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

The realization of miniaturized optofluidic platforms offers potential for achieving more functional and more compact devices. Such integrated systems bring fluid and light together and exploit their microscale interaction for a large variety of applications. The high sensitivity of compact microphotonic devices can generate effective microfluidic sensors, with integration capabilities. By turning the technology around, the exploitation of fluid properties holds the promise of highly flexible, tunable or reconfigurable microphotonic devices. We overview some of the exciting developments so far.

/pdf/integrated-optofluidics-a-new-river-of-light-3c3hleoeeg.pdf

Integrated optofluidics: A new river of light

The trend towards miniaturization in optical imaging, diagnostics and lab-on-a-chip technology is creating a demand for sophisticated microlenses. A new type of smart liquid microlens has been developed that differs from most current devices in that it is self-focusing. The key component is a stimuli-responsive hydrogel integrated into a microfluidic system and acting as a container for a liquid droplet. The hydrogel simultaneously senses stimuli and actuates a change in droplet shape — and hence focal length. Stimuli can include biological and chemical agents and physical parameters. At this micrometre scale, pinned liquid-liquid interfaces are used to attain stable devices, and response times of ten to a few tens of seconds. Lenses can have virtually any focal length and are readily integrated into arrays. Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles1. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths2,3,4,5, or use external control to adjust the microlens focal length6,7,8,9,10,11,12. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel13 integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape—and hence focal length—of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably14, we can use pinned liquid–liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -∞ to +∞ (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies15,16,17,18,19.

Adaptive liquid microlenses activated by stimuli-responsive hydrogels

Technology 4403 Microfabrication 4403 Assembly and Interfacing 4404 Optical Integration 4405 Flow Control 4405 Standard Operations 4406 Sample Preparation 4406 Injection and Separation 4407 Fluidic Reactors 4407 Particle and Cell Sorting 4409 Cell Trapping and Culture 4409 Applications 4410 Clinical Diagnostics 4410 Nucleic Acids 4411 Proteins 4412 Cell and Tissue Studies 4413 Environmental Monitoring 4414 Literature Cited 4414

Micro total analysis systems: latest achievements.

An elastomer-based tunable liquid-filled microlens array integrated on top of a microfluidic network is fabricated using soft lithographic techniques. The simultaneous control of the focal length of all the microlenses composing the elastomeric array is accomplished by pneumatically regulating the pressure of the microfluidic network. A focal length tuning range of hundreds of microns to several millimeters is achieved. Such an array can be used potentially in dynamic imaging systems and adaptive optics.

Tunable liquid-filled microlens array integrated with microfluidic network.

Fluidic adaptive lenses with an adjustable focal length over a wide range were demonstrated in this letter. The focal length adjustment was achieved by changing the shape of the fluidic lens without any mechanical moving parts. The shortest focal length demonstrated in such devices is 41 mm, which corresponds to a large numerical aperture of 0.24 and a small F number of 2.05. The highest resolution measured using a positive standard is 25.39 lp/mm in this fluidic adaptive lens.

Fluidic adaptive lens with high focal length tunability

We demonstrate an integrated microfluidic flow sensor with ultra-wide dynamic range, suitable for high throughput applications such as flow cytometry and particle sorting/counting. A fiber-tip cantilever transduces flow rates to optical signal readout, and we demonstrate a dynamic range from 0 to 1500 µL min−1 for operation in water. Fiber-optic sensor alignment is guided by preformed microfluidic channels, and the dynamic range can be adjusted in a one-step chemical etch. An overall non-linear response is attributed to the far-field angular distribution of single-mode fiber output.

/pdf/microfluidic-flow-rate-detection-based-on-integrated-optical-4jlwvonylu.pdf

Microfluidic flow rate detection based on integrated optical fiber cantilever.

We have demonstrated a microfluidic device that can not only achieve three-dimensional flow focusing but also confine particles to the center stream along the channel. The device has a sample channel of smaller height and two sheath flow channels of greater height, merged into the downstream main channel where 3D focusing effects occur. We have demonstrated that both beads and cells in our device display significantly lower CVs in velocity and position distributions as well as reduced probability of coincidental events than they do in conventional 2D-confined microfluidic channels. The improved particle confinement in the microfluidic channel is highly desirable for microfluidic flow cytometers and in fluorescence-activated cell sorting (FACS). We have also reported a novel method to measure the velocity of each individual particle in the microfluidic channel. The method is compatible with the flow cytometer setup and requires no sophisticated visualization equipment. The principles and methods of device design and characterization can be applicable to many types of microfluidic systems.

/pdf/universally-applicable-three-dimensional-hydrodynamic-2t9lg65kbf.pdf

Universally applicable three-dimensional hydrodynamic microfluidic flow focusing

The focusing capabilities of a two-dimensional fluid-filled lens microfabricated in an optical polymer are demonstrated. The illumination path is visualized by localized scattering centers. Functionality for flow cytometry applications is demonstrated by localization of the excitation of large-angle scatter. Integrated in-plane optical systems offer simple, compact, and inexpensive alternatives to external optics, as well as the potential for increased detection efficiency and low-power operation.

Demonstration of two-dimensional fluidic lens for integration into microfluidic flow cytometers

High-performance fluidic lenses with an adjustable focal length spanning a very wide range (30 mm to infinite) are demonstrated. We show that the focal length, F-number, and numerical aperture can be dynamically controlled by changing the shape of the fluidic adaptive lens without moving the lens position mechanically. The shortest focal length demonstrated is less than 30 mm for a 20-mm lens aperture. The fluidic adaptive lens has a nearly perfect spherical profile and shows a resolution better than 40 line pairs/mm in a plano-convex structure and 57 line pairs/mm in a biconvex structure.

Victor Lien

Papers

Fluidic adaptive lens with high focal length tunability

Microfluidic flow rate detection based on integrated optical fiber cantilever.

Universally applicable three-dimensional hydrodynamic microfluidic flow focusing

Demonstration of two-dimensional fluidic lens for integration into microfluidic flow cytometers

High-performance fluidic adaptive lenses