Theoretical framework of radiation force in surface acoustic waves for modulated particle sorting

Sorting specific target entities from sample mixtures is commonly used in many macroscale laboratory processing, such as disease diagnosis or treatment. Downscaling of sorting systems enables less laboratory space and fewer quantities of sample and reagent. Such lab-on-a-chip devices can perform separation functions using passive or active sorting methods. Such a method, acoustic sorting, when used in microfluidics, offers contactless, label-free, non-invasive manipulation of target cells or particles and is therefore the topic of active current research. Our phase-modulated sorting technique complements traditional time-of-flight techniques and offers higher sensitivity separation using a periodic signal. By cycling of this periodic signal, the target entities are gradually displaced compared to the background debris, thereby achieving sorting. In this paper, we extend the knowledge on phase-modulated sorting techniques. Firstly, using numerical simulations, we confirm the sorting role of our proposed primary acoustic radiation force within surface wave devices. Secondly, a threefold agreement between analytical, numerical and experimental sorting trajectories is presented

Numerical determination of the secondary acoustic radiation force on a small sphere in a plane standing wave field

Two numerical methods based on the Finite Element Method are presented for calculating the secondary acoustic radiation force between interacting spherical particles. The first model only considers the acoustic waves scattering off a single particle, while the second model includes re-scattering effects between the two interacting spheres. The 2D axisymmetric simplified model combines the Gor’kov potential approach with acoustic simulations to find the interacting forces between two small compressible spheres in an inviscid fluid. The second model is based on 3D simulations of the acoustic field and uses the tensor integral method for direct calculation of the force. The results obtained by both models are compared with analytical equations, showing good agreement between them. The 2D and 3D models take, respectively, seconds and tens of seconds to achieve a convergence error of less than 1%. In comparison with previous models, the numerical methods presented herein can be easily implemented in commercial Finite Element software packages, where surface integrals are available, making it a suitable tool for investigating interparticle forces in acoustic manipulation devices

Theoretical Framework of Radiation Force in Surface Acoustic Waves for Modulated Particle Sorting

Sorting specific target entities from sample mixtures is commonly used in many macroscale laboratory processing, such as disease diagnosis or treatment. Downscaling of sorting systems enables less laboratory space and fewer quantities of sample and reagent. Such lab-on-a-chip devices can perform separation functions using passive or active sorting methods. Such a method, acoustic sorting, when used in microfluidics, offers contactless, label-free, non-invasive manipulation of target cells or particles and is therefore the topic of active current research. Our phase-modulated sorting technique complements traditional time-of-flight techniques and offers higher sensitivity separation using a periodic signal. By cycling of this periodic signal, the target entities are gradually displaced compared to the background debris, thereby achieving sorting. In this paper, we extend the knowledge on phase-modulated sorting techniques. Firstly, using numerical simulations, we confirm the sorting role of our proposed primary acoustic radiation force within surface wave devices. Secondly, a threefold agreement between analytical, numerical and experimental sorting trajectories is presented

Monte-Carlo based sensitivity analysis of acoustic sorting methods

Separation in microfluidic devices is a crucial enabling step for many industrial, biomedical, clinical or chemical applications. Acoustic methods offer contactless, biocompatible, scalable sorting with high degree of reconfigurability and are therefore favored techniques. The literature reports on various techniques to achieve particle separation, but these do not investigate the sensitivity of these methods or are difficult to compare due to the lack of figures of merit. In this paper, we present analytical and numerical sensitivity analysis of the time-of-flight and a phase-modulated sorting scheme against various extrinsic and intrinsic properties. The results reveal great robustness of the phase-modulated sorting method against variations of the flow rate or acoustic energy density, while the time-of-flight method shows lower efficiency drop against size and density variations. The results presented in this paper provide a better understanding of the two sorting methods and offer advice on the selection of the right technique for a given sorting application

Particle separation by phase modulated surface acoustic waves

High efficiency isolation of cells or particles from a heterogeneous mixture is a critical processing step in lab-on-a-chip devices. Acoustic techniques offer contactless and label-free manipulation, preserve viability of biological cells, and provide versatility as the applied electrical signal can be adapted to various scenarios. Conventional acoustic separation methods use time-of-flight and achieve separation up to distances of quarter wavelength with limited separation power due to slow gradients in the force. The method proposed here allows separation by half of the wavelength and can be extended by repeating the modulation pattern and can ensure maximum force acting on the particles. In this work, we propose an optimised phase modulation scheme for particle separation in a surface acoustic wave microfluidic device. An expression for the acoustic radiation force arising from the interaction between acoustic waves in the fluid was derived. We demonstrated, for the first time, that the expression of the acoustic radiation force differs in surface acoustic wave and bulk devices, due to the presence of a geometric scaling factor. Two phase modulation schemes are investigated theoretically and experimentally. Theoretical findings were experimentally validated for different mixtures of polystyrene particles confirming that the method offers high selectivity. A Monte-Carlo simulation enabled us to assess performance in real situations, including the effects of particle size variation and non-uniform acoustic field on sorting efficiency and purity, validating the ability to separate particles with high purity and high resolution

Particle separation in surface acoustic wave microfluidic devices using reprogrammable, pseudo-standing waves

We report size and density/compressibility-based particle sorting using on-off quasi-standing waves based on the frequency difference between two ultrasonic transducers. The 13.3 MHz fundamental operating frequency of the surface acoustic wave microfluidic device allows the manipulation of particles on the micrometer scale. Experiments, validated by computational fluid dynamics, were carried out to demonstrate size-based sorting of 5–14.5 μm diameter polystyrene (PS) particles and density/compressibility-based sorting of 10 μm PS, iron-oxide, and poly(methyl methacrylate) particles, with densities ranging from 1.05 to 1.5 g/cm3. The method shows a sorting efficiency of >90% and a purity of >80% for particle separation of 10 μm and 14.5 μm, demonstrating better performance than similar sorting methods recently published (72%–83% efficiency). The sorting technique demonstrates high selectivity separation of particles, with the smallest particle ratio being 1.33, compared to 2.5 in previous work. Density/compressibility-based sorting of polystyrene and iron-oxide particles showed an efficiency of 97 ± 4% and a purity of 91 ± 5%. By varying the sign of the acoustic excitation signal, continuous batch acoustic sorting of target particles to a desired outlet was demonstrated with good sorting stability against variations of the inflow rates

Hypoxia Attenuates Pressure Overload-Induced Heart Failure

Background Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)–induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device‐mediated mechanical unloading and circulatory support. Methods and Results We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia‐inducible factor)‐1α–mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased Tbx5 and increased Hsd11b1 mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia‐mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device–mediated myocardial recovery revealed a similar expression pattern for TBX5 and HSD11B1 as observed in HxTAC hearts. Conclusions Hypoxia attenuates LVPO‐induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia‐mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO‐induced heart failure and mediate cardiac recovery following mechanical circulatory support

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Since 2015 the SinoGerman research project SIGN supports water quality improvement in the Taihu region, China

The Taihu (Tai lake) region is one of the most economically prospering areas of China. Due to its location within this district of high anthropogenic activities, Taihu represents a drastic example of water pollution with nutrients (nitrogen, phosphate), organic contaminants and heavy metals. High nutrient levels combined with very shallow water create large eutrophication problems, threatening the drinking water supply of the surrounding cities. Within the international research project SIGN (SinoGerman Water Supply Network, www.water-sign.de), funded by the German Federal Ministry of Education and Research (BMBF), a powerful consortium of fifteen German partners is working on the overall aim of assuring good water quality from the source to the tap by taking the whole water cycle into account: The diverse research topics range from future proof strategies for urban catchment, innovative monitoring and early warning approaches for lake and drinking water, control and use of biological degradation processes, efficient water treatment technologies, adapted water distribution up to promoting sector policy by good governance. The implementation in China is warranted, since the leading Chinese research institutes as well as the most important local stakeholders, e.g. water suppliers, are involved