Numerical and experimental analysis of a hybrid material acoustophoretic device for manipulation of microparticles.

Acoustophoretic microfluidic devices have been developed for accurate, label-free, contactless, and non-invasive manipulation of bioparticles in different biofluids. However, their widespread application is limited due to the need for the use of high quality microchannels made of materials with high specific acoustic impedances relative to the fluid (e.g., silicon or glass with small damping coefficient), manufactured by complex and expensive microfabrication processes. Soft polymers with a lower fabrication cost have been introduced to address the challenges of silicon- or glass-based acoustophoretic microfluidic systems. However, due to their small acoustic impedance, their efficacy for particle manipulation is shown to be limited. Here, we developed a new acoustophoretic microfluid system fabricated by a hybrid sound-hard (aluminum) and sound-soft (polydimethylsiloxane polymer) material. The performance of this hybrid device for manipulation of bead particles and cells was compared to the acoustophoretic devices made of acoustically hard materials. The results show that particles and cells in the hybrid material microchannel travel to a nodal plane with a much smaller energy density than conventional acoustic-hard devices but greater than polymeric microfluidic chips. Against conventional acoustic-hard chips, the nodal line in the hybrid microchannel could be easily tuned to be placed in an off-center position by changing the frequency, effective for particle separation from a host fluid in parallel flow stream models. It is also shown that the hybrid acoustophoretic device deals with smaller temperature rise which is safer for the actuation of bioparticles. This new device eliminates the limitations of each sound-soft and sound-hard materials in terms of cost, adjusting the position of nodal plane, temperature rise, fragility, production cost and disposability, making it desirable for developing the next generation of economically viable acoustophoretic products for ultrasound particle manipulation in bioengineering applications

Acoustic Manipulation of Bio-Particles at High Frequencies: An Analytical and Simulation Approach

Manipulation of micro and nano particles in microfluidic devices with high resolution is a challenge especially in bioengineering applications where bio-particles (BPs) are separated or patterned. While acoustic forces have been used to control the position of BPs, its theoretical aspects need further investigation particularly for high-resolution manipulation where the wavelength and particle size are comparable. In this study, we used a finite element method (FEM) to amend analytical calculations of acoustic radiation force (ARF) arising from an imposed standing ultrasound field. First, an acoustic solid interaction (ASI) approach was implemented to calculate the ARF exerted on BPs and resultant deformation induced to them. The results were then used to derive a revised expression for the ARF beyond the small particle assumption. The expression was further assessed in numerical simulations of one- and multi-directional standing acoustic waves (SAWs). Furthermore, a particle tracing scheme was used to investigate the effect of actual ARF on separation and patterning applications under experimentally-relevant conditions. The results demonstrated a significant mismatch between the actual force and previous analytical predictions especially for high frequencies of manipulation. This deviation found to be not only because of the shifted ARF values but also due to the variation in force maps in multidirectional wave propagation. Findings of this work can tackle the simulation limitations for spatiotemporal control of BPs using a high resolution acoustic actuation

Bioprocessing of Mesenchymal Stem Cells and Their Derivatives: Toward Cell-Free Therapeutics

Mesenchymal stem cells (MSCs) have attracted tremendous research interest due to their ability to repair tissues and reduce inflammation when implanted into a damaged or diseased site. These therapeutic effects have been largely attributed to the collection of biomolecules they secrete (i.e., their secretome). Recent studies have provided evidence that similar effects may be produced by utilizing only the secretome fraction containing extracellular vesicles (EVs). EVs are cell-derived, membrane-bound vesicles that contain various biomolecules. Due to their small size and relative mobility, they provide a stable mechanism to deliver biomolecules (i.e., biological signals) throughout an organism. The use of the MSC secretome, or its components, has advantages over the implantation of the MSCs themselves: (i) signals can be bioengineered and scaled to specific dosages, and (ii) the nonliving nature of the secretome enables it to be efficiently stored and transported. However, since the composition and therapeutic benefit of the secretome can be influenced by cell source, culture conditions, isolation methods, and storage conditions, there is a need for standardization of bioprocessing parameters. This review focuses on key parameters within the MSC culture environment that affect the nature and functionality of the secretome. This information is pertinent to the development of bioprocesses aimed at scaling up the production of secretome-derived products for their use as therapeutics

Influence of Electric Fields and Conductivity on Pollen Tube Growth assessed via Electrical Lab-on-Chip

Pollen tubes are polarly growing plant cells that are able to rapidly respond to a combination of chemical, mechanical, and electrical cues. This behavioural feature allows them to invade the flower pistil and deliver the sperm cells in highly targeted manner to receptive ovules in order to accomplish fertilization. How signals are perceived and processed in the pollen tube is still poorly understood. Evidence for electrical guidance in particular is vague and highly contradictory. To generate reproducible experimental conditions for the investigation of the effect of electric fields on pollen tube growth we developed an Electrical Lab-on-Chip (ELoC). Pollen from the species Camellia displayed differential sensitivity to electric fields depending on whether the entire cell or only its growing tip was exposed. The response to DC fields was dramatically higher than that to AC fields of the same strength. However, AC fields were found to restore and even promote pollen growth. Surprisingly, the pollen tube response correlated with the conductivity of the growth medium under different AC frequencies—consistent with the notion that the effect of the field on pollen tube growth may be mediated via its effect on the motion of ions

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.This work was supported by the Alberta Prion Research Institute, Alberta Innovates BioSolutions, Natural Sciences and Engineering Research of Canada, NPRP9-144-3-021 from Qatar Foundation , GCC-2017-005 from GCC co-fund program, QUUG-CENG-MIE-15/16-7 and QUST-CENG-FALL-15/16-20 from Qatar University , the Farouk Jabre interdisciplinary research award from American University of Beirut , and the CNRS grant from National Council for Scientific Research , Lebanon, for the support for this paper.Scopu