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

Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.

Emerging applications of stimuli-responsive polymer materials

https://nanomechanics.mit.edu/sites/default/files/documents/2007_Acta_Bio_Cancer_S.Suresh.pdf

Biomechanics and biophysics of cancer cells.

Current single-molecule detection techniques require labeling the target molecule. We report a highly specific and sensitive optical sensor based on an ultrahigh quality (Q) factor (Q > 10^8) whispering-gallery microcavity. The silica surface is functionalized to bind the target molecule; binding is detected by a resonant wavelength shift. Single-molecule detection is confirmed by observation of single-molecule binding events that shift the resonant frequency, as well as by the statistics for these shifts over many binding events. These shifts result from a thermo-optic mechanism. Additionally, label-free, single-molecule detection of interleukin-2 was demonstrated in serum. These experiments demonstrate a dynamic range of 10^(12) in concentration, establishing the microcavity as a sensitive and versatile detector.

/pdf/label-free-single-molecule-detection-with-optical-13uzbeuo9v.pdf

Label-Free, Single-Molecule Detection with Optical Microcavities

The ability to detect and size individual nanoparticles with high resolution is crucial to understanding the behaviour of single particles and effectively using their strong size-dependent properties to develop innovative products. We report realtime, in situ detection and sizing of single nanoparticles, down to 30 nm in radius, using mode splitting in a monolithic ultrahigh-quality-factor (Q) whispering-gallery-mode microresonator. Particle binding splits a whispering-gallery mode into two spectrally shifted resonance modes, forming a self-referenced detection scheme. This technique provides superior noise suppression and enables the extraction of accurate particle size information with a single-shot measurement in a microscale device. Our method requires neither labelling of the particles nor a priori information on their presence in the medium, providing an effective platform to study nanoparticles at single-particle resolution. With the rapid progress in nanotechnology, nanoparticles of different materials and sizes have been synthesized and engineered as key components in various applications ranging from solar cell

On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh- Q microresonator

Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity. Previously, samples as light as 7 zeptograms (1 zg = 10(-21) g) have been weighed in vacuum, and proton-level resolution seems to be within reach. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum. Here we demonstrate that suspended microchannel resonators can weigh single nanoparticles, single bacterial cells and sub-monolayers of adsorbed proteins in water with sub-femtogram resolution (1 Hz bandwidth). Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles.

/pdf/weighing-of-biomolecules-single-cells-and-single-35bbp7ev6j.pdf

Weighing of biomolecules, single cells and single nanoparticles in fluid

We demonstrate the measurement of mass, density, and size of cells and nanoparticles using suspended microchannel resonators. The masses of individual particles are quantified as transient frequency shifts, while the particles transit a microfluidic channel embedded in the resonating cantilever. Mass histograms resulting from these data reveal the distribution of a population of heterogeneously sized particles. Particle density is inferred from measurements made in different carrier fluids since the frequency shift for a particle is proportional to the mass difference relative to the displaced solution. We have characterized the density of polystyrene particles, Escherichia coli, and human red blood cells with a resolution down to 10−4g∕cm3.

/pdf/measuring-the-mass-density-and-size-of-particles-and-cells-26f1fmg0xw.pdf

Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator

Precision frequency detection has enabled the suspended microchannel resonator (SMR) to weigh single living cells, single nanoparticles, and adsorbed protein layers in fluid. To date, the SMR resonance frequency has been determined optically, which requires the use of an external laser and photodiode and cannot be easily arrayed for multiplexed measurements. Here we demonstrate the first electronic detection of SMR resonance frequency by fabricating piezoresistive sensors using ion implantation into single crystal silicon resonators. To validate the piezoresistive SMR, buoyant mass histograms of budding yeast cells and a mixture of 1.6, 2.0, 2.5, and 3.0 µm diameter polystyrene beads are measured. For SMRs designed to weigh micron-sized particles and cells, the mass resolution achieved with piezoresistive detection (∼3.4 fg in a 1 kHz bandwidth) is comparable to what can be achieved by the conventional optical-lever detector. Eliminating the need for expensive and delicate optical components will enable new uses for the SMR in both multiplexed and field deployable applications.

/pdf/suspended-microchannel-resonators-with-piezoresistive-1ydsorzpui.pdf

Suspended microchannel resonators with piezoresistive sensors

We review the principles of magnetic force microscopy and describe recent advances in imaging methods and probes. Some current applications of MFM in experimental micromag-netism and materials development are also discussed, as well as challenges in image interpretation and in using MFM for quantitative work.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S1946427400369214

Magnetic Force Microscopy: Recent Advances and Applications

The method and apparatus of the present invention detects changes in cell biomechanics caused by any of a variety of diseases and conditions. In one embodiment, the method and apparatus of the invention detect infection of red blood cells. In one embodiment, the invention is a method and apparatus comprising a microfluidic channel with a constriction, for trapping infected red blood cells while allowing healthy red blood cells to deform and pass through the channel. In another embodiment, the invention comprises a suspended microchannel resonator for detecting and counting red blood cells at the constriction of the microfluidic channel.

Ken Babcock

Papers

Weighing of biomolecules, single cells and single nanoparticles in fluid

Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator

Suspended microchannel resonators with piezoresistive sensors

Magnetic Force Microscopy: Recent Advances and Applications

Method and apparatus for high throughput diagnosis of diseased cells with microchannel devices