Manipulation Of Beads Research Articles

Synthesis and active manipulation of magnetic liquid beads

We report the fabrication and characterisation of magnetic liquid beads with a solid magnetic shell and liquid core using microfluidic techniques. The liquid beads consist of a fluorinated oil core and a polymer shell with magnetite particles. The beads are generated in a flow-focusing polydimethylsiloxane (PDMS) device and cured by photo polymerisation. We investigated the response of the liquid beads to an external magnetic field by characterising their motion towards a permanent magnet. Magnetic sorting of liquid beads in a channel was achieved with 90% efficiency. The results show that the liquid beads can be controlled magnetically and have potential applications in digital microfluidics including nucleic acid amplification, drug delivery, cell culture, sensing, and tissue engineering. The present paper also discusses the magnetophoretic behaviour of the liquid bead by varying its mass and magnetite concentration in the shell. We also demonstrated the two-dimensional self-assembly of magnetic liquid beads for potential use in digital polymerase chain reaction and digital loop mediated isothermal amplification.Graphical abstract

Manipulation of magnetic beads for actively capturing Vibrio parahaemolyticus and nucleic acid based on microfluidic system.

Rapid biological detection of pathogen micro-organisms has attracted much attention for practical biomedical applications. Despite the development in this field, it is still challenging to achieve simple and rapid biological detection using the microfluidic method. Herein, we propose a novel strategy of biological detection that combines precise detection control of the capillary microfluidic chip and versatile manipulation of magnetic beads. The microfluidic chip was fabricated via laser cutting, which utilized capillary pressure to realize rapid passive injection of liquid samples. Under an external magnetic field, the aptamer-modified magnetic beads were actuated to mix with Vibrio parahaemolyticus (V. parahaemolyticus) and its nucleic acid in the capillary microfluidic chip for rapid selective capture and detection, which could be achieved within 40 min. The experimental results demonstrated that V. parahaemolyticus could be captured using on-chip immunomagnetic beads with a high efficiency and significantly enhanced detection value. Due to these superior performances, the capillary microfluidic system, based on the manipulation of magnetic beads, demonstrated great potential for automatic biological detection.

Abacus Algorithms: A Pure Mathematical Approach to Ancient Calculation Tools

The abacus is one of the oldest calculating tools still in use today. Despite its simplicity, the bead-based interface allows users to conduct complex mathematical operations through a system of sliding beads along wires or rods. While the physical abacus itself provides an intuitive and visual approach to calculation, the underlying operations rely on fundamental mathematical principles. This paper provides a comprehensive mathematical framework that formally describes the algorithms behind abacus calculations. Beginning with basic abacus configuration, we define key components like rods, beads, and bead values required to model abacus states. We then characterize the core abacus algorithms for addition, subtraction, multiplication, and division through set notation, recurrence relations, and state transition diagrams. Our formalized abacus algorithms leverage concepts from number theory, modular arithmetic, combinatorics, and algebra. In addition to offering new mathematical insights into ancient technologies, our work helps bridge connections between the tangible abacus interface and the abstract algorithms powering it. Through examples and proofs, we show how bead manipulations precisely correspond to mathematical transformations. This level of formalization not only helps explain the effectiveness of the abacus, but also illustrates how even rudimentary calculation tools utilize profound mathematical ideas. Our mathematical abacus framework lays the foundation for further analysis as well as modifications and extensions of the classic abacus approach.

Fully Integrated Microfluidic Device for Magnetic Bead Manipulation to Assist Rapid Reaction and Cleaning.

Methods to manipulate magnetic beads are essential factors to determine the efficiency and dimension of an in vitro diagnostic system. Currently, using movable permanent magnets and planar electromagnets is still the major approach to achieve magnetic bead control, causing significant constraint in the miniaturization of in vitro diagnostic systems. Here, we propose techniques to construct a fully integrated microfluidic device that can conduct automatic magnetic bead manipulation as well as rapid chemical reaction and cleaning in a minimized dimension similar to a USB disk. The device combines the precision control of multiple electromagnetic coils with the compactness of microfluidic channels, leading to one of the smallest automatic magnetic bead manipulation systems that can complete several major magnetic bead-based operation steps such as sample injection, reaction, cleaning, and collection. The influencing factors such as coil driving parameters, surface treatment of the microchannels, and properties of magnetic particles have also been investigated to optimize the device performance. The device can drive mixtures of Fe3O4 microparticles and polymer magnetic beads (PMBs) with a weight ratio of 1:1 at a maximum speed of 0.5 cm·s-1 and reduce the time for DNA binding and dissociation reactions from 20 min to only 48 s. This device has significantly advanced the conventional manipulation methods of magnetic beads and has demonstrated the possibility to construct an automatic and ultraminiaturized in vitro diagnostic system that may facilitate portable or even wearable chemical analysis.

Continuous Manipulation and Characterization of Colloidal Beads and Liposomes via Diffusiophoresis in Single- and Double-Junction Microchannels.

We reveal a physical mechanism that enables the preconcentration, sorting, and characterization of charged polystyrene nanobeads and liposomes dispersed in a continuous flow within a straight micron-sized channel. Initially, a single Ψ-junction microfluidic chip is used to generate a steady-state salt concentration gradient in the direction perpendicular to the flow. As a result, fluorescent nanobeads dispersed in the electrolyte solutions accumulate into symmetric regions of the channel, appearing as two distinct symmetric stripes when the channel is observed from the top via epi-fluorescence microscopy. Depending on the electrolyte flow configuration and, thus, the direction of the salt concentration gradient field, the fluorescent stripes get closer to or apart from each other as the distance from the inlet increases. Our numerical and experimental analysis shows that although nanoparticle diffusiophoresis and hydrodynamic effects are involved in the accumulation process, diffusio-osmosis along the top and bottom channel walls plays a crucial role in the observed particles dynamics. In addition, we developed a proof-of-concept double Ψ-junction microfluidic device that exploits this accumulation mechanism for the size-based separation and size detection of nanobeads as well as for the measurement of zeta potential and charged lipid composition of liposomes under continuous flow settings. This device is also used to investigate the effect of fluid-like or gel-like states of the lipid membranes on the liposome diffusiophoretic response. The proposed strategy for solute-driven manipulation and characterization of colloids has great potential for microfluidic bioanalytical testing applications, including bioparticle preconcentration, sorting, sensing, and analysis.

High-Throughput Generation, Manipulation, and Degradation of Magnetic Nanoparticleladen Alginate Core-shell Beads for Single Bacteria Culturing Analysis.

Microbes could be found almost everywhere around us and have significant impacts on our human society. The treatment of microorganisms has long been seen as a complex problem. Till now, most of the genetic and phenotypic information regarding rare species is buried in the bulk microbial colony due to a lack of efficient tools to screen live bacteria. Droplet microfluidics offers a powerful approach to address this problem. However, the interactions among bacteria and their living environment are entirely restricted by the water/oil interfaces in conventional water/oil single emulsion-based microfluidic systems. Here, we demonstrate an oil-mediated all-aqueous microfluidic workflow that can overcome this drawback. In contrast to the previous works, our all-aqueous culturing environment allows cell-cell and cell-environment interactions, thus facilitating the growth of bacteria. Fe3O4 magnetic nanoparticles added into the alginate beads enables on-chip manipulation of the microcapsules. The core-shell structure separately encapsulates bacteria and magnetic particles in the core and shell to avoid contamination. We demonstrate the feasibility of this approach by single bacterium culturing in droplet-templated alginate beads. Finally, a new approach is proposed to degrade the alginate beads for post-treatment. This novel microfluidic workflow can create new opportunities for microbial applications, such as bacteria culturing and screening.

Low-cost acoustic force trap in a microfluidic channel

A low-cost glass-based microfluidic flow cell with a piezo actuator is built using off-the-shelf parts (total cost €9 per device) to apply acoustophoretic force on polystyrene micro-beads. The main challenge in the fabrication of these devices was to ensure their leak tightness, which we solved using double-sided tape and nail polish. Beads with 1.5 μm diameter flowing in a 100 μm deep channel were trapped at 7.5 MHz using a 23.7 peak-to-peak voltage (Vpp) sinusoidal input. The trap located at 50 ± 0.1 μm depth was measured to have a stiffness of approximately 0.6 pN/μm. With this simple device we can trap and control the axial position of micrometer scale objects, which allows for the manipulation of beads and cells. We intend to use the device for force spectroscopy on micro-bead tethered DNA. This can be combined with super-resolution imaging techniques to study mechanics and binding of protein structures along a DNA strand as a function of induced tension.

Magnetic Bead Manipulation in Microfluidic Chips for Biological Application.

Magnetic beads manipulation in microfluidic chips is a promising research field for biological application, especially in the detection of biological targets. In this review, we intend to present a thorough and in-depth overview of recent magnetic beads manipulation in microfluidic chips and its biological application. First, we introduce the mechanism of magnetic manipulation in microfluidic chip, including force analysis, particle properties, and surface modification. Then, we compare some existing methods of magnetic manipulation in microfluidic chip and list their biological application. Besides, the suggestions and outlook for future developments in the magnetic manipulation system are also discussed and summarized.

Characterization of a Droplet Containing the Clustered Magnetic Beads Manipulation by Magnetically Actuated Chips

A magnetically actuated chip was successfully developed in this study to perform the purpose of transportation for a droplet containing clustered magnetic beads. The magnetic field gradient is generated by the chip of the two-layer 4 × 4 array micro-coils, which was commercially fabricated by printing circuit board (PCB) technology. A numerical model was first established to investigate the magnetic field and thermal field for such a micro-coil. Consequently, the numerical simulations were in reasonable agreement with the experimental results. Moreover, a theoretical analysis was derived to predict the dynamic behaviors of the droplets. This analysis will offer the optimal operation for such a magnetically actuated chip. This study aims to successfully implement the concept of “digital microfluidics” in “point-of-care testing” (POCT). In the future, the micro-coil chip will be of substantial benefit to genetic analysis and infectious disease detection.

The Utilization of Tunable Transducer Elements Formed by the Manipulation of Magnetic Beads with Different Sizes via Optically Induced Dielectrophoresis (ODEP) for High Signal-to-Noise Ratios (SNRs) and Multiplex Fluorescence-Based Biosensing Applications.

Magnetic beads improve biosensing performance by means of their small volume and controllability by magnetic force. In this study, a new technique composed of optically induced dielectrodphoresis (ODEP) manipulation and image processing was used to enhance the signal-to-noise ratio of the fluorescence for stained magnetic beads. According to natural advantages of size-dependent particle isolation by ODEP manipulation, biomarkers in clinical samples can be easily separated by different sizes of magnetic beads with corresponding captured antibodies, and rapidly distinguished by separated location of immunofluorescence. To verify the feasibility of the concept, magnetic beads with three different diameters, including 21.8, 8.7, and 4.2 μm, were easily separated and collected into specific patterns in the defined target zone treated as three dynamic transducer elements to evaluate fluorescence results. In magnetic beads with diameter of 4.2 μm, the lowest signal-to-noise ratio between stained and nonstained magnetic beads was 3.5. With the help of ODEP accumulation and detection threshold setting of 32, the signal-to-noise ratio was increased to 77.4, which makes this method more reliable. With the further optimization of specific antibodies immobilized on different-size magnetic beads in the future, this platform can be a potential candidate for a high-efficiency sensor array in clinical applications.

Forces of Change: Optical Tweezers in Membrane Remodeling Studies.

Optical tweezers allow precise measurement of forces and distances with piconewton and nanometer precision, and have thus been instrumental in elucidating the mechanistic details of various biological processes. Some examples include the characterization of motor protein activity, studies of protein-DNA interactions, and characterizing protein folding trajectories. The use of optical tweezers (OT) to study membranes is, however, much less abundant. Here, we review biophysical studies of membranes that utilize optical tweezers, with emphasis on various assays that have been developed and their benefits and limitations. First, we discuss assays that employ membrane-coated beads, and overview protein-membrane interactions studies based on manipulation of such beads. We further overview a body of studies that make use of a very powerful experimental tool, the combination of OT, micropipette aspiration, and fluorescence microscopy, that allow detailed studies of membrane curvature generation and sensitivity. Finally, we describe studies focused on membrane fusion and fission. We then summarize the overall progress in the field and outline future directions.

Bead Number Effect in a Magnetic-Beads-Based Digital Microfluidic Immunoassay.

In a biomedical diagnosis with a limited sample volume and low concentration, droplet-based microfluidics, also called digital microfluidics, becomes a very attractive approach. Previously, our group developed a magnetic-beads-based digital microfluidic immunoassay with a bead number of around 100, requiring less than 1 μL of sample volume to achieve a pg/mL level limit of detection (LOD). However, the bead number in each measurement was not the same, causing an unstable coefficient of variation (CV) in the calibration curve. Here, we investigated whether a fixed number of beads in this bead-based digital microfluidic immunoassay could provide more stable results. First, the bead screening chips were developed to extract exactly 100, 49, and 25 magnetic beads with diameters of less than 6 μm. Then, four calibration curves were established. One calibration curve was constructed by using varying bead numbers (50–160) in the process. The other three calibration curves used a fixed number of beads, (100, 49, and 25). The results indicated that the CVs for a fixed number of beads were evidently smaller than the CVs for varying bead numbers, especially in the range of 1 pg/mL to 100 pg/mL, where the CVs for 100 beads were less than 10%. Furthermore, the calculated LOD, based on the composite calibration curves, could be reduced by three orders, from 3.0 pg/mL (for the unfixed bead number) to 0.0287 pg/mL (for 100 beads). However, when the bead numbers were too high (more than 500) or too low (25 or fewer), the bead manipulation for aggregation became more difficult in the magnetic-beads-based digital microfluidic immunoassay chip.

A versatile and automated microfluidic platform for a quantitative magnetic bead based protocol: application to gluten detection.

A microfluidic platform for the integration of multi-step biological assays has been developed. The presented system is a unique instrument compatible with microfluidic chips for various applications based on bead manipulation. Two examples of microfluidic cartridges are presented here. The first one contains two rows of eight chambers (40 and 80 μL), six reagent inlets, eight testing solution (calibrators and samples) inlets and eight outlets to reproduce precisely each step of a biological assay. This configuration is versatile enough to integrate many different biological assays and save a lot of development time. The second architecture is dedicated to one specific protocol and is completely automated from the standard and sample dilutions to the optical detection. Linear dilutions have been integrated to prepare automatically a range of standard concentrations and outlets have been modified for integrated colorimetric detection. The technology uses pneumatically collapsible chambers to perform all the fluidic operations for a fully automated protocol such as volume calibrations, fluid transport, mixing, and washing steps. A programmable instrument with a software interface has been developed to adapt rapidly a protocol to this cartridge. As an example, these new microfluidic cartridges have been used to successfully perform an immunoassay for gluten detection in the dynamic range of 10-30 ppm with good sensitivity (2 ppm) and specificity.

A MEMS room-temperature resettable thermomagnetic-track-guided magnetic-bead manipulation integrated with magnetoresistive sensing for bead-motion monitoring

In this paper, we report a MEMS room-temperature resettable thermomagnetic-track-guided magnetic-bead manipulation integrated with magnetoresistive sensing for bead-motion monitoring on a silicon wafer. The manipulation/monitoring approach consists of a magnetic bead, a chip (including thermomagnetic NiCu micro-disk tracks, Pt micro heating wires, and Ni magnetoresistive sensing elements, all fabricated on a silicon wafer), pulse-generation circuit, magnetoresistive measuring circuit, thermoelectric generator (TEG), and four external electromagnets. Because Curie temperature of the NiCu micro-disk tracks is in room-temperature range, when a NiCu track is cooled by TEG to lower than the room temperature, the track becomes ferromagnetic and thus is able to attract the bead. When the electromagnets are used to apply magnetic fields to move the bead, the bead motion is guided by the ferromagnetic track. Oppositely, when the heating-wire is used to heat the track higher than the room temperature, the track switches to paramagnetic-like and thus cannot attract the bead. When the magnetic field is applied to move the bead, the bead motion is not-guided by the paramagnetic-like track. By using these approaches, we successfully demonstrated guiding the bead moving around a track and across different tracks. By using magnetoresistive sensing, location of the bead is obtained and consequently monitoring of the bead-motion is achieved. The most important feature is that our approach can easily reset any track anytime during the bead-manipulation in room-temperature range, when comparing to conventional resetting approach which is complicated and requires to several hundred °C. In addition, our approach is the first one to combine the magnetic-track guided magnetic-bead manipulation and magnetoresistive-sensing-element based magnetic-bead motion monitoring on a silicon chip (toward a fully on-chip actuating/sensing MEMS system for magnetic bead manipulation). The results are important and alternative solutions for magnetic-track-guided magnetic bead manipulation for biomedical MEMS.

Magnetophoretic Decoupler for Disaggregation and Interparticle Distance Control.

The manipulation of superparamagnetic beads has attracted various lab on a chip and magnetic tweezer platforms for separating, sorting, and labeling cells and bioentities, but the irreversible aggregation of beads owing to magnetic interactions has limited its actual functionality. Here, an efficient solution is developed for the disaggregation of magnetic beads and interparticle distance control with a magnetophoretic decoupler using an external rotating magnetic field. A unique magnetic potential energy distribution in the form of an asymmetric magnetic thin film around the gap is created and tuned in a controlled manner, regulated by the size ratio of the bead with a magnetic pattern. Hence, the aggregated beads are detached into single beads and transported in one direction in an array pattern. Furthermore, the simultaneous and accurate spacing control of multiple magnetic bead pairs is performed by adjusting the angle of the rotating magnetic field, which continuously changes the energy well associated with a specific shape of the magnetic patterns. This technique offers an advanced solution for the disaggregation and controlled manipulation of beads, can allow new possibilities for the enhanced functioning of lab on a chip and magnetic tweezers platforms for biological assays, intercellular interactions, and magnetic biochip systems.

Paper-thin multilayer microfluidic devices with integrated valves.

Integrated valve microfluidics has an unparalleled capability to automate rapid delivery of fluids at the nanoliter scale for high-throughput biological experimentation. However, multilayer soft lithography, which is used to fabricate valve-microfluidics, produces devices with a minimum thickness of around five millimeters. This form-factor limitation prevents the use of such devices in experiments with limited sample thickness tolerance such as 4-pi microscopy, stimulated Raman scattering microscopy, and many forms of optical or magnetic tweezer applications. We present a new generation of integrated valve microfluidic devices that are less than 300 μm thick, including the cover-glass substrate, that resolves the thickness limitation. This "thin-chip" was fabricated through a novel soft-lithography technique that produces on-chip micro-valves with the same functionality and reliability of traditional thick valve-microfluidic devices despite the orders of magnitude reduction in thickness. We demonstrated the advantage of using our thin-chip over traditional thick devices to automate fluid control while imaging on a high-resolution inverted microscope. First, we demonstrate that the thin-chip provides an improved signal to noise when imaging single cells with two-color stimulated Raman scattering (SRS). We then demonstrated how the thin-chip can be used to simultaneously perform on-chip magnetic manipulation of beads and fluorescent imaging. This study reveals the potential of our thin-chip in high-resolution imaging, sorting, and bead capture-based single-cell multi-omics applications.

Publisher’s Note: “Slippery and magnetically responsive micropillared surfaces for manipulation of droplets and beads” [AIP Adv. 10, 085021 (2020)

First Page

Slippery and magnetically responsive micropillared surfaces for manipulation of droplets and beads

Stimuli-responsive surfaces are of practical importance for applications ranging from enhanced mixing of reagents in lab-on-a-chip systems until probing cellular traction forces. Non-destructive reversible bending of cilia-inspired magnetic pillars can be used for controlled transportation of non-magnetic objects and bio-inspired sensing. Magnetic actuation of micropillars suspended in liquids allows controlled mixing, propelling, and stirring of fluids as well as droplet manipulation, which are important for various applications including generation of cell spheroids and droplet coalescence in microfluidic systems. In order to expand their practical applications, fabrication processes capable of rapid prototyping have to be developed. Inspired by biological cilia and their functionalities, actuating hairy surfaces are herein fabricated and implemented to manipulate both microbeads and droplets. The artificial cilia are based on microscale magnetic pillar arrays made of flexible polydimethylsiloxane functionalized with magnetic microparticles. The arrays are fabricated by a new method using patterned molds that relies on cryogenic separation to produce transparent cilia-inspired arrays without requiring manual interference to clean the templates during the process. Magnetic actuation of the pillar arrays is demonstrated in isopropanol and silicone oil. Filling with oil yields magnetically responsive slippery lubricated surfaces allowing directional motion of droplets by repetitive bending and recovery of the flexible magnetic pillars. The achieved structures allow manipulation of microbeads and droplets which is uncommon even at the sub-mm scale; directional motion is demonstrated for 250 μm–550 μm sized droplets. Droplet transportation is facilitated by extremely low hysteresis and a high degree of omnidirectional bending of the pillar array.

A Multiplexed Microarray Platform for Targeted Proteomics

A Multiplexed Microarray Platform for Targeted Proteomics

Novel coil-less room-temperature resettable magnetic-bead manipulation by using thermomagnetic tracks

In this paper, we report a novel coil-less room-temperature resettable magnetic bead manipulation by using thermomagnetic Gd tracks. When comparing to conventional magnetic-track-guided magnetic bead motion, the thermomagnetic Gd tracks (whose Curie temperature is at room temperature) not only can guide the bead motion (as well as the conventional tracks) but also can be reset (demagnetized) in room temperature range without use of any conventional reset coil (i.e., superior than the conventional tracks). The operation and reset principles are described below. When a Gd track is cooled (by a thermoelectric generator, TEG) lower than its Curie temperature (for example: 5 °C), the Gd track becomes ferromagnetic. Furthermore, under a magnetic field, the ferromagnetic Gd track enables the magnetic-track-guided magnetic-bead manipulation. Oppositely, when the Gd track is heated (by the TEG) higher than its Curie temperature (for example: 50 °C), the Gd track becomes paramagnetic. Thus, under the magnetic field, the paramagnetic Gd track cannot attract the bead. This achieves the track resetting/demagnetizing through a coil-less room-temperature approach and thus disables the magnetic-track-guided magnetic bead manipulation. Furthermore, according to above principles, we can sequentially use TEGs to cool and heat different Gd tracks to guide the bead moving across different tracks, and also reset/demagnetize any track anytime during the bead motion through our approach. These results would be important fundamental elements to provide an alternative magnetic-bead-manipulation for biomedical MEMS systems.