The synthesis and STM/AFM imaging of 'olympicene' benzo[cd]pyrenes.

H-Benzo[cd]pyrene ('Olympicene') is a polyaromatic hydrocarbon and non-Kekulé fragment of graphene. A new synthetic method has been developed for the formation of 6H-benzo[cd]pyrene and related ketones including the first time isolation of the unstable alcohol 6H-benzo[cd]pyren-6-ol. Molecular imaging of the reaction products with scanning tunnelling microscopy (STM) and non-contact atomic force microscopy (NC-AFM) characterised the 6H-benzo[cd]pyrene as well as the previously intangible and significantly less stable 5H-benzo[cd]pyrene, the fully conjugated benzo[cd]pyrenyl radical and the ketones as oxidation products.

Interactions between two C60 molecules measured by scanning probe microscopies.

C60-functionalized tips are used to probe C60 molecules on Cu(111) with scanning tunneling and atomic force microscopy. Distinct and complex intramolecular contrasts are found. Maximal attractive forces are observed when for both molecules a [6,6] bond faces a hexagon of the other molecule. Density functional theory calculations including parameterized van der Waals interactions corroborate the observations.

Resonant inductive coupling network for human-sized magnetic particle imaging.

In magnetic particle imaging, a field-free region is maneuvered throughout the field of view using a time-varying magnetic field known as the drive-field. Human-sized systems operate the drive-field in the kHz range and generate it by utilizing strong currents that can rise to the kA range within a coil called the drive field generator. Matching and tuning between a power amplifier, a band-pass filter, and the drive-field generator is required. Here, for reasons of safety in future human scanners, a symmetrical topology and a transformer called an inductive coupling network are used. Our primary objectives are to achieve floating potentials to ensure patient safety while attaining high linearity and high gain for the resonant transformer. We present a novel systematic approach to the design of a loss-optimized resonant toroid with a D-shaped cross section, employing segmentation to adjust the inductance-to-resistance ratio while maintaining a constant quality factor. Simultaneously, we derive a specific matching condition for a symmetric transmit-receive circuit for magnetic particle imaging. The chosen setup filters the fundamental frequency and allows simultaneous signal transmission and reception. In addition, the decoupling of multiple drive field channels is discussed, and the primary side of the transformer is evaluated for maximum coupling and minimum stray field. Two prototypes were constructed, measured, decoupled, and compared to the derived theory and method-of-moment based simulations.

Characterization of the clinically approved MRI tracer resotran for magnetic particle imaging in a comparison study.

Objective.The availability of magnetic nanoparticles (MNPs) with medical approval for human intervention is fundamental to the clinical translation of magnetic particle imaging (MPI). In this work, we thoroughly evaluate and compare the magnetic properties of an magnetic resonance imaging (MRI) approved tracer to validate its performance for MPI in future human trials.Approach.We analyze whether the recently approved MRI tracer Resotran is suitable for MPI. In addition, we compare Resotran with the previously approved and extensively studied tracer Resovist, with Ferrotran, which is currently in a clinical phase III study, and with the tailored MPI tracer Perimag.Main results.Initial magnetic particle spectroscopy (MPS) measurements indicate that Resotran exhibits performance characteristics akin to Resovist, but below Perimag. We provide data on four different tracers using dynamic light scattering, transmission electron microscopy, vibrating sample magnetometry measurements, MPS to derive hysteresis, point spread functions, and a serial dilution, as well as system matrix based MPI measurements on a preclinical scanner (Bruker 25/20 FF), including reconstructed images.Significance.Numerous approved MNPs used as tracers in MRI lack the necessary magnetic properties essential for robust signal generation in MPI. The process of obtaining medical approval for dedicated MPI tracers optimized for signal performance is an arduous and costly endeavor, often only justifiable for companies with a well-defined clinical business case. Resotran is an approved tracer that has become available in Europe for MRI. In this work, we study the eligibility of Resotran for MPI in an effort to pave the way for human MPI trials.

Saline bolus for negative contrast perfusion imaging in magnetic particle imaging.

Objective.Magnetic particle imaging (MPI) is capable of high temporal resolution measurements of the spatial distribution of magnetic nanoparticles and therefore well suited for perfusion imaging, which is an important tool in medical diagnosis. Perfusion imaging in MPI usually requires a fresh bolus of tracer material to capture the key signal dynamics. Here, we propose a method to decouple the imaging sequence from the injection of additional tracer material, without further increasing the administered iron dose in the body with each image.Approach.A bolus of physiological saline solution without any particles (negative contrast) diminishes the steady-state concentration of a long-circulating tracer during passage. This depression in the measured concentration contributes to the required contrast dynamics. The presence of a long-circulating tracer is therefore a prerequisite to obtain the negative contrast. As a quantitative tracer based imaging method, the signal is linear in the tracer concentration for any location that contains nanoparticles and zero in the surrounding tissue which does not provide any intrinsic signal. After tracer injection, the concentration over time (positive contrast) can be utilized to calculate dynamic diagnostic parameters like perfusion parameters in vessels and organs. Every acquired perfusion image thus requires a new bolus of tracer with a sufficiently large iron dose to be visible above the background.Main results.Perfusion parameters are calculated based on the time response of the proposed negative bolus and compared to a positive bolus. Results from phantom experiments show that normalized signals from positive and negative boli are concurrent and deviations of calculated perfusion maps are low.Significance.Our method opens up the possibility to increase the total monitoring time of a future patient by utilizing a positive-negative contrast sequence, while minimizing the iron dose per acquired image.

Real-time multi-contrast magnetic particle imaging for the detection of gastrointestinal bleeding.

Gastrointestinal bleeding, as a potentially life-threatening condition, is typically diagnosed by radiation-based imaging modalities like computed tomography or more invasively catheter-based angiography. Endoscopy enables examination of the upper gastrointestinal tract and the colon but not of the entire small bowel. Magnetic Particle Imaging (MPI) enables non-invasive, volumetric imaging without ionizing radiation. The aim of this study was to evaluate the feasibility of detecting gastrointestinal bleeding by single- and multi-contrast MPI using human-sized organs. A 3D-printed small bowel phantom and porcine small bowel specimens were prepared with a defect within the bowel wall as the source of a bleeding. For multi-contrast MPI, the bowel lumen was filled with an intestinal tracer representing an orally administered tracer. MPI was performed to evaluate the fluid exchange between the vascular compartment of the bowel wall and the lumen while a blood pool tracer was applied. Leakage of the blood pool tracer was observed to the bowel lumen. Multi-contrast MPI enabled co-registration of both tracers at the same location within the bowel lumen indicating gastrointestinal bleeding. Single- and multi-contrast MPI are feasible to visualize gastrointestinal bleeding. Therefore, MPI might emerge as a useful tool for radiation-free detection of bleeding within the entire gastrointestinal tract.

Scanning probe microscopy of atoms and molecules on insulating films: from imaging to molecular manipulation.

Scanning tunneling microscopy (STM) and atomic force microscopy (AFM) of single atoms and molecules on ultrathin insulating films have led to a wealth of novel observations and insights. Based on the reduced electronic coupling to the metallic substrate, these techniques allow the charge state of individual atoms to be controlled, orbitals of individual molecules to be imaged and metal-molecule complexes to be built up. Near-contact AFM adds the unique capabilities of imaging and probing the chemical structure of single molecules with atomic resolution. With the help of atomic/molecular manipulation techniques, chemical binding processes and molecular switches can be studied in detail.

System Matrix Based Reconstruction for Pulsed Sequences in Magnetic Particle Imaging.

Improving resolution and sensitivity will widen possible medical applications of magnetic particle imaging. Pulsed excitation promises such benefits, at the cost of more complex hardware solutions and restrictions on drive field amplitude and frequency. State-of-the-art systems utilize a sinusoidal excitation to drive superparamagnetic nanoparticles into the non-linear part of their magnetization curve, which creates a spectrum with a clear separation of direct feed-through and higher harmonics caused by the particles response. One challenge for rectangular excitation is the discrimination of particle and excitation signals, both broad-band. Another is the drive-field sequence itself, as particles that are not placed at the same spatial position, may react simultaneously and are not separable by their signal phase or shape. To overcome this potential loss of information in spatial encoding for high amplitudes, a superposition of shifting fields and drive-field rotations is proposed in this work. Upon close view, a system matrix approach is capable to maintain resolution, independent of the sequence, if the response to pulsed sequences still encodes information within the phase. Data from an Arbitrary Waveform Magnetic Particle Spectrometer with offsets in two spatial dimensions is measured and calibrated to guarantee device independence. Multiple sequence types and waveforms are compared, based on frequency space image reconstruction from emulated signals, that are derived from measured particle responses. A resolution of 1.0 mT (0.8 mm for a gradient of (-1.25,-1.25,2.5) Tm-1) in x- and y-direction was achieved and a superior sensitivity for pulsed sequences was detected on the basis of reference phantoms.

High-resolution molecular orbital imaging using a p-wave STM tip.

Individual pentacene and naphthalocyanine molecules adsorbed on a bilayer of NaCl grown on Cu(111) were investigated by means of scanning tunneling microscopy using CO-functionalized tips. The images of the frontier molecular orbitals show an increased lateral resolution compared with those of the bare tip and reflect the modulus squared of the lateral gradient of the wave functions. The contrast is explained by tunneling through the p-wave orbitals of the CO molecule. Comparison with calculations using a Tersoff-Hamann approach, including s- and p-wave tip states, demonstrates the significant contribution of p-wave tip states.

Reversible bond formation in a gold-atom-organic-molecule complex as a molecular switch.

We report on the formation of a metal-molecule complex that can be used as a molecular switch. Using a cryogenic scanning tunneling microscope, a covalent bond was formed reversibly between a gold atom and a perylene-3,4,9,10-tetracarboxylic dianhydride molecule supported by a thin insulating film. The bonded and the nonbonded state of the complex were found to be associated with different charge states, and the switching between the two states was accompanied by a considerable change in the tunneling current. Atomic force microscopy molecular imaging was employed to determine precisely the atomic structure of the complex, and the experimental results were corroborated by density functional theory calculations.

Reversible Bergman cyclization by atomic manipulation.

The Bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Here we demonstrate a reversible Bergman cyclization for the first time. We induced the on-surface transformation of an individual aromatic diradical into a highly strained ten-membered diyne using atomic manipulation and verified the products by non-contact atomic force microscopy with atomic resolution. The diyne and diradical were stabilized by using an ultrathin NaCl film as the substrate, and the diyne could be transformed back into the diradical. Importantly, the diradical and the diyne exhibit different reactivity, electronic, magnetic and optical properties associated with the changes in the bond topology, and spin multiplicity. With this reversible, triggered Bergman cyclization we demonstrated switching on demand between the two reactive intermediates by means of selective C-C bond formation or cleavage, which opens up the field of radical chemistry for on-surface reactions by atomic manipulation.

Imaging the charge distribution within a single molecule.

Scanning tunnelling microscopy and atomic force microscopy can be used to study the electronic and structural properties of surfaces, as well as molecules and nanostructures adsorbed on surfaces, with atomic precision, but they cannot directly probe the distribution of charge in these systems. However, another form of scanning probe microscopy, Kelvin probe force microscopy, can be used to measure the local contact potential difference between the scanning probe tip and the surface, a quantity that is closely related to the charge distribution on the surface. Here, we use a combination of scanning tunnelling microscopy, atomic force microscopy and Kelvin probe force microscopy to examine naphthalocyanine molecules (which have been used as molecular switches) on a thin insulating layer of NaCl on Cu(111). We show that Kelvin probe force microscopy can map the local contact potential difference of this system with submolecular resolution, and we use density functional theory calculations to verify that these maps reflect the intramolecular distribution of charge. This approach could help to provide fundamental insights into single-molecule switching and bond formation, processes that are usually accompanied by the redistribution of charge within or between molecules.

Bond-order discrimination by atomic force microscopy.

We show that the different bond orders of individual carbon-carbon bonds in polycyclic aromatic hydrocarbons and fullerenes can be distinguished by noncontact atomic force microscopy (AFM) with a carbon monoxide (CO)-functionalized tip. We found two different contrast mechanisms, which were corroborated by density functional theory calculations: The greater electron density in bonds of higher bond order led to a stronger Pauli repulsion, which enhanced the brightness of these bonds in high-resolution AFM images. The apparent bond length in the AFM images decreased with increasing bond order because of tilting of the CO molecule at the tip apex.

Organic structure determination using atomic-resolution scanning probe microscopy.

Nature offers a huge and only partially explored variety of small molecules with potential pharmaceutical applications. Commonly used characterization methods for natural products include spectroscopic techniques such as nuclear magnetic resonance spectroscopy and mass spectrometry. In some cases, however, these techniques do not succeed in the unambiguous determination of the chemical structure of unknown compounds. To validate the usefulness of scanning probe microscopy as an adjunct to the other tools available for organic structure analysis, we used the natural product cephalandole A, which had previously been misassigned, and later corrected. Our results, corroborated by density functional theory, demonstrate that direct imaging of an organic compound with atomic-resolution force microscopy facilitates the accurate determination of its chemical structure. We anticipate that our method may be developed further towards molecular imaging with chemical sensitivity, and will become generally useful in solving certain classes of natural product structures.

The chemical structure of a molecule resolved by atomic force microscopy.

Resolving individual atoms has always been the ultimate goal of surface microscopy. The scanning tunneling microscope images atomic-scale features on surfaces, but resolving single atoms within an adsorbed molecule remains a great challenge because the tunneling current is primarily sensitive to the local electron density of states close to the Fermi level. We demonstrate imaging of molecules with unprecedented atomic resolution by probing the short-range chemical forces with use of noncontact atomic force microscopy. The key step is functionalizing the microscope's tip apex with suitable, atomically well-defined terminations, such as CO molecules. Our experimental findings are corroborated by ab initio density functional theory calculations. Comparison with theory shows that Pauli repulsion is the source of the atomic resolution, whereas van der Waals and electrostatic forces only add a diffuse attractive background.

Measuring the charge state of an adatom with noncontact atomic force microscopy.

Charge states of atoms can be investigated with scanning tunneling microscopy, but this method requires a conducting substrate. We investigated the charge-switching of individual adsorbed gold and silver atoms (adatoms) on ultrathin NaCl films on Cu(111) using a qPlus tuning fork atomic force microscope (AFM) operated at 5 kelvin with oscillation amplitudes in the subangstrom regime. Charging of a gold atom by one electron charge increases the force on the AFM tip by a few piconewtons. Moreover, the local contact potential difference is shifted depending on the sign of the charge and allows the discrimination of positively charged, neutral, and negatively charged atoms. The combination of single-electron charge sensitivity and atomic lateral resolution should foster investigations of molecular electronics, photonics, catalysis, and solar photoconversion.