Nanodiagnostics as a field makes use of fundamental advances in nanobiotechnology to diagnose, characterize and manage disease at the molecular scale. As these strategies move closer to routine clinical use, a proper understanding of different imaging modalities, relevant biological systems and physical properties governing nanoscale interactions is necessary to rationally engineer next-generation bionanomaterials. In this Review, we analyse the background physics of several clinically relevant imaging modalities and their associated sensitivity and specificity, provide an overview of the materials currently used for in vivo nanodiagnostics, and assess the progress made towards clinical translation. This work provides a framework for understanding both the impressive progress made thus far in the nanodiagnostics field as well as presenting challenges that must be overcome to obtain widespread clinical adoption.
Polyhedral gold nanocrystals with decahedral, icosahedral, and truncated tetrahedral shapes are synthesized by a simple one-pot polyol process in the prescence of poly(vinyl pyrrolidone) (PVP). High PVP concentration up to 360 equiv of the gold precursor, HAuCl 4 , effectively stabilizes decahedral seeds to yield uniform decahedra with various edge sizes. Decreased PVP concentration subsequently leads to selective formation of icosahedra and truncated tetrahedra. This results from a combination between the relative energy difference of the polyhedral structures and the oxidative etching rate of the seeds by Cl -/O 2 during the reaction. The distinct morphologies of gold nanocrystals exhibit characteristic extinction patterns in the UV-vis-NIR ranges, and these properties are successfully analyzed by the discrete dipole approximation (DDA) calculation. Most extinctions stem from the polar and azimuthal dipolar excitations, and azimuthal quardrupole resonance appears between two dipolar bands in the 88-nm decahedra. Given these shape-and size-dependent optical properties, gold nanocrystals hold considerable promise for biomedical and photonic applications.
Nanofluidics represents a promising solution to problems in fields ranging from biomolecular analysis to optical property tuning. Recently a number of simple nanofluidic fabrication techniques have been introduced that exploit the deformability of elastomeric materials like polydimethylsiloxane (PDMS). These techniques are limited by the complexity of the devices that can be fabricated, which can only create straight or irregular channels normal to the direction of an applied strain. Here, we report a technique for nanofluidic fabrication based on the controlled collapse of microchannel structures. As is demonstrated, this method converts the easy to control vertical dimension of a PDMS mold to the lateral dimension of a nanochannel. We demonstrate here the creation of complex nanochannel structures as small as 60 nm and provide simple design rules for determining the conditions under which nanochannel formation will occur. The applicability of the technique to biomolecular analysis is demonstrated by showing DNA elongation in a nanochannel and a technique for optofluidic surface enhanced Raman detection of nucleic acids.concentrator ͉ nanofluidic channel ͉ single molecule manipulation ͉ surface enhanced raman scattering O f the many reasons why nanofluidic (1-8) systems are of interest, the most well developed applications revolve around sensing, detection, and species handling in single or ''few'' molecule environments. Researchers have recently demonstrated unique bioanalytical capabilities in nanofluidic devices including the ability to elongate single DNA molecules (2), concentrate protein samples by more than four orders of magnitude (9), and efficiently separate both large (3, 10) and small (4) biomolecules. As a result of their technological promise, numerous methods have been developed to fabricate these systems, including electron beam lithography (11, 12), focused ion beam milling (13), interference lithography (14), AFM lithography (15), and nano-imprint lithography (2, 16). The significant advantages of these high-end nanofabrication technologies are their high resolution, reproducibility, and flexibility. Despite these advantages, these methods are somewhat limited when it comes to rapid prototyping of nanofluidic systems. To augment these high-resolution techniques, several groups have developed simpler nanofluidic fabrication in polydimethylsiloxane (PDMS) using lower resolution lithography methods. Huh et al. (17) for example used crack formation in a surface oxide layer to make nanochannels with mechanically tunable widths. Similarly, Chung et al. (18) used wrinkles on an elastomeric PDMS surface that, when bonded to another surface, formed discrete nanochannels. While these approaches greatly simplify the fabrication of nanochannels, the complexity of the devices that can be created is relatively low, in that only straight lines orthogonal to the stretching force can be fabricated.An additional challenge of nanofluidic fabrication with soft materials like PDMS is the relatively low stiffness ...
The purpose of this research was to contribute to the development of a resilience‐promoting programme for patients with chronic diseases. A systematic review of literature concerning resilience interventions for patients with chronic diseases was conducted by searching PubMed (including Medline), Science Direct, Web of Science, PsycARTICLES, CINAHL Plus, Embase, and the Cochrane Database for articles featuring the terms “resilience,” “resiliency,” “resilient,” “cancer,” “stroke,” “heart disease,” “diabetes” and “COPD” and published between 8 January 2017 and 15 January 2017. We included all English studies relevant to the topic; however, we excluded: (1) nonrandomised controlled trials and (2) those that mentioned the term “resilience” but did not apply it in their analysis. Seventeen studies—10 on cancer, four on cardiovascular diseases and three on diabetes—were deemed suitable for analysis. We found that, in these studies, (1) diverse definitions of resilience were applied, (2) various intervention durations were used and (3) complex programmes were applied within the resilience‐improving programmes. Our research encourages efforts to operationalise the construct of resilience, so it can be applied in clinical settings, and for the development of more systematic intervention programmes.
SUMMARY Pref-1 is an EGF-repeat containing protein that inhibits adipocyte differentiation. To better understand the origin and development of white adipose tissue (WAT), we generated transgenic mouse models for transient or permanent fluorescent labeling of cells using the Pref-1 promoter, facilitating inducible ablation. We show that Pref-1 marked cells retain proliferative capacity and are very early adipose precursors, prior to expression of Zfp423 or PPAR g. In addition, Pref-1 marked cells establish adipose precursors as mesenchymal, but not endothelial or pericyte in origin. During embryogenesis, Pref-1 marked cells first appear in the dorsal mesenteric region as early as E10.5. These cells become lipid-laden adipocytes at E17.5 in the subcutaneous region, whereas visceral WAT develops after birth. Finally, ablation of Pref-1 marked cells prevents not only embryonic WAT development but also later adult adipose expansion upon high fat feeding, demonstrating the requirement of Pref-1 cells for adipogenesis.
Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Inspired by emerging adoptive cell transfer immunotherapies and the natural migration of immune cells to pathology, here we describe a new class of cell-based in vivo sensors for ultrasensitive disease detection. In our proof of concept, we perform adoptive transfer of syngeneic macrophages which were engineered to produce a synthetic biomarker upon adopting a 'tumor-associated' metabolic profile. Notably, the macrophage sensor detected tumors as small as 25-50 mm 3 , effectively tracked the immunological response in two models of acute inflammation, and was more sensitive than both protein and nucleic acid cancer biomarkers. This technology establishes a clinically translatable approach to early cancer detection and provides a conceptual framework for the use of engineered immune cells for the monitoring of many disease states in addition to cancer.
Photocurrent of a single ZnO nanowire synthesized by a sol-gel route was investigated. In vacuum, the dark current was bigger but the photoresponse was slower than that in air, attributed to the release of the available charge carriers by the desorption of water molecules and the decrease of the exchange rates of molecular ions. Under the steady radiation of the ultraviolet light (λ=325nm), a gradual decrease of the photocurrent was noticeable, which can be explained in terms of the annihilation of the carriers by the replacement of hydroxyl groups (OH−) by O2−, resulting in the decrease of charge carriers.
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