From an obliquely falling rod in a viscous fluid to the motion of suspended magnetic bead chains that are driven by a gradient magnetic field and that make an arbitrary angle with the magnetic force vector: A Stokes flow study.

In view of the growing role of magnetic particles under magnetic field influence in medical and other applications, and perforce the bead chaining, it is important to understand more generally the chain dynamics. As is well known, in the presence of a magnetic field, magnetic beads tend to form chains that are aligned with the magnetic field vector. In addition, if there is a magnetic field gradient, there will be a magnetic force acting on this chain. The main goal of the present research is to study the motion of a magnetic bead chain that makes an arbitrary angle with the magnetic force vector in the Stokes flow limit, that is, in the limit of zero Reynolds number. We used the public-domain computer program HYDRO++ to calculate the mobility matrix, which relates the magnetic force acting on the chain to the velocity of the chain, for a chain of N beads making an arbitrary angle with the magnetic force vector. Because of the presence of off-diagonal elements of the mobility matrix, as the chain is drawn in the direction of the magnetic force, it is also deflected to the side. We derived analytic solutions for this motion. Also, for bead chains moving in directions both parallel and perpendicular to their lengths, we fit three-parameter functions to solutions from HYDRO++. We found the fits to be excellent. Combining these results with the analytic solutions, we obtained expressions for the velocity components for the bead chains that provide excellent fits to HYDRO++ solutions for arbitrary angles. Finally, we apply the methodology used for the bead chain studies to the study of an obliquely falling rod in a viscous fluid and derive analytic solutions for the velocity components of the obliquely falling rod.

Engineering Magnetic Nanoclusters for Highly Efficient Heating in Radio-Frequency Nanowarming.

Effective thawing of cryopreserved samples requires rapid and uniform heating. This is achievable through nanowarming, an approach that heats magnetic nanoparticles by using alternating magnetic fields. Here we demonstrate the synthesis and surface modification of magnetic nanoclusters for efficient nanowarming. Magnetite (Fe3O4) nanoclusters with an optimal diameter of 58 nm exhibit a high specific absorption rate of 1499 W/g Fe under an alternating magnetic field at 43 kA/m and 413 kHz, more than twice that of commercial iron oxide cores used in prior nanowarming studies. Surface modification with a permeable resorcinol-formaldehyde resin (RFR) polymer layer significantly enhances their colloidal stability in complex cryoprotective solutions, while maintaining their excellent heating capacity. The Fe3O4@RFR nanoparticles achieved a high average heating rate of 175 °C/min in cryopreserved samples at a concentration of 10 mg Fe/mL and were successfully applied in nanowarming porcine iliac arteries, highlighting their potential for enhancing the efficacy of cryopreservation.

A comprehensive approach to characterize navigation instruments for magnetic guidance in biological systems.

Achieving non-invasive spatiotemporal control over cellular functions, tissue organization, and behavior is a desirable aim for advanced therapies. Magnetic fields, due to their negligible interaction with biological matter, are promising for in vitro and in vivo applications, even in deep tissues. Particularly, the remote manipulation of paramagnetic (including superparamagnetic and ferromagnetic, all with a positive magnetic susceptibility) entities through magnetic instruments has emerged as a promising approach across various biological contexts. However, variations in the properties and descriptions of these instruments have led to a lack of reproducibility and comparability among studies. This article addresses the need for standardizing the characterization of magnetic instruments, with a specific focus on their ability to control the movement of paramagnetic objects within organisms. While it is well known that the force exerted on magnetic particles depends on the spatial variation (gradient) of the magnetic field, the magnitude of the field is often overlooked in the literature. Therefore, we comprehensively analyze and discuss both actors and propose a novel descriptor, termed 'effective gradient', which combines both dependencies. To illustrate the importance of both factors, we characterize different magnet systems and relate them to experiments involving superparamagnetic nanoparticles. This standardization effort aims to enhance the reproducibility and comparability of studies utilizing magnetic instruments for biological applications.

A novel magnetic compression technique for establishment of a vesicovaginal fistula model in Beagle dogs.

Vesicovaginal fistula lacks a standard, established animal model, making surgical innovations for this condition challenging. Herein, we aimed to non-surgically establish vesicovaginal fistula using the magnetic compression technique, and the feasibility of this method was explored using eight female Beagle dogs as model animals. In these dogs, cylindrical daughter and parent magnets were implanted into the bladder and vagina, respectively, after anesthesia, and the positions of these magnets were adjusted under X-ray supervision to make them attract each other, thus forming the structure of daughter magnet-bladder wall-vaginal wall-parent magnet. Operation time and collateral damage were recorded. The experimental animals were euthanized 2 weeks postoperatively, and the vesicovaginal fistula gross specimens were obtained. The size of the fistula was measured. Vesicovaginal fistula was observed by naked eye and under a light microscope. Magnet placement was successful in all dogs, and remained in the established position for the reminder of the experiment. The average operation time was 14.38 min ± 1.66 min (range, 12-17 min). The dogs were generally in good condition postoperatively and were voiding normally, with no complications like bleeding and urine retention. The magnets were removed from the vagina after euthanasia. The vesicovaginal fistula was successfully established according to gross observation, and the fistula diameters were 4.50-6.24 mm. Histological observation revealed that the bladder mucosa and vaginal mucosa were in close contact on the internal surface of the fistula. Taken together, magnetic compression technique is a simple and feasible method to establish an animal model of vesicovaginal fistula using Beagle dogs. This model can help clinicians study new surgical techniques and practice innovative approaches for treating vesicovaginal fistula.

Magnetic tweezers principles and promises.

Magnetic tweezers have become popular with the outbreak of single molecule micromanipulation: catching a single molecule of DNA, RNA or a single protein and applying mechanical constrains using micron-size magnetic beads and magnets turn out to be easy. Various factors have made this possible: the fact that manufacturers have been preparing these beads to catch various biological entities-the ease of use provided by magnets which apply a force or a torque at a distance thus inside a flow cell-some chance: since the forces so generated are in the right range to stretch a single molecule. This is a little less true for torque. Finally, one feature which also appears very important is the simplicity of their calibration using Brownian motion. Here we start by describing magnetic tweezers used routinely in our laboratory where we have tried to develop a device as simple as possible so that the experimentalist can really focus on the biological aspect of the biomolecules that he/she is interested in. We discuss the implications of the various components and their important features. Next, we summarize what is easy to achieve and what is less easy. Then we refer to contributions by other groups who have brought valuable insights to improve magnetic tweezers.

Construction and operation of high-resolution magnetic tape head tweezers for measuring single-protein dynamics under force.

Mechanical forces are critical to protein function across many biological contexts-from bacterial adhesion to muscle mechanics and mechanotransduction processes. Hence, understanding how mechanical forces govern protein activity has developed into a central scientific question. In this context, single-molecule magnetic tweezers has recently emerged as a valuable experimental tool, offering the capability to measure single proteins over physiologically relevant forces and timescales. In this chapter, we present a detailed protocol for the assembly and operation of our magnetic tape head tweezers instrument, specifically tailored to investigate protein dynamics. Our instrument boasts a simplified microscope design and incorporates a magnetic tape head as the force-generating apparatus, facilitating precise force control and enhancing its temporal stability, enabling the study of single protein mechanics over extended timescales spanning several hours or even days. Moreover, its straightforward and cost-effective design ensures its accessibility to the wider scientific community. We anticipate that this technique will attract widespread interest within the growing field of mechanobiology and expect that this chapter will provide facilitated accessibility to this technology.

Magnetic Control of Nonmagnetic Living Organisms.

Living organisms inspire the design of microrobots, but their functionality is unmatched. Next-generation microrobots aim to leverage the sensing and communication abilities of organisms through magnetic hybridization, attaching magnetic particles to them for external control. However, the protocols used for magnetic hybridization are morphology specific and are not generalizable. We propose an alternative approach that leverages the principles of negative magnetostatics and magnetophoresis to control nonmagnetic organisms with external magnetic fields. To do this, we disperse model organisms in dispersions of Fe3O4 nanoparticles and expose them to either uniform or gradient magnetic fields. In uniform magnetic fields, living organisms align with the field due to external torque, while gradient magnetic fields generate a negative magnetophoretic force, pushing objects away from external magnets. The magnetic fields enable controlling the position and orientation of Caenorhabditis elegans larvae and flagellated bacteria through directional interactions and magnitude. This control is diminished in live spermatozoa and adult C. elegans due to stronger internal biological activity, i.e., force/torque. Our study presents a method for spatiotemporal organization of living organisms without requiring magnetic hybridization, opening the way for the development of controllable living microbiorobots.

Highly efficient Cu(II) capture by salicylaldoxime functionalized magnetic polydopamine core-shell hybrids: Behavior and mechanism.

Functionalized magnetic nanocomposites were considered as promising adsorbents owing to their abundant functional groups and ease of separation properties. Herein, we combined the solvothermal method with molecular copolymerization to synthesize a salicylaldoxime-grafted magnetic polydopamine (SMP) core-shell hybrid and exploited it for Cu(II) adsorption. The physicochemical properties of SMP were comprehensively studied by SEM, TEM, XRD, FT-IR, TGA, XPS, and VSM measurements. The results manifested that polydopamine acts as a bridge connecting magnetic iron oxide and salicylaldoxime to fabricated core-shell hybrids with rich functional groups. The batch experimental results showed that the Cu(II) adsorption was consumingly pH-reliant behavior, while adsorption data fitted the pseudo-second-order kinetic model and Langmuir isothermal model well, and the adsorption process achieved equilibrium within 60 min. Moreover, SMP exhibited remarkable anti-interference and can be recycled for 5 times with an inconspicuous decrease in adsorption performance. Importantly, salicylaldoxime functionalization endowed SMP with maximum Cu(II) adsorption capacity of 141.24 mg/g at pH 6.0 and 25 °C as compared with pure MP. Based on FT-IR and XPS study, the main adsorption mechanisms were proposed with a synergistic effect including a strong chemical chelation and partial Cu(II) reduction. Importantly, this strategy can be extended to multifunctional magnetic composites for Cu-contaminated wastewater cleanup.

One-pot preparation of magnetic composite containing boronic acid groups and aminated multwalled carbon nanotubes for the speciation of Se(IV) and Se(VI) in water and milk samples by combination with chromatographic quantification.

Speciation of Se(IV) and Se(VI) is essential due to their significant differences in reactivity, toxicity and bioavailability. Efficient extraction is the pivotal step in the quantification of inorganic selenium species. In this work, a new magnetic nano-composite (MNC) containing boronic acid group and aminated multwalled carbon nanotubes was facilely fabricated by means of one-pot hydrothermal strategy. The prepared MNC contained abundant functional groups and satisfactory magnetic saturation value. Combining with magnetic solid phase extraction (MSPE) format, the MNC displayed satisfactory capture performance towards the complex formed by the coordination of Se(IV) and o-phenylenediamine (OPA). Adsorption isotherm and adsorption kinetics were studied in detail to investigate the adsorption procedure of Se(IV)/OPA complex on MNC. Under the optimal preparation conditions of MNC and extraction parameters, the MNC/MSPE was connected with HPLC equipped with a diode array detector (DAD) to quantify trace Se(IV) and Se(VI) species in water and milk samples. Se(VI) was reduced to Se(IV) and then the total inorganic Se was quantified by the developed method. Subtraction method was used to measure the concentration of Se(VI). The achieved limits of detection were in the ranges of 0.0082-0.013 µg/L and 0.041-0.13 µg/kg for water and milk samples, respectively. Recoveries in actual samples spiked with different amounts of analytes varied from 81.0 % and 117 %, and the RSDs for repeatability varied from 1.0 % to 10 %. In comparison with existing studies based on MSPE, the established method presents some merits such as greenness in the preparation of magnetic adsorbent, rapid extraction procedure, low cost and satisfactory sensitivity in the speciation of inorganic Se species.

Navigation by magnetic signatures in a realistic model of Earth's magnetic field.

Certain animal species use the Earth's magnetic field (i.e. magnetoreception) alongside their other sensory modalities to navigate long distances that include continents and oceans. It is hypothesized that several animals use geomagnetic parameters, such as field intensity and inclination, to recognize specific locations or regions, potentially enabling migration without a pre-surveyed map. However, it is unknown how animals use geomagnetic information to generate guidance commands, or where in the world this type of strategy would maximize an animal's fitness. While animal experiments have been invaluable in advancing this area, the phenomenon is difficult to studyin vivoorin situ, especially on the global scale where the spatial layout of the geomagnetic field is not constant. Alongside empirical animal experiments, mathematical modeling and simulation are complementary tools that can be used to investigate animal navigation on a global scale, providing insights that can be informative across a number of species. In this study, we present a model in which a simulated animal (i.e. agent) navigates via an algorithm which determines travel heading based on local and goal magnetic signatures (here, combinations of geomagnetic intensity and inclination) in a realistic model of Earth's magnetic field. By varying parameters of the navigation algorithm, different regions of the world can be made more or less reliable to navigate. We present a mathematical analysis of the system. Our results show that certain regions can be navigated effectively using this strategy when these parameters are properly tuned, while other regions may require more complex navigational strategies. In a real animal, parameters such as these could be tuned by evolution for successful navigation in the animal's natural range. These results could also help with developing engineered navigation systems that are less reliant on satellite-based methods.

Bare-Metal Stent Tracking with Magnetic Particle Imaging.

Purpose: Magnetic particle imaging (MPI) is an emerging medical imaging modality that is on the verge of clinical use. In recent years, cardiovascular applications have shown huge potential like, e.g., intraprocedural imaging guidance of stent placement through MPI. Due to the lack of signal generation, nano-modifications have been necessary to visualize commercial medical instruments until now. In this work, it is investigated if commercial interventional devices can be tracked with MPI without any nano-modification. Material and Methods: Potential MPI signal generation of nine endovascular metal stents was tested in a commercial MPI scanner. Two of the stents revealed sufficient MPI signal. Because one of the two stents showed relevant heating, the imaging experiments were carried out with a single stent model (Boston Scientific/Wallstent-Uni Endoprothesis, diameter: 16 mm, length: 60 mm). The nitinol stent and its delivery system were investigated in seven different scenarios. Therefore, the samples were placed at 49 defined spatial positions by a robot in a meandering pattern during MPI scans. Image reconstruction was performed, and the mean absolute errors (MAE) between the signals' centers of mass (COM) and ground truth positions were calculated. The stent material was investigated by magnetic particle spectroscopy (MPS) and vibrating sample magnetometry (VSM). To detect metallic components within the delivery system, nondestructive testing via computed tomography was performed. Results: The tracking of the stent and its delivery system was possible without any nano-modification. The MAE of the COM were 1.49 mm for the stent mounted on the delivery system, 3.70 mm for the expanded stent and 1.46 mm for the delivery system without the stent. The results of the MPS and VSM measurements indicate that besides material properties eddy currents seem to be responsible for signal generation. Conclusion: It is possible to image medical instruments with dedicated designs without modifications by means of MPI. This enables a variety of applications without compromising the mechanical and biocompatible properties of the instruments.

Spatially selective delivery of living magnetic microrobots through torque-focusing.

Rotating magnetic fields enable biomedical microrobots to overcome physiological barriers and promote extravasation and accumulation in tumors. Nevertheless, targeting deeply situated tumors requires suppression of off-target actuation in healthy tissue. Here, we investigate a control strategy for applying spatially selective torque density to microrobots by combining rotating fields with magnetostatic selection fields. Taking magnetotactic bacteria as diffuse torque-based actuators, we numerically model off-target torque suppression, indicating the feasibility of centimeter to millimeter resolution for human applications. We study focal torque application in vitro, observing off-target suppression of actuation-dependent effects such as colonization of bacteria in tumor spheroids. We then design and construct a mouse-scale torque-focusing apparatus capable of maneuvering the focal point. Applying this system to a mouse tumor model increased accumulation of intravenously injected bacteria within tumors receiving focused actuation compared to non-actuated or globally actuated groups. This control scheme combines the advantages of torque-based actuation with spatial targeting.

Determination of trace morphine and its metabolites in mouse urine using a TpBD functionalized bivalve magnetic nano-adsorbent.

In this study, a new type of covalent organic framework (TpBD) functionalized bivalved magnetic microsphere (TpBD-DS MNS) adsorbent was applied for the enrichment and detection of trace morphine and its metabolites in mouse urine. The main factors affecting the efficiency of magnetic solid phase extraction were optimized, and the optimal MSPE conditions were obtained. Combined with the UPLC-MS/MS technique, a new method for determining trace morphine and its metabolites in urine was established. The detection (LOD) and quantification (LOQ) limits for morphine and its metabolites ranged from 0.16 pg mL-1 to 0.53 pg mL-1 and 0.26 pg mL-1 to 1.25 pg mL-1, respectively. The recovery of the methods ranged from 87.4-97.3%, and the RSD was less than 5%. By employing this methodology, we successfully obtained the temporal change curve of morphine and its metabolites in mouse urine through collection and measurement post intravenous administration of morphine. This approach not only presents a novel means for investigating pharmacokinetics and drug monitoring but also demonstrates significant potential in the fields of forensic toxicology and drug abuse surveillance.

Multifunctional flexible magnetic drive gripper for target manipulation in complex constrained environments.

Soft actuators capable of remote-controlled guidance and manipulation within complex constrained spaces hold great promise in various fields, especially in medical fields such as minimally invasive surgery. However, most current magnetic drive soft actuators only have the functions of position control and guidance, and it is still challenging to achieve more flexible operations on different targets within constrained spaces. Herein, we propose a multifunctional flexible magnetic drive gripper that can be steered within complex constrained spaces and operate on targets of various shapes. On the one hand, changing the internal pressure of the magnetic gripper can achieve functions such as suction or injection of liquid and transportation of targets with smooth surfaces. On the other hand, with the help of slit structures in the constrained environment, by simply changing the position and orientation of the permanent magnet in the external environment, the magnetic gripper can be controlled to clamp and release targets of linear, flaked, and polyhedral shapes. The full flexibility and multifunctionality of the magnetic gripper suggest new possibilities for precise remote control and object transportation in constrained spaces, so it could serve as a direct contact operation tool for hazardous drugs in enclosed spaces or a surgical tool in human body cavities.

Magnetic tweezers in cell mechanics.

The chapter provides an overview of the applications of magnetic tweezers in living cells. It discusses the advantages and disadvantages of magnetic tweezers technology with a focus on individual magnetic tweezers configurations, such as electromagnetic tweezers. Solutions to the disadvantages identified are also outlined. The specific role of magnetic tweezers in the field of mechanobiology, such as mechanosensitivity, mechano-allostery and mechanotransduction are also emphasized. The specific usage of magnetic tweezers in mechanically probing cells via specific cell surface receptors, such as mechanosensitive channels is discussed and why mechanical probing has revealed the opening and closing of the channels. Finally, the future direction of magnetic tweezers is presented.

Amino-functional magnetic covalent organic framework as an effective adsorbent for the determination of neonicotinoids in food samples.

Recently, covalent organic frameworks have gained popularity in sample pretreatment. However, the application of covalent organic frameworks in the enrichment of hydrophilic compounds remains a challenge. Thus, a functionalized magnetic covalent organic framework equipped with amino groups was constructed using a bottom-up functionalization strategy. Considering the advantages of this novel adsorbent such as high porosity, large adsorption capacity, and hydrophilic surface, a sensitive magnetic solid-phase extraction coupled with high-performance liquid chromatography-tandem mass spectrometry method was established for the effective determination of neonicotinoids. This method exhibited good linearities with correlation coefficients ranging from 0.9983 to 0.9995, low detection limits in the range 0.003-0.009 ng g-1 and 0.001-0.013 ng mL-1, and limits of quantification in the range 0.010-0.031 ng g-1 and 0.004-0.044 ng mL-1. Furthermore, satisfactory repeatability with relative standard deviations ≤ 6.7% and spiked recoveries between 82.3 and 99.8% were obtained. This work not only provided a promising adsorbent for the sensitive determination of trace-level neonicotinoids but also represented a unique insight for effective enrichment of super hydrophilic hazards.

Programmable metachronal motion of closely packed magnetic artificial cilia.

Despite recent advances in artificial cilia technologies, the application of metachrony, which is the collective wavelike motion by cilia moving out-of-phase, has been severely hampered by difficulties in controlling closely packed artificial cilia at micrometer length scales. Moreover, there has been no direct experimental proof yet that a metachronal wave in combination with fully reciprocal ciliary motion can generate significant microfluidic flow on a micrometer scale as theoretically predicted. In this study, using an in-house developed precise micro-molding technique, we have fabricated closely packed magnetic artificial cilia that can generate well-controlled metachronal waves. We studied the effect of pure metachrony on fluid flow by excluding all symmetry-breaking ciliary features. Experimental and simulation results prove that net fluid transport can be generated by metachronal motion alone, and the effectiveness is strongly dependent on cilia spacing. This technique not only offers a biomimetic experimental platform to better understand the mechanisms underlying metachrony, it also opens new pathways towards advanced industrial applications.

Multiparametric modulation of magnetic transduction for biomolecular sensing in liquids.

The recent COVID19 pandemic has remarkably boosted the research on in vitro diagnosis assays to detect biomarkers in biological fluids. Specificity and sensitivity are mandatory for diagnostic kits aiming to reach clinical stages. Whilst the modulation of sensitivity can significantly improve the detection of biomarkers in liquids, this has been scarcely explored. Here, we report on the proof of concept and parametrization of a novel biosensing methodology based on the changes of AC magnetic hysteresis areas observed for magnetic nanoparticles following biomolecular recognition in liquids. Several parameters are shown to significantly modulate the transducing capacity of magnetic nanoparticles to detect analytes dispersed in saline buffer at concentrations of clinical relevance. Magnetic nanoparticles were bio-conjugated with an engineered recognition peptide as a receptor. Analytes are engineered tetratricopeptide binding domains fused to the fluorescent protein whose dimerization state allows mono- or divalent variants. Our results unveil that the number of receptors per particle, analyte valency and concentration, nanoparticle composition and concentration, and field conditions play a key role in the formation of assemblies driven by biomolecular recognition. Consequently, all these parameters modulate the nanoparticle transduction capacity. Our study provides essential insights into the potential of AC magnetometry for customizing biomarker detection in liquids.

Counting cells in motion by quantitative real-time magnetic particle imaging.

Magnetic Particle Imaging (MPI) is an advanced and powerful imaging modality for visualization and quantitative real-time detection of magnetic nanoparticles (MNPs). This opens the possibility of tracking cells in vivo once they have been loaded by MNPs. Imaging modalities such as optical imaging, X-ray computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) face limitations, from depth of penetration and radiation exposure to resolution and quantification accuracy. MPI addresses these challenges, enabling radiation-free tracking of MNP-loaded cells with precise quantification. However, the real-time tracking of MNP-loaded cells with MPI has not been demonstrated yet. This study establishes real-time quantitative tracking of MNP-loaded cells. Therefore, THP-1 monocytes were loaded with three different MNP systems, including the MPI gold standard Resovist and Synomag. The real-time MPI experiments reveal different MPI resolution behaviors of the three MNP systems after cellular uptake. Real-time quantitative imaging was achieved by time-resolved cell number determination and comparison with the number of inserted cells. About 95% of the inserted cells were successfully tracked in a controlled phantom environment. These results underline the potential of MPI for real-time investigation of cell migration and interaction with tissue in vivo.