Towards Single Biomolecule Imaging via Optical Nanoscale Magnetic Resonance Imaging

Nuclear magnetic resonance (NMR) spectroscopy is a physical marvel in which electromagnetic radiation is charged and discharged by nuclei in a magnetic field. In conventional NMR, the specific nuclei resonance frequency depends on the strength of the magnetic field and the magnetic properties of the isotope of the atoms. NMR is routinely utilized in clinical tests by converting nuclear spectroscopy in magnetic resonance imaging (MRI) and providing 3D, noninvasive biological imaging. While this technique has revolutionized biomedical science, measuring the magnetic resonance spectrum of single biomolecules is still an intangible aspiration, due to MRI resolution being limited to tens of micrometers. MRI and NMR have, however, recently greatly advanced, with many breakthroughs in nano‐NMR and nano‐MRI spurred by using spin sensors based on an atomic impurities in diamond. These techniques rely on magnetic dipole–dipole interactions rather than inductive detection. Here, novel nano‐MRI methods based on nitrogen vacancy centers in diamond are highlighted, that provide a solution to the imaging of single biomolecules with nanoscale resolution in‐vivo and in ambient conditions.     

Super‐Resolution Nonlinear Photothermal Microscopy

Super‐resolution fluorescence microscopy enables imaging of fluorescent structures beyond the diffraction limit. However, this technique cannot be applied to weakly fluorescent cellular components or labels. As an alternative, photothermal microscopy based on nonradiative transformation of absorbed energy into heat has demonstrated imaging of nonfluorescent structures including single molecules and ~1‐nm gold nanoparticles. However, previously photothermal imaging has been performed with a diffraction‐limited resolution only. Herein, super‐resolution, far‐field photothermal microscopy based on nonlinear signal dependence on the laser energy is introduced. Among various nonlinear phenomena, including absorption saturation, multiphoton absorption, and signal temperature dependence, signal amplification by laser‐induced nanobubbles around overheated nano‐objects is explored. A Gaussian laser beam profile is used to demonstrate the image spatial sharpening for calibrated 260‐nm metal strips, resolving of a plasmonic nanoassembly, visualization of 10‐nm gold nanoparticles in graphene, and hemoglobin nanoclusters in live erythrocytes with resolution down to 50 nm. These nonlinear phenomena can be used for 3D imaging with improved lateral and axial resolution in most photothermal methods, including photoacoustic microscopy.     

High‐Resolution SPECT Imaging of Stimuli‐Responsive Soft Microrobots

Untethered small‐scale robots have great potential for biomedical applications. However, critical barriers to effective translation of these miniaturized machines into clinical practice exist. High resolution tracking and imaging in vivo is one of the barriers that limit the use of micro‐ and nanorobots in clinical applications. Here, the inclusion of radioactive compounds in soft thermoresponsive magnetic microrobots is investigated to enable their single‐photon emission computed tomography imaging. Four microrobotic platforms differing in hydrogel structure and four ^99mTc[Tc]‐based radioactive compounds are investigated in order to achieve optimal contrast agent retention and optimal imaging. Single microrobot imaging of structures as low as 100 µm in diameter, as well as tracking of shape switching from tubular to planar configurations by inclusion of ^99mTc[Tc] colloid in the hydrogel structure, is reported.     

On‐Chip Magnetic Platform for Single‐Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated.     

AFM‐Based Spin‐Exchange Microscopy Using Chiral Molecules

Local magnetic imaging at nanoscale resolution is desirable for basic studies of magnetic materials and for magnetic logic and memories. However, such local imaging is hard to achieve by means of standard magnetic force microscopy. Other techniques require low temperatures, high vacuum, or strict limitations on the sample conditions. A simple and robust method is presented for locally resolved magnetic imaging based on short‐range spin‐exchange interactions that can be scaled down to atomic resolution. The presented method requires a conventional AFM tip functionalized with a chiral molecule. In proximity to the measured magnetic sample, charge redistribution in the chiral molecule leads to a transient spin state, caused by the chiral‐induced spin‐selectivity effect, followed by the exchange interaction with the imaged sample. While magnetic force microscopy imaging strongly depends on a large working distance, an accurate image is achieved using the molecular tip in proximity to the sample. The chiral molecules' spin‐exchange interaction is found to be 150 meV. Using the tip with the adsorbed chiral molecules, two oppositely magnetized samples are characterized, and a magnetic imaging is performed. This method is simple to perform at room temperature and does not require high‐vacuum conditions.     

Exploring the Magnetic Properties of Individual Barcode Nanowires using Wide-Field Diamond Microscopy

A barcode magnetic nanowire typically comprises a multilayer magnetic structure in a single body with more than one segment type. Interestingly, due to selective functionalization and novel interactions between the layers, it has attracted significant attention, particularly in bioengineering. However, analyzing the magnetic properties at the individual nanowire level remains challenging. Herein, the characterization of a single magnetic nanowire is investigated at room temperature under ambient conditions based on magnetic images obtained via wide-field quantum microscopy with nitrogen-vacancy centers in diamond. Consequently, critical magnetic properties of a single nanowire can be extracted, such as saturation magnetization and coercivity, by comparing the experimental result with that of micromagnetic simulation. This study opens up the possibility for a versatile in situ characterization method suited to individual magnetic nanowires.     

Unusual Magnetic Phase Transitions in Gd<Superscript>3+</Superscript> Clusters in Multicomponent Oxide Glasses

Magnetic susceptibility, EPR and optical properties have been studied in a glass system {20La₂O₃−22Al₂O₃−23 B₂O₃−35(SiO₂+GeO₂)} with a part of La₂O₃ substituted by Gd₂O₃ in different concentrations. Positive Weiss constants have been found in more heavily doped glasses; two magnetic transitions at 55 and 12 K have been detected and ascribed, respectively, to ferromagnetic and antiferromagnetic clusters of Gd³⁺ ions. The EPR spectra confirm the clustering at higher Gd contents. At low temperatures the cluster-related resonance indicates an onset of magnetic anisotropy. The clustering, depending on the Gd concentration, correlates with a shift to lower energies of the strong optical absorption band edge.