Quantifying stiffness and forces of tumor colonies and embryos using a magnetic microrobot.

Stiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality. Biocompatible ferromagnetic cobalt-platinum microcrosses were fabricated, and each microcross (about 30 micrometers) was trapped inside an arginine-glycine-apartic acid-conjugated stiff poly(ethylene glycol) (PEG) round microgel (about 50 micrometers) using a microfluidic device. The stiff magnetic microrobot was seeded inside a cell colony and acted as a stiffness probe by rigidly rotating in response to an oscillatory magnetic field. Then, brief episodes of ultraviolet light exposure were applied to dynamically photodegrade and soften the fluorescent nanoparticle-embedded PEG microgel, whose deformation and 3D traction forces were quantified. Using the microrobot probe, we show that malignant tumor-repopulating cell colonies altered their modulus but not traction forces in response to different 3D substrate elasticities. Stiffness and 3D traction forces were measured, and both normal and shear traction force oscillations were observed in zebrafish embryos from blastula to gastrula. Mouse embryos generated larger tensile and compressive traction force oscillations than shear traction force oscillations during blastocyst. The microrobot probe with controllable functionality via magnetic fields could potentially be useful for studying the mechanoregulation of cells, tissues, and embryos.

Overcoming the rise in local deposit resistance during electrophoretic deposition via suspension replenishing.

Nanomaterials have unique properties, functionalities, and excellent performance, and as a result have gained significant interest across disciplines and industries. However, currently, there is a lack of techniques that can assemble as-synthesized nanomaterials in a scalable manner. Electrophoretic deposition (EPD) is a promising method for the scalable assembly of colloidally stable nanomaterials into thick films and arrays. In EPD, an electric field is used to assemble charged colloidal particles onto an oppositely charged substrate. However, in constant voltage EPD the deposition rate decreases with increasing deposition time, which has been attributed in part to the fact that the electric field in the suspension decreases with time. This decreasing electric field has been attributed to two probable causes, (i) increased resistance of the particle film and/or (ii) the growth of an ion-depletion region at the substrate. Here, to increase EPD yield and scalability we sought to distinguish between these two effects and found that the growth of the ion-depletion region plays the most significant role in the increase of the deposit resistance. Here, we also demonstrate a method to maintain constant deposit resistance in EPD by periodic replenishing of suspension, thereby improving EPD's scalability.

Hybrid Piezo/Magnetic Electromechanical Transformer.

This paper presents a hybrid electromechanical transformer that passively transfers electrical power between galvanically isolated ports by coupling electrodynamic and piezoelectric transducers. The use of these two complementary electromechanical transduction methods along with a high-Q mechanical resonance affords very large transformations of voltage, current, or impedance at particular electrical frequencies. A chip-size prototype is designed, simulated, fabricated, and experimentally characterized. The 7.6 mm × 7.6 mm × 1.65 mm device achieves an open-circuit voltage gain of 31.4 and 48.7 when operating as a step-up transformer at 729.5 Hz and 1015 Hz resonance frequencies, respectively. When operating as a step-down transformer, the resonance frequencies and the corresponding voltage gains are 728 Hz, 1002 Hz, and 0.0097, 0.0128, respectively. In one operational mode, the system shows a minimum power dissipation of only 0.9 µW corresponding to a power conversion efficiency of 11.8%.

Model of Magnetic Particle Capture Under Physiological Flow Rates for Cytokine Removal During Cardiopulmonary Bypass.

OBJECTIVE: The objective of this study is to design a physical model of a magnetic filtration system which can separate magnetic nanoparticle (MNP)-tagged cytokines from fluid at physiologically relevant flow rates employed during cardiopulmonary bypass (CPB) procedures. METHODS: The Navier-Stokes equations for the pressure driven flow in the chamber and the quasistatic stray magnetic field produced by an array of permanent magnets were solved using finite element analysis in COMSOL Multiphysics for 2D and 3D representations of the flow chamber. Parameters affecting the drag and magnetic forces including flow chamber dimensions, high gradient magnet array configurations, and particle properties, were changed and evaluated for their effect on MNP capture. RESULTS: Flow chamber dimensions which achieve appropriate flow conditions for CPB were identified, and magnetic force within the chamber decreased with increased chamber height. A magnetic "block" array produced the highest magnetic force within the chamber. Polymeric microparticles loaded with MNPs were shown to have increased particle capture with increased hydrodynamic diameter. CONCLUSION: The model achieved a predicted efficiency up to 100% capture in a single-pass of fluid flowing at 1.75 L/min. SIGNIFICANCE: This work is an important step in designing a magnetic flow chamber that can remove the magnetically tagged cytokines under high flow employed during CPB. Cytokines have been shown to stimulate the systemic inflammatory response (SIR) associated with CPB and are an established therapeutic target to mitigate the SIR. In the long term, this work aims to guide researchers in the more accurate design of magnetic separation systems.

Effects of particle diameter and magnetocrystalline anisotropy on magnetic relaxation and magnetic particle imaging performance of magnetic nanoparticles.

The dynamic magnetization of immobilized spherical single-domain magnetic nanoparticles (MNPs) with uniaxial or cubic magnetocrystalline anisotropy was studied computationally by executing simulations based on the Landau-Lifshitz-Gilbert (LLG) equation. For situations when a static magnetic field was suddenly applied and then removed, the effects of particle diameter and anisotropy (considering both type of symmetry and characteristic energy) on the characteristic magnetic relaxation time were studied parametrically. The results, for both anisotropy symmetries, show that when a static magnetic field is suddenly turned on or off the MNPs undergo a successive two-step or combined one-step relaxation. Whether a MNP relaxes with one or two steps when the field is turned on is determined by the competition between the energy of the applied magnetic field, the magnetic anisotropy energy, and thermal energy. When the applied magnetic field is suddenly turned off, our results show good agreement with theoretical predictions for the cases of [Formula: see text] and [Formula: see text], where [Formula: see text] represents the magnetic anisotropy energy barrier, [Formula: see text] is the Boltzmann constant and [Formula: see text] represents the absolute temperature. For the case of an applied alternating magnetic field (AMF) that is typical of magnetic particle imaging (MPI) applications, the effects of particle diameter and anisotropy symmetry were studied in terms of time-domain magnetization dynamics, dynamic hysteresis loops, harmonic spectra, and x-space point spread functions (PSFs). Results illustrate that the type of magnetocrystalline anisotropy (uniaxial versus cubic) has a significant effect on the MPI performance of the nanoparticles. These computational studies provide insight into the role of particle diameter and magnetic anisotropy on the performance of MNPs for applications in magnetorelaxometry and MPI.

A High-Throughput Microfluidic Magnetic Separation (µFMS) Platform for Water Quality Monitoring.

The long-term aim of this work is to develop a biosensing system that rapidly detects bacterial targets of interest, such as Escherichia coli, in drinking and recreational water quality monitoring. For these applications, a standard sample size is 100 mL, which is quite large for magnetic separation microfluidic analysis platforms that typically function with <20 µL/s throughput. Here, we report the use of 1.5-µm-diameter magnetic microdisc to selectively tag target bacteria, and a high-throughput microfluidic device that can potentially isolate the magnetically tagged bacteria from 100 mL water samples in less than 15 min. Simulations and experiments show ~90% capture efficiencies of magnetic particles at flow rates up to 120 µL/s. Also, the platform enables the magnetic microdiscs/bacteria conjugates to be directly imaged, providing a path for quantitative assay.

Benchtop magnetic particle relaxometer for detection, characterization and analysis of magnetic nanoparticles.

This paper presents the design, construction, and testing of a magnetic particle relaxometer (MPR) to assess magnetic nanoparticle response to dynamic magnetic fields while subjected to a bias field. The designed MPR can characterize magnetic particles for use as tracers in magnetic particle imaging (MPI), with the variation of an applied bias field emulating the scan of the MPI field free point. The system applies a high-frequency time-varying excitation field (up to 45 mT at 30 kHz), while slowly ramping a bias field (±100 mT in 1 s). The time-resolved response of the sample is measured using an inductive sensing coil system, made of a pick-up coil and a rotating and translating balancing coil to finely cancel the induction feed-through from the excitation field. A post-processing algorithm is presented to extract the tracer response related to the point spread function for MPI applications, and the performance of the MPR is demonstrated using superparamagnetic iron oxide particles (ferucarbotran).

Magnetic field sensors using arrays of electrospun magnetoelectric Janus nanowires.

The fabrication and characterization of the first magnetoelectric sensors utilizing arrays of Janus magnetoelectric composite nanowires composed of barium titanate and cobalt ferrite are presented. By utilizing magnetoelectric nanowires suspended across electrodes above the substrate, substrate clamping is reduced when compared to layered thin-film architectures; this results in enhanced magnetoelectric coupling. Janus magnetoelectric nanowires are fabricated by sol-gel electrospinning, and their length is controlled through the electrospinning and calcination conditions. Using a directed nanomanufacturing approach, the nanowires are then assembled onto pre-patterned metal electrodes on a silicon substrate using dielectrophoresis. Using this process, functional magnetic field sensors are formed by connecting many nanowires in parallel. The observed magnetic field sensitivity from the parallel array of nanowires is 0.514 ± .027 mV Oe-1 at 1 kHz, which translates to a magnetoelectric coefficient of 514 ± 27 mV cm-1 Oe-1.

Design and validation of magnetic particle spectrometer for characterization of magnetic nanoparticle relaxation dynamics.

The design and validation of a magnetic particle spectrometer (MPS) system used to study the linear and nonlinear behavior of magnetic nanoparticle suspensions is presented. The MPS characterizes the suspension dynamic response, both due to relaxation and saturation effects, which depends on the magnetic particles and their environment. The system applies sinusoidal excitation magnetic fields varying in amplitude and frequency and can be configured for linear measurements (1 mT at up to 120 kHz) and nonlinear measurements (50 mT at up to 24 kHz). Time-resolved data acquisition at up to 4 MS/s combined with hardware and software-based signal processing allows for wide-band measurements up to 50 harmonics in nonlinear mode. By cross-calibrating the instrument with a known sample, the instantaneous sample magnetization can be quantitatively reconstructed. Validation of the two MPS modes are performed for iron oxide and cobalt ferrite suspensions, exhibiting Néel and Brownian relaxation, respectively.

Thermal Decomposition Synthesis of Iron Oxide Nanoparticles with Diminished Magnetic Dead Layer by Controlled Addition of Oxygen.

Decades of research focused on size and shape control of iron oxide nanoparticles have led to methods of synthesis that afford excellent control over physical size and shape but comparatively poor control over magnetic properties. Popular synthesis methods based on thermal decomposition of organometallic precursors in the absence of oxygen have yielded particles with mixed iron oxide phases, crystal defects, and poorer than expected magnetic properties, including the existence of a thick "magnetically dead layer" experimentally evidenced by a magnetic diameter significantly smaller than the physical diameter. Here, we show how single-crystalline iron oxide nanoparticles with few defects and similar physical and magetic diameter distributions can be obtained by introducing molecular oxygen as one of the reactive species in the thermal decomposition synthesis. This is achieved without the need for any postsynthesis oxidation or thermal annealing. These results address a significant challenge in the synthesis of nanoparticles with predictable magnetic properties and could lead to advances in applications of magnetic nanoparticles.

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 µL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat.

Investigation of the Capture of Magnetic Particles From High-Viscosity Fluids Using Permanent Magnets.

GOAL: This paper investigates the practicality of using a small, permanent magnet to capture magnetic particles out of high-viscosity biological fluids, such as synovial fluid. METHODS: Numerical simulations are used to predict the trajectory of magnetic particles toward the permanent magnet. The simulations are used to determine a "collection volume" with a time-dependent size and shape, which determines the number of particles that can be captured from the fluid in a given amount of time. RESULTS: The viscosity of the fluid strongly influences the velocity of the magnetic particles toward the magnet, hence, the collection volume after a given time. In regards to the design of the magnet, the overall size is shown to most strongly influence the collection volume in comparison to the magnet shape or aspect ratio. CONCLUSION: Numerical results showed good agreement with in vitro experimental magnetic collection results. SIGNIFICANCE: In the long term, this paper aims to facilitate optimization of the collection of magnetic particle-biomarker conjugates from high-viscosity biological fluids without the need to remove the fluid from a patient.

Magnetic Assembly and Cross-Linking of Nanoparticles for Releasable Magnetic Microstructures.

This article describes a versatile method to fabricate magnetic microstructures with complex two-dimensional geometric shapes using magnetically assembled iron oxide (Fe3O4) and cobalt ferrite (CoFe2O4) nanoparticles. Magnetic pole patterns are imprinted into magnetizable media, onto which magnetic nanoparticles are assembled from a colloidal suspension into defined shapes via the shaped magnetic field gradients. The kinetics of this assembly process are studied by evaluation of the microstructure features (e.g., line width and height) as a function of time, particle type, and volume fraction. After assembly, the iron oxide particles are cross-linked in situ and subsequently released by dissolving a sacrificial layer. The free-floating magnetic structures are shown to retain their patterned shape during manipulation with external magnetic fields.

Defining the coupling coefficient for electrodynamic transducers.

This paper provides a simple, practical definition of the coupling coefficient for electrodynamic transducers. Comparing to efforts made in previous works that assumed a lossless spring-inductor model, the definition presented here is based on a lossy mass-inductor model. Time-harmonic analysis is used to model the energy flow in the transducer. Both energy storage and energy dissipation are included in the electrodynamic coupling coefficient definition. An in-depth discussion is provided to explain and justify the derivation and overall methodology. This definition is expected to provide a useful and practical measure of the electromechanical energy conversion performance of electrodynamic transducers, both actuators and generators.

A directional acoustic array using silicon micromachined piezoresistive microphones.

The need for noise source localization and characterization has driven the development of advanced sound field measurement techniques using microphone arrays. Unfortunately, the cost and complexity of these systems currently limit their widespread use. Directional acoustic arrays are commonly used in wind tunnel studies of aeroacoustic sources and may consist of hundreds of condenser microphones. A microelectromechanical system (MEMS)-based directional acoustic array system is presented to demonstrate key technologies to reduce the cost, increase the mobility, and improve the data processing efficiency versus conventional systems. The system uses 16 hybrid-packaged MEMS silicon piezoresistive microphones that are mounted to a printed circuit board. In addition, a high-speed signal processing system was employed to generate the array response in near real time. Dynamic calibrations of the microphone sensor modules indicate an average sensitivity of 831 microV/Pa with matched magnitude (+/-0.6 dB) and phase (+/-1 degree) responses between devices. The array system was characterized in an anechoic chamber using a monopole source as a function of frequency, sound pressure level, and source location. The performance of the MEMS-based array is comparable to conventional array systems and also benefits from significant cost savings.