Pushing super-resolution microscopy with MINFLUX
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Diffraction minima resolve point scatterers at few hundredths of the wavelength
Resolving two or more constantly scattering identical point sources using freely propagating waves is limited by diffraction. Here we show that, by illuminating with a diffraction minimum, a given number of point scatterers can be resolved at distances of small fractions of the wavelength. Specifically, we identify an 8 nm distance, which corresponds to 1/80 of the employed 640 nm wavelength, between two constantly emitting fluorescent molecules in the focal plane of an optical microscope. We also measure 22 nm side length for a quadratic array of four molecules. Moreover, we show that the measurement precision improves with decreasing distance and with increased scatterer density. This work opens up the prospect of resolving individual scatterers in clusters that are far smaller than the wavelength.
Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma
Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.
Signal theory based encryption of faster-than-Nyquist signals for fiber and wireless transmission
New applications such as the Internet of Things, autonomous driving, Industry X.0 and many more will transmit sensitive information via fibers and over the air with envisioned data rates beyond terabits per second. Therefore, the encryption has to be simple, fast and spectrally efficient, so that the power consumption and latency are low and the scarce bandwidth is not wasted. Various encryption schemes, based on mathematical algorithms, quantum theory, chaos communication or spectral spreading below the noise level have been explored. Besides power, spectral efficiency and latency, most of these approaches face additional challenges such as limited data rates, compatibility issues with communication standards and integration. Here, we propose a signal theory based method that enables the encryption of super-signals with bandwidths of hundreds of gigahertz without any additional bandwidth. In proof-of-concept experiments we demonstrate the encryption of a 270 GBd faster than Nyquist super-signal in a 252.4 GHz bandwidth. The encryption is simple, fast and power efficient, and offers a solution for secure data transmission in existing and future communication networks.
Metasurface enabled high-order differentiator
Metasurface-enabled optical analog differentiation has garnered significant attention due to its inherent capacity of parallel operation, compactness, and low power consumption. Most previous works focused on the first- and second-order operations, while several significant works have also achieved higher-order differentiation in both real space and k-space. However, how to construct the desired optical transfer function in a practical system to realize scalable and multi-order-parallel high-order differentiation of images in real space, and particularly how to leverage it to tackle practical problems, have not been fully explored. Here, drawing on the basic mathematical feature of the Fourier transform, we theoretically propose universal phase-gradient functions of the Pancharatnam-Berry-phase-based meta-device for performing arbitrary order differentiation. The fifth-order optical differentiations for both intensity and phase images are realized in the experiment. More importantly, by exploring this elaborately designed spatial differentiator, we construct another scheme for optical super-resolution and achieve the estimation of the distance between two incoherent point sources within 0.015 of the Rayleigh distance, which thereby provides a potential toolkit for optical alignment in high-precision semiconductor nano-fabrication. Our findings hold promise for image processing, microscopy imaging, and optical super-resolution imaging.
Fast, three-dimensional, live-cell super-resolution imaging with multiplane structured illumination microscopy
Three-dimensional structured illumination microscopy (3D-SIM) doubles the spatial resolution along all dimensions and is used widely in cellular imaging. However, its temporal resolution is constrained by the need for sequential plane-by-plane movement of the sample using a piezo stage for imaging, which often increases the acquisition time to several seconds per volume. To address this limitation, we develop 3D multiplane SIM (3D-MP-SIM), which simultaneously detects multiplane images and reconstructs them using synergistically evolved reconstruction algorithms. Compared with conventional 3D-SIM imaging, 3D-MP-SIM achieves an approximately eightfold increase in the temporal resolution of volumetric super-resolution imaging, with lateral and axial spatial resolutions of about 120 and 300 nm, respectively. The rapid acquisition substantially reduces motion artefacts during the imaging of dynamic structures, such as late endosomes, in live cells. Moreover, we demonstrate the capabilities of 3D-MP-SIM via high-speed time-lapse volumetric imaging of the endoplasmic reticulum at rates of up to 11 volumes per second. We also show the feasibility of dual-colour imaging by observing rapid and close interactions among intra- and intercellular organelles in 3D space. These results highlight the potential of 3D-MP-SIM for explaining dynamic behaviours and interactions at the subcellular level and in three dimensions.
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