Nanopores are emerging as powerful tools for the detection and identification of macromolecules in aqueous solution. In this review, we discuss the recent development of active and passive controls ...over molecular transport through nanopores with emphasis on biosensing applications. We give an overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores.
Nanopores are powerful single-molecule tools for label-free sensing of nanoscale molecules including DNA that can be used for building designed nanostructures and performing computations. Here, DNA ...hard drives (DNA-HDs) are introduced based on DNA nanotechnology and nanopore sensing as a rewritable molecular memory system, allowing for storing, operating, and reading data in the changeable three-dimensional structure of DNA. Writing and erasing data are significantly improved compared to previous molecular storage systems by employing controllable attachment and removal of molecules on a long double-stranded DNA. Data reading is achieved by detecting the single molecules at the millisecond time scale using nanopores. The DNA-HD also ensures secure data storage where the data can only be read after providing the correct physical molecular keys. Our approach allows for easy-writing and easy-reading, rewritable, and secure data storage toward a promising miniature scale integration for molecular data storage and computation.
Optimizing Brownian escape rates by potential shaping Chupeau, Marie; Gladrow, Jannes; Chepelianskii, Alexei ...
Proceedings of the National Academy of Sciences - PNAS,
01/2020, Letnik:
117, Številka:
3
Journal Article
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Brownian escape is key to a wealth of physico-chemical processes, including polymer folding and information storage. The frequency of thermally activated energy barrier crossings is assumed to ...generally decrease exponentially with increasing barrier height. Here, we show experimentally that higher, fine-tuned barrier profiles result in significantly enhanced escape rates, in breach of the intuition relying on the above scaling law, and address in theory the corresponding conditions for maximum speed-up. Importantly, our barriers end on the same energy on which they start. For overdamped dynamics, the achievable boost of escape rates is, in principle, unbounded so that the barrier optimization has to be regularized. We derive optimal profiles under 2 different regularizations and uncover the efficiency of N-shaped barriers. We then demonstrate the viability of such a potential in automated microfluidic Brownian dynamics experiments using holographic optical tweezers and achieve a doubling of escape rates compared to unhindered Brownian motion. Finally, we show that this escape rate boost extends into the low-friction inertial regime.
Solid-state nanopores are powerful tools for reading the three-dimensional shape of molecules, allowing for the translation of molecular structure information into electric signals. Here, we show a ...high-resolution integrated nanopore system for identifying DNA nanostructures that has the capability of distinguishing attached short DNA hairpins with only a stem length difference of 8 bp along a DNA double strand named the DNA carrier. Using our platform, we can read up to 112 DNA hairpins with a separating distance of 114 bp attached on a DNA carrier that carries digital information. Our encoding strategy allows for the creation of a library of molecules with a size of up to 5 × 1033 (2112) that is only built from a few hundred types of base molecules for data storage and has the potential to be extended by linking multiple DNA carriers. Our platform provides a nanopore- and DNA nanostructure-based data storage method with convenient access and the potential for miniature-scale integration.
Nanopore sensing is a versatile technique for the analysis of molecules on the single-molecule level. However, extracting information from data with established algorithms usually requires ...time-consuming checks by an experienced researcher due to inherent variability of solid-state nanopores. Here, we develop a convolutional neural network (CNN) for the fully automated extraction of information from the time-series signals obtained by nanopore sensors. In our demonstration, we use a previously published data set on multiplexed single-molecule protein sensing. The neural network learns to classify translocation events with greater accuracy than previously possible, while also increasing the number of analyzable events by a factor of 5. Our results demonstrate that deep learning can achieve significant improvements in single molecule nanopore detection with potential applications in rapid diagnostics.
Interactions between a single emitter and cavity provide the archetypical system for fundamental quantum electrodynamics. Here we show that a single molecule of Atto647 aligned using DNA origami ...interacts coherently with a sub-wavelength plasmonic nanocavity, approaching the cooperative regime even at room temperature. Power-dependent pulsed excitation reveals Rabi oscillations, arising from the coupling of the oscillating electric field between the ground and excited states. The observed single-molecule fluorescent emission is split into two modes resulting from anti-crossing with the plasmonic mode, indicating the molecule is strongly coupled to the cavity. The second-order correlation function of the photon emission statistics is found to be pump wavelength dependent, varying from g
(0) = 0.4 to 1.45, highlighting the influence of vibrational relaxation on the Jaynes-Cummings ladder. Our results show that cavity quantum electrodynamic effects can be observed in molecular systems at ambient conditions, opening significant potential for device applications.
Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the ...course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (<seconds). Intriguingly, only the two circulating myeloid cell types have increased short time scale compliance and flow better through microfluidic constrictions. Moreover, all three differentiated cell types reduce their steady-state viscosity by more than 50% and show over 140% relative increase in their ability to migrate through tissue-like pores at long time-scales (>minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies.
We introduce real-time deformability cytometry (RT-DC) for continuous cell mechanical characterization of large populations (>100,000 cells) with analysis rates greater than 100 cells/s. RT-DC is ...sensitive to cytoskeletal alterations and can distinguish cell-cycle phases, track stem cell differentiation into distinct lineages and identify cell populations in whole blood by their mechanical fingerprints. This technique adds a new marker-free dimension to flow cytometry with diverse applications in biology, biotechnology and medicine.
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