Quantum Logic Enhanced Sensing in Solid-State Spin Ensembles.

We demonstrate quantum logic enhanced sensitivity for a macroscopic ensemble of solid-state, hybrid two-qubit sensors. We achieve over a factor of 30 improvement in the single-shot signal-to-noise ratio, translating to an ac magnetic field sensitivity enhancement exceeding an order of magnitude for time-averaged measurements. Using the electronic spins of nitrogen vacancy (NV) centers in diamond as sensors, we leverage the on-site nitrogen nuclear spins of the NV centers as memory qubits, in combination with homogeneous and stable bias and control fields, ensuring that all of the ∼10^{9} two-qubit sensors are sufficiently identical to permit global control of the NV ensemble spin states. We find quantum logic sensitivity enhancement for multiple measurement protocols with varying optimal sensing intervals, including XY8 and DROID-60 dynamical decoupling, as well as correlation spectroscopy, using an applied ac magnetic field signal. The results are independent of the nature of the target signal and broadly applicable to measurements using NV centers and other solid-state spin ensembles. This work provides a benchmark for macroscopic ensembles of quantum sensors that employ quantum logic or quantum error correction algorithms for enhanced sensitivity.

Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19.

Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters­the need for intensive care unit admission and the need for mechanical intubation­were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.

Quantum diamond spectrometer for nanoscale NMR and ESR spectroscopy.

Nitrogen-vacancy (NV) quantum defects in diamond are sensitive detectors of magnetic fields. Owing to their atomic size and optical readout capability, they have been used for magnetic resonance spectroscopy of nanoscale samples on diamond surfaces. Here, we present a protocol for fabricating NV diamond chips and for constructing and operating a simple, low-cost 'quantum diamond spectrometer' for performing NMR and electron spin resonance (ESR) spectroscopy in nanoscale volumes. The instrument is based on a commercially available diamond chip, into which an NV ensemble is ion-implanted at a depth of ~10 nm below the diamond surface. The spectrometer operates at low magnetic fields (~300 G) and requires standard optical and microwave (MW) components for NV spin preparation, manipulation, and readout. We demonstrate the utility of this device for nanoscale proton and fluorine NMR spectroscopy, as well as for the detection of transition metals via relaxometry. We estimate that the full protocol requires 2-3 months to implement, depending on the availability of equipment, diamond substrates, and user experience.

High-resolution magnetic resonance spectroscopy using a solid-state spin sensor.

Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen-vacancy centres in combination with a narrowband synchronized readout protocol to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen-vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.

Mapping the microscale origins of magnetic resonance image contrast with subcellular diamond magnetometry.

Magnetic resonance imaging (MRI) is a widely used biomedical imaging modality that derives much of its contrast from microscale magnetic field patterns in tissues. However, the connection between these patterns and the appearance of macroscale MR images has not been the subject of direct experimental study due to a lack of methods to map microscopic fields in biological samples. Here, we optically probe magnetic fields in mammalian cells and tissues with submicron resolution and nanotesla sensitivity using nitrogen-vacancy diamond magnetometry, and combine these measurements with simulations of nuclear spin precession to predict the corresponding MRI contrast. We demonstrate the utility of this technology in an in vitro model of macrophage iron uptake and histological samples from a mouse model of hepatic iron overload. In addition, we follow magnetic particle endocytosis in live cells. This approach bridges a fundamental gap between an MRI voxel and its microscopic constituents.

Nanodiamond-enhanced MRI via in situ hyperpolarization.

Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery and as highly biostable fluorescent markers for cellular tracking. Beyond optical techniques, however, options for noninvasive imaging of nanodiamonds in vivo are severely limited. Here, we demonstrate that the Overhauser effect, a proton-electron polarization transfer technique, can enable high-contrast magnetic resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra-low magnetic field. The technique transfers spin polarization from paramagnetic impurities at nanodiamond surfaces to 1H spins in the surrounding water solution, creating MRI contrast on-demand. We examine the conditions required for maximum enhancement as well as the ultimate sensitivity of the technique. The ability to perform continuous in situ hyperpolarization via the Overhauser mechanism, in combination with the excellent in vivo stability of nanodiamond, raises the possibility of performing noninvasive in vivo tracking of nanodiamond over indefinitely long periods of time.

Efficiency of Cathodoluminescence Emission by Nitrogen-Vacancy Color Centers in Nanodiamonds.

Correlated electron microscopy and cathodoluminescence (CL) imaging using functionalized nanoparticles is a promising nanoscale probe of biological structure and function. Nanodiamonds (NDs) that contain CL-emitting color centers are particularly well suited for such applications. The intensity of CL emission from NDs is determined by a combination of factors, including particle size, density of color centers, efficiency of energy deposition by electrons passing through the particle, and conversion efficiency from deposited energy to CL emission. This paper reports experiments and numerical simulations that investigate the relative importance of each of these factors in determining CL emission intensity from NDs containing nitrogen-vacancy (NV) color centers. In particular, it is found that CL can be detected from NV-doped NDs with dimensions as small as ≈40 nm, although CL emission decreases significantly for smaller NDs.

Optical magnetic detection of single-neuron action potentials using quantum defects in diamond.

Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution-e.g., magnetic resonance imaging methods and magnetoencephalography-or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.

A genetic strategy for probing the functional diversity of magnetosome formation.

Model genetic systems are invaluable, but limit us to understanding only a few organisms in detail, missing the variations in biological processes that are performed by related organisms. One such diverse process is the formation of magnetosome organelles by magnetotactic bacteria. Studies of model magnetotactic α-proteobacteria have demonstrated that magnetosomes are cubo-octahedral magnetite crystals that are synthesized within pre-existing membrane compartments derived from the inner membrane and orchestrated by a specific set of genes encoded within a genomic island. However, this model cannot explain all magnetosome formation, which is phenotypically and genetically diverse. For example, Desulfovibrio magneticus RS-1, a δ-proteobacterium for which we lack genetic tools, produces tooth-shaped magnetite crystals that may or may not be encased by a membrane with a magnetosome gene island that diverges significantly from those of the α-proteobacteria. To probe the functional diversity of magnetosome formation, we used modern sequencing technology to identify hits in RS-1 mutated with UV or chemical mutagens. We isolated and characterized mutant alleles of 10 magnetosome genes in RS-1, 7 of which are not found in the α-proteobacterial models. These findings have implications for our understanding of magnetosome formation in general and demonstrate the feasibility of applying a modern genetic approach to an organism for which classic genetic tools are not available.

Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

OBJECTIVE: To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. DESIGN: This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. SETTING: Academic research environment. ANIMAL(S): Male and female CBAB(6) mice. INTERVENTION(S): Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. MAIN OUTCOME MEASURE(S): Fertilization rates and numbers of embryos were evaluated after treatment. RESULT(S): Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. CONCLUSION(S): The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro.

OBJECTIVE: To determine whether sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. DESIGN: Laboratory analysis of sperm motility after exposure to sildenafil citrate using computer-assisted semen analysis and acrosome reaction by fluorescein isothiocyanate-labeled peanut agglutinin staining. SETTING: An assisted reproductive technology (ART) unit. PATIENT(S): Fifty-seven male patients. INTERVENTION(S): Sperm were divided into 90% (those with the best fertilizing potential used in assisted conception) and 45% (the poorer population) fractions by density centrifugation and incubated with sildenafil citrate (0.67 muM) at 37 degrees C for up to 180 minutes. MAIN OUTCOME MEASURE(S): Both the number and velocity of progressively motile sperm were significantly increased by sildenafil citrate between 15 and 135 minutes. Furthermore, samples revealed that these effects were consistent in the 90% and 45% populations of sperm. In both populations, sildenafil also caused a significant increase in the proportion of acrosome-reacted sperm-22.1% compared with 11.8% in the control group of the good quality fraction and 16.6% compared with 9.4% in the control group of the poorer quality fraction. CONCLUSION(S): The use of sildenafil citrate may adversely affect male fertility.

The hidden impact of diabetes on male sexual dysfunction and fertility.

Diabetes affects an increasingly large number of young men of reproductive age. Erectile and ejaculatory difficulties arise due to vascular and neuropathic problems. The treatment of these may have effects on fertility potential. Erectile dysfunction can be treated with mechanical devices and intracavernosal injections. Although these have not been shown to affect fertility directly, they may result in poor compliance and hence reduced frequency of ejaculation with subsequent deterioration in sperm quality. Other medical treatments may have a more direct effect. The phosphodiesterase (PDE) inhibitor pentoxifylline has been shown to affect sperm quality and early embryo development. Therefore, Viagra, also a PDE inhibitor, may affect sperm quality. There is conflicting evidence about this in the literature. Ejaculatory difficulties are also more common in diabetics although treatments such as Trucut testicular biopsy and intracytoplasmic sperm injection have improved the outlook for these patients. There is also some evidence that spermatogenesis is affected by diabetes and that patients have a reduced sperm motility and semen volume. Therefore, diabetes has a significant impact on the fertility of men with this disease both directly and indirectly. The extent of iatrogenic influence on the reduced fertility potential of these patients needs to be researched as a matter of urgency.