There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

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

Optical detection and spectroscopy of single molecules and single nanoparticles have been achieved at room temperature with the use of surface-enhanced Raman scattering. Individual silver colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed molecules. For single rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were on the order of 10 14 to 10 15 , much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-molecule fluorescence.

http://science.sciencemag.org/content/sci/275/5303/1102.full.pdf

Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering

The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

The origins and the future of microfluidics

https://www.cell.com/cell/pdf/S0092-8674(15)00549-8.pdf

Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets

Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

Fabrication of microfluidic systems in poly(dimethylsiloxane)

This paper describes a simple, versatile method of generating gradients in composition in solution or on surfaces using microfluidic systems. This method is based on controlled diffusive mixing of species in solutions that are flowing laminarly, at low Reynolds number, inside a network of microchannels. We demonstrate the use of this procedure to generate (1) gradients in the compositions of solutions, measured directly by colorimetric assays and (2) gradients in topography of the surfaces produced by generating concentration gradients of etching reagents, and then using these gradients to etch profiles into the substrate. The lateral dimensions of the gradients examined here, which went from 350 to 900 μm, are determined by the width of the microchannels. Gradients of different size, resolution, and shape have been generated using this method. The shape of the gradients can be changed continuously (dynamic gradients) by varying the relative flow velocities of the input streams of fluids. The method is ex...

/pdf/generation-of-solution-and-surface-gradients-using-dk7idghq3y.pdf

Generation of Solution and Surface Gradients Using Microfluidic Systems

This paper describes the generation of gradients having complex shapes in solution using microfluidic networks. Flowing multiple streams of fluid each carrying different concentrations of substances laminarly and side-by-side generated step concentration gradients perpendicular to the direction of the flow. Appropriately designed networks of microchannels for controlled diffusive mixing of substances generated a range of shapes for the gradients, including linear, parabolic, and periodic. The lateral dimensions of the gradients ranged from 900 to 2200 μm. This paper also demonstrates the generation of overlapping gradients composed of different species. Since solutions in the microfluidic network exist as steady states and are continuously renewed, the gradients established in the capillaries are spatially and temporally constant and can be maintained easily for periods of hours. Using laminar flow to generate gradients should be useful in both biological and nonbiological research.

Generation of Gradients Having Complex Shapes Using Microfluidic Networks

This paper describes a procedure for making topologically complex three-dimensional microfluidic channel systems in poly(dimethylsiloxane) (PDMS). This procedure is called the “membrane sandwich” method to suggest the structure of the final system:  a thin membrane having channel structures molded on each face (and with connections between the faces) sandwiched between two thicker, flat slabs that provide structural support. Two “masters” are fabricated by rapid prototyping using two-level photolithography and replica molding. They are aligned face to face, under pressure, with PDMS prepolymer between them. The PDMS is cured thermally. The masters have complementary alignment tracks, so registration is straightforward. The resulting, thin PDMS membrane can be transferred and sealed to another membrane or slab of PDMS by a sequence of steps in which the two masters are removed one at a time; these steps take place without distortion of the features. This method can fabricate a membrane containing a channel...

/pdf/fabrication-of-topologically-complex-three-dimensional-5f4z92zag2.pdf

Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping.

Three-dimensional microfluidic systems were fabricated and used to pattern proteins and mammalian cells on a planar substrate. The three-dimensional topology of the microfluidic network in the stamp makes this technique a versatile one with which to pattern multiple types of proteins and cells in complex, discontinuous structures on a surface. The channel structure, formed by the stamp when it is in contact with the surface of the substrate, limits migration and growth of cells in the channels. With the channel structure in contact with the surface, the cells stop dividing once they form a confluent layer. Removal of the stamp permits the cells to spread and divide.

https://www.pnas.org/content/pnas/97/6/2408.full.pdf

Daniel T. Chiu

Papers

Fabrication of microfluidic systems in poly(dimethylsiloxane)

Generation of Solution and Surface Gradients Using Microfluidic Systems

Generation of Gradients Having Complex Shapes Using Microfluidic Networks

Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping.

Patterned deposition of cells and proteins onto surfaces by using three-dimensional microfluidic systems