In recent nanobiotechnology developments, a wide variety of functional nanomaterials and engineered biomolecules have been created, and these have numerous applications in cell biology. For these nanomaterials to fulfill their promises completely, they must be able to reach their biological targets at the subcellular level and with a high level of specificity. Traditionally, either nanocarrier- or membrane disruption-based method has been used to deliver nanomaterials inside cells; however, these methods are suboptimal due to their toxicity, inconsistent delivery, and low throughput, and they are also labor intensive and time-consuming, highlighting the need for development of a next-generation, intracellular delivery system. This study reports on the development of an intracellular nanomaterial delivery platform, based on unexpected cell-deformation phenomena via spiral vortex and vortex breakdown exerted in the cross- and T-junctions at moderate Reynolds numbers. These vortex-induced cell deformation and sequential restoration processes open cell membranes transiently, allowing effective and robust intracellular delivery of nanomaterials in a single step without the aid of carriers or external apparatus. By using the platform described here (termed spiral hydroporator), we demonstrate the delivery of different nanomaterials, including gold nanoparticles (200 nm diameter), functional mesoporous silica nanoparticles (150 nm diameter), dextran (hydrodynamic diameters between 2–55 nm), and mRNA, into different cell types. We demonstrate here that the system is highly efficient (up to 96.5%) with high throughput (up to 1 × 106 cells/min) and rapid delivery (∼1 min) while maintaining high levels of cell viability (up to 94%).
Flow-induced oscillations of a flexibly mounted triangular prism allowed to oscillate in the cross-flow direction are studied experimentally, covering the entire range of possible angles of attack. For angles of attack smaller than $\unicode[STIX]{x1D6FC}=25^{\circ }$ (where $0^{\circ }$ corresponds to the case where one of the vertices is facing the incoming flow), no oscillation is observed in the entire reduced velocity range tested. At larger angles of attack of $\unicode[STIX]{x1D6FC}=30^{\circ }$ and $\unicode[STIX]{x1D6FC}=35^{\circ }$, there exists a limited range of reduced velocities where the prism experiences vortex-induced vibration (VIV). In this range, the frequency of oscillations locks into the natural frequency twice: once approaching from the Strouhal frequencies and once from half the Strouhal frequencies. Once the lock-in is lost, there is a range with almost-zero-amplitude oscillations, followed by another range of non-zero-amplitude response. The oscillations in this range are triggered when the Strouhal frequency reaches a value three times the natural frequency of the system. Large-amplitude low-frequency galloping-type oscillations are observed in this range. At angles of attack larger than $\unicode[STIX]{x1D6FC}=35^{\circ }$, once the oscillations start, their amplitude increases continuously with increasing reduced velocity. At these angles of attack, the initial VIV-type response gives way to a galloping-type response at higher reduced velocities. High-frequency vortex shedding is observed in the wake of the prism for the ranges with a galloping-type response, suggesting that the structure’s oscillations are at a lower frequency compared with the shedding frequency and its amplitude is larger than the typical VIV-type amplitudes, when galloping-type response is observed.
Carotid intima-media thickness (CIMT) testing is recognized as a valid method for the noninvasive assessment of atherosclerosis. In addition to its association with known cardiovascular risk factors and both prevalent and incident coronary heart disease, the rate of CIMT progression is directly related to the risk for future cardiovascular events. Subsequently, CIMT has been a valuable research tool in clinical trials in the assessment of therapeutic agents directed against atherosclerosis. An overview of CIMT testing including its precise measurement, establishment as a surrogate for atherosclerosis by epidemiologic trials, role in clinical trials, and potential applications in both primary and secondary coronary heart disease prevention is presented.
A new correlation-filter design methodology is presented for achieving two objectives: synthetic discriminant function filters that can be implemented on arbitrary various criteria of interest. devices and that can provide optimal trade-off among various criteria of interest.
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