Early detection of kidney cancer using urinary proteins: a truly non-invasive strategy.

OBJECTIVES: To review urinary protein biomarkers as potential non-invasive, easily obtainable, early diagnostic tools in renal cell carcinoma (RCC). METHODS: A PubMed database search was performed up to the year 2020 to identify primary studies reporting potential urinary protein biomarkers for RCC. Separate searches were conducted to identify studies describing appropriate methods of developing cancer screening programmes and detection of cancer biomarkers. RESULTS: Several urinary protein biomarkers are under validation for RCC diagnostics, e.g. aquaporin-1, perilipin-2, carbonic anhydrase-9, Raf-kinase inhibitory protein, nuclear matrix protein-22, 14-3-3 Protein ß/α and neutrophil gelatinase-associated lipocalin. However, none has yet been validated or approved for clinical use due to low sensitivity or specificity, inconsistencies in appropriate study design, or lack of external validation. CONCLUSIONS: Evaluation of biomarkers' feasibility, sample preparation and storage, biomarker validation, and the application of novel technologies may provide a solution that maximises the potential for a truly non-invasive biomarker in early RCC diagnostics.

Symmetry-breaking interlayer Dzyaloshinskii-Moriya interactions in synthetic antiferromagnets.

The magnetic interfacial Dzyaloshinskii-Moriya interaction (DMI) in multilayered thin films can lead to chiral spin states, which are of paramount importance for future spintronic technologies1,2. Interfacial DMI typically manifests as an intralayer interaction, mediated via a paramagnetic heavy metal in systems lacking inversion symmetry3. Here we show that, by designing synthetic antiferromagnets with canted magnetization states4,5, it is also possible to observe direct evidence of the interfacial interlayer DMI at room temperature. The interlayer DMI breaks the symmetry of the magnetic reversal process via the emergence of non-collinear spin states, which results in chiral exchange-biased hysteresis loops. The spin chiral interlayer interactions reported here are expected to manifest in a range of multilayered thin-film systems, opening up as yet unexplored avenues for the development and exploitation of chiral effects in magnetic heterostructures6-8.

Magnetic ratchet for three-dimensional spintronic memory and logic.

One of the key challenges for future electronic memory and logic devices is finding viable ways of moving from today's two-dimensional structures, which hold data in an x-y mesh of cells, to three-dimensional structures in which data are stored in an x-y-z lattice of cells. This could allow a many-fold increase in performance. A suggested solution is the shift register--a digital building block that passes data from cell to cell along a chain. In conventional digital microelectronics, two-dimensional shift registers are routinely constructed from a number of connected transistors. However, for three-dimensional devices the added process complexity and space needed for such transistors would largely cancel out the benefits of moving into the third dimension. 'Physical' shift registers, in which an intrinsic physical phenomenon is used to move data near-atomic distances, without requiring conventional transistors, are therefore much preferred. Here we demonstrate a way of implementing a spintronic unidirectional vertical shift register between perpendicularly magnetized ferromagnets of subnanometre thickness, similar to the layers used in non-volatile magnetic random-access memory. By carefully controlling the thickness of each magnetic layer and the exchange coupling between the layers, we form a ratchet that allows information in the form of a sharp magnetic kink soliton to be unidirectionally pumped (or 'shifted') from one magnetic layer to another. This simple and efficient shift-register concept suggests a route to the creation of three-dimensional microchips for memory and logic applications.

Systematic layer-by-layer characterization of multilayers for three-dimensional data storage and logic.

Magnetic kink solitons are used as a probe to experimentally measure the layer-by-layer coercivity and interlayer coupling strength of an antiferromagnetically coupled perpendicularly magnetized Co multilayer. The magnetic response is well described by a nearest neighbor Ising macrospin model. By controlling the position of one, two or three solitons in the stack using globally applied magnetic fields, we successfully probe the switching of individual buried layers under different neighboring configurations, allowing us to access individual layer's characteristic parameters. We found the coercivity to increase dramatically up the multilayer, while the interlayer coupling strength decreased slightly. We corroborate these findings with scanning transmission electron microscopy images where a degrading quality of the multilayer is observed. This method provides a very powerful tool to characterize the quality of individual layers in complex multilayers, without the need for depth-sensitive magnetic characterization equipment.

Multi-bit operations in vertical spintronic shift registers.

Spintronic devices have in general demonstrated the feasibility of non-volatile memory storage and simple Boolean logic operations. Modern microprocessors have one further frequently used digital operation: bit-wise operations on multiple bits simultaneously. Such operations are important for binary multiplication and division and in efficient microprocessor architectures such as reduced instruction set computing (RISC). In this paper we show a four-stage vertical serial shift register made from RKKY coupled ultrathin (0.9 nm) perpendicularly magnetised layers into which a 3-bit data word is injected. The entire four stage shift register occupies a total length (thickness) of only 16 nm. We show how under the action of an externally applied magnetic field bits can be shifted together as a word and then manipulated individually, including being brought together to perform logic operations. This is one of the highest level demonstrations of logic operation ever performed on data in the magnetic state and brings closer the possibility of ultrahigh density all-magnetic microprocessors.

Lithographically defined encoded magnetic heterostructures for the targeted screening of kidney cancer.

Renal cell carcinoma (RCC) is the 7th commonest cancer in the UK and the most lethal urological malignancy; 50% of all RCC patients will die from the condition. However, if identified early enough, small RCCs are usually cured by surgery or percutaneous procedures, with 95% 10 year survival. This study describes a newly developed non-invasive urine-based assay for the early detection of RCC. Our approach uses encoded magnetically controllable heterostructures as a substrate for immunoassays. These heterostructures have molecular recognition abilities and embedded patterned codes for a rapid identification of RCC biomarkers. The magnetic heterostructures developed for this study have a magnetic configuration designed for a remote multi axial control of their orientation by external magnetic fields, this control facilitates the code readout when the heterostructures are in liquid. Furthermore, the optical encoding of each set of heterostructures provides a multiplexed analyte capture platform, as different sets of heterostructures, specific to different biomarkers can be mixed together in a patient sample. Our results show a precise magnetic control of the heterostructures with an efficient code readout during liquid immunoassays. The use of functionalised magnetic heterostructures as a substrate for immunoassay is validated for urine specimen spiked with recombinant RCC biomarkers. Initial results of the newly proposed screening method on urine samples from RCC patients, and controls with no renal disorders are presented in this study. Comprehensive optimisation cycles are in progress to validate the robustness of this technology as a novel, non-invasive screening method for RCC.

Forgery: 'fingerprinting' documents and packaging.

We have found that almost all paper documents, plastic cards and product packaging contain a unique physical identity code formed from microscopic imperfections in the surface. This covert 'fingerprint' is intrinsic and virtually impossible to modify controllably. It can be rapidly read using a low-cost portable laser scanner. Most forms of document and branded-product fraud could be rendered obsolete by use of this code.

Non-Planar Geometrical Effects on the Magnetoelectrical Signal in a Three-Dimensional Nanomagnetic Circuit.

Expanding nanomagnetism and spintronics into three dimensions (3D) offers great opportunities for both fundamental and technological studies. However, probing the influence of complex 3D geometries on magnetoelectrical phenomena poses important experimental and theoretical challenges. In this work, we investigate the magnetoelectrical signals of a ferromagnetic 3D nanodevice integrated into a microelectronic circuit using direct-write nanofabrication. Due to the 3D vectorial nature of both electrical current and magnetization, a complex superposition of several magnetoelectrical effects takes place. By performing electrical measurements under the application of 3D magnetic fields, in combination with macrospin simulations and finite element modeling, we disentangle the superimposed effects, finding how a 3D geometry leads to unusual angular dependences of well-known magnetotransport effects such as the anomalous Hall effect. Crucially, our analysis also reveals a strong role of the noncollinear demagnetizing fields intrinsic to 3D nanostructures, which results in an angular dependent magnon magnetoresistance contributing strongly to the total magnetoelectrical signal. These findings are key to the understanding of 3D spintronic systems and underpin further fundamental and device-based studies.

Impact of surface roughness on laser surface authentication signatures under linear and rotational displacements.

Laser surface authentication (LSA) is a technique for authenticating optically rough surfaces based on the intensity of diffusely scattered light. The degradation in the LSA signature over linear and rotational displacement is examined. Randomly roughened glass surfaces with roughness amplitudes ranging from 0.4 microm to 3 microm and correlation lengths from 16 microm to 45 microm are examined experimentally, showing that the average size of the surface feature has a negligible impact on the rate of LSA signature degradation. The average size of the surface features is shown to have a greater effect on the fractional intensity of the variations in diffuse light and on the quality of LSA signature match.

Controlling All-Optical Helicity-Dependent Switching in Engineered Rare-Earth Free Synthetic Ferrimagnets.

All-optical helicity-dependent switching in ferromagnetic layers has revealed an unprecedented route to manipulate magnetic configurations by circularly polarized femtosecond laser pulses. In this work, rare-earth free synthetic ferrimagnetic heterostructures made from two antiferromagnetically exchange coupled ferromagnetic layers are studied. Experimental results, supported by numerical simulations, show that the designed structures enable all-optical switching which is controlled, not only by light helicity, but also by the relative Curie temperature of each ferromagnetic layer. Indeed, through the antiferromagnetic exchange coupling, the layer with the larger Curie temperature determines the final orientation of the other layer and so the synthetic ferrimagnet. For similar Curie temperatures, helicity-independent back switching is observed and the final magnetic configuration is solely determined by the initial magnetic state. This demonstration of electrically-detected, optical control of engineered rare-earth free heterostructures opens a novel route toward practical opto-spintronics.

Magnetic particles with perpendicular anisotropy for mechanical cancer cell destruction.

We demonstrate the effectiveness of out-of-plane magnetized magnetic microdiscs for cancer treatment through mechanical cell disruption under an applied rotating magnetic field. The magnetic particles are synthetic antiferromagnets formed from a repeated motif of ultrathin CoFeB/Pt layers. In-vitro studies on glioma cells are used to compare the efficiency of the CoFeB/Pt microdiscs with Py vortex microdiscs. It is found that the CoFeB/Pt microdiscs are able to damage 62 ± 3% of cancer cells compared with 12 ± 2% after applying a 10 kOe rotating field for one minute. The torques applied by each type of particle are measured and are shown to match values predicted by a simple Stoner-Wohlfarth anisotropy model, giving maximum values of 20 fNm for the CoFeB/Pt and 75 fNm for the Py vortex particles. The symmetry of the anisotropy is argued to be more important than the magnitude of the torque in causing effective cell destruction in these experiments. This work shows how future magnetic particles can be successfully designed for applications requiring control of applied torques.

Controlled Payload Release by Magnetic Field Triggered Neural Stem Cell Destruction for Malignant Glioma Treatment.

Stem cells have recently garnered attention as drug and particle carriers to sites of tumors, due to their natural ability to track to the site of interest. Specifically, neural stem cells (NSCs) have demonstrated to be a promising candidate for delivering therapeutics to malignant glioma, a primary brain tumor that is not curable by current treatments, and inevitably fatal. In this article, we demonstrate that NSCs are able to internalize 2 µm magnetic discs (SD), without affecting the health of the cells. The SD can then be remotely triggered in an applied 1 T rotating magnetic field to deliver a payload. Furthermore, we use this NSC-SD delivery system to deliver the SD themselves as a therapeutic agent to mechanically destroy glioma cells. NSCs were incubated with the SD overnight before treatment with a 1T rotating magnetic field to trigger the SD release. The potential timed release effects of the magnetic particles were tested with migration assays, confocal microscopy and immunohistochemistry for apoptosis. After the magnetic field triggered SD release, glioma cells were added and allowed to internalize the particles. Once internalized, another dose of the magnetic field treatment was administered to trigger mechanically induced apoptotic cell death of the glioma cells by the rotating SD. We are able to determine that NSC-SD and magnetic field treatment can achieve over 50% glioma cell death when loaded at 50 SD/cell, making this a promising therapeutic for the treatment of glioma.

Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma.

Magnetic particles that can be precisely controlled under a magnetic field and transduce energy from the applied field open the way for innovative cancer treatment. Although these particles represent an area of active development for drug delivery and magnetic hyperthermia, the in vivo anti-tumor effect under a low-frequency magnetic field using magnetic particles has not yet been demonstrated. To-date, induced cancer cell death via the oscillation of nanoparticles under a low-frequency magnetic field has only been observed in vitro. In this report, we demonstrate the successful use of spin-vortex, disk-shaped permalloy magnetic particles in a low-frequency, rotating magnetic field for the in vitro and in vivo destruction of glioma cells. The internalized nanomagnets align themselves to the plane of the rotating magnetic field, creating a strong mechanical force which damages the cancer cell structure inducing programmed cell death. In vivo, the magnetic field treatment successfully reduces brain tumor size and increases the survival rate of mice bearing intracranial glioma xenografts, without adverse side effects. This study demonstrates a novel approach of controlling magnetic particles for treating malignant glioma that should be applicable to treat a wide range of cancers.

Three dimensional magnetic nanowires grown by focused electron-beam induced deposition.

Control of the motion of domain walls in magnetic nanowires is at the heart of various recently proposed three-dimensional (3D) memory devices. However, fabricating 3D nanostructures is extremely complicated using standard lithography techniques. Here we show that highly pure 3D magnetic nanowires with aspect-ratios of ~100 can be grown using focused electron-beam-induced-deposition. By combining micromanipulation, Kerr magnetometry and magnetic force microscopy, we determine that the magnetisation reversal of the wires occurs via the nucleation and propagation of domain walls. In addition, we demonstrate that the magnetic switching of individual 3D nanostructures can be directly probed by magneto-optical Kerr effect.

Strain-controlled magnetic domain wall propagation in hybrid piezoelectric/ferromagnetic structures.

The control of magnetic order in nanoscale devices underpins many proposals for integrating spintronics concepts into conventional electronics. A key challenge lies in finding an energy-efficient means of control, as power dissipation remains an important factor limiting future miniaturization of integrated circuits. One promising approach involves magnetoelectric coupling in magnetostrictive/piezoelectric systems, where induced strains can bear directly on the magnetic anisotropy. While such processes have been demonstrated in several multiferroic heterostructures, the incorporation of such complex materials into practical geometries has been lacking. Here we demonstrate the possibility of generating sizeable anisotropy changes, through induced strains driven by applied electric fields, in hybrid piezoelectric/spin-valve nanowires. By combining magneto-optical Kerr effect and magnetoresistance measurements, we show that domain wall propagation fields can be doubled under locally applied strains. These results highlight the prospect of constructing low-power domain wall gates for magnetic logic devices.

Rapid fabrication of nanoneedle arrays by ion sputtering.

We report a novel method for rapidly fabricating ordered nanoneedles using an ion beam that cuts through the Fe/GaAs single thin layer or the Fe/MgO/Fe/GaAs multilayer producing a pillar pattern followed by raster-scanning normal to the patterned area. However, such ordered nanoneedles were not formed on the pure GaAs substrate surface without the thin Fe film coating, nor were nanoneedles formed on the GaAs substrate coated with a thin Cr epitaxial film, when this method was used. It has advantages over other methods, being simple, fast and well controlled for fabricating one-dimensional nanostructure arrays, leading to a range of applications such as high aspect ratio sharp tips for atomic force microscope/atom probes and consequent possible quantum confinement effects or arrays of nanostructures for field-optical/photoluminescence emission and data recording.

Magnetic domain-wall dynamics in a submicrometre ferromagnetic structure.

As fabrication technology pushes the dimensions of ferromagnetic structures into the nanoscale, understanding the magnetization processes of these structures is of fundamental interest, and key to future applications in hard disk drives, magnetic random access memory and other 'spintronic' devices. Measurements on elongated magnetic nanostructures highlighted the importance of nucleation and propagation of a magnetic boundary, or domain wall, between opposing magnetic domains in the magnetization reversal process. Domain-wall propagation in confined structures is of basic interest and critical to the performance of a recently demonstrated magnetic logic scheme for spintronics. A previous study of a 500-nm-wide NiFe structure obtained very low domain-wall mobility in a three-layer device. Here we report room-temperature measurements of the propagation velocity of a domain wall in a single-layer planar Ni80Fe20 ferromagnetic nanowire 200 nm wide. The wall velocities are extremely high and, importantly, the intrinsic wall mobility is close to that in continuous films, indicating that lateral confinement does not significantly affect the gyromagnetic spin damping parameter to the extreme extent previously suggested. Consequently the prospects for high-speed domain-wall motion in future nanoscale spintronic devices are excellent.