Fluidic Trapping Research Articles

Quantifying DNA-mediated liposome fusion kinetics with a fluidic trap.

Self-assembly of synthetic lipid vesicles via lipid membrane fusion is a versatile tool for creating biomimetic nano- and micron-sized particles. These so-called liposomes are used in the development of biosensing platforms, design of drug delivery schemes, and for investigating protein-mediated fusion of biological membranes. This work demonstrates DNA-induced liposome fusion in a nanofluidic trap where the reaction occurs in a 15 femtoliter volume at homogeneous mixing. In contrast to current methods for fusion in bulk, we show that the fusion reaction follows second-order kinetics with a fusion rate of (170 ± 30)/(M-1s-1) times the square number of DNA molecules per liposome. The nanofluidic trapping gives a full characterization of the size and charge of the liposomes before and after fusion. The chip-based approach limits the amount of sample (down to 440 vesicles) and can be parallelized for systematic studies in synthetic biology, diagnostics, and drug delivery.

Surface-modified elastomeric nanofluidic devices for single nanoparticle trapping

Our work focuses on the development of simpler and effective production of nanofluidic devices for high-throughput charged single nanoparticle trapping in an aqueous environment. Single nanoparticle confinement using electrostatic trapping has been an effective approach to study the fundamental properties of charged molecules under a controlled aqueous environment. Conventionally, geometry-induced electrostatic trapping devices are fabricated using SiOx-based substrates and comprise nanochannels imbedded with nanoindentations such as nanopockets, nanoslits and nanogrids. These geometry-induced electrostatic trapping devices can only trap negatively charged particles, and therefore, to trap positively charged particles, modification of the device surface is required. However, the surface modification process of a nanofluidic device is cumbersome and time consuming. Therefore, here, we present a novel approach for the development of surface-modified geometry-induced electrostatic trapping devices that reduces the surface modification time from nearly 5 days to just a few hours. We utilized polydimethylsiloxane for the development of a surface-modified geometry-induced electrostatic trapping device. To demonstrate the device efficiency and success of the surface modification procedure, a comparison study between a PDMS-based geometry-induced electrostatic trapping device and the surface-modified polydimethylsiloxane-based device was performed. The device surface was modified with two layers of polyelectrolytes (1: poly(ethyleneimine) and 2: poly(styrenesulfonate)), which led to an overall negatively charged surface. Our experiments revealed the presence of a homogeneous surface charge density inside the fluidic devices and equivalent trapping strengths for the surface-modified and native polydimethylsiloxane-based geometry-induced electrostatic trapping devices. This work paves the way towards broader use of geometry-induced electrostatic trapping devices in the fields of biosensing, disease diagnosis, molecular analysis, fluid quality control and pathogen detection.

Propulsion Gait Analysis and Fluidic Trapping of Swinging Flexible Nanomotors.

Micro- and nanomachines as feasible agents to exploit the microworld have attracted extensive research interest, particularly in the manipulation of soft nanorobots at small scales. Herein, we propose a model for regulating the motion of a swinging flexible nanomotor (SFN) driven by an oscillating magnetic field. Multisegments of an SFN are synthesized from nickel, gold, and porous silver. The coupling of magnetic actuation and the swinging pattern of SFNs are studied to reveal their mobility. Additionally, an optimal frequency occurs from the coupling of magnetic torque and structural deformation, rather than the simply considered step-out phenomenon. Meanwhile, a fluidic trapping region is formulated alongside the SFN. Such a trapping region is demonstrated by trapping a living neutrophil and accomplishing in vitro transportation using fluidic mediation. On-demand cargo delivery can be realized using a programmable magnetic field, and SFNs can be recycled with ease after manipulation owing to environmental concerns. In this study, we demonstrated the properties of SFNs that are useful bases for their customization and control. These flexible nanomotors may have the potential to promote drug delivery and biomedical operations in noncontact modes.

Magnetomicrofluidic Platforms for Organizing Arrays of Single-Particles and Particle-Pairs

Magnetomicrofluidic platforms for precise transport of magnetized particles on-chip are introduced. These hybrid platforms are composed of microfluidic trapping systems and the previously proposed magnetophoretic circuits. In the fluidic trapping step, single-particles are captured in a large array, at speeds of more than an order of magnitude higher than the one achieved in our original magnetophoretic circuits. Then, magnetic forces, provided by the magnetophoretic circuits, are used to precisely transfer trapped particles into adjacent larger compartments, where no considerable shear stress is applied to them. We show that, for the first time, the magnetic particles of various sizes can be stored in large arrays of semi-isolated micro-compartments, with efficiencies of ~70%. In addition to single particle arrays, we show forming arrays of magnetic particle pairs, with potential applications in cellular biology and drug screening. [2018-0236]

An acoustofluidic trap and transfer approach for organizing a high density single cell array.

We demonstrate a hybrid microfluidic system that combines fluidic trapping and acoustic switching to organize an array of single cells at high density. The fluidic trapping step is achieved by balancing the hydrodynamic resistances of three parallel channel segments forming a microfluidic trifurcation, the purpose of which was to capture single cells in a high-density array. Next, the cells were transferred into adjacent larger compartments by generating an array of streaming micro-vortices to move the cells to the desired streamlines in a massively parallel format. This approach can compartmentalize single cells with efficiencies of ≈67% in compartments that have diameters on the order of ∼100 um, which is an appropriate size for single cell proliferation studies and other single cell biochemical measurements.

Fluidic trapping and optical detection of microparticles with a functional optical fiber

A fiber probe is presented that traps single micro-sized particles and allows detection of their optical properties. The trapping mechanism used is based on fluid suction with a micro-structured op ...

Spectrally resolved single-molecule electrometry.

Escape-time electrometry is a recently developed experimental technique that offers the ability to measure the effective electrical charge of a single biomolecule in solution with sub-elementary charge precision. The approach relies on measuring the average escape-time of a single charged macromolecule or molecular species transiently confined in an electrostatic fluidic trap. Comparing the experiments with the predictions of a mean-field model of molecular electrostatics, we have found that the measured effective charge even reports on molecular conformation, e.g., folded or disordered state, and non-uniform charge distribution in disordered proteins or polyelectrolytes. Here we demonstrate the ability to use the spectral dimension to distinguish minute differences in electrical charge between individual molecules or molecular species in a single simultaneous measurement, under identical experimental conditions. Using one spectral channel for referenced measurement, this kind of photophysical distinguishability essentially eliminates the need for accurate knowledge of key experimental parameters, otherwise obtained through intensive characterization of the experimental setup. As examples, we demonstrate the ability to detect small differences (∼5%) in the length of double-stranded DNA fragments as well as single amino acid exchange in an intrinsically disordered protein, prothymosin α.

Dumbbell Fluidic Tweezers for Dynamical Trapping and Selective Transport of Microobjects

Mobile microvortices generated by rotating nickel (Ni) nanowires (NW) have been reported as capable of inducing fluidic trapping that can be precisely focused and translated to manipulate microobjects. Here, a new design for significantly enhanced fluidic trapping is reported, which is a dumbbell (DB)‐shaped magnetic actuator, assembled by a Ni NW and two polystyrene microbeads. In contrast to the single mode of tumbling trapping possessed by Ni NW, the magnetic dumbbell is able to perform dynamical trapping and implement on‐demand transport of microobjects in three modes, i.e., tumbling, wobbling, and rolling. Experiments are conducted to demonstrate the robustness and efficacy of the fluidic trap by the DB actuator. And simulations using a finite element model compare the fluidic traps induced by NW and DB, followed by further discussion on the actuation and transport efficiency of NW and DB fluidic tweezers (FT). At last, some practical issues regarding the application of DB FT are addressed.

Measured electrical charge of SiO2 in polar and nonpolar media.

We present measurements of the net electrical surface charge of silicon dioxide (SiO2) in contact with solvents of dielectric constants between 5 and 80. Our experimental approach relies on observing the thermal motion of single silica particles confined in an electrostatic fluidic trap created by SiO2 surfaces. We compare the experimentally measured functional form of the trapping potential with that from free energy calculations and thereby determine the net surface charge in the system. Our findings clearly demonstrate that contrary to popular perception, even in the absence of surfactants, the net electrical charge of ionizable surfaces in contact with apolar solvents can be large enough to lead to significant repulsive forces. A charge regulation model for SiO2 surfaces with a single tunable parameter explains our measurements. This model may find general applicability in estimating the net charge of ionizable surfaces, given system parameters such as the dissociation or association constants of the ionizable groups and the pH, ionic strength, and dielectric constant of the solvent phase.

Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers.

In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562).

An optical fiber optofluidic particle aspirator

A fiberized optofluidic particle trapping device based on a micro-slot fabricated in a standard single-mode optical fiber by femtosecond laser micromachining is demonstrated. While fluidic convective motions move a large number of microparticles into the slot, the optical mode propagating in the nearby optical fiber core is exploited to trap and propel the particles inside the slot, thereby facilitating their collection at one of the slot extremities. The combined effect of fluidic and optical trapping allows for the collection of particles from as far as 60 μm away from the optical trap. Application to particle and live cell trapping and propulsion is demonstrated.

A microfluidic device integrating plasmonic nanodevices for Raman spectroscopy analysis on trapped single living cells

In this work we developed a microfluidic device integrating nanoplasmonic devices combined with fluidic trapping regions. The microfuidic traps allow to capture single cells in areas where plasmonic sensors are placed. In this way it is possible to perform Enhanced Raman analysis on the cell membranes. Moreover, by changing direction of the flux it is possible to change the orientation of the cell in the trap, so that it is possible to analyze different points of the membrane of the same cell. We shows an innovative procedure to fabricate and assembly the microfluidic device which combine photolithography, focused ion beam machining, and hybrid bonding between a polymer substrate and lid of Calcium fluoride. This procedure is compatible with the fabrication of the plasmonic sensors in close proximity of the microfluidic traps. Moreover, the use of Calcium fluoride as lid allows full compatibility with Raman measurements producing negligible Raman background signal and avoids Raman artifacts. Finally, we performed Raman analysis on cells to monitor their oxidative stress under particular non physiological conditions.

Angular Trapping of Anisometric Nano-Objects in a Fluid

We demonstrate the ability to trap, levitate, and orient single anisometric nanoscale objects with high angular precision in a fluid. An electrostatic fluidic trap confines a spherical object at a spatial location defined by the minimum of the electrostatic system free energy. For an anisometric object and a potential well lacking angular symmetry, the system free energy can further strongly depend on the object's orientation in the trap. Engineering the morphology of the trap thus enables precise spatial and angular confinement of a single levitating nano-object, and the process can be massively parallelized. Since the physics of the trap depends strongly on the surface charge of the object, the method is insensitive to the object's dielectric function. Furthermore, levitation of the assembled objects renders them amenable to individual manipulation using externally applied optical, electrical, or hydrodynamic fields, raising prospects for reconfigurable chip-based nano-object assemblies.

Measuring the size and charge of single nanoscale objects in solution using an electrostatic fluidic trap

Measuring the size and charge of objects suspended in solution, such as dispersions of colloids or macromolecules, is a significant challenge. Measurements based on light scattering are inherently biased to larger entities, such as aggregates in the sample, because the intensity of light scattered by a small object scales as the sixth power of its size. Techniques that rely on the collective migration of species in response to external fields (electric or hydrodynamic, for example) are beset with difficulties including low accuracy and dispersion-limited resolution. Here, we show that the size and charge of single nanoscale objects can be directly measured with high throughput by analysing their thermal motion in an array of electrostatic traps. The approach, which is analogous to Millikan's oil drop experiment, could in future be used to detect molecular binding events with high sensitivity or carry out dynamic single-charge resolved measurements at the solid/liquid interface.

Selective Trapping and Manipulation of Microscale Objects Using Mobile Microvortices

Controlled manipulation of individual micro- and nanoscale objects requires the use of trapping forces that can be focused and translated with high spatial and time resolution. We report a new strategy that uses the flow of mobile microvortices to trap and manipulate single objects in fluid with essentially no restrictions on their material properties. Fluidic trapping forces are generated toward the center of microvortices formed by magnetic microactuators, that is, rotating nanowire or self-assembled microbeads, actuated by a weak rotating magnetic field (|B|< 5 mT). We demonstrate precise manipulation of single microspheres and microorganisms near a solid surface in water.

A microfluidic array with cellular valving for single cell co-culture

We present a highly parallel microfluidic approach for contacting single cell pairs. The approach combines a differential fluidic resistance trapping method with a novel cellular valving principle for homotypic and heterotypic single cell co-culturing. Differential fluidic resistance was used for sequential single cell arraying, with the adhesion and flattening of viable cells within the microstructured environment acting to produce valves in the open state. Reversal of the flow was used for the sequential single cell arraying of the second cell type. Plasma stencilling, along the linear path of least resistance, was required to confine the cells within the trap regions. Prime flow conditions with minimal shear stress were identified for highly efficient cell arraying (∼99%) and long term cell culture. Larger trap dimensions enabled the highest levels of cell pairing (∼70%). The single cell co-cultures were in close proximity for the formation of connexon structures and the study of contact modes of communication. The research further highlights the possibility of using the natural behaviour of cells as the working principle behind responsive microfluidic elements.

Fluidic trapping of deformable polymers in microflows

We report that a polymer molecule can be trapped spatially and conformationally using a microflow that has at least two stagnation points (or two points with equal velocity) and a net flow orthogonal to the line connecting them. Examples include a Taylor vortex flow and an electro-osmotic flow in a channel with surfaces that have a sinusoidal charge. Simulating the motion of a polymer molecule in these flows using Brownian dynamics, we find that such flows produce a curved polymer conformation, leading to an elastic force that drives migration against the flow, thus stabilizing this conformation. Simulations with hydrodynamic interactions confirm these predictions and show that there exists a repulsive interaction between two trapped polymers.

Dynamic microarray system with gentle retrieval mechanism for cell-encapsulating hydrogel beads

This paper describes a selective retrieval method for arrayed monodisperse hydrogel beads containing cells. We implemented modifications such as: (i) the incorporation of cavities as nucleation sites, (ii) indirect retrieval using bubble powered jets and (iii) the use of low boiling point fluid in our device to realize a gentle optical-based retrieval method. Parametric studies confirmed that these modifications dramatically reduced both the intensity and duration of applied laser for bubble formation. We also demonstrated for the first time the formation of a bead-based dynamic cell microarray by introducing cell-encapsulating alginate beads into our dynamic microfluidic system, and successfully retrieved an alginate bead from a fluidic trap. Tests with trypan blue revealed that membrane integrity of the encapsulated cells was not compromised by the retrieval process.