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

A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry

Quantitative phase imaging (QPI) has emerged as a valuable method for investigating cells and tissues. QPI operates on unlabelled specimens and, as such, is complementary to established fluorescence microscopy, exhibiting lower phototoxicity and no photobleaching. As the images represent quantitative maps of optical path length delays introduced by the specimen, QPI provides an objective measure of morphology and dynamics, free of variability due to contrast agents. Owing to the tremendous progress witnessed especially in the past 10–15 years, a number of technologies have become sufficiently reliable and translated to biomedical laboratories. Commercialization efforts are under way and, as a result, the QPI field is now transitioning from a technology-development-driven to an application-focused field. In this Review, we aim to provide a critical and objective overview of this dynamic research field by presenting the scientific context, main principles of operation and current biomedical applications. Over the past 10–15 years, quantitative phase imaging has moved from a research-driven to an application-focused field. This Review presents the main principles of operation and representative basic and clinical science applications.

Quantitative phase imaging in biomedicine

The present invention relates to systems and methods for quantitative three-dimensional mapping of refractive index in living or non-living cells, tissues, or organisms using a phase-shifting laser interferometric microscope with variable illumination angle. A preferred embodiment provides tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure and the quantitative characterization of specimen-induced aberrations in high-resolution microscopy with multiple applications in tissue light scattering.

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Tomographic phase microscopy

We have developed diffraction phase microscopy as a new technique for quantitative phase imaging of biological structures. The method combines the principles of common path interferometry and single-shot phase imaging and is characterized by subnanometer path-length stability and millisecond-scale acquisition time. The potential of the technique for quantifying nanoscale motions in live cells is demonstrated by experiments on red blood cells.

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Diffraction phase microscopy for quantifying cell structure and dynamics

We introduce Hilbert phase microscopy (HPM) as a novel optical technique for measuring high transverse resolution quantitative phase images associated with optically transparent objects. Because of its single-shot nature, HPM is suitable for investigating rapid phenomena that take place in transparent structures such as biological cells. The potential of this technique for studying biological systems is demonstrated with measurements of red blood cells, and its ability to quantify dynamic processes on a millisecond scale is exemplified with measurements of evaporating micrometer-sized water droplets.

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Hilbert phase microscopy for investigating fast dynamics in transparent systems.

Using a novel noncontact technique based on optical interferometry, we quantify the nanoscale thermal fluctuations of red blood cells (RBCs) and giant unilamellar vesicles (GUVs). The measurements reveal a nonvanishing tension coefficient for RBCs, which increases as cells transition from a discocytic shape to a spherical shape. The tension coefficient measured for GUVs is, however, a factor of 4-24 smaller. By contrast, the bending moduli for cells and vesicles have similar values. This is consistent with the cytoskeleton confinement model, in which the cytoskeleton inhibits membrane fluctuations [Gov et al., Phys. Rev. Lett. 90, 228101, (2003).

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Optical measurement of cell membrane tension.

We present a new quantitative method for investigating red blood cell morphology and dynamics The instrument integrates quantitative phase microscopy with an inverted microscope, which makes it particularly suitable for the noninvasive assessment of live erythrocytes In particular, we demonstrate the ability of this approach to quantify noninvasively cell volume and dynamic morphology The subnanometer path-length sensitivity at the millisecond time scales is exemplified by measuring the hemoglobin flow out of the cell during hemolysis

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Takahiro Ikeda

Papers

Diffraction phase microscopy for quantifying cell structure and dynamics

Hilbert phase microscopy for investigating fast dynamics in transparent systems.

Optical measurement of cell membrane tension.

Erythrocyte structure and dynamics quantified by Hilbert phase microscopy

Erythrocyte structure and dynamics quantified by Hilbert phase microscopy