Dynamics simulation of positioning and assembling multi-microparticles utilizing optoelectronic tweezers

Optoelectronic tweezer (OET) has become a powerful and versatile technique for manipulating microparticles and cells using real-time reconfigurable optical patterns. However, detailed research in the dynamics of particles in an OET device is still scarce, and the multiple-particle interactions still need further quantitative investigation. In this study, a dynamics simulation model coupling optically induced dielectrophoretic force, interaction forces between particles, and hydrodynamic and sedimentary forces is established and numerically solved by utilizing a finite element method and a dynamics simulation frame for multi-microparticles’ positioning and assembling in a typical OET device. The spatial distributions of particles in the energized OET device before optically projecting are simulated first and the condition for particle chain formation is discussed. Then, the most representative ring-shaped optical pattern is applied, and the influences of optical-ring tweezer’ dimensions of inner radius R _e and width d _e on positioning and assembling effect are dynamically simulated and discussed for 5- and 2-μm radius particles. The simulation results indicate the particles inside and outside optical ring both undergo negative DEP and are distributed centre-symmetrically under the action of ring virtual tweezers. Average distance between the particle and center of ring (ADPC) at equilibrium and the system equilibrium time characterizing particle positioning effect dramatically increase for both 5- and 2-μm radius particles while R _e increases from 35 to 55?μm. Specially, the captured particles will pile up and immediately form a three-dimensional micropyramid structure when R _e approximately equals 25?μm for the 5-μm radius particle. Moreover, ADPC decreases very slowly for both two particle-sizes and the system equilibrium time of 2-μm radius particle vary more obviously than that of 5-μm radius particle with d _e increasing from 10 to 30?μm. And the system equilibrium time for 2-μm radius particle is always larger than that for 5-μm radius particle. The primary simulation results are in good agreement with experimental observations; hence this dynamics simulation model can truly predict the particle-moving trajectory and equilibrium positions in an OET device. Moreover, this dynamics simulation holds promise for designing and optimizing optical patterns for accuracy in assembling particles in order to form a specific microstructure.     

Lab-on-a-display: a new microparticle manipulation platform using a liquid crystal display (LCD)

This paper reports a new portable microfluidic platform, “lab-on-a-display,” that microparticles are manipulated by optoelectronic tweezers (OET) on a liquid crystal display (LCD). The OET has been constructed by assembling a ground layer, a liquid chamber, and a photoconductive layer. Without lens or optical alignments, the LCD image directly forms virtual electrodes on the photoconductive layer for dielectrophoretic manipulation. The lab-on-a-display was first realized by a conventional monochromatic LCD module and a light source brighter than 5,000 lux. It was successfully applied to the programmable manipulation of 45 μm polystyrene beads; more than 100 particles were transported with an optical image-driven control, following the moving edge of the image at every moment. The effects of bead size and bias voltage on the manipulation speed were also investigated. Due to the portability and compatibility for disposable applications, this new platform has potential for programmable particle manipulation or chip-based bioprocessing including cell separation and bead-based analysis.     

Micromachining of biocompatible polymer substrate for cancer cell separation applications

Isolation of circulating tumor cells from human blood plays a significant role in diagnosis and treatment of cancer. The most effective way of isolating cells is the use of lab on-chip microfluidic devices. This paper presents the development of cyclic olefin polymer membrane with an array of micropores for separating circulating tumour cells using ultrashort laser ablation process. Initially, the substrate is tested for its cell viability. The laser Fluence is varied from 1–12 J/cm² and its observed that at a fluence of 2.5 J/cm² the desired diameter of 12 μm with ablation depth of 1 μm is obtained which is necessary for CTC separation. The treated and untreated structure is characterized using Fourier transform infrared spectrometer and it shows that the treated region shows no significant shift in the spectrum after femtosecond laser ablation.

     

Separation of micro-particles utilizing spatial difference of optically induced dielectrophoretic forces

This paper presents new methods to accurately separate micro-particles with different sizes using optically induced dielectrophoretic (ODEP) forces. It is found that the strength of the ODEP force induced on the hydrogenated amorphous silicon surface is determined by the color, line-width and intensity of the optical beams, which provide an innovative design for particle separation. Two linear-segment virtual electrodes which produced the ODEP forces were firstly defined by illuminating lights onto a photoconductive chip. One moving line and one stationary illuminated line were used to generate a stronger and a weaker ODEP force, respectively. The micro-particles were then continuously pushed forward by the stronger ODEP force. As these lines approached each other, larger micro-particles entrained by the higher ODEP forces were squeezed through the stationary electrode and subsequently separated from the smaller particles. With this approach, continuous particle separation can be automatically achieved within a few seconds. This developed method may be promising for a variety of applications such as cell-based assays and sample pretreatment using micro-particles.     

Interlayer cooling potential in vertically integrated packages

The heat-removal capability of area-interconnect-compatible interlayer cooling in vertically integrated, high-performance chip stacks was characterized with de-ionized water as coolant. Correlation-based predictions and computational fluid dynamic modeling of cross-flow heat-removal structures show that the coolant temperature increase due to sensible heat absorption limits the cooling performance at hydraulic diameters ≤200 μm. An experimental investigation with uniform and double-side heat flux at Reynolds numbers ≤1,000 and heat transfer areas of 1 cm² was carried out to identify the most efficient interlayer heat-removal structure. The following structures were tested: parallel plate, microchannel, pin fin, and their combinations with pins using in-line and staggered configurations with round and drop-like shapes at pitches ranging from 50 to 200 μm and fluid structure heights of 100–200 μm. A hydrodynamic flow regime transition responsible for a local junction temperature minimum was observed for pin fin in-line structures. The experimental data was extrapolated to predict maximal heat flux in chip stacks having a 4-cm² heat transfer area. The performance of interlayer cooling strongly depends on this parameter, and drops from >200 W/cm² at 1 cm² and >50 μm interconnect pitch to <100 W/cm² at 4 cm². From experimental data, friction factor and Nusselt number correlations were derived for pin fin in-line and staggered structures.     

A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

The interface between the blood pool and the extravascular matrix is fundamental in regulating the transport of molecules, nanoparticles and cells under physiological and pathological conditions. In this work, a microfluidic chip is presented comprising two parallel microchannels connected laterally via an array of high aspect ratio micropillars, constituting the permeable vascular membrane. A double-step lithographic process combined with a replica molding approach is employed to realize 80 different arrays of micropillars exhibiting three cross-sectional geometries (rectangular, elliptical and curved); two orientations (normal and parallel) with respect to the flow; and a variety of width and gap sizes, respectively, ranging from 10 to 20 μm and 2 to 5 μm. As compared to conventional rectangular structures, the curved pillars provide higher bending stiffness, lower adhesive interactions, and smaller intra-channel separation distances. Specifically, 10-μm-wide curved pillars, laying parallel to the flow, offered the highest mechanical stability. To assess vascular permeability, the extravascular channel was filled with a hyaluronic acid hydrogel, while fluorescent Dextran molecules and calibrated polystyrene beads were injected in the vascular channel. Membrane permeability was observed to reduce with the molecular weight of Dextran and diameter of the beads, ranging from about 6 × 10^?5 to 2 × 10^?5 cm/s for 40 and 250 kDa Dextran and up to zero for 1.5 μm beads. The presented data demonstrate the potential of the proposed microfluidic chip for analyzing the vascular and extravascular mass transport, over multiple spatial and temporal scales, in a variety of diseases involving differential permeation across vascular walls.     

Design,simulation and experiment of electroosmotic microfluidic chip for cell sorting

A microfluidic cell sorting chip has been developed using micromachining technology, where electroosmotic flow (EOF) is exploited to drive and switch cells. For this electroosmotically driven system, it is found that the effect of induced hydrostatic pressure caused by unequal levels in solution reservoirs is not negligible. In this work, the numerical simulation of EOF and opposing pressure induced flow in microchannels is presented and the velocity profiles in the microchannels are measured experimentally using microparticle imaging velocimetry (PIV) system. The result shows that the final resulting velocity is the superposition of the two flows. A total volume of 0.305 μl is transported in the 50 μm microchannel and the back flow occurs after 240 s transportation. The task of sorting cells is realized at the switching structure by adjusting the electric fields in the microchannels. The performance of the cell sorting chip is optimized by investigating the effect of different switching structures. A Y-junction switching structure with 90° switching angle is highly recommended with simulated leakage distance of 53 μm and switching time of 8 ms.     

Dean flow focusing and separation of small microspheres within a narrow size range

Rapid, selective particle separation and concentration within the bacterial size range (1–3 μm) in clinical or environmental samples promises significant improvements in detection of pathogenic microorganisms in areas including diagnostics and bio-defence. It has been proposed that microfluidic Dean flow-based separation might offer simple, efficient sample clean-up: separation of larger, bioassay contaminants to prepare bioassay targets including spores, viruses and proteins. However, reports are limited to focusing spherical particles with diameters of 5 μm or above. To evaluate Dean flow separation for (1–3 μm) range samples, we employ a 20 μm width and depth, spiral microchannel. We demonstrate focusing, separation and concentration of particles with closely spaced diameters of 2.1 and 3.2 μm, significantly smaller than previously reported as separated in Dean flow devices. The smallest target, represented by 1.0 μm particles, is not focused due to the high pressures associated with focussing particles of this size; however, it is cleaned of 93 % of 3.2 μm and 87 % of 2.1 μm microparticles. Concentration increases approaching 3.5 times, close to the maximum, were obtained for 3.2 μm particles at a flow rate of 10 μl min^?1. Increasing concentration degraded separation, commencing at significantly lower concentrations than previously predicted, particularly for particles on the limit of being focused. It was demonstrated that flow separation specificity can be fine-tuned by adjustment of output pressure differentials, improving separation of closely spaced particle sizes. We conclude that Dean flow separation techniques can be effectively applied to sample clean-up within this significant microorganism size range.     

A facile strategy to integrate robust porous aluminum foil into microfluidic chip for sorting particles

High efficiency integration of functional microdevices into microchips is crucial for broad microfluidic applications. Here, a device-insertion and pressure sealing method was proposed to integrate robust porous aluminum foil into a microchannel for microchip functionalization which demonstrate the advantage of high efficient foil microfabrication and facile integration into the microfluidic chip. The porous aluminum foil with large area (10 × 10 mm²) was realized by one-step femtosecond laser perforating technique within few minutes and its pores size could be precisely controlled from 3 μm to millimeter scale by adjusting the laser pulse energy and pulse number. To verify the versatility and flexibility of this method, two kinds of different microchips were designed and fabricated. The vertical-sieve 3D microfluidic chip can separate silicon dioxide (SiO₂) microspheres of two different sizes (20 and 5 μm), whereas the complex stacking multilayered structures (sandwich-like) microfluidic chip can be used to sort three different kinds of SiO₂ particles (20, 10 and 5 μm) with ultrahigh separation efficiency of more than 92%. Furthermore, these robust filters can be reused via cleaning by backflow (mild clogging) or disassembling (heavy clogging).     

Simulation and analysis of particle trajectory caused by the optical-induced dielectrophoresis force

Optical-induced dielectrophoresis (ODEP) is a novel technology used in the field of micro-/nanoparticles manipulation. The finite element method was applied for ODEP to research the particles motion in this paper. The potential distribution in the optoelectronic chip, which was induced by the incident light spot, was attained through electric current module in the COMSOL 4.3a. The particles motion was studied by coupling the module of electric current and particle tracing for fluid flow. Compared with molecular dynamics, the method proposed in the paper could effectively simplify the tedious programming. The polystyrene sphere (PS) particles with the radius of 2, 5, 10, and 15 μm were, respectively, used as the objects. The kinetic energy of the PS created by the dielectrophoresis (DEP) forces, the Stokes drag forces, the gravity forces, and the Brownian motion forces was calculated during the whole manipulation process. The simulation results indicated that with the decreasing in the particle size, the time on enrichment of the smaller PS would become longer. It was because that for the smaller PS, the effect of DEP forces would play less important role in the system. The conclusions in this paper could be used as a theoretical guidance in the further research.     

Development of a nanofluidic preconcentrator with precise sample positioning and multi-channel preconcentration

A nanofluidic preconcentrator with the capability of rapidly preconcentrating and precisely positioning protein bands in multiple microchannels has been developed for highly sensitive detection of biomolecules. A novel electrical resistive network model is developed to guide the design of the nanofluidic preconcentrator which consists of a PDMS slab bonded with a glass slide. In the prototype design, two microchannels (23 mm long, 25–50 μm wide, and 5–15 μm deep), one preconcentration microchannel and one ground microchannel are connected in the middle via 16 nanochannels (25–50 μm long, 25 μm wide, and 50–80 nm deep). With two sets of optimal voltage settings applied on the opposite ends of the nanofluidic chip, the ion depletion region and electrokinetic trapping were generated to carry out the preconcentration. With the optimal voltage settings (30–30 V) predicted by the model, the ionic current of the nanochannel in our optimized preconcentrator was adjusted to be greater than the threshold value (3.9 nA) needed for the occurrence of the preconcentration, and a preconcentration factor >10⁵ was achieved in 5 min. The sample positioning capability of the preconcentrator was demonstrated by adjusting the applied voltages and moving the preconcentrated protein bands to multiple sites by a distance from several micrometers to several millimeters in the preconcentration channel. The multi-channel preconcentration capability was also demonstrated by preconcentrating two protein bands in two separate microchannels. In this work, the resistive network model was developed and validated to optimize nanofluidic preconcentrators for rapid, high throughput and highly sensitive sensing of low abundance analytes.     

Operational Regimes and Physics Present in Optoelectronic Tweezers

Optoelectronic tweezers (OET) are a powerful light-based technique for the manipulation of micro- and nanoscopic particles. In addition to an optically patterned dielectrophoresis (DEP) force, other light-induced electrokinetic and thermal effects occur in the OET device. In this paper, we present a comprehensive theoretical and experimental investigation of various fluidic, optical, and electrical effects present during OET operation. These effects include DEP, light-induced ac electroosmosis, electrothermal flow, and buoyancy-driven flow. We present finite-element modeling of these effects to establish the dominant mode for a given set of device parameters and bias conditions. These results are confirmed experimentally and present a comprehensive outline of the operational regimes of the OET device.     

Microfluidic chips for cells capture using 3-D hydrodynamic structure array

Microfluidic chips were designed and fabricated to capture cells in a relative small volume to generate the desired concentration needed for analysis. The microfluidic chips comprise three-dimensional (3-D) cell capture structures array fabricated in PDMS. The capture structure includes two layers. The first layer consists of spacers to create small gap between the upper layer and glass. The second layer is a sharp corner U-shaped compartment with sharp corners at the fore-end. And another type capture structure with Y-shaped fluidic guide has been designed. It was demonstrated that the structures can capture cells in theory, using Darcy–Weisbach equation and COMSOL Multiphysics. Then yeast cell was chosen to test the performance of the chips. The chip without fluid guides captured ~1.44 × 10⁵ cells and the capture efficiency was up to 71 %. And the chip with fluid guides captured ~5.0 × 10⁴ cells and the capture efficiency was ~25 %. The chip without fluid guides can capture more cells because the yeast cells in the chip without fluid guides are subject to larger hydrodynamic drag force.     

A superposable double-gradient droplet array chip for preparation of PEGDA microspheres containing concentration-gradient drugs

This article describes a superposable double-concentration-gradient droplet array chip, which allows a variety of concentration combinations of two components to be formed simultaneously. The concentration gradients generated from two layers of the chip could be arbitrarily superimposed by adjusting the center angle between the two bonding layers. With the aqueous phase flow rate of 1.0 μL min^?1 and the oil phase flow rate of 30.0 μL min^?1, the droplets about 58 μm in diameter were produced, and the coefficients of variation were below 6.0% for single channel and 5.7% for all the channels. Using a dual-32-channel superposable gradient droplet array chip, poly(ethylene glycol) diacrylate (PEGDA) microspheres containing concentration-gradient combinations of rhodamine B and fluorescein were fabricated to demonstrate the capability of PEGDA for encapsulating hydrophilic and hydrophobic substances, as well as the proper concentration-gradient distribution. Furthermore, PEGDA microspheres loaded with two anticancer drugs, hydrophilic doxorubicin hydrochloride and hydrophobic paclitaxel, of 17 concentration combinations were simultaneously prepared. The drug-induced apoptosis of human uterine cervix cancer cells was investigated using the dual-drug-loaded PEGDA microspheres. The optimum synergistic concentration combination of the two drugs was 12.5 μg mL^?1 for doxorubicin hydrochloride and 43.75 μg mL^?1 for paclitaxel according to the preliminary screening. The superposable double-gradient droplet array generator was demonstrated to be a promising platform for screening multiple drug combination in microcarriers.     

Magnetically actuated micromechanical tweezers

Two planar actuators with magnetic thin films are used for magnetic tweezers. The planar actuators consisting of a pair of a 75 × 0.8 × 0.3 μm³ silicon oxide beam and a 72 × 13 × 0.3 μm³ silicon oxide plate deposited with a 65 × 4 × 0.1 μm³ Ni magnetic thin film are successfully fabricated and successfully gripped to a single NPC-tw01 cell consisting of Fe₃O₄ magnetic nanoparticles under a vertical magnetic field. The planar actuator bends under an external magnetic field because of the high shape magnetic anisotropy of the Ni magnetic thin film and a highly sensitive microcantilever. NPC-tw01 cells, which are adherent cells, are cultivated in a culture solution. The two planar actuators are placed in water to move and grip a living cell.     

Mechanical design and characterization of a resonant magnetic field microsensor with linear response and high resolution

A resonant magnetic field microsensor based on Microelectromechanical Systems (MEMS) technology including a piezoresistive detection system has been designed, fabricated, and characterized. The mechanical design for the microsensor includes a symmetrical resonant structure integrated into a seesaw rectangular loop (700 μm × 450 μm) of 5 μm thick silicon beams. An analytical model for estimating the first resonant frequency and deflections of the resonant structure by means of Rayleigh and Macaulay's methods is developed. The microsensor exploits the Lorentz force and presents a linear response in the weak magnetic field range (40–2000 μT). It has a resonant frequency of 22.99 kHz, a sensitivity of 1.94 V T^?1, a quality factor of 96.6 at atmospheric pressure, and a resolution close to 43 nT for a frequency difference of 1 Hz. In addition, the microsensor has a compact structure, requires simple signal processing, has low power consumption (16 mW), as well as an uncomplicated fabrication process. This microsensor could be useful in applications such as the automotive sector, the telecommunications industry, in consumer electronic products, and in some medical applications.     

Dynamic Cell and Microparticle Control via Optoelectronic Tweezers

This paper reports on cell and microparticle manipulation using optically induced dielectrophoresis. Our novel optoelectronic tweezers (OET) device enables optically controlled trapping, transportation, and sorting via dielectrophoretic forces. By integrating a spatial light modulator and using direct imaging, arbitrary dynamic manipulation patterns are obtained. Here, we demonstrate manipulation functions, including particle collectors, single-particle traps, individually addressable single-particle arrays, light-defined particle channels, and size-based particle sorting. OET-induced particle manipulation velocities are analyzed as a function of the applied voltage, optical pattern linewidth, and single-particle trap dimensions.     

基于光导电渗流的碳纳米颗粒自动化装配仿真

研究碳纳米自动化装配优化问题.50nm碳纳米颗粒的自动化装配,在工业领域中有广泛的应用价值.光电子镊器件的光导电渗流操作方法,可用于纳米尺度自动化装配中.为此,首次通过建立光导电渗流等效电路模型,得到有效装配的交流电源的频率范围.可通过有限元仿真软件Comsol Multiphysics 3.5a,进行了光导电渗流自动化装配50nm碳纳米颗粒的仿真.仿真结果证明,选择合适的频率,可以利用光导电渗流方法实现50nm碳纳米颗粒的自动化富集、装配.从而从理论上解决了光导电渗流可应用于纳米尺度自动化装配系统中,并将为实现碳纳米颗粒的三维器件和纳米传感器提供理论依据.     

Perception of fore-and-aft whole-body vibration intensity measured by two methods

This experimental study investigated the perception of fore-and-aft whole-body vibration intensity using cross-modality matching (CM) and magnitude estimation (ME) methods. Thirteen subjects were seated on a rigid seat without a backrest and exposed to sinusoidal stimuli from 0.8 to 12.5 Hz and 0.4 to 1.6 ms^? 2 r.m.s. The Stevens exponents did not significantly depend on vibration frequency or the measurement method. The ME frequency weightings depended significantly on vibration frequency, but the CM weightings did not. Using the CM and ME weightings would result in higher weighted exposures than those calculated using the ISO (2631-1, 1997) W_d. Compared with ISO W_k, the CM and ME-weighted exposures would be greater at 1.6 Hz and lesser above that frequency. The CM and ME frequency weightings based on the median ratings for the reference vibration condition did not differ significantly. The lack of a method effect for weightings and for Stevens exponents suggests that the findings from the two methods are comparable.     

Optimized design and fabrication of a microfluidic platform to study single cells and multicellular aggregates in 3D

A microfluidic platform for cell motility analysis in a three-dimensional environment is presented. The microfluidic device is designed to study migration of both single cells and cell spheroids, in particular under spatially and temporally controlled chemical stimuli. A layout based on a central microchannel confined by micropillars and two lateral reservoirs was selected as the most effective. The microfluidics have an internal height of 350 μm to accommodate cell spheroids of a considerable size. The chip is fabricated using well-established micromachining techniques, by obtaining the polydimethylsiloxane replica from a Si/SU-8 master. The chip is then bonded on a 170-μm-thick microscope glass slide to allow high spatial resolution live microscopy. In order to allow the cost-effective and highly repeatable production of chips with high aspect ratio (5:1) micropillars, specific design and fabrication processes were optimized. This design permits spatial confinement of the gel where cells are grown, the creation of a stable gel–liquid interface and the formation of a diffusive gradient of a chemoattractant (>48 h). The chip accomplishes both the tasks of a microfluidic bioreactor system and a cell analysis platform avoiding critical handling of the sample. The experimental fluidic tests confirm the easy handling of the chip and in particular the effectiveness of the micropillars to separate the Matrigel? from the culture media. Experimental tests of (i) the stability of the gradient, (ii) the biocompatibility and (iii) the suitability for microscopy are presented.