Hypoxia results when the oxygen supply to rapidly growing tumors becomes inadequate to support various physiological processes. This plays a role in tumor metastasis and treatment resistance. Therefore, identifying tumor hypoxia can guide treatment planning and predict patient responses. However, hypoxic volumes are heterogeneously dispersed throughout a tumor, making it a challenge to pinpoint them with any degree of accuracy. Herein, we report the development of ratiometric hypoxia probe 1 (rHyP-1), which is a hypoxia-responsive small-molecule probe designed for reliable hypoxia detection using photoacoustic imaging. Photoacoustic imaging utilizes near-infrared (NIR) light to induce the production of ultrasound signals, enabling high-resolution image acquisition at centimeter depths. Together with the ratiometric capability of rHyP-1, reliable hypoxia detection with unprecedented spatial resolution is possible while minimizing error associated with concentration dependence and tissue heterogeneity.

We present a promising method for creating high-density ensembles of nitrogen-vacancy centers with narrow spin-resonances for high-sensitivity magnetic imaging. Practically, narrow spinresonance linewidths substantially reduce the optical and RF power requirements for ensemble-based sensing. The method combines isotope purified diamond growth, in situ nitrogen doping, and helium ion implantation to realize a 100 nm-thick sensing surface. The obtained 10 17 cm −3 nitrogen-vacancy density is only a factor of 10 less than the highest densities reported to date, with an observed spin resonance linewidth over 10 times more narrow. The 200 kHz linewidth is most likely limited by dipolar broadening indicating even further reduction of the linewidth is desirable and possible.The nitrogen-vacancy (NV) center in diamond is a versatile room-temperature magnetic sensor which can operate in a wide variety of modalities, from nanometerscale imaging with single centers [1, 2] to sub-picotesla sensitivities using ensembles [3]. Ensemble-based magnetic imaging, utilizing a two-dimensional array of NV centers [4][5][6], combines relatively high spatial resolution with high magnetic sensitivity. These arrays are ideal for imaging applications ranging from detecting magnetically tagged biological specimens [7,8] to fundamental studies of magnetic thin films [9]. A key challenge for array-based sensors is creating a high density of NV centers while still preserving the desirable NV spin properties. Here we report on a promising method which combines isotope purified diamond growth, in situ nitrogen doping and helium ion implantation. In the 100 nmthick sensor layer, we realize an NV density of 10 17 cm −3 with a 200 kHz magnetic resonance linewidth. This corresponds to a a DC magnetic sensitivity ranging from 170 nT (current experimental conditions) to 10 nT (optimized experimental conditions) for a 1 µm 2 pixel and 1 second measurement time.Magnetic sensing utilizing NV centers is based on optically-detected magnetic resonance (ODMR) [10][11][12]. In the ideal shot-noise limit, the DC magnetic sensitivity is given by [9] in which h/gµ B = 36 µT/MHz, C is the resonance dip contrast, η is the photon collection efficiency, δν is the full-width at half maximum resonance linewidth, n N V is the density of NV centers in imaging pixel volume V , and t is the measurement time. From Eq. 1, it is apparent that to minimize δB ideal for a given linewidth δν, one would like to maximize the NV density n N V . Increasing n N V , however, can also increase δν. For example, lattice damage during the NV creation process can create inhomogeneous strain-fields [13]. More fundamentally, eventually NV-NV and NV-N dipolar interactions will contribute to line broadening. This dipolar broadening, δν dp , is proportional to the nitrogen density n N [14,15]. Since n N V is typically proportional to n N , we can divide δ ν into two components, δν = δν 0 + δν dp = δν 0 + An N V , to obtainin which δν 0 depends on factors independent of NV density (e.g. hyperfi...

Stimulated emission depletion (STED) and structured illumination (SIM) are two commonly used techniques for super-resolution imaging. However, the performance of these two techniques has never been quantitatively compared side-by-side. Taking advantage of the non-photobleaching characteristic of NV centres in fluorescent nanodiamond (FND), we performed a comparative study for the resolution of these two methods with 35 nm FNDs at the single particle level, as well as with FND grown in bulk diamond material. Results show that STED provides more structural details, whereas SIM provides a larger field of view with a higher imaging speed. SIM may induce deconvolution smooth and orientational artifacts during its post-processing.

Metasurfaces with metallic [1] and dielectric [2] nanophotonic building blocks manipulate light scattering in the subwavelength

COMMUNICATION (1 of 8)charged-particle beam lithography technique, has shown great potential in 3D nanoscale fabrication with high precision at the submicron scale. 3D nanofabrication has been demonstrated using low-energy EBL based on the saturation of exposure depth and width, [24] multiple electron beam exposures at different exposure energies, [20,25] continuous overlay electron beam exposures, [26][27][28] and grayscale EBL [29,30] among others. To the same end, 3D nanostructures have also been fabricated in bilayer resist stacks by EBL, [31] which was enabled by the difference in dose sensitivity of two different resists. However, in this approach, multiple coatings of resists with different sensitivities are required. Moreover, there is a limited selection of suitable combinations of high-resolution resists. The recently introduced scanning helium ion microscope (HIM) is a superior tool in high-resolution imaging, thanks to its minimized sample charging through flood charge neutralization, enhanced depth of field, and short De Broglie wavelength. As a scanning focused-ion-beam instrument, HIM can perform high-resolution nanofabrication by milling, [32,33] etching, [34] deposition, [35,36] modification of materials, [37,38] and lithographic patterning in resists. [39,40] When used as a high-resolution lithography tool, helium ion beam lithography (HIBL) has achieved record-high-resolution patterning of 8 nm pitch dense lines. [41] Moreover, the narrow interaction volume of helium ions in resist materials makes HIBL a promising candidate for In this paper, 3D volumetric energy deposition and local crosslinking of hydrogen silsesquioxane (HSQ) are experimentally and numerically explored in focused helium ion beam lithography (HIBL). In particular, a throughmembrane exposure method is developed to make visible and subsequently to measure the 3D interaction volume and energy deposition of helium ions in HSQ. By comparing the actual dimensions of the crosslinked HSQ structures with Monte Carlo modeling of the spatial distribution of the energy deposition, the critical energy density for crosslinking HSQ is obtained. Finally, 3D nanofabrication of complex crosslinked HSQ nanostructures such as embedded nanochannels and suspended grids is demonstrated using two different exposure configurations. The proposed method expands the 2D point spread function of HIBL into three dimensions, thus opening a new avenue for nanoscale 3D fabrication. Helium Ion Beam LithographyThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/admi.201800203.3D micro/nanostructures are important for electronic, [1] photonic, [2] plasmonic, [3] microfluidic, [4] bio-MEMS, [5] and chemical synthesis [6] applications. Directly patterning materials into 3D micro/nanostructures has recently attracted considerable attention. Significant effort has been devoted to investigating methods for defining functional 3D micro/nanoscale structures, including direct material deposition, [7][8][9][10] ...