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

We present a comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theoretical contributions to the modeling and analysis of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomechanical sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resolution are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temperature, or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a physical and biological context and consider how they may yet push the detection envelope further.

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Whispering gallery mode sensors

In this perspective, the authors present the basic features of lens-free computational imaging tools and report performance comparisons with conventional microscopy methods. They also discuss the challenges that these computational on-chip microscopes face for their wide-scale biomedical application.

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Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy

Optical microcavities that confi ne light in high-Q resonance promise all of the capabilities required for a successful nextgeneration microsystem biodetection technology. Label-free detection down to single molecules as well as operation in aqueous environments can be integrated cost-effectively on microchips, together with other photonic components, as well as electronic ones. We provide a comprehensive review of the sensing mechanisms utilized in this emerging fi eld, their physics, engineering and material science aspects, and their application to nanoparticle analysis and biomolecular detection. We survey the most recent developments such as the use of mode splitting for self-referenced measurements, plasmonic nanoantennas for signal enhancements, the use of optical force for nanoparticle manipulation as well as the design of active devices for ultra-sensitive detection. Furthermore, we provide an outlook on the exciting capabilities of functionalized high-Q microcavities in the life sciences.

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Label-free detection with high-Q microcavities: a review of biosensing mechanisms for integrated devices.

Whispering-gallery modes (WGM) on a spherical surface were first described by Lord Rayleigh at the beginning of the last century, but only after the invention of laser did they start to have some scientific relevance and only during the last two decades there has been a substantial move towards real devices and practical applications. WGM resonators have peculiar properties, the most notable being the potential of having an ultrahigh quality factor Q, which makes them very appealing both as laser cavities and as extremely sensitive sensors. Among the different types of WGM resonators, the microspherical ones represent a very important category, due to their simplicity, easy fabrication, and very high quality. In this review we provide a description of their fundamental properties and we summarize recent works on their application as filters, sensors and lasers.

Spherical whispering‐gallery‐mode microresonators

We present a refractometric sensor based on quantum dot-embedded polystyrene microspheres. Optical resonances within a microsphere, known as whispering-gallery modes (WGMs), produce narrow spectral peaks. For sensing applications, spectral shifts of these peaks are sensitive to changes in the local refractive index. In this work, two-photon excited luminescence from the quantum dots couples into several WGMs within the microresonator. By optimizing the detection area, the spectral visibility of the WGMs is improved. The spectral shifts are measured as the surrounding index of the refraction changes. The experimental sensitivity is about five times greater than that predicted by the Mie theory.

Quantum dot-embedded microspheres for remote refractive index sensing

We report the implementation of an on-chip microscope system, termed fluorescence optofluidic microscope (FOFM), which is capable of fluorescence microscopy imaging of samples in fluid media. The FOFM employs an array of Fresnel zone plates (FZP) to generate an array of focused light spots within a microfluidic channel. As a sample flows through the channel and across the array of focused light spots, the fluorescence emissions are collected by a filter-coated CMOS sensor, which serves as the channel's floor. The collected data can then be processed to render fluorescence microscopy images at a resolution determined by the focused light spot size (experimentally measured as 0.65 μm FWHM). In our experiments, our established resolution was 1.0 μm due to Nyquist criterion consideration. As a demonstration, we show that such a system can be used to image the cell nuclei stained by Acridine Orange and cytoplasm labeled by Qtracker®.

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Fluorescence microscopy imaging with a Fresnel zone plate array based optofluidic microscope

This paper describes an optofluidic droplet interrogation device capable of counting fluorescent drops at a throughput of 254000 drops per second. To our knowledge, this rate is the highest interrogation rate published thus far. Our device consists of 16 parallel microfluidic channels bonded directly to a filter-coated two-dimensional Complementary Metal-Oxide-Semiconductor (CMOS) sensor array. Fluorescence signals emitted from the drops are collected by the sensor that forms the bottom of the channel. The proximity of the drops to the sensor facilitates efficient collection of fluorescence emission from the drops, and overcomes the trade-off between light collection efficiency and field of view in conventional microscopy. The interrogation rate of our device is currently limited by the acquisition speed of CMOS sensor, and is expected to increase further as high-speed sensors become increasingly available.

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Optofluidic ultrahigh-throughput detection of fluorescent drops

A compressive high-speed stereo imaging system is reported. The system is capable of reconstructing 3D videos at a frame rate 10 times higher than the sampling rate of the imaging sensors. An asymmetric configuration of stereo imaging system has been implemented by including a high-speed spatial modulator in one of the binocular views, and leaving the other view unchanged. We have developed a two-step reconstruction algorithm to recover the irradiance and depth information of the high-speed scene. The experimental results have demonstrated high-speed video reconstruction at 800fps from 80fps measurements. The reported compressive stereo imaging method does not require active illumination, offering a robust yet inexpensive solution to high-speed 3D imaging.

Compressive high-speed stereo imaging.

We report the implementation of a color-capable on-chip lensless microscope system, termed color optofluidic microscope (color OFM), and demonstrate imaging of double stained Caenorhabditis elegans with lacZ gene expression at a light intensity about 10 mW/cm2.

/pdf/implementation-of-a-color-capable-optofluidic-microscope-on-4tgxz93k8w.pdf

Shuo Pang

Papers

Quantum dot-embedded microspheres for remote refractive index sensing

Fluorescence microscopy imaging with a Fresnel zone plate array based optofluidic microscope

Optofluidic ultrahigh-throughput detection of fluorescent drops

Compressive high-speed stereo imaging.

Implementation of a color-capable optofluidic microscope on a RGB CMOS color sensor chip substrate