Highlights d Heterogeneity and plasticity of non-parenchymal cells in healthy and NASH liver d Landscape of intrahepatic ligand-receptor signaling at single-cell resolution d Emergence of Trem2+ NASH-associated macrophages (NAMs) in mouse and human NASH d Stellakine secretion and contractile response to vasoactive hormones by HSCs
Precise monitoring of the rapidly changing immune status during the course of a disease requires multiplex analysis of cytokines from frequently sampled human blood. However, the current lack of rapid, multiplex, and low volume assays makes immune monitoring for clinical decision-making (e.g., critically ill patients) impractical. Without such assays, immune monitoring is even virtually impossible for infants and neonates with infectious diseases and/or immune mediated disorders as access to their blood in large quantities is prohibited. Localized surface plasmon resonance (LSPR)-based microfluidic optical biosensing is a promising approach to fill this technical gap as it could potentially permit real-time refractometric detection of biomolecular binding on a metallic nanoparticle surface and sensor miniaturization, both leading to rapid and sample-sparing analyte analysis. Despite this promise, practical implementation of such a microfluidic assay for cytokine biomarker detection in serum samples has not been established primarily due to the limited sensitivity of LSPR biosensing. Here, we developed a high-throughput, label-free, multiarrayed LSPR optical biosensor device with 480 nanoplasmonic sensing spots in microfluidic channel arrays and demonstrated parallel multiplex immunoassays of six cytokines in a complex serum matrix on a single device chip while overcoming technical limitations. The device was fabricated using easy-to-implement, one-step microfluidic patterning and antibody conjugation of gold nanorods (AuNRs). When scanning the scattering light intensity across the microarrays of AuNR ensembles with dark-field imaging optics, our LSPR biosensing technique allowed for high-sensitivity quantitative cytokine measurements at concentrations down to 5–20 pg/mL from a 1 µL serum sample. Using the nanoplasmonic biosensor microarray device, we demonstrated the ability to monitor the inflammatory responses of infants following cardiopulmonary bypass (CPB) surgery through tracking the time-course variations of their serum cytokines. The whole parallel on-chip assays, which involved the loading, incubation, and washing of samples and reagents, and 10-fold replicated multianalyte detection for each sample using the entire biosensor arrays, were completed within 40 min.
This work measures the thermal conductivities along free-standing silicon layers doped with boron and phosphorus at concentrations ranging from 1ϫ10 17 to 3ϫ10 19 cm Ϫ3 at temperatures between 15 and 300 K. The impurity concentrations are measured using secondary ion mass spectroscopy ͑SIMS͒ and the thermal conductivity data are interpreted using phonon transport theory accounting for scattering on impurities, free electrons, and the layer boundaries. Phonon-boundary scattering in the 3-m-thick layers reduces the thermal conductivity of the layers at low temperatures regardless of the level of impurity concentration. The present data suggest that unintentional impurities may have strongly reduced the conductivities reported previously for bulk samples, for which impurity concentrations were determined from the electrical resistivity rather than from SIMS data. This work illustrates the combined effects of phonon interactions with impurities, free electrons, and material interfaces, which can be particularly important in semiconductor devices.
We developed a molecular sorter that operates without external power or control by integrating the microtubule-based, biological motor kinesin into a microfluidic channel network to sort, transport, and concentrate molecules. In our devices, functionalized microtubules that capture analyte molecules are steered along kinesin-coated microchannel tracks toward a collector structure, concentrated, and trapped. Using fluorescent analyte molecules and nanoliter sample volumes, we demonstrated 14 fM sensitivity, even in the presence of high concentrations of other proteins.
Polymer films are playing an important role in the development of micromachined sensors and actuators, fast logic circuits, and organic optoelectronic devices. The thermal properties of polyimide films govern the temporal response of many micromachined thermomechanical actuators, such as ciliary arrays. This work develops three experimental techniques for measuring both the in-plane and the out-of-plane thermal conductivities of spin-coated polyimide films with thicknesses between 0.5 and 2.5 m, which are common in MEMS. Two of the techniques use transient electrical heating and thermometry in micromachined structures to isolate the in-plane and outof-plane components. These techniques establish confidence in a third, simpler technique, which measures both components independently and uses IC-compatible processing. The data illustrate the anisotropy in the thermal conductivity of the polyimide films investigated here, with the in-plane conductivity larger by a factor between four and eight depending on film thickness and temperature. The anisotropy diminishes the time constants of thermal actuators made from polyimide films. [375]
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