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This meta-analysis aims to screen the risk factors for severe illness and death and provide help for early clinical treatment of the new coronavirus (COVID-19). Based on a comprehensive search of PubMed, Embase, and Web of Science databases, we included studies that explored the cause and risk factors for severe illness and death in COVID-19 patients. We evaluated the strength of this relationship using odds ratios (ORs) with 95% confidence intervals (CIs). A total of 17 articles were included; 16 of the 17 articles were from China, and the risk factors associated with severe illness and death were age, sex, and multiple comorbidities. Advanced age (≥65 years, severe illness, OR = 2.62; death, OR = 6.00), male (severe illness, OR = 1.49; death, OR = 1.54), chronic respiratory diseases (severe illness, OR = 5.67; death, OR = 3.72), diabetes (severe illness, OR = 3.27; death, OR = 2.60), hypertension (severe illness, OR = 3.08; death, OR = 3.53), chronic kidney disease (severe illness, OR = 3.59; death, OR = 5.38), and cardiovascular diseases (severe illness, OR = 3.87; death, OR = 4.91) were all risk factors. For COVID-19 patients, advanced age, male, and patients with chronic disease are at higher risk of developing severe illness or even death., Competing Interests: The authors declare that there are no conflicts of interest associated with the publication of this manuscript., (Copyright © 2021 Pengqiang Du et al.)

Continuous Positive Airway Pressure (CPAP) therapy is commonly prescribed for longstanding, acute cases of Obstructive Sleep Apnea (OSA) during which patients must wear a tight-fitting breathing mask overnight for the duration of the treatment. Because this condition frequently leads to the permanent use of CPAP masks, interface selection is a crucial factor influencing the treatment quality and effectiveness. Masks/interface selection is normally performed on a trial an error basis with clinicians informing their selection based on OSA-related factors with basic fitting feedback from patients. However, it is not uncommon for patients to abandon the treatment or request additional consultations due to ill-fitting CPAP mask with the main sources of discomfort being perceived air leakage and mask/strap overtightening leading to skin damage. This work introduces a novel system (Smart-Fit), for CPAP interface selection using advanced digital technologies, such as Reverse Engineering and Computational Modeling (Finite Element Analysis) which are paired to evaluate and determine the best fitting interface for each clinical case. The model simplifies the number of 3D facial landmarks to 12 and established that a 2 mm scan resolution is enough for accurate scans. The Von Mises stress map in ANSYS serves as an indicator of potential high-pressure areas, triggering the need for a chance of mask size. Current results indicate the Smart Fit System can enable a "best fit CPAP interface" to be selected considering individual's physical characteristics and existing CPAP interface configurations. The development of the Smart Fit System is an evolution compared to traditional CPAP interface selection approach, which optimizes the CPAP interface selection process.

What Is Known and Objectives: The association between inosine triphosphatase (ITPA) rs1127354 polymorphisms in HCV-infected patients receiving ribavirin (RBV)-based therapy, and the risk of adverse drug reaction and outcomes is still unclear. A meta-analysis was conducted to summarize and clarify this association systematically., Methods: A comprehensive search was performed in PubMed, Embase and Web of Sciences, and twenty-two studies were selected from the literature search. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated by either fixed- or random-effects models., Results: Four outcomes were evaluated: (a) haemoglobin decline: significant associations with haemoglobin decline were found for rs1127354 CC VS CA + AA (OR = 10.59, 95% CI = 6.39-17.54); (b) severe anaemia: significant association with severe anaemia was observed for rs1127354 CC VS CA + AA (OR = 16.24, 95% CI = 6.21-42.43); (c) sustained virological response (SVR): CC genotype carriers had a decrease SVR during treatment (OR = 0.65, 95% CI = 0.52-0.81); (d) RBV dose reduction or stopping treatment: although statistical evidence of an association was found between the polymorphism and RBV dose reduction during treatment (OR = 1.80, 95% CI = 1.03-3.13), the sensitivity analysis suggested this result was not robust., What Is New and Conclusion: Patients with ITPA rs1127354 CC polymorphism are more likely to develop haemolytic anaemia, severe anaemia and decreased SVR. Testing for this genetic polymorphism may benefit patients., (© 2020 John Wiley & Sons Ltd.)

Acoustofluidics have been widely used for particle and cell manipulations. Given the scaling of acoustic radiation forces and acoustic streaming flow velocities with increasing frequency, existing acoustofluidic manipulation of submicron particles require actuation at MHz and even GHz frequencies. In this work, we explore a novel acoustofluidic phenomenon, where an ultralow frequency (800 Hz) acoustic vibration is capable of concentrating and patterning submicron particles at two poles of each pillar in an array embedded in a microfluidic device. This unprecedented phenomenon is attributed to a collective effect of acoustic streaming induced drag force and non-Newtonian fluid induced elastic lift force, arising from symmetric acoustic microstreaming flows around each pillar uniformly across the entire pillar array. To our knowledge, this is the first demonstration that particles can be manipulated by an acoustic wave with a wavelength that is 6 orders of magnitude larger than the particle size. This ultralow frequency acoustofluidics will enable a simple and cost-effective solution to effective and uniform manipulation of submicron biological particles in large scales, which has the potential to be widely exploited in clinical and biomedical fields.

Precisely controllable transport and rotation of microparticles and cells has great potential to enable new capabilities for single-cell level analysis. In this work, we present versatile ultrasonic microstreaming based manipulation that enables active and precise control of transport and rotation of individual microscale particles and biological cells in a microfluidic device. Two different types of ultrasonic microstreaming flow patterns can be produced by oscillating embedded microstructures in circular and rectilinear vibration modes, which have been validated by both numerical simulation and experimental observation. We have further showcased the ability to transport individual microparticles along the outlines of complex alphabet letters, demonstrating the versatility and simplicity of single-particle level manipulation with bulk vibration.

Short-chain acyl-CoA dehydrogenase (SCAD), the rate-limiting enzyme for fatty acid β-oxidation, has a negative regulatory effect on pathological cardiac hypertrophy and fibrosis. Furthermore, flavin adenine dinucleotide (FAD) can enhance the expression and enzyme activity of SCAD. However, whether FAD can inhibit pathological cardiac hypertrophy and fibrosis remains unclear. Therefore, we observed the effect of FAD on pathological cardiac hypertrophy and fibrosis. FAD significantly inhibited PE-induced cardiomyocyte hypertrophy and AngII-induced cardiac fibroblast proliferation. In addition, FAD ameliorated pathological cardiac hypertrophy and fibrosis in SHR. FAD significantly increased the expression and enzyme activity of SCAD. Meanwhile, ATP content was increased, the content of free fatty acids and reactive oxygen species were decreased by FAD in vivo and in vitro. In addition, molecular dynamics simulations were also used to provide insights into the structural stability and dynamic behavior of SCAD. The results demonstrated that FAD may play an important structural role on the SCAD dimer stability and maintenance of substrate catalytic pocket to increase the expression and enzyme activity of SCAD. In conclusion, FAD can inhibit pathological cardiac hypertrophy and fibrosis through activating SCAD, which may be a novel effective treatment for pathological cardiac hypertrophy and fibrosis, thus prevent them from developing into heart failure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Exercise-induced autophagy is associated with physiological left ventricular hypertrophy (LVH), and a growing body of evidence suggests that microRNAs (miRNAs) can regulate autophagy-related genes. However, the precise role of miRNAs in exercise induced autophagy in physiological LVH has not been fully defined. In this study, we investigated the microRNA-autophagy axis in physiological LVH and deciphered the underlying mechanism using a rat swimming exercise model. Rats were assigned to sedentary control (CON) and swimming exercise (EX) groups; those in the latter group completed a 10-week swimming exercise without any load. For in vitro studies, H9C2 cardiomyocyte cell line was stimulated with IGF-1 for hypertrophy. We found a significant increase in autophagy activity in the hearts of rats with exercise-induced physiological hypertrophy, and miRNAs showed a high score in the pathway enriched in autophagy. Moreover, the expression levels of miR-26b-5p, miR-204-5p, and miR-497-3p showed an obvious increase in rat hearts. Adenovirus-mediated overexpression of miR-26b-5p, miR-204-5p, and miR-497-3p markedly attenuated IGF-1-induced hypertrophy in H9C2 cells by suppressing autophagy. Furthermore, miR-26b-5p, miR-204-5p, and miR-497-3p attenuated autophagy in H9C2 cells through targeting ULK1, LC3B, and Beclin 1, respectively. Taken together, our results demonstrate that swimming exercise induced physiological LVH, at least in part, by modulating the microRNA-autophagy axis, and that miR-26b-5p, miR-204-5p, and miR-497-3p may help distinguish physiological and pathological LVH., (Copyright © 2020 Qi, Luo, Ma, Zhang, Li and Zhang.)

Inertial particle separation using passive hydrodynamic forces has attracted great attention in the microfluidics community because of its operation simplicity and high throughput sample processing. Due to the passive nature of inertial microfluidics, each inertial sorting device is typically fixed to a certain cut-off size for particle separation that is mainly dependent on the channel geometry and dimensions, which however lacks tunability in the separation threshold to fulfill the needs of different sorting applications. In this work, we explore the use of non-Newtonian viscoelastic fluids to achieve size-tunable elasto-inertial particle focusing and sorting in a microfluidic device with reverse wavy channel structures. The balance and competition among inertial lift force, Dean drag force and the controllable elastic lift force give rise to interesting size-based particle focusing phenomena with tunability in the equilibrium focusing positions. Seven differently sized fluorescent microspheres (0.3, 2, 3, 5, 7, 10 and 15 μm) are used to investigate the effects of the flow rate, viscoelastic fluid concentration and particle size on the tunable elasto-inertial focusing behavior. With the sorting tunability, we have achieved a highly effective sorting of a particle mixture into three subpopulations based on the particle size, i.e., small, intermediate and large subpopulations. We even demonstrate the controllable tunability among three separation thresholds for elasto-inertial particle sorting without changing the geometry and dimensions of the microfluidic device. The tunability of the developed elasto-inertial particle focusing and sorting can significantly broaden its application in a variety of biomedical research studies.

Nonpharmaceutical therapies such as exercise training and diet intervention are widely used for the treatment of insulin resistance (IR). Although the skeletal muscle is the major peripheral tissue of glucose metabolism under insulin stimulation, the mechanism underlying muscle IR is poorly understood. Using a high-fat diet-induced IR mouse model, we here show that NADPH oxidase 4 (Nox4) upregulation mediates the production of reactive oxygen species (ROS) that causes metabolic syndrome featuring IR. The Nox4 expression level was markedly elevated in IR mice, and Nox4 overexpression was sufficient to trigger IR. Conversely, downregulation of Nox4 expression through exercise training prevented diet-induced IR by reducing the production of ROS and enhancing the AKT signaling pathway. Thus, this study indicates that exercise might improve IR through a reduction of Nox4-induced ROS in the skeletal muscle and enhancement of AKT signal transduction., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2020 Jie Qi et al.)

Cardiac hypertrophy is one of the significant risk factors that result in maladaptive cardiac remodeling and heart failure, and exercise is known to exert cardioprotection. In this research, the cardioprotective function and exercise mechanisms were explored.The rats underwent transverse aortic constriction (TAC) or a sham operation. The rats that received TAC were randomly assigned to five groups: (1) rats subjected to a sham operation as control group (SC), (2) rats that underwent TAC group (TC), (3) TAC and moderate-intensity exercise group (TE), (4) TE plus 3-MA group (TEM), and (5) TE plus Compound C group (TEC). The heart function was measured via echocardiography. Histological analysis and relative protein testing were conducted to analyze collagen deposition and apoptosis. Furthermore, western blot was employed to measure the protein expression of relevant signaling pathways. Impaired cardiac function, interstitial fibrosis, enhanced apoptosis, and ER stress were observed in the TAC-induced left ventricular hypertrophy. Exercise attenuated TAC-induced cardiac dysfunction, interstitial fibrosis, and ER stress-related apoptosis. In addition, exercise significantly improved autophagy and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor Compound C repressed the activation of AMPK, and autophagy inhibitor 3-methyladenine reversed exercise-induced autophagy. All of these abolished the protection of exercise against cardiac dysfunction and fibrosis induced by TAC.Our results indicated that 4 weeks of treadmill exercise could alleviate pressure overload-induced LV dysfunction and remodeling via an autophagy-dependent mechanism, which was induced by enhancing autophagy through the activation of AMPK.

The ability to isolate rare circulating tumor cells (CTCs) from blood samples is essential to perform liquid biopsy as a routine diagnostic and prognostic test. Both label-free and surface biomarker-based cell sorting technologies have been developed to address the demand in high-integrity isolation of rare CTCs for cancer research. Label-free cell sorting mainly relies on the size difference between CTCs and blood cells; thus, it lacks sufficient sorting specificity. Surface biomarker-based cell sorting is highly specific; however, it requires expensive, labor-intensive, and time-consuming labeling due to the use of multiple sets of surface biomarkers. Because of the complex nature and high heterogeneity of tumorigenesis, it is difficult to rely on a single sorting process for high-integrity rare cell isolation. In this study, for the first time, we present a hybrid microfluidic cell sorting method combining high throughput size-dependent inertial focusing for size-based pre-enrichment and high accuracy fluorescence activated acoustic sorting for single cell isolation. After one single hybrid sorting process, we have demonstrated at least 2500-fold purity enrichment of MCF-7 breast cancer cells spiked in diluted whole blood samples with cell viability maintained at 91 ± 1% (viability before sorting was 94 ± 2%). This developed hybrid microfluidic cell sorting technique provides a promising solution for rare cell isolation needed in a variety of biological research and clinical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Droplet-based single-cell sequencing has emerged as a very powerful tool to study the cellular heterogeneity in diseased tissues for a variety of biological problems. However, the current droplet generation with a single particle and cell encapsulation is a random process and suffers from a low yield that is unable to fulfill the high-throughput analysis requirement. In this work, we present a new fluorescence-activated droplet sorting (FADS) system that can isolate single-cell droplets at high accuracy and high yield using a highly focused surface acoustic wave (HFSAW) with a beam width around 50 μm. The acoustic wave is locally coupled into the microfluidic channel for droplet sorting through a micropillar waveguide structure between the channel and the interdigitated transducer (IDT). This detachable acoustic sorting system allows the disposal of the microfluidic channel after a single use to avoid cross-contamination and keeps the expensive IDT device reusable. We have achieved rapid and accurate isolation of single-cell droplets with purity higher than 90% at ∼1 kHz sorting rate with three different encapsulation contents. In addition, with the uniformly produced droplet size at ∼40 μm, the present acoustic FADS system enables effective sorting of small particles down to submicrometer size, which is challenging for existing fluorescence-activated cell sorting systems.

Exosomes, submicron membrane vesicles (30-200 nm) secreted by almost all cells, containing significant information such as proteins, microRNAs and DNAs, are closely associated with disease diagnostic and prognostic tests for liquid biopsy in clinical practice. However, their inherently small sizes lead to great challenges for isolating them from complex body fluids with high-throughput and high-purity. In this work, a reverse wavy channel structure using viscoelastic fluids with the addition of biocompatible polymer was presented for elasto-inertial focusing and sorting of submicron particles and exosomes. The microfluidic periodically reversed Dean secondary flow generated by repeated wavy channel structures could facilitate particle focusing compared with traditional straight channels. Four differently sized fluorescent submicron spheres (1 μm, 500 nm, 300 and 100 nm) were used to study the focusing behavior under various conditions. We have achieved simple, high-throughput, and label-free sorting of exosomes with purity higher than 92% and recovery higher than 81%. This developed elasto-inertial exosome sorting technique may provide a promising platform in various exosome-related biological research and pharmaceutical applications.

Objective: To Study the changes of short-chain acyl-CoA dehydrogenase (SCAD) in heart failure (HF) after myocardial infarction (MI), and the effect of aerobic exercise on SCAD., Methods: Healthy male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), sham operation swimming group (Sham+swim group), HF model group (LAD group) and HF swimming group (LAD+swim group) by random number table method, with 9 rats in each group. The left anterior descending branch of coronary artery (LAD) was ligated to establish a rat model of HF after MI. In Sham group, only one loose knot was threaded under the left coronary artery, and the rest operations were the same as those in LAD group. Rats in Sham+swim group and LAD+swim group were given swimming test for 1 week after operation (from 15 minutes on the 1st day to 60 minutes on the 5th day). Then they were given swimming endurance training (from the 2nd week onwards, 60 minutes daily, 6 times weekly, 10 weeks in a row). Tail artery systolic pressure (SBP) was measured before swimming endurance training and every 2 weeks until the end of the 10th week. Ten weeks after swimming training, echocardiography was performed to measure cardiac output (CO), stroke volume (SV), left ventricular ejection fraction (LVEF), shortening fraction (FS), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). Morphological changes of heart were observed by Masson staining. Apoptosis of myocardial cells was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling stain (TUNEL) and apoptosis index (AI) was calculated. Reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot were used to detect the mRNA and protein expression of myocardial SCAD respectively. In addition, the enzyme activity of SCAD, the content of adenosine triphosphate (ATP) and free fatty acid (FFA) in serum and myocardium were detected according to the kit instruction steps., Results: Compared with Sham group, Sham+swim group showed SBP did not change significantly, with obvious eccentric hypertrophy and increased myocardial contractility, and LAD group showed persistent hypotension, obvious MI, thinning of left ventricle, and decreased myocardial systolic/diastolic function. Compared with LAD group, SBP, systolic/diastolic function and MI in LAD+swim group were significantly improved [SBP (mmHg, 1 mmHg = 0.133 kPa): 119.5±4.4 vs. 113.2±4.5 at 4 weeks, 120.3±4.0 vs. 106.5±3.7 at 6 weeks, 117.4±1.3 vs. 111.0±2.3 at 8 weeks, 126.1±1.6 vs. 119.4±1.9 at 10 weeks; CO (mL/min): 59.10±6.31 vs. 33.19±4.76, SV (μL): 139.42±17.32 vs. 84.02±14.26, LVEF: 0.523±0.039 vs. 0.309±0.011, FS: (28.17±2.57)% vs. (15.93±3.64)%, LVEDD (mm): 8.80±0.19 vs. 9.35±0.30, LVESD (mm): 5.90±0.77 vs. 7.97±0.60, LVEDV (μL): 426.57±20.84 vs. 476.24±25.18, LVESV (μL): 209.50±25.18 vs. 318.60±16.10; AI: (20.4±1.4)% vs. (31.2±4.6)%; all P < 0.05]. Compared with Sham group, the mRNA and protein expression of myocardium SCAD, the activity of SCAD in Sham+swim group were significantly increased, the content of ATP was slightly increased, the content of serum FFA was significantly decreased, and the content of myocardial FFA was slightly decreased; conversely, the mRNA and protein expression of myocardium SCAD, the activity of SCAD and the content of ATP in LAD group were significantly decreased, the content of serum and myocardial FFA were significantly increased. Compared with LAD group, the mRNA and protein expression of myocardium SCAD, the content of ATP were significantly increased in LAD+swim group [SCAD mRNA (2 -ΔΔCt ): 0.52±0.16 vs. 0.15±0.01, SCAD/GAPDH (fold increase from Sham group): 0.94±0.08 vs. 0.60±0.11, ATP content (μmol/g): 52.8±10.1 vs. 14.7±6.1, all P < 0.05], the content of serum and myocardial FFA were significantly decreased [serum FFA (nmol/L): 0.11±0.03 vs. 0.29±0.04, myocardial FFA (nmol/g): 32.7±8.2 vs. 59.7±10.7, both P < 0.05], and the activity of SCAD was slightly increased (kU/g: 12.3±4.3 vs. 8.9±5.8, P > 0.05)., Conclusions: The expression of SCAD in HF was significantly down-regulated, and the expression was significantly up-regulated after aerobic exercise intervention, indicating that swimming may improve the severity of HF by up-regulating the expression of SCAD.

Introduction: Continuous positive airway pressure (CPAP) therapy is a clinical treatment for moderate or severe obstructive sleep apnea (OSA). Commercial CPAP mask designs normally come in standard sizes and the configuration is not commonly tailored to the patients' characteristics such as face topology, skin sensitivity, and severity of OSA syndrome; however, an optimal mask/interface selection is a key factor influencing the compliance and effectiveness of CPAP treatment., Areas Covered: This review investigates the conventional CPAP mask design, its effect on OSA treatment, and the related risk factors that can lead to skin damage after long-term repeated use. Through a literature search on common databases, Scopus, PubMed, and Google Scholar, we identified reported facts on the influence of the mask interface and current trends toward customized devices., Expert Commentary: There is potential for optimizing the CPAP mask fit by adapting the interface to the patients' individual characteristics. This holds particularly true for users with abnormal features or simply outside conventional industry sizing standards. Enabling technologies for undertaking this adaptation include reverse engineering, computational modeling, and additive manufacturing. There is to date no integrated system that integrates those elements into a standard solution, but several studies have shown its effectiveness for specific cohorts.

The characteristics of the electromagnetically induced transparency (EIT) analog exposed under different illumination powers have been investigated theoretically and experimentally. The EIT analog is composed of a fixed aluminum structure fabricated on the silicon substrate. It was found that the resonance degree of the transparent window displayed a decreasing trend, and a blueshift phenomenon emerged by increasing the powers of the laser. Similarly, the properties of the time delay under different illumination powers have also been researched. The realization of the tuning effect may provide a possible choice for the modulation of the slow light devices.

Inertial microfluidics utilizing passive hydrodynamic forces has been attracting significant attention in the field of precise microscale manipulation owing to its low cost, simplicity and high throughput. In this paper, we present a novel channel design with a series of reverse wavy channel structures for sheathless inertial particle focusing and cell sorting. A single wavy channel unit consists of four semicircular segments, which produce periodically reversed Dean secondary flow along the cross-section of the channel. The balance between the inertial lift force and the Dean drag force results in deterministic equilibrium focusing positions, which also depends on the size of the flow-through particles and cells. Six sizes of fluorescent microspheres (15, 10, 7, 5, 3 and 1 μm) were used to study the size-dependent inertial focusing behavior. Our novel design with sharp-turning subunits could effectively focus particles as small as 3 μm, the average size of platelets, enabling the sorting of cancer cells from whole blood without the use of sheath flows. Utilizing an optimized channel design, we demonstrated the size-based sorting of MCF-7 breast cancer cells spiked in diluted whole blood samples without using sheath flows. A single sorting process was able to recover 89.72% of MCF-7 cells from the original mixture and enrich MCF-7 cells from an original purity of 5.3% to 68.9% with excellent cell viability., Competing Interests: The authors declare that they have no conflict of interest.

Acoustic fields have been widely used for manipulation of particles and cells within microfluidic systems. In this Letter, we explore a novel acoustofluidic phenomenon for particle patterning and focusing, where a periodic acoustic pressure field is produced parallel to internal channel boundaries with the imposition of either a traveling or standing surface acoustic wave (SAW). This effect results from the propagation and intersection of edge waves from the channel walls according to the Huygens-Fresnel principle and classical wave fronts from the substrate-fluid interface. We demonstrate versatile control over this effect to produce both one- and two-dimensional acoustic patterning from one-dimensional SAW fields and its utility for continuous particle focusing. Uniquely, this channel-guided acoustic focusing permits the generation of robust acoustic fields without channel resonance conditions and particle focusing positions that are difficult or impossible to produce otherwise.

Fluorescence activated cell sorting (FACS) has become an essential technique widely exploited in biological studies and clinical applications. However, current FACS systems are quite complex, expensive, bulky, and pose potential sample contamination and biosafety issues due to the generation of aerosols in an open environment. Microfluidic technology capable of precise cell manipulation has great potential to reinvent and miniaturize conventional FACS systems. In this work, we demonstrate a benchtop scale FACS system that makes use of a highly focused traveling surface acoustic wave beam to sort out micron-sized particles and biological cells upon fluorescence interrogation at ∼kHz rates. The highly focused acoustic wave beam has a width of ∼50 μm that enables highly accurate sorting of individual particles and cells. We have applied our acoustic FACS system to isolate fluorescently labeled MCF-7 breast cancer cells from diluted whole blood samples with the purity of sorted MCF-7 cells higher than 86%. The cell viability before and after acoustic sorting is higher than 95%, indicating excellent biocompatibility that should enable a variety of cell sorting applications in biomedical research.

Acoustic streaming has emerged as a promising technique for refined microscale manipulation, where strong rotational flow can give rise to particle and cell capture. In contrast to hydrodynamically generated vortices, acoustic streaming is rapidly tunable, highly scalable and requires no external pressure source. Though streaming is typically ignored or minimized in most acoustofluidic systems that utilize other acoustofluidic effects, we maximize the effect of acoustic streaming in a continuous flow using a high-frequency (381 MHz), narrow-beam focused surface acoustic wave. This results in rapid fluid streaming, with velocities orders of magnitude greater than that of the lateral flow, to generate fluid vortices that extend the entire width of a 400 μm wide microfluidic channel. We characterize the forces relevant for vortex formation in a combined streaming/lateral flow system, and use these acoustic streaming vortices to selectively capture 2 μm from a mixed suspension with 1 μm particles and human breast adenocarcinoma cells (MDA-231) from red blood cells.

Despite increasing demand in the manipulation of nanoscale objects for next generation biological and industrial processes, there is a lack of methods for reliable separation, concentration and purification of nanoscale objects. Acoustic methods have proven their utility in contactless manipulation of microscale objects mainly relying on the acoustic radiation effect, though the influence of acoustic streaming has typically prevented manipulation at smaller length scales. In this work, however, we explicitly take advantage of the strong acoustic streaming in the vicinity of a highly focused, high frequency surface acoustic wave (SAW) beam emanating from a series of focused 6 μm substrate wavelength interdigital transducers patterned on a piezoelectric lithium niobate substrate and actuated with a 633 MHz sinusoidal signal. This streaming field serves to focus fluid streamlines such that incoming particles interact with the acoustic field similarly regardless of their initial starting positions, and results in particle displacements that would not be possible with a travelling acoustic wave force alone. This streaming-induced manipulation of nanoscale particles is maximized with the formation of micro-vortices that extend the width of the microfluidic channel even with the imposition of a lateral flow, occurring when the streaming-induced flow velocities are an order of magnitude larger than the lateral one. We make use of this acoustic streaming to demonstrate the continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.

Most microfluidics-based sorting methodologies utilize size differences between suspended micro-objects as the defining characteristic by which they are sorted. Sorting based on mechanical properties, however, would provide a new avenue for sample preparation, detection and diagnosis for a number of emerging biological and medical analyses. In this study, we demonstrate separation of polystyrene (PS) and poly(methyl methacrylate) (PMMA) microspheres based entirely on their difference in mechanical properties using traveling surface acoustic waves (TSAWs). We theoretically examine the correlation of the applied TSAW frequency, particle density and sound speed with respect to the resultant acoustic radiation force (ARF) that acts to translate particles, and experimentally corroborate these predictions by translating PS and PMMA particles simultaneously in a stationary flow. Even when PS and PMMA particles have the same diameters, they exhibit strongly nonlinear and distinct acoustophoretic responses as a function of their mechanical properties and the applied TSAW frequency. By specifically matching the appropriate acoustic frequency to the desired particle size, each particle population can be selectively translated and sorted. We demonstrate that this mechanical property based sorting can continuously separate these particle populations with at least 95% efficiency in the mixed 10/15 μm diameter PS and PMMA particle solutions tested.

The surface acoustic wave (SAW) is effective for the manipulation of fluids and particles at microscale. The current approach of integrating interdigitated transducers (IDTs) for SAW generation into microfluidic channels involves complex and laborious microfabrication steps. These steps often require full access to clean room facilities and hours to align the transducers to the precise location. This work presents an affordable and innovative method for fabricating SAW-based microfluidic devices without the need for clean room facilities and alignment. The IDTs and microfluidic channels are fabricated using the same process and thus are precisely self-aligned in accordance with the device design. With the use of the developed fabrication approach, a few types of different SAW-based microfluidic devices have been fabricated and demonstrated for particle separation and active droplet generation.

Micrometer-scale acoustic waves are highly useful for refined optomechanical and acoustofluidic manipulation, where these fields are spatially localized along the transducer aperture but not along the acoustic propagation direction. In the case of acoustic tweezers, such a conventional acoustic standing wave results in particle and cell patterning across the entire width of a microfluidic channel, preventing selective trapping. We demonstrate the use of nanosecond-scale pulsed surface acoustic waves (SAWs) with a pulse period that is less than the time of flight between opposing transducers to generate localized time-averaged patterning regions while using conventional electrode structures. These nodal positions can be readily and arbitrarily positioned in two dimensions and within the patterning region itself through the imposition of pulse delays, frequency modulation, and phase shifts. This straightforward concept adds new spatial dimensions to which acoustic fields can be localized in SAW applications in a manner analogous to optical tweezers, including spatially selective acoustic tweezers and optical waveguides.

Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.

Components in biomedical analysis tools that have direct contact with biological samples, especially biohazardous materials, are ideally discarded after use to prevent cross-contamination. However, a conventional acoustofluidic device is typically a monolithic integration that permanently bonds acoustic transducers with microfluidic channels, increasing processing costs in single-use platforms. In this study, we demonstrate a detachable acoustofluidic system comprised of a disposable channel device and a reusable acoustic transducer for noncontact continuous particle separation via a traveling surface acoustic wave (TSAW). The channel device can be placed onto the SAW transducer with a high alignment tolerance to simplify operation, is made entirely of polydimethylsiloxane (PDMS), and does not require any additional coupling agent. A microstructured pillar is used to couple acoustic waves into the fluid channel for noncontact particle manipulation. We demonstrate the separation of 10 and 15 μm particles at high separation efficiency above 98% in a 49.5 MHz TSAW using the developed detachable acoustofluidic system. Its disposability and ease of assembly should enable broad use of noncontact, disposable particle manipulation techniques in practical biomedical applications related to sample preparation.

The microdefects of structure frequently act as the source to generate initial cracks and lead to the fracture failure. Study on the deformation behaviors of embedded defects would be conducive to better understand the failure mechanisms of structural materials. Micro-indentation technique was applied to prepare the initial indentations as embedded surface defects at the gauge length section and central section of a cross-shaped AZ31B magnesium alloy specimen. A novel in situ biaxial tensile device was developed to apply the synchronous biaxial loads. Via the observation by an optical microscope with three-dimensional imaging and measurement functions, the changing laws of the indentation topographies under uniaxial and biaxial tensile loads were discussed. Compared with the gauge length section, the increasing trend of the indentation length of the central section was relatively flat, and the decreasing trend of the indentation depth was more significant. The changes of indentation topographies were explained by the Poisson effect, and the significant plastic tensile stress has led to the releasing of the residual stress around the indentation location and also promoted the planarization of the pileup.

The nanoparticles (NPs) provide a promising prospect for tumor therapy, and exercise is also becoming readily and accepted as a beneficial adjunct therapy to maintain or enhance quality of life in cancer patients. We investigate the antitumor efficacy of paclitaxel (PT) loaded polylactide/poly(ethylene glycol) NPs (PT-PLA/PEG NPs) under the exercise conditions. Results showed that within the first 7 days, the PT concentration in tumor maintained at a higher level in the PT-PLA/PEG NPs + exercise (PT-PLA/PEG NPs + EX) group as compared with the PT-PLA/PEG NPs group. All the phagocytosis rates of macrophages were significantly decreased below the CON in exercise group. The most significant antitumor effect was observed in PT-PLA/PEG NPs + EX group, demonstrating that the PT-PLA/PEG NPs improved the concentration of PT, and exercise could further increased its therapeutic efficiency for tumor. These researches may provide an effective means for tumor therapy.

The physical properties of the machining-induced new surface depend on the performance of the initial defect surface and deformed layer in the subsurface of the bulk material. In this paper, three-dimensional molecular dynamics simulations of nanoindentation are preformed on the single-point diamond turning surface of single-crystal copper comparing with that of pristine single-crystal face-centered cubic copper. The simulation results indicate that the nucleation of dislocations in the nanoindentation test on the machining-induced surface and pristine single-crystal copper is different. The dislocation embryos are gradually developed from the sites of homogeneous random nucleation around the indenter in the pristine single-crystal specimen, while the dislocation embryos derived from the vacancy-related defects are distributed in the damage layer of the subsurface beneath the machining-induced surface. The results show that the hardness of the machining-induced surface is softer than that of pristine single-crystal copper. Then, the nanocutting simulations are performed along different crystal orientations on the same crystal surface. It is shown that the crystal orientation directly influences the dislocation formation and distribution of the machining-induced surface. The crystal orientation of nanocutting is further verified to affect both residual defect generations and their propagation directions which are important in assessing the change of mechanical properties, such as hardness and Young's modulus, after nanocutting process.

We have developed a convenient method for the efficient monofluorination via the electrophilic fluorocyclization reaction of 2,3-allenoic acids with Selectfluor in MeCN in the presence of 10 equiv of H2O or even in pure water to afford beta-fluorobutenolides in moderate to high yields.

[reaction: see text] Optically active pyrazolidine derivatives have been constructed by the Cu- and Pd-catalyzed asymmetric one-pot tandem addition-cyclization reaction of 2-(2',3'-dienyl)-beta-ketoesters, organic halides, and dibenzyl azodicarboxylate. The absolute configurations of the final products depend on the structure of the ligand.