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.

Exploiting compositional disorder in collectives of light-driven circle walkers.

Emergent behavior in collectives of "robotic" units with limited capabilities that is robust and programmable is a promising route to perform tasks on the micro and nanoscale that are otherwise difficult to realize. However, a comprehensive theoretical understanding of the physical principles, in particular steric interactions in crowded environments, is still largely missing. Here, we study simple light-driven walkers propelled through internal vibrations. We demonstrate that their dynamics is well captured by the model of active Brownian particles, albeit with an angular speed that differs between individual units. Transferring to a numerical model, we show that this polydispersity of angular speeds gives rise to specific collective behavior: self-sorting under confinement and enhancement of translational diffusion. Our results show that, while naively perceived as imperfection, disorder of individual properties can provide another route to realize programmable active matter.

Demonstration of diamond nuclear spin gyroscope.

We demonstrate the operation of a rotation sensor based on the nitrogen-14 (14N) nuclear spins intrinsic to nitrogen-vacancy (NV) color centers in diamond. The sensor uses optical polarization and readout of the nuclei and a radio-frequency double-quantum pulse protocol that monitors 14N nuclear spin precession. This measurement protocol suppresses the sensitivity to temperature variations in the 14N quadrupole splitting, and it does not require microwave pulses resonant with the NV electron spin transitions. The device was tested on a rotation platform and demonstrated a sensitivity of 4.7°/s (13 mHz/Hz), with a bias stability of 0.4 °/s (1.1 mHz).

Magnetic Guiding with Permanent Magnets: Concept, Realization and Applications to Nanoparticles and Cells.

The idea of remote magnetic guiding is developed from the underlying physics of a concept that allows for bijective force generation over the inner volume of magnet systems. This concept can equally be implemented by electro- or permanent magnets. Here, permanent magnets are in the focus because they offer many advantages. The equations of magnetic fields and forces as well as velocities are derived in detail and physical limits are discussed. The special hydrodynamics of nanoparticle dispersions under these circumstances is reviewed and related to technical constraints. The possibility of 3D guiding and magnetic imaging techniques are discussed. Finally, the first results in guiding macroscopic objects, superparamagnetic nanoparticles, and cells with incorporated nanoparticles are presented. The constructed magnet systems allow for orientation, movement, and acceleration of magnetic objects and, in principle, can be scaled up to human size.

Core Cross-Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages.

Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild-type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox-responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.

Contactless Nanoparticle-Based Guiding of Cells by Controllable Magnetic Fields.

Controlled and contactless movements of magnetic nanoparticles are crucial for fundamental biotechnological and clinical research (eg, cell manipulation and sorting, hyperthermia, and magnetic drug targeting). However, the key technological question, how to generate suitable magnetic fields on various length scales (µm-m), is still unsolved. Here, we present a system of permanent magnets which allows for steering of iron oxide nanoparticles (SPIONs) on arbitrary trajectories observable by microscopy. The movement of the particles is simply controlled by an almost force-free rotation of cylindrical arrangements of permanent magnets. The same instrument can be used to move suspended cells loaded with SPIONs along with predetermined directions. Surprisingly, it also allows for controlled movements of intracellular compartments inside of individual cells. The exclusive use of permanent magnets simplifies scaled up versions for animals or even humans, which would open the door for remotely controlled in vivo guidance of nanoparticles or micro-robots.

Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution.

Hyperpolarized fumarate is a promising biosensor for carbon-13 magnetic resonance metabolic imaging. Such molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting solutions are contaminated with the catalyst, unreacted reagents, and reaction side-product molecules, and are hence unsuitable for use in vivo. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved to a desired concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow for formation of hyperpolarized fumarate at 13C polarization levels of 30-45%.

High homogeneity permanent magnet for diamond magnetometry.

Halbach magnets are a source of homogeneous magnetic field in an enclosed volume while keeping stray fields at a minimum. Here, we present the design, construction, and characterization for a stack of two Halbach rings with 10 cm inner diameter providing a homogeneous (<100 ppm over 1.0×1.0×0.5cm3) magnetic field of around 105 mT, which will be used for a diamond based microwave-free widefield imaging setup. The final characterization is performed with a novel fiberized diamond-based sensor on a 3D translation stage documenting the high homogeneity of the constructed Halbach array and its suitability for the proposed use.

Spherical fused silica cells filled with pure helium for nuclear magnetic resonance-magnetometry.

High magnetic fields (>1 T) are measured by NMR magnetometers with unrivaled precision if the precessing spin sample provides long coherence times. The longest coherence times are found in diluted (3)He samples, which can be hyperpolarized for sufficient signal strength. In order to have minimal influence on the homogeneity and value of the measured magnetic field, the optimal container for the (3)He should be a perfect sphere. A fused silica sphere with an inner diameter of 8 mm and an outer diameter of 12 mm was made from two hemispheres by diffusion bonding leaving only a small hole for cleaning and evacuation. This hole was closed in vacuum by a CO2 laser and the inner volume was filled with a few mbars of (3)He via wall permeation. NMR-measurements on such a sample had coherence times of 5 min. While the hemispheres were produced with <1 µm deviation from sphericity, the bonding left a step of ca. 50 µm at maximum. The influence of such a mismatch, its orientation, and the immediate environment of the sample is analyzed by FEM-simulations and discussed in view of coherence times and absolute field measurements.

Systematic T1 improvement for hyperpolarized 129xenon.

The spin-lattice relaxation time T1 of hyperpolarized (HP)-(129)Xe was improved at typical storage conditions (i.e. low and homogeneous magnetic fields). Very long wall relaxation times T(1)(wall) of about 18 h were observed in uncoated, spherical GE180 glass cells of ∅=10 cm which were free of rubidium and not permanently sealed but attached to a standard glass stopcock. An "aging" process of the wall relaxation was identified by repeating measurements on the same cell. This effect could be easily removed by repeating the initial cleaning procedure. In this way, a constant wall relaxation was ensured. The Xe nuclear spin-relaxation rate 1/T1(Xe-Xe) due to van der Waals molecules was investigated too, by admixing three different buffer gases (N(2), SF(6) and CO(2)). Especially CO(2) exhibited an unexpected high efficiency (r) in shortening the lifetime of the Xe-Xe dimers and hence prolonging the total T1 relaxation even further. These measurements also yielded an improved accuracy for the van der Waals relaxation for pure Xe (with 85% (129)Xe) of T(1)(Xe-Xe)=(4.6±0.1)h. Repeating the measurements with HP (129)Xe in natural abundance in mixtures with SF6, a strong dependence of T(1)(Xe-Xe) and r on the isotopic enrichment was observed, uncovering a shorter T(1)(Xe-Xe) relaxation for the (129)Xe in natural composition as compared to the 85% isotopically enriched gas.

A portable NMR sensor to measure dynamic changes in the amount of water in living stems or fruit and its potential to measure sap flow.

Nuclear magnetic resonance (NMR) and NMR imaging (magnetic resonance imaging) offer the possibility to quantitatively and non-invasively measure the presence and movement of water. Unfortunately, traditional NMR hardware is expensive, poorly suited for plants, and because of its bulk and complexity, not suitable for use in the field. But does it need to be? We here explore how novel, small-scale portable NMR devices can be used as a flow sensor to directly measure xylem sap flow in a poplar tree (Populus nigra L.), or in a dendrometer-like fashion to measure dynamic changes in the absolute water content of fruit or stems. For the latter purpose we monitored the diurnal pattern of growth, expansion and shrinkage in a model fruit (bean pod, Phaseolus vulgaris L.) and in the stem of an oak tree (Quercus robur L.). We compared changes in absolute stem water content, as measured by the NMR sensor, against stem diameter variations as measured by a set of conventional point dendrometers, to test how well the sensitivities of the two methods compare and to investigate how well diurnal changes in trunk absolute water content correlate with the concomitant diurnal variations in stem diameter. Our results confirm the existence of a strong correlation between the two parameters, but also suggest that dynamic changes in oak stem water content could be larger than is apparent on the basis of the stem diameter variation alone.

Magnetically actuated micropatterns for switchable wettability.

Arrays of actuated magnetic micropillars that can be tilted, twisted, and rotated in the presence of a magnetic field gradient were obtained. The type and extent of the movements are dependent on the distribution (isotropic, anisotropic) of the magnetizable particles inside the pillars and the strength and the direction of the magnetic field gradient. Independent motion of groups of pillars in the same or opposite directions or homogeneous motion of the whole pattern has been realized. Changing the pattern geometry causes changes in the roll-off angle (ROA) of water droplets on the surface. We show magnetically induced changes in the ROA and direction-dependent ROAs as a consequence of the anisotropy of tilted patterns. We also demonstrate transfer of microparticles between magnetically actuated neighboring pillars.

Magnetically actuated patterns for bioinspired reversible adhesion (dry and wet).

A facile strategy to obtain magnetically actuated arrays of micropillars able to undergo reversible, homogeneous, drastic, and tunable geometrical changes upon application of a magnetic field with variable strength is demonstrated. A magnetically tunable gecko-inspired adhesive that works under dry and wet conditions is realized using elastomeric micropatterns containing magnetic microparticles.

Analytical model for long-distance tracer-transport in plants.

Recent investigations of long-distance transport in plants using non-invasive tracer techniques such as (11)C radiolabeling monitored by positron emission tomography (PET) combined with magnetic resonance imaging (MRI) revealed the need of dedicated methods to allow a quantitative data analysis and comparison of such experiments. A mechanistic compartmental tracer transport model is presented, defined by a linear system of partial differential equations (PDEs). This model simplifies the complexity of axial transport and lateral exchanges in the transport pathways of plants (e.g. the phloem) by simulating transport and reversible exchange within three compartments using just a few parameters which are considered to be constant in space and time. For this system of PDEs an analytical solution in Fourier-space was found allowing a fast and numerically precise evaluation. From the steady-state behavior of the model, the system loss (steadily fixed tracer along the transport conduits) was derived as an additional parameter that can be readily interpreted in a physiological way. The presented framework allows the model to be fitted to spatio-temporal tracer profiles including error and sensitivity analysis of the estimated parameters. This is demonstrated for PET data sets obtained from radish, sugar beet and maize plants.

A portable Halbach magnet that can be opened and closed without force: the NMR-CUFF.

Portable equipment for nuclear magnetic resonance (NMR) is becoming increasingly attractive for use in a variety of applications. One of the main scientific challenges in making NMR portable is the design of light-weight magnets that possess a strong and homogeneous field. Existing NMR magnets can provide such magnetic fields, but only for small samples or in small regions, or are rather heavy. Here we show a simple yet elegant concept for a Halbach-type permanent magnet ring, which can be opened and closed with minimal mechanical force. An analytical solution for an ideal Halbach magnet shows that the magnetic forces cancel if the structure is opened at an angle of 35.3° relative to its poles. A first prototype weighed only 3.1 kg, and provided a flux density of 0.57 T with a homogeneity better than 200 ppm over a spherical volume of 5mm in diameter without shimming. The force needed to close it was found to be about 20 N. As a demonstration, intact plants were imaged and water (xylem) flow measured. Magnets of this type (NMR-CUFF = Cut-open, Uniform, Force Free) are ideal for portable use and are eminently suited to investigate small or slender objects that are part of a larger or immobile whole, such as branches on a tree, growing fruit on a plant, or non-metallic tubing in industrial installations. This new concept in permanent-magnet design enables the construction of openable, yet strong and homogeneous magnets, which aside from use in NMR or MRI could also be of interest for applications in accelerators, motors, or magnetic bearings.

Contrasting dynamics of water and mineral nutrients in stems shown by stable isotope tracers and cryo-SIMS.

Lateral exchange of water and nutrients between xylem and surrounding tissues helps to de-couple uptake from utilization in all parts of a plant. We studied the dynamics of these exchanges, using stable isotope tracers for water (H(2)(18)O), magnesium ((26)Mg), potassium ((41)K) and calcium ((44)Ca) delivered via a cut stem for various periods to the transpiration stream of bean shoots (Phaseolus vulgaris cv. Fardenlosa Shiny). Tracers were subsequently mapped in stem cross-sections with cryo-secondary ion mass spectrometry. The water tracer equilibrated within minutes across the entire cross-section. In contrast, the nutrient tracers showed a very heterogeneous exchange between xylem vessels and the different stem tissues, even after 4 h. Dynamics of nutrients in the tissues revealed a fast and extensive exchange of nutrients in the xylem parenchyma, with, for example, calcium being completely replaced by tracer in less than 5 min. Dilution of potassium tracer during its 30 s transit in xylem sap through the stem showed that potassium concentration was up-regulated over many hours, to the extent that some of it was probably supplied by phloem recirculation from the shoot.

Combined MRI-PET dissects dynamic changes in plant structures and functions.

Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non-invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short-lived radioactive carbon isotope (11)C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species-specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI-PET co-registration opens the door for non-invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.

Non-invasive determination of plant biomass with microwave resonators.

Non-invasive and rapid determination of plant biomass would be beneficial for a number of research aims. Here, we present a novel device to non-invasively determine plant water content as a proxy for plant biomass. It is based on changes of dielectric properties inside a microwave cavity resonator induced by inserted plant material. The water content of inserted shoots leads to a discrete shift in the centre frequency of the resonator. Calibration measurements with pure water showed good spatial homogeneity in the detection volume of the microwave resonators and clear correlations between water content and centre frequency shift. For cut tomato and tobacco shoots, linear correlations between fresh weight and centre frequency shift were established. These correlations were used to continuously monitor diel growth patterns of intact plants and to determine biomass increase over several days. Interferences from soil and root water were excluded by shielding pots with copper. The presented proof of principle shows that microwave resonators are promising tools to quantitatively detect the water content of plants and to determine plant biomass. As the method is non-invasive, integrative and fast, it provides the opportunity for detailed, dynamic analyses of plant growth, water status and phenotype.

Influencia de la difusión en imágenes de resonancia magnética de gases / Diffusion influence on gas magnetic resonance imaging

La resolución en experimentos de resonancia magnética nuclear (RMN) con gases que hacen uso de gradientes de campo magnético, suele verse reducida debido a la rápida difusión de los mismos. En este artículo se presenta una solución a este problema basada en la mezcla de gases hiperpolarizados con láser (3He o Xe) con otros gases más pesados o más ligeros. De este modo, el coeficiente de difusión es modificado hasta en un orden de magnitud. La señal de imágenes en una dimensión de 3He es descrita en función de la concentración en una mezcla binaria de gases, y se muestra la existencia de una concentración óptima para ciertos parámetros de resolución en las imágenes. Los experimentos muestran que con dicha concentración, se consiguen ganancias de hasta 10 veces la señal del 3He puro, concordando con la teoría para difusión no restringida. Finalmente, se ilustra el método en imágenes 2D de 3He mezclado con diversos gases en un pulmón, que contiene cavidades restrictivas de diversos tamaños.

Resolution of nuclear magnetic resonance (NMR) experiments with gases employing magnetic field gradients is greatly reduced due to their rapid diffusion. In this paper, we present a solution to this problem basedon a mixture of gases hyperpolarized with laser (LP) (3He or Xe) with other heavier and lighter buffer gases. In this way the diffusion coefficient can be modified up to one order of magnitude. The signal of 1D images of 3He is described as a function of the concentration in a binary mixture of gases, and we show the existence of an optimum concentration for some image resolution parameters. Experimentsshow that with this concentration, the signal can gain an increase of up to 10 times the signal with pure 3He, in agreement with the theory of non-restricted diffusion. Finally, the method is illustrated with 2D images of LP-3He mixed with several gases in a lung containing restrictive cavities with different sizes.

A resolução nos experimentos de ressonância magnética nuclear (RMN) com gases que usam gradientes de campo magnético, frequentemente é reduzida por causa da rápida difusão dos mesmos. Neste artigo apresenta-se uma solução para este problema baseada na mistura de gases hiperpolarizados com laser (3He ou Xe) com outros gases mais pesados ou mais leves. Desta forma, o coeficiente de difusão é modificado até uma ordem de magnitude. O sinal de imagensnuma dimensão de 3He é descrita em função da concentração numa mistura binária de gases, e se mostra a existência de uma concentraçãootimizada para certos parâmetros de resolução das imagens. Os experimentos mostram que com essa concentração, conseguem-se ganânciasde até 10 vezes o sinal do 3He puro, concordando com a teoria para a difusão não restringida. Finalmente, ilustra-se o método em imagens2D de 3He misturando com diversos gases num pulmão, que contem cavidades restritivas de diversos tamanhos.