抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.

Cells on chips

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

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Present and Future of Surface-Enhanced Raman Scattering

Coating is an essential step in adjusting the surface properties of materials. Superhydrophobic coatings with contact angles greater than 150° and roll-off angles below 10° for water have been developed, based on low-energy surfaces and roughness on the nano- and micrometer scales. However, these surfaces are still wetted by organic liquids such as surfactant-based solutions, alcohols, or alkanes. Coatings that are simultaneously superhydrophobic and superoleophobic are rare. We designed an easily fabricated, transparent, and oil-rebounding superamphiphobic coating. A porous deposit of candle soot was coated with a 25-nanometer-thick silica shell. The black coating became transparent after calcination at 600°C. After silanization, the coating was superamphiphobic and remained so even after its top layer was damaged by sand impingement.

Candle Soot as a Template for a Transparent Robust Superamphiphobic Coating

After having reviewed some aspects of microfluidic system preparation in the first part (1), in this second part of the review we will cover a number of standard operations (namely: sample preparation, sample injection, sample manipulation, reaction, separation, and detection) as well as some biological applications of micro total analysis systems (namely: cell culture, polymerase chain reaction, DNA separation, DNA sequencing, and clinical diagnostics). As previously, we will include papers issued from different scientific journals as well as useful abstracts from three conference proceedings: MEMS, Transducers, and μTAS. In this second part, we do not include the period covered by the history section (1975-1997) from part 1 but try to cover the relevant examples of the literature published between January 1998 and March 2002. We briefly describe articles that struck us as needing special attention, while more “standard” papers are dutifully reported in groups of interest. An article might be included in more than one section, depending on the ideas developed in it.

Micro total analysis systems. 2. Analytical standard operations and applications.

Microfluidic systems have become more and more important in the field of analytical chemistry. Detection methods on these microsystems are essential for the identification and quantification of chemical species that are being analyzed. This review concentrates on the latest developments of optical detection methods and mass spectrometry in conjunction with microfluidic systems. Electrochemical methods are discussed in another review in the same issue of this journal. Within the optical detection section, topics such as multiplexed detection and the use of waveguides are discussed. Within the discussion of mass spectrometry, the main focus is on electrospray emitters as interfaces between microsystem and spectrometer. Apart from optical detection and mass spectrometry, other techniques such as flame ionization and nuclear magnetic resonance are also mentioned.

Recent developments in detection for microfluidic systems

Taking the next step from individual functional components to higher integrated devices, we present a feasibility study of a lab-on-a-chip system with five different components monolithically integrated on one substrate. These five components represent three main domains of microchip technology: optics, fluidics and electronics. In particular, this device includes an on-chip optically pumped liquid dye laser, waveguides and fluidic channels with passive diffusive mixers, all defined in one layer of SU-8 polymer, as well as embedded photodiodes in the silicon substrate. The dye laser emits light at 576 nm, which is directly coupled into five waveguides that bring the light to five different locations along a fluidic channel for absorbance measurements. The transmitted portion of the light is collected at the other side of this cuvette, again by waveguides, and finally detected by the photodiodes. Electrical read-out is accomplished by integrated metal connectors. To our knowledge, this is the first time that integration of all these components has been demonstrated.

Lab-on-a-chip with integrated optical transducers

Flow cytometry is widely used for analyzing microparticles, such as cells and bacteria. In this paper, we report an innovative microsystem, in which several different optical elements (waveguides, lens and fiber-to-waveguide couplers) are integrated with microfluidic channels to form a complete microchip flow cytometer. All the optical elements, the microfluidic system, and the fiber-to-waveguide couplers were defined in one layer of polymer (SU-8, negative photoresist) by standard photolithography. With only a single mask procedure required, all the fabrication and packaging processes can be finished in one day. Polystyrene beads were measured in the microchip flow cytometer, and three signals (forward scattering, large angle scattering and extinction) were measured simultaneously for each bead. To our knowledge this is the first time forward scattered light and incident light extinction were measured in a microsystem using integrated optics. The microsystem can be applied for analyzing different kinds of particles and cells, and can easily be integrated with other microfluidic components.

Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements

Multimode polymer waveguides and fiber-to-waveguide couplers have been integrated with microfluidic channels by use of a single-mask-step procedure, which ensured self-alignment between the optics and the fluidics and allowed a fabrication and packaging time of only one day Three fabrication procedures for obtaining hermetically sealed channels were investigated, and the spectrally resolved propagation loss (400–900 nm) of the integrated waveguides was determined for all three procedures Two chemical absorbance cells with optical path lengths of 100 and 1000 μm were furthermore fabricated and characterized in terms of coupling loss, sensitivity, and limit of detection for measurements of the dye bromothymol blue

Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems.

A study of the size dependent blue- and red-shift of the plasmon band of silver nanoparticle films in aqueous solution is reported. A detection scheme, where the particle size is continuously decreased by means of controlled dissolution, while measuring the plasmon band position by UV–vis absorption spectroscopy is used. Both blue- and red-shifts of the peak position are observed, depending on the presence of electron donors and/or acceptors in the solution, respectively. A great increase in plasmon shifts for smaller particle sizes (R 10 nm) is demonstrated, which we ascribe to a transition from an extrinsic regime for the larger particles, where shifts of the plasmon frequency are related to changes in the dielectric environment, while the dielectric function of the metal is constant, to an intrinsic regime for the smaller particles. For this intrinsic regime, operative for small particles, nonlocality of the dielectric constant has to be considered. The experimental data are fitted with a...

Size-Dependent Shifts of Plasmon Resonance in Silver Nanoparticle Films Using Controlled Dissolution: Monitoring the Onset of Surface Screening Effects

Klaus Bo Mogensen

Papers

Recent developments in detection for microfluidic systems

Lab-on-a-chip with integrated optical transducers

Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements

Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems.

Size-Dependent Shifts of Plasmon Resonance in Silver Nanoparticle Films Using Controlled Dissolution: Monitoring the Onset of Surface Screening Effects