Constrained Volume Micro- and Nanoparticle Collection Methods in Microfluidic Systems.

Particle trapping and enrichment into confined volumes can be useful in particle processing and analysis. This review is an evaluation of the methods used to trap and enrich particles into constrained volumes in microfluidic and nanofluidic systems. These methods include physical, optical, electrical, magnetic, acoustic, and some hybrid techniques, all capable of locally enhancing nano- and microparticle concentrations on a microscale. Some key qualitative and quantitative comparison points are also explored, illustrating the specific applicability and challenges of each method. A few applications of these types of particle trapping are also discussed, including enhancing biological and chemical sensors, particle washing techniques, and fluid medium exchange systems.

Capillary-based, multifunctional manipulation of particles and fluids via focused surface acoustic waves.

Surface acoustic wave (SAW)-enabled acoustofluidic technologies have recently atttracted increasing attention for applications in biology, chemistry, biophysics, and medicine. Most SAW acoustofluidic devices generate acoustic energy which is then transmitted into custom microfabricated polymer-based channels. There are limited studies on delivering this acoustic energy into convenient commercially-available glass tubes for manipulating particles and fluids. Herein, we have constructed a capillary-based SAW acoustofluidic device for multifunctional fluidic and particle manipulation. This device integrates a converging interdigitated transducer to generate focused SAWs on a piezoelectric chip, as well as a glass capillary that transports particles and fluids. To understand the actuation mechanisms underlying this device, we performed finite element simulations by considering piezoelectric, solid mechanic, and pressure acoustic physics. This experimental study shows that the capillary-based SAW acoustofluidic device can perform multiple functions including enriching particles, patterning particles, transporting particles and fluids, as well as generating droplets with controlled sizes. Given the usefulness of these functions, we expect that this acoustofluidic device can be useful in applications such as pharmaceutical manufacturing, biofabrication, and bioanalysis.

Spontaneous Particle Ordering, Sorting, and Assembly on Soap Films.

Soap bubbles exhibit abundant fascinating phenomena throughout the entire life of evolution with different fundamental physics governing them. Nevertheless, the complicated dynamics of small objects in soap films are still unrevealed. Here, we report the first observation of spontaneous particle ordering in a complicated galaxy of soap films without any external energy. The balance of interfacial tension at two liquid-gas interfaces is theoretically predicted to govern belted wetted particles (BWPs) traveling along a specified path spontaneously. Such spontaneous particle path-finding is found to depend on the particle size and hydrophilic properties. Spontaneous particle sorting is directly realized via these discrete and distinctive paths for different particles. The deformation of the soap membrane facilitates 1D/2D particle organization along the path. This observation represents the discovery of a new spontaneous order phenomenon in soap film systems and provides a new energy-free approach for particle separation and soft colloidal crystal assembly.

4D Printed Soft Microactuator for Particle Manipulation via Surrounding Medium Variation.

Soft actuators have assumed vital roles in a diverse number of research and application fields, driving innovation and transformative advancements. Using 3D molding of smart materials and combining these materials through structural design strategies, a single soft actuator can achieve multiple functions. However, it is still challenging to realize soft actuators that possess high environmental adaptability while capable of different tasks. Here, the response threshold of a soft actuator is modulated by precisely tuning the ratio of stimulus-responsive groups in hydrogels. By combining a heterogeneous bilayer membrane structure and in situ multimaterial printing, the obtained soft actuator deformed in response to changes in the surrounding medium. The response medium is suitable for both biotic and abiotic environments, and the response rate is fast. By changing the surrounding medium, the precise capture, manipulation, and release of micron-sized particles of different diameters in 3D are realized. In addition, static capture of a single red blood cell is realized using biologically responsive medium changes. Finally, the experimental results are well predicted using finite element analysis. It is believed that with further optimization of the structure size and autonomous navigation platform, the proposed soft microactuator has significant potential to function as an easy-to-manipulate multifunctional robot.

OxyHbMeter-a novel bedside medical device for monitoring cell-free hemoglobin in the cerebrospinal fluid-proof of principle.

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

Acoustic Trapping and Manipulation of Hollow Microparticles under Fluid Flow Using a Single-Lens Focused Ultrasound Transducer.

Microparticle manipulation and trapping play pivotal roles in biotechnology. To achieve effective manipulation within fluidic flow conditions and confined spaces, it is necessary to consider the physical properties of microparticles and the types of trapping forces applied. While acoustic waves have shown potential for manipulating microparticles, the existing setups involve complex actuation mechanisms and unstable microbubbles. Consequently, the need persists for an easily deployable acoustic actuation setup with stable microparticles. Here, we propose the use of hollow borosilicate microparticles possessing a rigid thin shell, which can be efficiently trapped and manipulated using a single-lens focused ultrasound (FUS) transducer under physiologically relevant flow conditions. These hollow microparticles offer stability and advantageous acoustic properties. They can be scaled up and mass-produced, making them suitable for systemic delivery. Our research demonstrates the successful trapping dynamics of FUS within circular tubings of varying diameters, validating the effectiveness of the method under realistic flow rates and ultrasound amplitudes. We also showcase the ability to remove hollow microparticles by steering the FUS transducer against the flow. Furthermore, we present potential biomedical applications, such as active cell tagging and navigation in bifurcated channels as well as ultrasound imaging in mouse cadaver liver tissue.

Review of Ultrasonic Particle Manipulation Techniques: Applications and Research Advances.

Ultrasonic particle manipulation technique is a non-contact label-free method for manipulating micro- and nano-scale particles using ultrasound, which has obvious advantages over traditional optical, magnetic, and electrical micro-manipulation techniques; it has gained extensive attention in micro-nano manipulation in recent years. This paper introduces the basic principles and manipulation methods of ultrasonic particle manipulation techniques, provides a detailed overview of the current mainstream acoustic field generation methods, and also highlights, in particular, the applicable scenarios for different numbers and arrangements of ultrasonic transducer devices. Ultrasonic transducer arrays have been used extensively in various particle manipulation applications, and many sound field reconstruction algorithms based on ultrasonic transducer arrays have been proposed one after another. In this paper, unlike most other previous reviews on ultrasonic particle manipulation, we analyze and summarize the current reconstruction algorithms for generating sound fields based on ultrasonic transducer arrays and compare these algorithms. Finally, we explore the applications of ultrasonic particle manipulation technology in engineering and biological fields and summarize and forecast the research progress of ultrasonic particle manipulation technology. We believe that this review will provide superior guidance for ultrasonic particle manipulation methods based on the study of micro and nano operations.

Microfluidic based single cell or droplet manipulation: Methods and applications.

The isolation of single cell or droplet is first and crucial step to single-cell analysis, which is important for cancer research and diagnostic methods. This review provides an overview of technologies that are currently used or in development to realize the isolation. Microfluidic based manipulation is an emerging technology with the distinct advantages of miniaturization and low cost. Therefore, recent developments in microfluidic isolated methods have attracted extensive attention. We introduced herein five strategies based on microfluid: trap, microfluidic discrete manipulation, bioprinter, capillary and inertial force. For every technology, their basic principles and features were discussed firstly. Then some modified approaches and applications were listed as the extension. Finally, we compared the advantages and drawbacks of these methods, and analyzed the trend of the manipulation based on microfluidics.

Continuous Submicron Particle Separation Via Vortex-Enhanced Ionic Concentration Polarization: A Numerical Investigation.

Separation and isolation of suspended submicron particles is fundamental to a wide range of applications, including desalination, chemical processing, and medical diagnostics. Ion concentration polarization (ICP), an electrokinetic phenomenon in micro-nano interfaces, has gained attention due to its unique ability to manipulate molecules or particles in suspension and solution. Less well understood, though, is the ability of this phenomenon to generate circulatory fluid flow, and how this enables and enhances continuous particle capture. Here, we perform a comprehensive study of a low-voltage ICP, demonstrating a new electrokinetic method for extracting submicron particles via flow-enhanced particle redirection. To do so, a 2D-FEM model solves the Poisson-Nernst-Planck equation coupled with the Navier-Stokes and continuity equations. Four distinct operational modes (Allowed, Blocked, Captured, and Dodged) were recognized as a function of the particle's charges and sizes, resulting in the capture or release from ICP-induced vortices, with the critical particle dimensions determined by appropriately tuning inlet flow rates (200-800 [µm/s]) and applied voltages (0-2.5 [V]). It is found that vortices are generated above a non-dimensional ICP-induced velocity of U*=1, which represents an equilibrium between ICP velocity and lateral flow velocity. It was also found that in the case of multi-target separation, the surface charge of the particle, rather than a particle's size, is the primary determinant of particle trajectory. These findings contribute to a better understanding of ICP-based particle separation and isolation, as well as laying the foundations for the rational design and optimization of ICP-based sorting systems.

Fabrication and Manipulation of Non-Spherical Particles in Microfluidic Channels: A Review.

Non-spherical shape is a general appearance feature for bioparticles. Therefore, a mechanical mechanism study of non-spherical particle migration in a microfluidic chip is essential for more precise isolation of target particles. With the manipulation of non-spherical particles, refined disease detection or medical intervention for human beings will be achievable in the future. In this review, fabrication and manipulation of non-spherical particles are discussed. Firstly, various fabrication methods for non-spherical microparticle are introduced. Then, the active and passive manipulation techniques for non-spherical particles are briefly reviewed, including straight inertial microchannels, secondary flow inertial microchannels and deterministic lateral displacement microchannels with extremely high resolution. Finally, applications of viscoelastic flow are presented which obviously increase the precision of non-spherical particle separation. Although various techniques have been employed to improve the performance of non-spherical particle manipulation, the universal mechanism behind this has not been fully discussed. The aim of this review is to provide a reference for non-spherical particle manipulation study researchers in every detail and inspire thoughts for non-spherical particle focused device design.

Residue-free acoustofluidic manipulation of microparticles via removal of microchannel anechoic corner.

Surface acoustic wave (SAW)-based acoustofluidics has shown significant promise to manipulate micro/nanoscale objects for biomedical applications, e.g. cell separation, enrichment, and sorting. A majority of the acoustofluidic devices utilize microchannels with rectangular cross-section where the acoustic waves propagate in the direction perpendicular to the sample flow. A region with weak acoustic wave intensity, termed microchannel anechoic corner (MAC), is formed inside a rectangular microchannel of the acoustofluidic devices where the ultrasonic waves refract into the fluid at the Rayleigh angle with respect to the normal to the substrate. Due to the absence of a strong acoustic field within the MAC, the microparticles flowing adjacent to the microchannel wall remain unaffected by a direct SAW-induced acoustic radiation force (ARF). Moreover, an acoustic streaming flow (ASF) vortex produced within the MAC pulls the particles further into the corner and away from the direct ARF influence. Therefore, a residue of particles continues to flow past the SAWs without intended deflection, causing a decrease in microparticle manipulation efficiency. In this work, we introduce a cross-type acoustofluidic device composed of a half-circular microchannel, fabricated through a thermal reflow of a positive photoresist mold, to overcome the limitations associated with rectangular microchannels, prone to the MAC formation. We investigated the effects of different microchannel cross-sectional shapes with varying contact angles on the microparticle deflection in a continuous flow and found three distinct regimes of particle deflection. By systematically removing the MAC out of the microchannel cross-section, we achieved residue-free acoustofluidic microparticle manipulation via SAW-induced ARF inside a half-circular microchannel. The proposed method was applied to efficient fluorescent coating of the microparticles in a size-selective manner without any residue particles left undeflected in the MAC.

Metasurface Micro/Nano-Optical Sensors: Principles and Applications.

Metasurfaces are 2D artificial materials consisting of arrays of metamolecules, which are exquisitely designed to manipulate light in terms of amplitude, phase, and polarization state with spatial resolutions at the subwavelength scale. Traditional micro/nano-optical sensors (MNOSs) pursue high sensitivity through strongly localized optical fields based on diffractive and refractive optics, microcavities, and interferometers. Although detections of ultra-low concentrations of analytes have already been demonstrated, the label-free sensing and recognition of complex and unknown samples remain challenging, requiring multiple readouts from sensors, e.g., refractive index, absorption/emission spectrum, chirality, etc. Additionally, the reliability of detecting large, inhomogeneous biosamples may be compromised by the limited near-field sensing area from the localization of light. Here, we review recent advances in metasurface-based MNOSs and compare them with counterparts using micro-optics from aspects of physics, working principles, and applications. By virtue of underlying the physics and design flexibilities of metasurfaces, MNOSs have now been endowed with superb performances and advanced functionalities, leading toward highly integrated smart sensing platforms.

Multicurvature viscous streaming: Flow topology and particle manipulation.

Viscous streaming refers to the rectified, steady flows that emerge when a liquid oscillates around an immersed microfeature. Relevant to microfluidics, the resulting local, strong inertial effects allow manipulation of fluid and particles effectively, within short time scales and compact footprints. Nonetheless, practically, viscous streaming has been stymied by a narrow set of achievable flow topologies, limiting scope and application. Here, by moving away from classically employed microfeatures of uniform curvature, we experimentally show how multicurvature designs, computationally obtained, give rise, instead, to rich flow repertoires. The potential utility of these flows is then illustrated in compact, robust, and tunable devices for enhanced manipulation, filtering, and separation of both synthetic and biological particles. Overall, our mixed computational/experimental approach expands the scope of viscous streaming application, with opportunities in manufacturing, environment, health, and medicine, from particle self-assembly to microplastics removal.

Trapping and releasing of single microparticles and cells in a microfluidic chip.

A microfluidic device was designed and fabricated to capture single microparticles and cells by using hydrodynamic force and selectively release the microparticles and cells of interest via negative dielectrophoresis by activating selected individual microelectrodes. The trap microstructure was optimized based on numerical simulation of the electric field as well as the flow field. The capture and selective release functions of the device were verified by multi-types microparticles with different diameters and K562 cells. The capture efficiencies/release efficiencies were 95.55% ± 0.43%/96.41% ± 1.08% and 91.34% ± 0.01%/93.67% ± 0.36% for microparticles and cells, respectively. By including more traps and microelectrodes, the device can achieve high throughput and realize the visual separation of microparticles/cells of interest in a large number of particle/cell groups.

An analytical study of spatial resolution enhancement for a dual-frequency acoustic beamformer.

In this paper, we address an acoustic directed-self-assembly (DSA) problem for aiming to pattern particles based on creating an appropriate acoustic field by the fine adjustment of transducer operating parameters. The proposed idea is to incorporate the DSA problem with multi-frequency beamforming techniques. First, the boundary element method (BEM) is implemented for the direct modeling of the proposed DSA problem. Then, it is integrated with the concept of dual-frequency beamforming. In this study, the influence of changing excitation frequency is investigated on the spatial resolution enhancement of the pressure field. Also, the optimal frequency difference is calculated theoretically to produce two adjacent pressure traps with maximum separability and, therefore, maximum spatial resolution in a two-frequency acoustic beamformer without any restriction on the chamber shape. The performance of the proposed Dual-Frequency Beamforming (DFB) method is evaluated by simulations based on the finite element method (FEM) and compared with conventional Delay-And-Sum (DAS), Eigen Vector-Based (EigVec-based), and Bessel Beam techniques. Several evaluation metrics such as Full Width at Half Maximum (FWHM), Peak Side-lobe Level (PSL), Contrast Ratio (CR), Positioning Accuracy (PA), and processing time are considered for comparisons. Simulation results indicate the superiority of the proposed DFB method over the mentioned methods in separability and focusing precision when the two pressure traps are close to each other.

Lab-on-a-Chip Platforms for Airborne Particulate Matter Applications: A Review of Current Perspectives.

Lab-on-a-Chip (LoC) devices are described as versatile, fast, accurate, and low-cost platforms for the handling, detection, characterization, and analysis of a wide range of suspended particles in water-based environments. However, for gas-based applications, particularly in atmospheric aerosols science, LoC platforms are rarely developed. This review summarizes emerging LoC devices for the classification, measurement, and identification of airborne particles, especially those known as Particulate Matter (PM), which are linked to increased morbidity and mortality levels from cardiovascular and respiratory diseases. For these devices, their operating principles and performance parameters are introduced and compared while highlighting their advantages and disadvantages. Discussing the current applications will allow us to identify challenges and determine future directions for developing more robust LoC devices to monitor and analyze airborne PM.

Particle Manipulation in 2D Space Using a Capacitive Micromachined Ultrasonic Transducer.

Ultrasonic particle manipulation is a noncontact method for controlling microscale objects, such as cells or microparticles, using an acoustic field. In this study, a 2D array of capacitive micromachined ultrasonic transducers (CMUTs), placed horizontally in immersion, generated ultrasonic waves in the vertical direction, and the oil's surface increased due to the radiation force of the ultrasonic waves. In addition, the radiation force directly exerted a force on a floating particle. By measuring the movement of the reflected laser light by the moving oil surface, the height of the oil's surface deformed by the acoustic radiation force (ARF) was measured. The ARF made a floating particle, as well as the oil's surface, move. The particle moved radially away from the surface position above the transducer, and its velocity was determined by its position on the fluid's surface. When a single channel was operated, it moved 0.4 mm at an average speed of 90 µm/s, and when two adjacent channels were operated, it moved 1.2 mm at a speed of 272 µm/s. The particles moved in any direction on the surface of the oil by controlling the actuation channel using an electrical switch.

Near-wall velocities of particles suspended in shear flow and a streamwise electric field.

Particles with a diameter of ∼0.5 µm in a dilute (volume fractions φ∞  < 4 × 10-3 ) suspension assemble into highly elongated structures called "bands" under certain conditions in combined Poiseuille and electroosmotic flows in opposite directions through microchannels at particle-based Reynolds numbers Rep  < < 1. The particles are first concentrated near, then form "bands" within ∼6 µm of, the channel wall. The experiments described here examine the near-wall dynamics of individual "tracer" particles during the initial concentration, or accumulation, of particles, and the steady-state stage when the particles have formed relatively stable bands at different near-wall shear rates and electric field magnitudes. Surprisingly, the near-wall upstream particle velocities are found to be consistently greater in magnitude than the expected values based on the particles being convected by the superposition of both flows and subject to electrophoresis, which is in the same direction as the Poiseuille flow. However, the particle velocities scale linearly with the change in electric field magnitude, suggesting that the particle dynamics are dominated by linear electrokinetic phenomena. If this discrepancy with theory is only due to changes in particle electrophoresis, electrophoresis is significantly reduced to values as small as 20%-50% of the Smoluchowski relation, or well below previous model predictions, even for high particle potentials.

In Situ Quantification of Polyhydroxybutyrate in Photobioreactor Cultivations of Synechocystis sp. Using an Ultrasound-Enhanced ATR-FTIR Spectroscopy Probe.

Polyhydroxybutyrate (PHB) is a very promising alternative to most petroleum-based plastics with the huge advantage of biodegradability. Biotechnological production processes utilizing cyanobacteria as sustainable source of PHB require fast in situ process analytical technology (PAT) tools for sophisticated process monitoring. Spectroscopic probes supported by ultrasound particle traps provide a powerful technology for in-line, nondestructive, and real-time process analytics in photobioreactors. This work shows the great potential of using ultrasound particle manipulation to improve spectroscopic attenuated total reflection Fourier-transformed mid-infrared (ATR-FTIR) spectra as a monitoring tool for PHB production processes in photobioreactors.

Magnetic Nanoprobes for Spatio-Mechanical Manipulation in Single Cells.

Magnetic nanoparticles (MNPs) are widely known as valuable agents for biomedical applications. Recently, MNPs were further suggested to be used for a remote and non-invasive manipulation, where their spatial redistribution or force response in a magnetic field provides a fine-tunable stimulus to a cell. Here, we investigated the properties of two different MNPs and assessed their suitability for spatio-mechanical manipulations: semisynthetic magnetoferritin nanoparticles and fully synthetic 'nanoflower'-shaped iron oxide nanoparticles. As well as confirming their monodispersity in terms of structure, surface potential, and magnetic response, we monitored the MNP performance in a living cell environment using fluorescence microscopy and asserted their biocompatibility. We then demonstrated facilitated spatial redistribution of magnetoferritin compared to 'nanoflower'-NPs after microinjection, and a higher magnetic force response of these NPs compared to magnetoferritin inside a cell. Our remote manipulation assays present these tailored magnetic materials as suitable agents for applications in magnetogenetics, biomedicine, or nanomaterial research.