator. Thus, trust may be substituted by the social relationship in certain specific contexts.     

Influence of the microbiota on epigenetics in colorectal cancer

Colorectal cancer is one of the most common malignancies and is the second leading cause of cancer death worldwide. Generally, there are three categories of colorectal cancer development mechanism—genetic, epigenetic and aberrant immunological signaling pathways—all of which may be initiated by an imbalanced gut microbiota. Epigenetic modifications enable host cells to change gene expression without modifying the gene sequence. The microbiota can interact with the host genome dynamically through the interface presented by epigenetic modifications. In particular, bacterially derived short-chain fatty acids have been identified as one clear link in the interaction of the microbiota with host epigenetic pathways. This review discusses recent findings relating to the cross talk between the microbiota and epigenetic modifications in colorectal cancer.     

犬细小病毒流行毒株的分离与鉴定

从西安某警犬基地罹患病毒性肠炎疫病病犬的粪便标本中分离出一株病毒 (暂命名为CPV XN93 1株 ) ,对其系统地进行了细胞培养、形态观察、核酸型测定、理化特性分析、复归动物实验和血清抗体检测。结果表明 :所分离的毒株与美国犬细小病毒标准毒株的特性相符 ,从而证明在我国西北地区首次分离的犬细小病毒与国外毒株的生物学和免疫学特性相一致。     

Construction of nanocarriers based on nucleic acids and their applications in nanobiology delivery systems

In recent years, nanocarriers based on nucleic acids have emerged as powerful and novel nanocarriers that are able to meet the demand for cancer-cell-specific targeting. Functional dynamics analysis revealed good biocompatibility, low toxicity and programmable structures, and their advantages include controllable size and modifiability. The development of novel hybrids has focused on the distinct roles of biosensing, drug and gene delivery, vaccine transport, photosensitization, counteracting drug resistance and functioning as carriers and logic gates. This review is divided into three parts: (i) DNA nanocarriers, (ii) RNA nanocarriers and (iii) DNA/RNA hybrid nanocarriers and their applications in nanobiology delivery systems. We also provide perspectives on possible future directions for growth in this field.     

“纳米-生物”会聚技术的测度及启示

运用专利计量与信息可视化技术手段,对会聚技术进行测度与可视化分析,是一个较新的研究课题。对纳米-生物(NB)会聚技术测度与可视化分析的结果显示,2000-2009年间,NB会聚技术呈现出快速发展的势头;NB会聚技术共涉及到4 998个不同的技术小类,其中"细菌、真菌、病毒等的测试与探测技术"是最重要的领域;NB会聚技术的热点主题,主要集中在核酸、碳纳米管、制备方法、生物标本、癌症治疗、靶标分子等方面。中国政府和科学技术界,应通过加强纳米与生物技术领域的合作,拓展纳米与生物技术的合作领域和合作主题,培养更多的NB会聚技术领域人才等途径,推动中国NB会聚技术的不断发展。NB会聚技术的测度与可视化分析方法,可应用于其他会聚技术领域。     

从年鉴学派到全球史观——对历史认识主体的时代性的分析

不同的时代不同的历史学家对历史的认识千差万别,不仅因为他们主观条件不一样,还因为客观的历史本身在不同的时代不同的场所起着不相同的实际作用。这也就表明,时代性这一因素影响的不仅仅是作为历史认识的主体——历史学家,它还影响到客观的历史事实本身在特定的时代被怎样地理解与运用。     

病毒——昆虫—植物三者互作研究进展及展望

全球气候变暖,极端天气频发,入侵型、新发和重发昆虫传作物病毒病害已经成为限制我国农作物优质高产的主要因素。因缺乏抗病抗虫的种质资源、育种周期长,虫传病害防治难度极大,目前我国农业处于几乎完全依赖化学防控媒介昆虫的被动应付局面,生态与环境成本极大。以往研究虫传病毒病害往往注重病毒和植物寄主两个方面,这些研究为理解作物病毒病害的暴发机制提供了基础知识,但尚未能深入到病害防控的关键节点——媒介昆虫介导的病毒侵染循环这一根本性问题上,导致目前在病毒病害防治实践上缺乏有效抓手。近年来,随着分子生物学和组学研究的飞速发展,以及微观生物学技术和理念对宏观生物学的快速渗透与交叉,病毒—昆虫—植物三者互作机制研究取得了诸多重要进展,在寻找病毒病害流行暴发的宏观生态学现象背后的分子生物学与生物化学机制上取得了长足进步,不但为复杂生态系统多元互作分子机制提供了参考模型,也为通过人工干扰和操纵生物间互作关键节点,从而促进虫传病毒病害的持久防控提供了科学依据和新的有效抓手,变被动应付为主动调控病害灾变过程。文章简要回顾了近年来病毒—昆虫—植物三者互作领域的主要研究进展和发展趋势,并抛砖引玉提出了对未来发展的建议和思考。建议国家组织研究力量,大力加强:(1)大田生产条件下病毒病害发生的多元生物体系互作机制及科学防控科技支撑能力建设;(2)前沿基础和新方法新策略探索及应用平台建设;(3)虫媒病害绿色防控的微生物组学颠覆性技术等方向的探索与突破,力求在虫传作物病毒病害绿色生态防控方面为农业供给侧改革提供强有力的科技创新和支撑能力。     

The 2008 Benjamin Franklin Medal in Chemistry is presented to Albert Eschenmoser, Dr. sc.nat

The Franklin Institute, Philadelphia, Pennsylvania, awards the 2008 Benjamin Franklin Medal in Chemistry to Professor Albert Eschenmoser for his seminal efforts in the chemical etiology of nucleic acid structure, which through systematic exploration employing chemical synthesis of potentially natural structural alternatives to DNA, demonstrated that Watson-Crick base pairing is not unique to the ribofuranosyl system, and that DNA’s structure represents an optimization of several factors rather than a maximization of base-pairing strength.In his early scientific career, Professor Albert Eschenmoser established himself as one of the premier synthetic organic chemists in the world, with the monumental achievement of two total syntheses of Vitamin B₁₂, the first in collaboration with Professor Robert B. Woodward of Harvard University.However, since the 1980s, Professor Eschenmoser has concentrated his research interest in establishing the area of chemical etiology of nucleic acid structures to understand better the structural and functional uniqueness of the molecular basis of nature’s genetic information carrier—DNA and RNA. This systematic investigation of potential natural nucleic acid alternatives has demonstrated experimentally that Watson-Crick base pairing is not a unique property of DNA and RNA. Moreover, his research on homo-DNA revealed that the helicality of the famous double-stranded DNA is a direct outcome of the 5-membered ring nature of the deoxyribofuranose structure unit, while the study on p-RNA demonstrated that nature did not choose her genetic system by the standard of maximal base pairing strength, but instead optimization. Of equal significance, his recent design and synthesis of TNA (α-threofuranosyl nucleic acid), found to possess extraordinary base-paring properties, led to the hypothesis suggesting TNA as a possible precursor to the “RNA World”. Finally, his research on the correlation between the differences in the pKa of nucleic bases and their base-pairing strength led to a novel principal for the selection of nucleic base alternatives with proper bonding strength.     

榆科种子油脂肪酸成分与榆科分类

 22 kinds of seed oils were extracted from 8 genera of the family Ulmaceae in China The seed oils were examined for their characteristics and fatty acid compositions by gas liquid chromatography.  The fatty acid compositions of these oils were found to fall into two classes. Some genera (such as  Ulmus,  Zelkova)  contain  mainly lower saturated acids, in which the chief acid is capric acid 10:0, while the genera (such as Celtis, Pteroceltis, Aphananthe, Trema, Gironniera) contain mainly unsaturat- ed acids, in which the chief acid is linoleic acid  18:2.  Hemiptelea  davidii  (Hance) Planch contain however either certain amount of short-chain saturated acids or higher unsaturated acids, it appears a intermediate genus between the two classes.  According to the component acids we support that the Ulmaceae be split into two subfamilies. The genera arrangement based on the component acids corresponds basically with the view based on mophological characters and flavonoids found in leaves of Ulmaceae, but there are some discrepancies in certain genera, for example, the Aphananthe should beplaced in Celtoid instead of Ulmoid by the present study.