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Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 1019 W cm−2 and ion flux levels of up to 1022 ions cm−2 s−1, about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors.

Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 1019 W cm−2 and ion flux levels of up to 1022 ions cm−2 s−1, about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors.

Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain., Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain., Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produced a ≲20 nm thick surface layer with magnetic order at room temperature. We measured the magnetic moment of five natural and six CVD diamond crystals of different sizes, nitrogen contents and surface orientations with a SQUID magnetometer. A robust ferromagnetic response at 300 K was observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals were much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

The ability to measure the passage of electrical current with high spatial and temporal resolution is vital for applications ranging from inspection of microscopic electronic circuits to biosensing. The ability to image such signals passively and remotely is of great importance, in order to measure without invasive disruption of the system under study or the signal itself. A recent approach to achieving this utilizes point defects in solid-state materials; in particular, nitrogen-vacancy centers in diamond. Acting as a high-density array of independent sensors, addressable opto-electronically and highly sensitive to factors including temperature and magnetic field, these are ideally suited to microscopic wide-field imaging. In this work, we demonstrate simultaneous spatially and temporally resolved recovery signals from a microscopic lithographically patterned circuit. Through application of a lock-in amplifier camera, we demonstrate micrometer-scale imaging resolution with a millimeter-scale field of view with simultaneous spatially resolved submillisecond (up to 3500 frames s-1) recovery of dc to kilohertz alternating and broadband pulsed-current electrical signals, without aliasing or undersampling. We demonstrate as examples of our method the recovery of synthetic signals replicating digital pulses in integrated circuits and signals that would be observed in a biological neuronal network in the brain.

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produced a ≲20 nm thick surface layer with magnetic order at room temperature. We measured the magnetic moment of five natural and six CVD diamond crystals of different sizes, nitrogen contents and surface orientations with a SQUID magnetometer. A robust ferromagnetic response at 300 K was observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals were much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

The detection of physiological activity at the microscopic level is key for understanding the function of biosystems and relating this to their physical structure. Current sensing methods for in vitro study of living tissue often rely on invasive probes to stimulate and detect activity, bearing the risk of inducing damage in the target system. In recent years, a new type of quantum sensor based on color centers in diamond has begun to offer the possibility to instead passively sense and image living biological systems. Here, we use such a sensor to realize the recording of the biomagnetic field generated by tightly focused, high intensity pulsed laser optogenetic neuromuscular stimulation of extensor digitorum longus muscles, dissected from mice and kept alive in carbogenated solution. Recordings captured a compound action potential response and a slow signal component, which we seek to explain using a detailed model of the biological system. We show proof-of-principle experimental recording of localized neuromuscular activity from the laser stimulation site without photovoltaic or fluorescence artifacts associated with alternative techniques. Our work represents a further step toward passive sensing and imaging at the microscopic level with quantum sensing, enabling further research into mapping of neural activity and intracellular processes.

The ability to measure the passage of electrical current with high spatial and temporal resolution is vital for applications ranging from inspection of microscopic electronic circuits to biosensing. The ability to image such signals passively and remotely is of great importance, in order to measure without invasive disruption of the system under study or the signal itself. A recent approach to achieving this utilizes point defects in solid-state materials; in particular, nitrogen-vacancy centers in diamond. Acting as a high-density array of independent sensors, addressable opto-electronically and highly sensitive to factors including temperature and magnetic field, these are ideally suited to microscopic wide-field imaging. In this work, we demonstrate simultaneous spatially and temporally resolved recovery signals from a microscopic lithographically patterned circuit. Through application of a lock-in amplifier camera, we demonstrate micrometer-scale imaging resolution with a millimeter-scale field of view with simultaneous spatially resolved submillisecond (up to 3500 frames s-1) recovery of dc to kilohertz alternating and broadband pulsed-current electrical signals, without aliasing or undersampling. We demonstrate as examples of our method the recovery of synthetic signals replicating digital pulses in integrated circuits and signals that would be observed in a biological neuronal network in the brain.

The detection of physiological activity at the microscopic level is key for understanding the function of biosystems and relating this to their physical structure. Current sensing methods for in vitro study of living tissue often rely on invasive probes to stimulate and detect activity, bearing the risk of inducing damage in the target system. In recent years, a new type of quantum sensor based on color centers in diamond has begun to offer the possibility to instead passively sense and image living biological systems. Here, we use such a sensor to realize the recording of the biomagnetic field generated by tightly focused, high intensity pulsed laser optogenetic neuromuscular stimulation of extensor digitorum longus muscles, dissected from mice and kept alive in carbogenated solution. Recordings captured a compound action potential response and a slow signal component, which we seek to explain using a detailed model of the biological system. We show proof-of-principle experimental recording of localized neuromuscular activity from the laser stimulation site without photovoltaic or fluorescence artifacts associated with alternative techniques. Our work represents a further step toward passive sensing and imaging at the microscopic level with quantum sensing, enabling further research into mapping of neural activity and intracellular processes.

We report on the systematic characterization of the optical properties of diamond color centers based on Pb impurities. An ensemble photoluminescence analysis of their spectral emission was performed at different excitation wavelengths in the 405–520 nm range and at different temperatures in the 4–300 K range. The series of observed spectral features consist of different emission lines associated with Pb-related defects. Finally, a room-temperature investigation of single-photon emitters under 490.5 nm laser excitation is reported, revealing different spectral signatures with respect to those already reported under 514 nm excitation. This work represents a substantial progress with respect to previous studies on Pb-related color centers, both in the attribution of an articulated series of spectral features and in the understanding of the formation process of this type of defect, thus clarifying the potential of this system for high-impact applications in quantum technologies.

We report on the systematic characterization of the optical properties of diamond color centers based on Pb impurities. An ensemble photoluminescence analysis of their spectral emission was performed at different excitation wavelengths in the 405–520 nm range and at different temperatures in the 4–300 K range. The series of observed spectral features consist of different emission lines associated with Pb-related defects. Finally, a room-temperature investigation of single-photon emitters under 490.5 nm laser excitation is reported, revealing different spectral signatures with respect to those already reported under 514 nm excitation. This work represents a substantial progress with respect to previous studies on Pb-related color centers, both in the attribution of an articulated series of spectral features and in the understanding of the formation process of this type of defect, thus clarifying the potential of this system for high-impact applications in quantum technologies.

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/Hz sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/Hz sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.

Nitrogen vacancy (NV) centers in diamond have attracted considerable recent interest for use in quantum sensing, promising increased sensitivity for applications ranging from geophysics to biomedicine. Conventional sensing schemes involve monitoring the change in red fluorescence from the NV center under green laser and microwave illumination. Due to the strong fluorescence background from emission in the NV triplet state and low relative contrast of any change in output, sensitivity is severely restricted by a high optical shot noise level. Here, we propose a means to avoid this issue, by using the change in green pump absorption through the diamond as part of a semiconductor external cavity laser run close to the lasing threshold. We show that theoretical sensitivity to the magnetic field on the pT/Hz level is possible using a diamond with an optimal density of NV centers. We discuss the physical requirements and limitations of the method, particularly the role of amplified spontaneous emission near threshold and explore realistic implementations using current technology.

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/Hz sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.

Sensing of signals from biological processes, such as action potential propagation in nerves, are essential for clinical diagnosis and basic understanding of physiology. Sensing can be performed electrically by placing sensor probes near or inside a living specimen or dissected tissue using well-established electrophysiology techniques. However, these electrical probe techniques have poor spatial resolution and cannot easily access tissue deep within a living subject, in particular within the brain. An alternative approach is to detect the magnetic field induced by the passage of the electrical signal, giving the equivalent readout without direct electrical contact. Such measurements are performed today using bulky and expensive superconducting sensors with poor spatial resolution. An alternative is to use nitrogen vacancy (NV) centers in diamond that promise biocompatibilty and high sensitivity without cryogenic cooling. In this work we present advances in biomagnetometry using NV centers, demonstrating magnetic field sensitivity of ∼100 pT/√Hz in the DC/low frequency range using a setup designed for biological measurements. Biocompatibility of the setup with a living sample (mouse brain slice) is studied and optimized, and we show work toward sensitivity improvements using a pulsed magnetometry scheme. In addition to the bulk magnetometry study, systematic artifacts in NV-ensemble widefield fluorescence imaging are investigated.

Sensing of signals from biological processes, such as action potential propagation in nerves, are essential for clinical diagnosis and basic understanding of physiology. Sensing can be performed electrically by placing sensor probes near or inside a living specimen or dissected tissue using well-established electrophysiology techniques. However, these electrical probe techniques have poor spatial resolution and cannot easily access tissue deep within a living subject, in particular within the brain. An alternative approach is to detect the magnetic field induced by the passage of the electrical signal, giving the equivalent readout without direct electrical contact. Such measurements are performed today using bulky and expensive superconducting sensors with poor spatial resolution. An alternative is to use nitrogen vacancy (NV) centers in diamond that promise biocompatibilty and high sensitivity without cryogenic cooling. In this work we present advances in biomagnetometry using NV centers, demonstrating magnetic field sensitivity of ∼100 pT/√Hz in the DC/low frequency range using a setup designed for biological measurements. Biocompatibility of the setup with a living sample (mouse brain slice) is studied and optimized, and we show work toward sensitivity improvements using a pulsed magnetometry scheme. In addition to the bulk magnetometry study, systematic artifacts in NV-ensemble widefield fluorescence imaging are investigated.

Sensing of signals from biological processes, such as action potential propagation in nerves, are essential for clinical diagnosis and basic understanding of physiology. Sensing can be performed electrically by placing sensor probes near or inside a living specimen or dissected tissue using well-established electrophysiology techniques. However, these electrical probe techniques have poor spatial resolution and cannot easily access tissue deep within a living subject, in particular within the brain. An alternative approach is to detect the magnetic field induced by the passage of the electrical signal, giving the equivalent readout without direct electrical contact. Such measurements are performed today using bulky and expensive superconducting sensors with poor spatial resolution. An alternative is to use nitrogen vacancy (NV) centers in diamond that promise biocompatibilty and high sensitivity without cryogenic cooling. In this work we present advances in biomagnetometry using NV centers, demonstrating magnetic field sensitivity of ~100 pT/ (Formula presented.) in the DC/low frequency range using a setup designed for biological measurements. Biocompatibility of the setup with a living sample (mouse brain slice) is studied and optimized, and we show work toward sensitivity improvements using a pulsed magnetometry scheme. In addition to the bulk magnetometry study, systematic artifacts in NV-ensemble widefield fluorescence imaging are investigated.

Sensing of signals from biological processes, such as action potential propagation in nerves, are essential for clinical diagnosis and basic understanding of physiology. Sensing can be performed electrically by placing sensor probes near or inside a living specimen or dissected tissue using well-established electrophysiology techniques. However, these electrical probe techniques have poor spatial resolution and cannot easily access tissue deep within a living subject, in particular within the brain. An alternative approach is to detect the magnetic field induced by the passage of the electrical signal, giving the equivalent readout without direct electrical contact. Such measurements are performed today using bulky and expensive superconducting sensors with poor spatial resolution. An alternative is to use nitrogen vacancy (NV) centers in diamond that promise biocompatibilty and high sensitivity without cryogenic cooling. In this work we present advances in biomagnetometry using NV centers, demonstrating magnetic field sensitivity of similar to 100 pT/root Hz in the DC/low frequency range using a setup designed for biological measurements. Biocompatibility of the setup with a living sample (mouse brain slice) is studied and optimized, and we show work toward sensitivity improvements using a pulsed magnetometry scheme. In addition to the bulk magnetometry study, systematic artifacts in NV-ensemble widefield fluorescence imaging are investigated.

Sensing of signals from biological processes, such as action potential propagation in nerves, are essential for clinical diagnosis and basic understanding of physiology. Sensing can be performed electrically by placing sensor probes near or inside a living specimen or dissected tissue using well-established electrophysiology techniques. However, these electrical probe techniques have poor spatial resolution and cannot easily access tissue deep within a living subject, in particular within the brain. An alternative approach is to detect the magnetic field induced by the passage of the electrical signal, giving the equivalent readout without direct electrical contact. Such measurements are performed today using bulky and expensive superconducting sensors with poor spatial resolution. An alternative is to use nitrogen vacancy (NV) centers in diamond that promise biocompatibilty and high sensitivity without cryogenic cooling. In this work we present advances in biomagnetometry using NV centers, demonstrating magnetic field sensitivity of similar to 100 pT/root Hz in the DC/low frequency range using a setup designed for biological measurements. Biocompatibility of the setup with a living sample (mouse brain slice) is studied and optimized, and we show work toward sensitivity improvements using a pulsed magnetometry scheme. In addition to the bulk magnetometry study, systematic artifacts in NV-ensemble widefield fluorescence imaging are investigated.

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

Image charge detection is presented as a possible candidate to realise deterministic ion implantation. The deterministic placement of single impurities in solid substrates will enable a variety of novel applications, using their quantum mechanical properties for sensors or qubit registers. In this work, experimental techniques are used together with theoretical calculations to develop, characterise and optimise the detection of charged objects in a single pass through an image charge detector. In the main experimental part, ion bunches are employed as a model system for highly charged ions in proof-of-principle measurements with detector prototypes built in our labs. Image charge signals are characterised in the time and frequency domain. Using a statistical measurement and data analysis protocol, the noise and signal probability density functions are determined to calculate error and detection rates. It was found that even at an extremely low signal-to-noise ratio of 2, error rates can be suppressed effectively for high fidelity implantation. Aiming to improve the sensitivity, the maximum possible signal-to-noise ratio is calculated and discussed in dependence on the design parameters of an optimised image charge detector and the kinetic ion parameters. Lastly, a new ion implantation set-up combining focused ion beam technology with a source able to produce highly charged ions is introduced.

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]) with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -potential of 18.0 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]. Conclusions

Image charge detection is a non-perturbative pre-detection approach for deterministic ion implantation. Using low energy ion bunches as a model system for highly charged single ions, we experimentally studied the error and detection rates of an image charge detector setup. The probability density functions of the signal amplitudes in the Fourier spectrum can be modelled with a generalised gamma distribution to predict error and detection rates. It is shown that the false positive error rate can be minimised at the cost of detection rate, but this does not impair the fidelity of a deterministic implantation process. Independent of the ion species, at a signal to-noise ratio of 2, a false positive error rate of 0.1% is achieved, while the detection rate is about 22%

Image charge detection is a non-perturbative pre-detection approach for deterministic ion implantation. Using low energy ion bunches as a model system for highly charged single ions, we experimentally studied the error and detection rates of an image charge detector setup. The probability density functions of the signal amplitudes in the Fourier spectrum can be modelled with a generalised gamma distribution to predict error and detection rates. It is shown that the false positive error rate can be minimised at the cost of detection rate, but this does not impair the fidelity of a deterministic implantation process. Independent of the ion species, at a signal to-noise ratio of 2, a false positive error rate of 0.1% is achieved, while the detection rate is about 22%

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]) with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -potential of 18.0 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]. Conclusions

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

We demonstrate a technique for precision sensing of temperature or the magnetic field by simultaneously driving two hyperfine transitions involving distinct electronic states of the nitrogen-vacancy center in diamond. Frequency modulation of both driving fields is used with either the same or opposite phase, resulting in the immunity to fluctuations in either the magnetic field or the temperature, respectively. In this way, a sensitivity of 1.4 nT Hz-1/2 or 430 μK Hz-1/2 is demonstrated. The presented technique only requires a single frequency demodulator and enables the use of phase-sensitive camera imaging sensors. A simple extension of the method utilizing two demodulators allows for simultaneous, independent, and high-bandwidth monitoring of both the magnetic field and temperature.

Nanoparticles, especially from carbon, have great potential in biomedicine. However, prior to clinical use, biocompatibility and biodistribution of these nanoobjects have to be assessed. Currently, particle detection is mostly based on surface-bound labels, inevitably altering materials' properties by surface modification. Further obstacles include bleaching, dissociation of labels from the surface, weak emission of fluorophores due to insufficient tissue opacity or hampered light penetration or the need for specific excitation wavelengths. These characteristics greatly constrain employment of such nanoparticles to address complex analytical questions. To overcome these drawbacks, the use of intrinsic structural features of nanoobjects is highly desirable: the particle surface remains unchanged and the nanoobject exhibits its innate behavior. Thus, for sensitive detection and quantification, labels should be incorporated in the nanoparticle core, thereby avoiding cleavage and warranting unchanged surface characteristics. The incorporation of clinically approved radionuclide P-32 into the lattice of nanodiamond particles using highly defined ion implantation is described here. The properties, uptake, and biodistribution are studied in vivo, in the developing hen's egg model (hen's egg test on chorioallantoic membrane assay). It is found that P-32 labeling of diamond nanoparticles allows their reliable localization and sensitive quantification in a cost efficient, highly reliable, and safe way using available autoradiographic devices and analytical methods.

In this work we investigated the time behavior of the polarization of bulk 13C nuclei in diamond above the thermal equilibrium. This nonthermal nuclear hyperpolarization is achieved by cross relaxation between two nitrogen related paramagnetic defect species in diamond in combination with optical pumping. The decay of the hyperpolarization at four different magnetic fields is measured. Furthermore, we use the comparison with conventional nuclear resonance measurements to identify the involved distances of the nuclear spin with respect to the defects and therefore the coupling strengths. Also, a careful look at the linewidth of the signal give valuable information to piece together the puzzle of the hyperpolarization mechanism.

In this work we investigated the time behavior of the polarization of bulk 13C nuclei in diamond above the thermal equilibrium. This nonthermal nuclear hyperpolarization is achieved by cross relaxation between two nitrogen related paramagnetic defect species in diamond in combination with optical pumping. The decay of the hyperpolarization at four different magnetic fields is measured. Furthermore, we use the comparison with conventional nuclear resonance measurements to identify the involved distances of the nuclear spin with respect to the defects and therefore the coupling strengths. Also, a careful look at the linewidth of the signal give valuable information to piece together the puzzle of the hyperpolarization mechanism.

Nanoparticles, especially from carbon, have great potential in biomedicine. However, prior to clinical use, biocompatibility and biodistribution of these nanoobjects have to be assessed. Currently, particle detection is mostly based on surface-bound labels, inevitably altering materials' properties by surface modification. Further obstacles include bleaching, dissociation of labels from the surface, weak emission of fluorophores due to insufficient tissue opacity or hampered light penetration or the need for specific excitation wavelengths. These characteristics greatly constrain employment of such nanoparticles to address complex analytical questions. To overcome these drawbacks, the use of intrinsic structural features of nanoobjects is highly desirable: the particle surface remains unchanged and the nanoobject exhibits its innate behavior. Thus, for sensitive detection and quantification, labels should be incorporated in the nanoparticle core, thereby avoiding cleavage and warranting unchanged surface characteristics. The incorporation of clinically approved radionuclide P-32 into the lattice of nanodiamond particles using highly defined ion implantation is described here. The properties, uptake, and biodistribution are studied in vivo, in the developing hen's egg model (hen's egg test on chorioallantoic membrane assay). It is found that P-32 labeling of diamond nanoparticles allows their reliable localization and sensitive quantification in a cost efficient, highly reliable, and safe way using available autoradiographic devices and analytical methods.

Sensitive, real-time optical magnetometry with nitrogen-vacancy centers in diamond relies on accurate imaging of small (≪10−2), fractional fluorescence changes across the diamond sample. We discuss the limitations on magnetic field sensitivity resulting from the limited number of photoelectrons that a camera can record in a given time. Several types of camera sensors are analyzed, and the smallest measurable magnetic field change is estimated for each type. We show that most common sensors are of a limited use in such applications, while certain highly specific cameras allow achieving nanotesla-level sensitivity in 1 s of a combined exposure. Finally, we demonstrate the results obtained with a lock-in camera that paves the way for real-time, wide-field magnetometry at the nanotesla level and with a micrometer resolution.

Purpose: COPD is associated with cognitive impairment. These impairments should be diagnosed, but due to time- and budget-reasons, they are often not investigated. The aim of this study is to examine the viability of a brief computerized cognitive test battery, Central Nervous System Vital Signs (CNSVS), in COPD patients.Patients and methods: Patients with COPD referred to tertiary pulmonary rehabilitation were included. Cognitive functioning of patients was assessed with CNSVS before pulmonary rehabilitation and compared with age-corrected CNSVS norms. CNSVS is a 30 minute computerized test battery that includes tests of verbal and visual memory, psychomotor speed, processing speed, cognitive flexibility, complex attention, executive functioning, and reaction time.Results: CNSVS was fully completed by 205 (93.2%, 105 females, 100 males) of the total group of patients (n=220, 116 females, 104 males). Z-tests showed that COPD patients performed significantly worse than the norms on all CNSVS cognitive domains. Slightly more than half of the patients (51.8%) had impaired functioning on 1 or more cognitive domains. Patients without computer experience performed significantly worse on CNSVS than patients using the computer frequently.Conclusion: The completion rate of CNSVS was high and cognitive dysfunctions measured with this screening were similar to the results found in prior research, including paper and pen cognitive tests. These results support the viability of this brief computerized cognitive screening in COPD patients, that may lead to better care for these patients. Cognitive performance of patients with little computer experience should be interpreted carefully. Future research on this issue is needed.

Using shallow implantation of ions and molecules with masses centred at 27 atomic mass units(amu) in diamond, a new artificial optical centre with unique properties has been created. The centre shows a linearly polarised fluorescence with a main narrow emission line mostly found at 582 nm, together with a weak vibronic sideband at room temperature. The fluorescence lifetime is∼2 ns and the brightest centres are more than three times brighter than the nitrogen-vacancy centres. A majority of the centres shows stable fluorescence whereas some others present a blinking behaviour, at faster or slower rates. Furthermore, a second kind of optical centre has been simultaneously created in the same diamond sample, within the same ion implantation run. This centre has a narrow zero-phonon line (ZPL) at∼546 nm and a broad phonon sideband at room temperature. Interestingly, optically detected magnetic resonance (ODMR) has been measured on several single 546 nm centres and two resonance peaks are found at 0.99 and 1.27 GHz. In view of their very similar ODMR and optical spectra, the 546 nm centre is likely to coincide with the ST1 centre, reported once (with a ZPL at 550 nm), but of still unknown nature. These new kinds of centres are promising for quantum information processing, sub-diffraction optical imaging or use as single-photon sources.

Using shallow implantation of ions and molecules with masses centred at 27 atomic mass units(amu) in diamond, a new artificial optical centre with unique properties has been created. The centre shows a linearly polarised fluorescence with a main narrow emission line mostly found at 582 nm, together with a weak vibronic sideband at room temperature. The fluorescence lifetime is∼2 ns and the brightest centres are more than three times brighter than the nitrogen-vacancy centres. A majority of the centres shows stable fluorescence whereas some others present a blinking behaviour, at faster or slower rates. Furthermore, a second kind of optical centre has been simultaneously created in the same diamond sample, within the same ion implantation run. This centre has a narrow zero-phonon line (ZPL) at∼546 nm and a broad phonon sideband at room temperature. Interestingly, optically detected magnetic resonance (ODMR) has been measured on several single 546 nm centres and two resonance peaks are found at 0.99 and 1.27 GHz. In view of their very similar ODMR and optical spectra, the 546 nm centre is likely to coincide with the ST1 centre, reported once (with a ZPL at 550 nm), but of still unknown nature. These new kinds of centres are promising for quantum information processing, sub-diffraction optical imaging or use as single-photon sources.

In this work we have used focused electron beam induced deposition of cobalt to functionalize atomic force microscopy Akiyama tips for application in magnetic force microscopy. The grown tips have a content of ≈90~\% Co after exposure to ambient air. The magnetic tips were characterized using energy dispersive x-ray spectroscopy and scanning electron microscopy. In order to investigate the magnetic properties, current loops were prepared by electron beam lithography. Measurements at room temperature as well as 4.2 K were carried out and the coercive field of ≈6.8 mT of the Co tip was estimated by applying several external fields in the opposite direction of the tip magnetization. Magnetic Akiyama tips open new possibilities for wide-range temperature magnetic force microscopy measurements.

Purpose: COPD is associated with cognitive impairment. These impairments should be diagnosed, but due to time- and budget-reasons, they are often not investigated. The aim of this study is to examine the viability of a brief computerized cognitive test battery, Central Nervous System Vital Signs (CNSVS), in COPD patients.Patients and methods: Patients with COPD referred to tertiary pulmonary rehabilitation were included. Cognitive functioning of patients was assessed with CNSVS before pulmonary rehabilitation and compared with age-corrected CNSVS norms. CNSVS is a 30 minute computerized test battery that includes tests of verbal and visual memory, psychomotor speed, processing speed, cognitive flexibility, complex attention, executive functioning, and reaction time.Results: CNSVS was fully completed by 205 (93.2%, 105 females, 100 males) of the total group of patients (n=220, 116 females, 104 males). Z-tests showed that COPD patients performed significantly worse than the norms on all CNSVS cognitive domains. Slightly more than half of the patients (51.8%) had impaired functioning on 1 or more cognitive domains. Patients without computer experience performed significantly worse on CNSVS than patients using the computer frequently.Conclusion: The completion rate of CNSVS was high and cognitive dysfunctions measured with this screening were similar to the results found in prior research, including paper and pen cognitive tests. These results support the viability of this brief computerized cognitive screening in COPD patients, that may lead to better care for these patients. Cognitive performance of patients with little computer experience should be interpreted carefully. Future research on this issue is needed.

Carlijn Campman,1 Dirk van Ranst,2 Jan Willem Meijer,2 Margriet Sitskoorn1 1Department of Cognitive Neuropsychology, Tilburg University, Tilburg, 2Pulmonary Rehabilitation Center ‘Schoondonck’, Revant, Breda, the Netherlands Purpose: COPD is associated with cognitive impairment. These impairments should be diagnosed, but due to time- and budget-reasons, they are often not investigated. The aim of this study is to examine the viability of a brief computerized cognitive test battery, Central Nervous System Vital Signs (CNSVS), in COPD patients. Patients and methods: Patients with COPD referred to tertiary pulmonary rehabilitation were included. Cognitive functioning of patients was assessed with CNSVS before pulmonary rehabilitation and compared with age-corrected CNSVS norms. CNSVS is a 30 minute computerized test battery that includes tests of verbal and visual memory, psychomotor speed, processing speed, cognitive flexibility, complex attention, executive functioning, and reaction time. Results: CNSVS was fully completed by 205 (93.2%, 105 females, 100 males) of the total group of patients (n=220, 116 females, 104 males). Z-tests showed that COPD patients performed significantly worse than the norms on all CNSVS cognitive domains. Slightly more than half of the patients (51.8%) had impaired functioning on 1 or more cognitive domains. Patients without computer experience performed significantly worse on CNSVS than patients using the computer frequently. Conclusion: The completion rate of CNSVS was high and cognitive dysfunctions measured with this screening were similar to the results found in prior research, including paper and pen cognitive tests. These results support the viability of this brief computerized cognitive screening in COPD patients, that may lead to better care for these patients. Cognitive performance of patients with little computer experience should be interpreted carefully. Future research on this issue is needed. Keywords: CN

De minister van (destijds) Landbouw Natuurbeheer & Visserij heeft in 2008 het Natura 2000-gebied duinen van Schiermonnikoog aangewezen als Habitatrichtlijnen Vogelrichtlijngebied door middel van een ‘aanwijzingsbesluit’. In dit besluit wordt aangegeven waarom het gebied is uitgekozen, voor welke habitattypen, habitatsoorten en vogels het gebied is aangewezen, welke instandhoudingsdoelen er gelden en hoe de begrenzing van het gebied loopt. Het Natura 2000-gebied ‘Duinen Schiermonnikoog’ heeft een oppervlakte van ca. 1025 ha en beslaat bijna het gehele duingebied.

Aanwijzing door Europa van een groot deel van Vlieland als Natura 2000-gebied is een erkenning van de uitzonderlijke waarde van het gebied. Bovendien is de natuur de basis voor veel economische activiteiten die op het eiland plaatsvinden. Alle maatregelen en andere inspanningen uit het beheerplan zijn bedoeld om de natuur in dit gebied in goede conditie te houden of te brengen.

Aanwijzing door Europa van een groot deel van Ameland als Natura 2000-gebied is een erkenning van de uitzonderlijke waarde van het gebied. Bovendien is de natuur de basis voor veel economische activiteiten die op het eiland plaatsvinden. Alle maatregelen en andere inspanningen uit het beheerplan zijn bedoeld om de natuur in dit gebied in goede conditie te houden of te brengen.

Aanwijzing door Europa van een groot deel van Terschelling als Natura 2000-gebied is een erkenning van de uitzonderlijke waarde van het gebied. Bovendien is de natuur de basis voor veel economische activiteiten die op het eiland plaatsvinden. Alle maatregelen en andere inspanningen uit het beheerplan zijn bedoeld om de natuur in dit gebied in goede conditie te houden of te brengen.