Reconstituted Super Paramagnetic Protein "Magnetotransferrin" for Brain Targeting to Attenuate Parkinsonism.

Transferrin is an iron transporting protein consisting of bilobal protein shells (apotransferrin) with dual domains in each lobe, holding an interdomain iron binding cleft. This cleft is useful in synthesizing an iron oxide core inside the transferrin shell. In vitro reconstitution chemistry provides a nano-dimensional synthesis of the mineral core inside the protein shell. The present study demonstrates the synthesis of magnetotransferrin with reconstitution of apotransferrin to form iron oxide nanoparticles within the transferrin. Transmission electron microscopy investigations along with analysis of electronic diffraction patterns and magnetometry studies indicate entrapment of superparamagnetic iron (III) oxide nanoparticles. In vivo/ex vivo imaging of the brain and immunogold staining of brain sections further validate the brain targeting potential of "magnetotransferrin". The in vivo therapeutic potential of magneto transferrin has been demonstrated by induction of TRPV1 magnetic stimuli protein, having an important regulatory role in Parkinsonism management. In an exploration of neuroprotective mechanisms, deacetylation of H3K27 of synuclein has been revealed through the TRPV1-mediated HDAC3 activation in the treatment of Parkinsonism. Thus, this magnetic protein could be a potent candidate for brain targeting, bio-imaging, and therapy of neurological infirmities.

Statistical Amplification of the Effects of Weak Magnetic Fields in Cellular Translation.

We assume that the enzymatic processes of recognition of amino acids and their addition to the synthesized molecule in cellular translation include the formation of intermediate pairs of radicals with spin-correlated electrons. The mathematical model presented describes the changes in the probability of incorrectly synthesized molecules in response to a change in the external weak magnetic field. A relatively high chance of errors has been shown to arise from the statistical enhancement of the low probability of local incorporation errors. This statistical mechanism does not require a long thermal relaxation time of electron spins of about 1 µs-a conjecture often used to match theoretical models of magnetoreception with experiments. The statistical mechanism allows for experimental verification by testing the usual Radical Pair Mechanism properties. In addition, this mechanism localizes the site where magnetic effects originate, the ribosome, which makes it possible to verify it by biochemical methods. This mechanism predicts a random nature of the nonspecific effects caused by weak and hypomagnetic fields and agrees with the diversity of biological responses to a weak magnetic field.

A self-healing magneto-responsive nanocellulose ferrogel and flexible soft strain sensor.

Crosslinks are the building blocks of hydrogels and play an important role in their overall properties. They may either be reversible and dynamic allowing for autonomous self-healing properties, or permanent and static resulting in robustness and mechanical strength. Hence, a combination of crosslinks is often required to engineer the 3D network of hydrogels with both autonomous self-healing and required robustness for strain sensing application; however, this complicates the fabrication of such hydrogels. The facile, yet versatile, approach used in this study is to forgo the use of extra crosslinks and instead rely solely on the properties of magnetic nanocellulose to fabricate a tough, stretchy, yet magneto-responsive, ionic conductive ferrogel for strain sensing. The ferrogel also gives stimuli-free and autonomous self-healing capacity, as well as the ability to monitor real-time strain under external magnetic actuation. The ferrogel also functions as a touch-screen pen. Based on our findings, this study has the potential to advance the rational design of multifunctional hydrogels, with applications in soft and flexible strain sensors, health monitoring and soft robotics.

Spintronic leaky-integrate-fire spiking neurons with self-reset and winner-takes-all for neuromorphic computing.

Neuromorphic computing using nonvolatile memories is expected to tackle the memory wall and energy efficiency bottleneck in the von Neumann system and to mitigate the stagnation of Moore's law. However, an ideal artificial neuron possessing bio-inspired behaviors as exemplified by the requisite leaky-integrate-fire and self-reset (LIFT) functionalities within a single device is still lacking. Here, we report a new type of spiking neuron with LIFT characteristics by manipulating the magnetic domain wall motion in a synthetic antiferromagnetic (SAF) heterostructure. We validate the mechanism of Joule heating modulated competition between the Ruderman-Kittel-Kasuya-Yosida interaction and the built-in field in the SAF device, enabling it with a firing rate up to 17 MHz and energy consumption of 486 fJ/spike. A spiking neuron circuit is implemented with a latency of 170 ps and power consumption of 90.99 µW. Moreover, the winner-takes-all is executed with a current ratio >104 between activated and inhibited neurons. We further establish a two-layer spiking neural network based on the developed spintronic LIFT neurons. The architecture achieves 88.5% accuracy on the handwritten digit database benchmark. Our studies corroborate the circuit compatibility of the spintronic neurons and their great potential in the field of intelligent devices and neuromorphic computing.

New Dinuclear Macrocyclic Copper(II) Complexes as Potentially Fluorescent and Magnetic Materials.

Two dinuclear copper(II) complexes with macrocyclic Schiff bases K1 and K2 were prepared by the template reaction of (R)-(+)-1,1'-binaphthalene-2,2'-diamine and 2-hydroxy-5-methyl-1,3-benzenedicarboxaldehyde K1, or 4-tert-butyl-2,6-diformylphenol K2 with copper(II) chloride dihydrate. The compounds were characterized by spectroscopic methods. X-ray crystal structure determination and DFT calculations confirmed their geometry in solution and in the solid phase. Moreover, intermolecular interactions in the crystal structure of K2 were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The magnetic study revealed very strong antiferromagnetic CuII-CuII exchange interactions, which were supported by magneto-structural correlation and DFT calculations conducted within a broken symmetry (BS) framework. Complexes K1 and K2 exhibited luminescent properties that may be of great importance in the search for new OLEDs. Both K1 and K2 complexes showed emissions in the range of 392-424 nm in solutions at various polarities. Thin materials of the studied compounds were deposited on Si(111) by the spin-coating method or by thermal vapor deposition and studied by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM), and fluorescence spectroscopy. The thermally deposited K1 and K2 materials showed high fluorescence intensity in the range of 318-531 nm for K1/Si and 326-472 nm for the K2/Si material, indicating that they could be used in optical devices.

Room-temperature synthesis of dual-functionalized magnetic microporous organic network for efficient extraction of vanillins in food.

Microporous organic networks (MONs) are promising materials for the magnetic solid-phase extraction (MSPE) of trace targets from diverse complex samples. However, all the reported magnetic MONs (MMONs) are mono-functionalized and synthesized by refluxing at high temperatures, which is not an energy-efficient and environmentally friendly method. Here, for the first time, we report the room-temperature fabrication of a novel dual-functionalized MMON (MMON-B) for the efficient MSPE of typical vanillin additives from food samples prior to high-performance liquid chromatography (HPLC). The conjugated MMON-B with numerous -OH and -NH2 groups afforded good extraction for vanillins via π-π, hydrophobic, and hydrogen-bonding interactions. The factors affecting the extraction were studied in detail. Under the optimal conditions, the developed MMON-B-MSPE-HPLC-UV method exhibited wide linear range (0.50-1200 µg L-1), low limits of detection (0.10-0.15 µg L-1), and good reusability and stability. Therefore, MMON-B was successfully used to enrich vanillins in complex food samples. The morphology and extraction efficiency of the room-temperature synthesized MMON-B were comparable with those of the MMON-B synthesized via the conventional reflux method, indicating that the room-temperature fabrication method is a good alternative to the reflux method. This study presents the feasibility of using a room-temperature method for synthesizing dual-functionalized MONs, and the findings may significantly promote the application of MONs in the MSPE of trace targets from complex matrices.

Identification of Microorganisms that Bind Specifically to Target Materials of Interest Using a Magnetophoretic Microfluidic Platform.

Discovery of microorganisms and their relevant surface peptides that specifically bind to target materials of interest can be achieved through iterative biopanning-based screening of cellular libraries having high diversity. Recently, microfluidics-based biopanning methods have been developed and exploited to overcome the limitations of conventional methods where controlling the shear stress applied to remove cells that do not bind or only weakly bind to target surfaces is difficult and the overall experimental procedure is labor-intensive. Despite the advantages of such microfluidic methods and successful demonstration of their utility, these methods still require several rounds of iterative biopanning. In this work, a magnetophoretic microfluidic biopanning platform was developed to isolate microorganisms that bind to target materials of interest, which is gold in this case. To achieve this, gold-coated magnetic nanobeads, which only attached to microorganisms that exhibit high affinity to gold, were used. The platform was first utilized to screen a bacterial peptide display library, where only the cells with surface peptides that specifically bind to gold could be isolated by the high-gradient magnetic field generated within the microchannel, resulting in enrichment and isolation of many isolates with high affinity and high specificity toward gold even after only a single round of separation. The amino acid profile of the resulting isolates was analyzed to provide a better understanding of the distinctive attributes of peptides that contribute to their specific material-binding capabilities. Next, the microfluidic system was utilized to screen soil microbes, a rich source of extremely diverse microorganisms, successfully isolating many naturally occurring microorganisms that show strong and specific binding to gold. The results show that the developed microfluidic platform is a powerful screening tool for identifying microorganisms that specifically bind to a target material surface of interest, which can greatly accelerate the development of new peptide-driven biological materials and hybrid organic-inorganic materials.

Lead determination in commercial juice samples by direct magnetic sorbent sampling flame atomic absorption spectrometry (DMSS-FAAS).

The direct magnetic sorbent sampling flame atomic absorption spectrometry (DMSS-FAAS), recently proposed by our research group, was applied to determine the lead in soy-based juice, whole grape juice, reconstituted grape juice, and orange nectar samples. A dispersive solid phase extraction (d-SPE) of lead was carried out using a magnetic orange peel powder, developed and optimized by Gupta et al (2012), that was inserted into flame by FAAS with a magnetic probe. The limits of quantification (<4.6 µg L-1) were smaller than maximum residue limits established in Brazil. Good precisions and accuracies were obtained. DMSS-FAAS presented a sensitivity at least 14 times greater than the d-SPE followed by conventional FAAS analysis, wherein the analytes were extracted and desorbed, and the eluate was introduced in FAAS via nebulization system. Lead was easily quantified in juice samples at very low concentrations, with satisfactory figures of merit, and without the need of a mineralization step.

Core-Shell Magnetic Imprinted Polymers for the Recognition of FLAG-Tagpeptide.

FLAG® tag (DYKDDDDK) is a small epitope peptide employed for the purification of recombinant proteins such as immunoglobulins, cytokines, and gene regulatory proteins. It provides superior purity and recoveries of fused target proteins when compared to the commonly used His-tag. Nevertheless, the immunoaffinity-based adsorbents required for their isolation are far more expensive than the ligand-based affinity resin used in combination with the His-tag. In order to overcome this limitation we report herein the development of molecularly imprinted polymers (MIPs) selective to the FLAG® tag. The polymers were prepared by the epitope imprinting approach using a four amino acids peptide, DYKD, including part of the FLAG® sequence as template molecule. Different kinds of magnetic polymers were synthesised in aqueous and organic media also using different sizes of magnetite core nanoparticles. The synthesised polymers were used as solid phase extraction materials with excellent recoveries and high specificity for both peptides. The magnetic properties of the polymers confer a new, effective, simple, and fast method in the purification using FLAG® tag.

Understanding the Exchange Interaction between Paramagnetic Metal Ions and Radical Ligands: DFT and Ab Initio Study on Semiquinonato Cu(II) Complexes.

The exchange coupling, represented by the J parameter, is of tremendous importance in understanding the reactivity and magnetic behavior of open-shell molecular systems. In the past, it was the subject of theoretical investigations, but these studies are mostly limited to the interaction between metallic centers. The exchange coupling between paramagnetic metal ions and radical ligands has hitherto received scant attention in theoretical studies, and thus the understanding of the factors governing this interaction is lacking. In this paper, we use DFT, CASSCF, CASSCF/NEVPT2, and DDCI3 methods to provide insight into exchange interaction in semiquinonato copper(II) complexes. Our primary objective is to identify structural features that affect this magnetic interaction. We demonstrate that the magnetic character of Cu(II)-semiquinone complexes are mainly determined by the relative position of the semiquinone ligand to the Cu(II) ion. The results can support the experimental interpretation of magnetic data for similar systems and can be used for the in-silico design of magnetic complexes with radical ligands.

Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels.

This study reports results of a mechanical platform-based screening assay (MICA) to evaluate the remote activation of mechanosensitive ion channels. Here, we studied ERK pathway activation and the elevation in intracellular Ca2+ levels in response to the MICA application using the Luciferase assay and Fluo-8AM assay, respectively. Functionalised magnetic nanoparticles (MNPs) targeting membrane-bound integrins and mechanosensitive TREK1 ion channels were studied with HEK293 cell lines under MICA application. The study demonstrated that active targeting of mechanosensitive integrins via RGD (Arginylglycylaspartic acid) motifs or TREK1 (KCNK2, potassium channel subfamily K member 2) ion channels can stimulate the ERK pathway and intracellular calcium levels compared to non-MICA controls. This screening assay offers a powerful tool, which aligns with existing high-throughput drug screening platforms for use in the assessment of drugs that interact with ion channels and influence ion channel-modulated diseases.

Surface functionalization modification of ultra-hydrophilic magnetic spheres with mesoporous silica for specific identification of glycopeptides in serum exosomes.

Protein glycosylation of human serum exosomes can reveal significant physiological information, and the development of large-scale identification strategies is crucial for the in-depth investigation of the serum exosome glycoproteome. In this study, using surface functionalization techniques, an ultra-hydrophilic mesoporous silica magnetic nanosphere (denoted as Fe3O4-CG@mSiO2) was synthesized for the quick and accurate detection of glycopeptides from HRP digests. The Fe3O4-CG@mSiO2 nanospheres demonstrated outstanding enrichment capability, high sensitivity (5 amol/µL), good size exclusion effect (HRP digests/BSA proteins, 1:10,000), stable reusability (at least 10 times), and an excellent recovery rate (108.6 ± 5.5%). Additionally, after enrichment by Fe3O4-CG@mSiO2, 156 glycopeptides assigned to 64 proteins derived from human serum exosomes were successfully identified, which demonstrates that the nanospheres have great potential for the research of the large-scale serum exosome glycoproteome.

Bionic Magnetic Sensor Based on the MagR/Cry4 Complex-Configured Graphene Transistor with an Integrated On-Chip Gate.

Magnetic-sensitive proteins are regarded as key factors in animals' precise perception of the geomagnetic field. Accurate feedback on the response of these tiny proteins to magnetic fields remains a challenge. Here, we first propose a real-time accurate magnetic sensor based on the MagR/Cry4 complex-configured graphene transistor with an integrated on-chip gate. A nanometer-thick denatured bovine serum albumin film was used as the bio-interface of graphene electrolyte-gated transistors (EGTs) to immobilize the MagR/Cry4 complex. With the optimization and characterization of this bionic graphene EGT, it could detect magnetic fields in real time with a sensitivity of 1 mT, which is far lower than in earlier research. It was concluded that our MagR/Cry4 complex-configured graphene EGTs with a side-gate held great promise in terms of geomagnetic field detection. Furthermore, the constructed approach in this paper could also be utilized as a general solution for recording the response of magnetically sensitive biomolecules to magnetic fields in real time.

Isolation of DNA from plant tissues using a miniaturized matrix solid-phase dispersion approach featuring ionic liquid and magnetic ionic liquid solvents.

The isolation of high-quality plant genomic DNA is a major prerequisite in many plant biomolecular analyses involving nucleic acid amplification. Conventional plant cell lysis and DNA extraction methods involve lengthy sample preparation procedures that often require large amounts of sample and chemicals, high temperatures and multiple liquid transfer steps which can introduce challenges for high throughput applications. In this study, a simple, rapid, miniaturized ionic liquid (IL)-based extraction method was developed for the isolation of genomic DNA from milligram fragments of Arabidopsis thaliana plant tissue. This method is based on a modification of vortex-assisted matrix solid-phase dispersion (VA-MSPD) in which the trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide ([P6,6,6,14+][NTf2-]) IL or trihexyl(tetradecyl)phosphonium tris(hexafluoroacetylaceto)nickelate(II) ([P6,6,6,14+][Ni(hfacac)3-]) magnetic IL (MIL) was directly applied to treated plant tissue (∼1.5 mg) and dispersed in an agate mortar to facilitate plant cell lysis and DNA extraction, followed by recovery of the mixture with a qPCR compatible co-solvent. This study represents the first approach to use ILs and MILs in a MSPD procedure to facilitate plant cell lysis and DNA extraction. The DNA-enriched IL- and MIL-cosolvent mixtures were directly integrated into the qPCR buffer without inhibiting the reaction while also circumventing the need for additional purification steps prior to DNA amplification. Under optimum conditions, the IL and MIL yielded 2.87 ± 0.28 and 1.97 ± 0.59 ng of DNA/mg of plant tissue, respectively. Furthermore, the mild extraction conditions used in the method enabled plant DNA in IL- and MIL-cosolvent mixtures to be preserved from degradation at room temperature.

Rotary Structural Color Spindles from Droplet Confined Magnetic Self-Assembly.

Structural colors materials are profoundly explored owing to their fantastic optical properties and widespread applications. Development of structural color materials bearing flexible morphologies and versatile functionalities is highly anticipated. Here, a droplet-confined, magnetic-induced self-assembly strategy for generating rotary structural color spindles (SCSPs) by fast solvent extraction is proposed. The as-prepared SCSPs exhibit an orderly close-packed lattice structure, thus appearing brilliant structural colors that serve as encoding tags for multiplexed bioassays. Besides, benefitting from the abundant specific surface area, biomarkers can be labeled on the SCSPs with high efficiency for specific detection of analytes in clinical samples. Moreover, the directional magnetic moment arrangement enables contactless magnetic manipulation of the SCSPs, and the resultant rotary motions of the SCSPs generates turbulence in the detection solution, thus significantly improving the detection efficiency and shortening the detection time. Based on these merits, a portable point-of-care-testing strip integrating the rotary SCSPs is further constructed and the capability and advantages of this platform for multiplexed detection of tumor-related exosomes in clinical samples are demonstrated. This study offers a new way for the control of bottom-up self-assembly and extends the configuration and application values of colloidal crystal structural colors materials.

Isotope Substitution Effects on the Magnetic Compass Properties of Cryptochrome-Based Radical Pairs: A Computational Study.

The biophysical mechanism of the magnetic compass sense of migratory songbirds is thought to rely on the photochemical reactions of flavin-containing radical pairs in cryptochrome proteins located in the birds' eyes. A consequence of this hypothesis is that the effect of the Earth's magnetic field on the quantum yields of reaction products should be sensitive to isotopic substitutions that modify the hyperfine interactions in the radicals. In this report, we use spin dynamics simulations to explore the effects of 1H → 2H, 12C → 13C, and 14N → 15N isotopic substitutions on the functioning of cryptochrome 4a as a magnetic direction sensor. Two main conclusions emerge. (1) Uniform deuteration of the flavin chromophore appears to be the best way to boost the anisotropy of the magnetic field effect and to change its symmetry. (2) 13C substitution of three of the 12 flavin carbons, in particular C4, C4a, and C8α, seems to be the best recipe for attenuating the anisotropy. These predictions should give insight into the factors that control the magnetic sensitivity once spectroscopic techniques are available for measuring magnetic field effects on oriented protein samples.

A Moving Magnetic Grid-Type Long-Range Linear Absolute Displacement Sensor.

In order to overcome the shortcomings of the traditional magnetic absolute linear displacement sensors in which cables affect the flexibility and measurement range in linear motor transmission systems, this paper proposes a novel cable-free moving magnetic grid-type long-range absolute displacement sensor. The sensor consists of a magnetic grid and a signal acquisition board. The magnetic grid is a moving component that contains two rows of permanent magnet arrays, one for relative displacement measurement and the other for the displacement interval code. The signal acquisition board is a fixed component that uses n groups of two-row Hall sensor arrays for continuous absolute displacement measurement. The principle of the sensor using the 2D magnetic field signal for the relative displacement measurement is analyzed, and a measurement method based on Hall sensor arrays for coding and absolute displacement detection over n cycles is proposed. Finally, a sensor prototype is fabricated and the experiments are performed. The experimental results show that the measurement resolution of the sensor is 5 µm, and the measurement accuracy is ±14.8 µm within the measurement range of 0-98.3 mm. The proposed sensor can realize continuous absolute displacement measurement over multiple cycles without cable binding.

Design Methodology for a Magnetic Levitation System Based on a New Multi-Objective Optimization Algorithm.

Multi-objective (MO) optimization is a developing technique for increasing closed-loop performance and robustness. However, its applications to control engineering mostly concern first or second order approximation models. This article proposes a novel MO algorithm, suitable for the design and control of mechanical systems, which does not require any order reduction techniques. The controller parameters are determined directly from a special type of rapid analysis of simulated transient responses. The case study presented in this article consists of a magnetic levitation system. Certain difficulties such as the nonlinearity identification of the magnetic force and duo magnetic field sensor scheme were addressed. To point out the advantages of using the developed approach, the simulations as well as the experiments performed with the help of the created algorithm were compared to those made with common MO algorithms.

High-Efficiency Plasma Source Using a Magnetic Mirror Trap for Miniature-Ion Pumps.

In this study, we design a highly efficient plasma source using a magnetic mirror trap with two opposing permanent magnets for a miniature high-efficiency ion pump. First, we simulated the distribution of the magnetic field line formed by the proposed magnetic mirror configuration. By optimizing the distance between two opposing permanent magnets and size of these magnets, a magnetic mirror ratio value of 27 could be obtained, which is an electron confinement efficiency of over 90%. We also conducted an experiment on a high-efficiency discharge plasma source for a miniature ion pump using an optimized magnetic circuit. As a result, we revealed that the proposed magnetic circuit has a pronounced effect on plasma generation, particularly in the high-vacuum region.

Development of a Personalised Device for Systemic Magnetic Drug Targeting to Brain Tumours.

Delivering therapies to deeply seated brain tumours (BT) is a major clinical challenge. Magnetic drug targeting (MDT) could overcome this by rapidly transporting magnetised drugs directly into BT. We have developed a magnetic device for application in murine BT models using an array of neodymium magnets with a combined strength of 0.7T. In a closed fluidic system, the magnetic device trapped magnetic nanoparticles (MNP) up to distances of 0.8cm. In mice, the magnetic device guided intravenously administered MNP (<50nm) from the circulation into the brain where they localised within mouse BT. Furthermore, MDT of magnetised Temozolomide (TMZmag+) significantly reduced tumour growth and extended mouse survival to 48 days compared to the other treatment groups. Using the same principles, we built a proof of principle scalable magnetic device for human use with a strength of 1.1T. This magnetic device demonstrated trapping of MNP undergoing flow at distances up to 5cm. MDT using our magnetic device provides an opportunity for targeted delivery of magnetised drugs to human BT.