One of the major thrusts in proximal probe techniques is combination of imaging capabilities with simultaneous measurements of physical properties. In tapping mode atomic force microscopy (TMAFM), the most straightforward way to accomplish this goal is to reconstruct the time-resolved force interaction between the tip and surface. These tip-sample forces can be used to detect interactions (e.g., binding sites) and map material properties with nanoscale spatial resolution. Here, we describe a previously unreported approach, which we refer to as scanning probe acceleration microscopy (SPAM), in which the TMAFM cantilever acts as an accelerometer to extract tip-sample forces during imaging. This method utilizes the second derivative of the deflection signal to recover the tip acceleration trajectory. The challenge in such an approach is that with real, noisy data, the second derivative of the signal is strongly dominated by the noise. This problem is solved by taking advantage of the fact that most of the information about the deflection trajectory is contained in the higher harmonics, making it possible to filter the signal by ''comb'' filtering, i.e., by taking its Fourier transform and inverting it while selectively retaining only the intensities at integer harmonic frequencies. Such a comb filtering method works particularly well in fluid TMAFM because of the highly distorted character of the deflection signal. Numerical simulations and in situ TMAFM experiments on supported lipid bilayer patches on mica are reported to demonstrate the validity of this approach.atomic force microscopy ͉ Fourier transform atomic force microscopy ͉ nanoaccelerometry
Nerve growth strongly relies on multiple chemical and physical signals throughout development and regeneration. Currently, a cure for injured neuronal tissue is an unmet need. Recent advances in fabrication technologies and materials led to the development of synthetic interfaces for neurons. Such engineered platforms that come in 2D and 3D forms can mimic the native extracellular environment and create a deeper understanding of neuronal growth mechanisms, and ultimately advance the development of potential therapies for neuronal regeneration. This progress report aims to present a comprehensive discussion of this field, focusing on physical feature design and fabrication with additional information about considerations of chemical modifications. We review studies of platforms generated with a range of topographies, from micro-scale features down to topographical elements at the nanoscale that demonstrate effective interactions with neuronal cells. Fabrication methods are discussed as well as their biological outcomes. This report highlights the interplay between neuronal systems and the important roles played by topography on neuronal differentiation, outgrowth, and development. The influence of substrate structures on different neuronal cells and parameters including cell fate, outgrowth, intracellular remodeling, gene expression and activity is discussed. Matching these effects to specific needs may lead to the emergence of clinical solutions for patients suffering from neuronal injuries or brain-machine interface (BMI) applications.
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promise in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a cell-in-shell (or artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy. A durable titanium oxide (TiO ) shell is formed on individual Jurkat T cells, and the CD3 and other antigens on cell surfaces remain accessible to the antibodies. Interleukin-2 (IL-2) secretion is also not hampered by the shell formation. This work suggests a chemical toolbox for effectively preserving lymphocytes in vitro and developing the lymphocyte-based cancer immunotherapy.
S. cerevisiae encapsulated with a poly(norepinephrine)/silica double-layered shell showed multiple resistance to enzymatic attack, desiccation, and UV-C irradiation. The biochemical response of the encapsulated yeast may also contribute to the UV-C resistance.
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