Radiation therapy (RT) employs ionizing radiation to kill cancerous cells. However, delivering radiation to tumors, typically embedded within normal tissues, inevitably exposes healthy organs to radiation, leading to collateral damage. This creates a tradeoff between the tumor control probability and normal tissue complication probability, ultimately limiting the dose that can be safely administered. While highly conformal RT techniques have improved tumor targeting and treatment efficacy, they remain inadequate for treating large and radioresistant tumors, pointing out the need for alternative strategies. Spatially fractionated RT, ultra-high dose rate RT, and nanoparticle-enhanced RT are emerging techniques with promise in enhancing tumor control while minimizing normal tissue toxicity. Successful clinical translation of these advanced techniques requires cross-disciplinary efforts aimed at technological innovation, a deeper understanding of the underlying radiobiological mechanisms, and the development of early-phase clinical trials. This paper provides an overview of these techniques and their associated challenges and opportunities.

Strain imaging using conventional x-ray tomography is a widely established technique for investigating the mechanical deformation of materials, including cement and batteries. However, its biomedical applications are primarily restricted to bone tissue due to the low contrast of soft tissues. X-ray phase contrast imaging, offering superior contrast-to-noise ratios in soft tissues, can in principle overcome this limitation. This study explores the feasibility of x-ray strain imaging for soft tissues using edge illumination (EI), a laboratory-based x-ray phase contrast technique. A phantom mimicking the mechanical properties of healthy and tumorous soft tissues, with a stiff inclusion invisible to conventional x-ray imaging, was tested alongside chicken soft tissue fixed in ethanol. While our study confirmed that EI phase contrast imaging provides improved contrast for such samples compared to absorption imaging, it also revealed a reduction in strain retrieval precision. Artefacts caused by absorbing bridges in the mask design and errors arising from differential phase signal integration, which vary spatially between scans, were identified as key limiting factors. Consequently, EI phase contrast strain imaging was unable to locate phantom inclusions based on mechanical contrast. However, EI's capability to increase spatial sampling frequency without compromising the field of view improved strain retrieval precision using its absorption contrast beyond that achieved with conventional x-ray strain imaging. These findings highlight the potential and challenges of applying EI to strain analysis in soft tissues, providing insights into its limitations and opportunities for further improvement.

Magnetic particle imaging (MPI) is a new tomographic imaging technique that can quantitatively correlate MPI signal intensity to the spatial distribution of magnetic nanoparticle (MNP) tracers. Due to its non-ionizing nature, low background signal from biological matrices, high contrast, and relatively good spatial and temporal resolution, MPI has been actively studied and applied to biomedical imaging and is expected to reach the clinical stage soon. To further improve the spatial resolution limit in MPI, researchers have been working towards optimizing the image reconstruction algorithms, magnetic field profiles, tracer designs, circuitry, etc. Recent studies reported that lower excitation field amplitudes can improve spatial resolution, though this comes at the expense of lower MPI signal and tracer sensitivity. Different excitation field profiles directly affect the collective dynamic magnetizations of tracers recorded by the receiver coil in MPI. However, there is a gap between understanding the relaxation dynamics of MNP tracers, the signal-to-noise ratio (SNR) of MPI signals, and the MPI spatial resolution. In this work, we used a stochastic Langevin equation with coupled Brownian and Néel relaxations to model the magnetic dynamics of different MNP tracers subjected to varying excitation fields. We analyzed the collective time-domain dynamic magnetizations (- curves), magnetic-field hysteresis loops ( curves), point spread functions (PSFs), higher harmonics, and SNR of the third harmonic to understand how the excitation field affects MPI performance. We employed Full Width at Half Maximum and SNR as evaluation metrics for imaging resolution and signal quality, respectively. Our study supports previous findings on the impact of excitation field amplitude on MPI performance while offering more profound insights into the interplay of nonequilibrium Néel and Brownian relaxation, tracer core size, and SNR.

Phase-sensitive Fourier-domain optical coherence tomography (FD-OCT) enables , label-free imaging of cellular movements with detection sensitivity down to the nanometer scale, and it is widely employed in emerging functional imaging modalities, such as optoretinography (ORG), Doppler OCT, and optical coherence elastography. However, when imaging tissue dynamics , inter-frame displacement introduces decorrelation noise that compromises motion detection performance, particularly in terms of sensitivity and accuracy. Here, we demonstrate that the displacement-related decorrelation noise in FD-OCT can be accurately corrected by restoring the initial sampling points using our proposed Phase-Restoring Subpixel Image Registration (PRESIR) method. Derived from a general FD-OCT model, the PRESIR method enables translational shifting of complex-valued OCT images over arbitrary displacements with subpixel precision, while accurately restoring phase components. Unlike conventional approaches that shift OCT images either in the spatial domain at the pixel level or in the spatial frequency domain for subpixel correction, our method reconstructs OCT images by correcting axial displacement in the spectral domain (k domain) and lateral displacement in the spatial frequency domain. We validated the PRESIR method through simulations, phantom experiments, and ORG in both rodents and human subjects. Our approach significantly reduced decorrelation noise during the imaging of moving samples, achieving phase sensitivity close to the fundamental limit determined by the signal-to-noise ratio.

Surface acoustic wave (SAW)-enabled acoustofluidic technologies have recently atttracted increasing attention for applications in biology, chemistry, biophysics, and medicine. Most SAW acoustofluidic devices generate acoustic energy which is then transmitted into custom microfabricated polymer-based channels. There are limited studies on delivering this acoustic energy into convenient commercially-available glass tubes for manipulating particles and fluids. Herein, we have constructed a capillary-based SAW acoustofluidic device for multifunctional fluidic and particle manipulation. This device integrates a converging interdigitated transducer to generate focused SAWs on a piezoelectric chip, as well as a glass capillary that transports particles and fluids. To understand the actuation mechanisms underlying this device, we performed finite element simulations by considering piezoelectric, solid mechanic, and pressure acoustic physics. This experimental study shows that the capillary-based SAW acoustofluidic device can perform multiple functions including enriching particles, patterning particles, transporting particles and fluids, as well as generating droplets with controlled sizes. Given the usefulness of these functions, we expect that this acoustofluidic device can be useful in applications such as pharmaceutical manufacturing, biofabrication, and bioanalysis.

X-ray phase contrast imaging (XPCI) methods give access to contrast mechanisms that are based on the refractive properties of matter on top of the absorption coefficient in conventional x-ray imaging. Ultra small angle x-ray scattering (USAXS) is a phase contrast mechanism that arises due to multiple refraction events caused by physical features of a scale below the physical resolution of the used imaging system. USAXS contrast can therefore give insight into subresolution structural information, which is an ongoing research topic in the vast field of different XPCI techniques. In this study, we quantitatively compare the USAXS signal retrieved by the beam tracking XPCI technique with the gold standard of the analyzer based imaging XPCI technique using a synchrotron x-ray source. We find that, provided certain conditions are met, the two methods measure the same quantity.

Estimating statistical significance of the difference between two spectra or series is a fundamental statistical problem. Multivariate significance tests exist but the limitations preclude their use in many common cases; e.g., one-sided testing, unequal variance and when few repetitions are acquired all of which are required in magnetic spectroscopy of nanoparticle Brownian motion (MSB). We introduce a test, termed the T-S test, that is powerful and exact (exact type I error). It is flexible enough to be one- or two-sided and the one-sided version can specify arbitrary regions where each spectrum should be larger. The T-S test takes the-one or two-sided p-value at each frequency and combines them using Stouffer's method. We evaluated it using simulated spectra and measured MSB spectra. For the single-sided version, mean of the spectrum, A-T, was used as a reference; the T-S test is as powerful when the variance at each frequency is uniform and outperforms when the noise power is not uniform. For the two-sided version, the Hotelling T2 two-sided multivariate test was used as a reference; the two-sided T-S test is only slightly less powerful for large numbers of repetitions and outperforms rather dramatically for small numbers of repetitions. The T-S test was used to estimate the sensitivity of our current MSB spectrometer showing 1 nanogram sensitivity. Using eight repetitions the T-S test allowed 15 pM concentrations of mouse IL-6 to be identified while the mean of the spectra only identified 76 pM.

We have used arrays of microwave-generated microplasmas operating at atmospheric pressure to generate high concentrations of singlet molecular oxygen, O(Δ ), which is of interest for biomedical applications. The discharge is sustained by a pair of microstrip-based microwave resonator arrays which force helium/oxygen gas mixtures through a narrow plasma channel. We have demonstrated the efficacy of both NO and less-hazardous NO additives for suppression of ozone and associated enhancement of the O(Δ ) yield. Quenching of O(Δ ) by ozone is sufficiently suppressed such that quenching by ground state molecular oxygen becomes the dominant loss mechanism in the post-discharge outflow. We verified the absence of other significant gas-phase quenching mechanisms by measuring the O(Δ ) decay along a quartz flow tube. These measurements indicated a first-order rate constant of (1.2 ± 0.3) × 10 m s, slightly slower than but consistent with prior measurements of singlet oxygen quenching on ground state oxygen. The discharge-initiated reaction mechanisms and data analysis are discussed in terms of a chemical kinetics model of the system.

Mechanical cues have been suggested to play an important role in cell functions and cell fate determination, however, such physical quantities are challenging to directly measure in living cells with single molecule sensitivity and resolution. In this review, we focus on two main technologies that are promising in probing forces at the single molecule level. We review their theoretical fundamentals, recent technical advancements, and future directions, tailored specifically for interrogating mechanosensitive molecules in live cells.

In this report, we report on the implementation of compressive sensing (CS) and sparse sampling in polarization sensitive optical coherence tomography (PS-OCT) to reduce the number of B-scans (frames consisting of an array of A-scans, where each represents a single depth profile of reflections) required for effective volumetric (3D dataset composed of an array of B-scans) PS-OCT measurements (i.e. OCT intensity, and phase retardation) reconstruction. Sparse sampling of PS-OCT is achieved through randomization of step sizes along the slow-axis of PS-OCT imaging, covering the same spatial ranges as those with equal slow-axis step sizes, but with a reduced number of B-scans. Tested on missing B-scan rates of 25%, 50% and 75%, we found CS could reconstruct reasonably good (as evidenced by a correlation coefficient >0.6) PS-OCT measurements with a maximum reduced B-scan rate of 50%, thereby accelerating and doubling the rate of volumetric PS-OCT measurements.

Despite advances in intraoperative surgical imaging, reliable discrimination of critical tissue during surgery remains challenging. As a result, decisions with potentially life-changing consequences for patients are still based on the surgeon's subjective visual assessment. Hyperspectral imaging (HSI) provides a promising solution for objective intraoperative tissue characterisation, with the advantages of being non-contact, non-ionising and non-invasive. However, while its potential to aid surgical decision-making has been investigated for a range of applications, to date no real-time intraoperative HSI (iHSI) system has been presented that follows critical design considerations to ensure a satisfactory integration into the surgical workflow. By establishing functional and technical requirements of an intraoperative system for surgery, we present an iHSI system design that allows for real-time wide-field HSI and responsive surgical guidance in a highly constrained operating theatre. Two systems exploiting state-of-the-art industrial HSI cameras, respectively using linescan and snapshot imaging technology, were designed and investigated by performing assessments against established design criteria and tissue experiments. Finally, we report the use of our real-time iHSI system in a clinical feasibility case study as part of a spinal fusion surgery. Our results demonstrate seamless integration into existing surgical workflows.

Mechanical forces regulate a diverse set of biological processes at cellular, tissue, and organismal length scales. Investigating the cellular and molecular mechanisms that underlie the conversion of mechanical forces to biological responses is challenged by limitations of traditional animal models and cell culture, including poor control over applied force and highly artificial cell culture environments. Recent advances in fabrication methods and material processing have enabled the development of microfluidic platforms that provide precise control over the mechanical microenvironment of cultured cells. These devices and systems have proven to be powerful for uncovering and defining mechanisms of mechanotransduction. In this review, we first give an overview of the main mechanotransduction pathways that function at sites of cell adhesion, many of which have been investigated with microfluidics. We then discuss how distinct microfluidic fabrication methods can be harnessed to gain biological insight, with description of both monolithic and replica molding approaches. Finally, we present examples of how microfluidics can be used to apply both solid forces (substrate mechanics, strain, and compression) and fluid forces (luminal, interstitial) to cells. Throughout the review, we emphasize the advantages and disadvantages of different fabrication methods and applications of force in order to provide perspective to investigators looking to apply forces to cells in their own research.

Probing the diffusion of molecules has become a routine measurement across the life sciences, chemistry and physics. It provides valuable insights into reaction dynamics, oligomerisation, molecular (re-)organisation or cellular heterogeneities. Fluorescence correlation spectroscopy (FCS) is one of the widely applied techniques to determine diffusion dynamics in two and three dimensions. This technique relies on the temporal autocorrelation of intensity fluctuations but recording these fluctuations has thus far been limited by the detection electronics, which could not efficiently and accurately time-tag photons at high count rates. This has until now restricted the range of measurable dye concentrations, as well as the data quality of the FCS recordings, especially in combination with super-resolution stimulated emission depletion (STED) nanoscopy. Here, we investigate the applicability and reliability of (STED-)FCS at high photon count rates (average intensities of more than 1 MHz) using novel detection equipment, namely hybrid detectors and real-time gigahertz sampling of the photon streams implemented on a commercial microscope. By measuring the diffusion of fluorophores in solution and cytoplasm of live cells, as well as in model and cellular membranes, we show that accurate diffusion and concentration measurements are possible in these previously inaccessible high photon count regimes. Specifically, it offers much greater flexibility of experiments with biological samples with highly variable intensity, e.g. due to a wide range of expression levels of fluorescent proteins. In this context, we highlight the independence of diffusion properties of cytosolic GFP in a concentration range of approx. 0.01-1 m. We further show that higher photon count rates also allow for much shorter acquisition times, and improved data quality. Finally, this approach also pronouncedly increases the robustness of challenging live cell STED-FCS measurements of nanoscale diffusion dynamics, which we testify by confirming a free diffusion pattern for a fluorescent lipid analogue on the apical membrane of adherent cells.

Super-resolution microscopy (SRM) enables non-invasive, molecule-specific imaging of the internal structure and dynamics of cells with sub-diffraction limit spatial resolution. One of its major limitations is the requirement for high-intensity illumination, generating considerable cellular phototoxicity. This factor considerably limits the capacity for live-cell observations, particularly for extended periods of time. Here, we give an overview of new developments in hardware, software and probe chemistry aiming to reduce phototoxicity. Additionally, we discuss how the choice of biological model and sample environment impacts the capacity for live-cell observations.

Line-scanning confocal microscopy provides high imaging speed and moderate optical sectioning strength, which makes it a useful tool for imaging various biospecimens ranging from living cells to fixed tissues. Conventional line-scanning systems have only used a single excitation line and slit, and thus have not fully exploited benefits of parallelization. Here we investigate the optical performance of multi-line scanning confocal microscopy (mLS) by employing a digital micro-mirror that provides programmable patterns of the illumination beam and the detection slit. Through experimental results and optical simulations, we assess the depth discrimination of mLS under different optical parameters and compare it with multi-point systems such as scanning disk confocal microscopy (SDCM). Under the same illumination duty cycle, we find that mLS has better optical sectioning than SDCM at a high degree of parallelization. The optimized mLS provides a low photobleaching rate and video-rate imaging while its optical sectioning is similar to single line-scanning confocal microscopy.

Outbreaks of airborne infectious diseases such as measles or severe acute respiratory syndrome can cause significant public alarm. Where ventilation systems facilitate disease transmission to humans or animals, there exists a need for control measures that provide effective protection while imposing minimal pressure differential. In the present study, viral aerosols in an airstream were subjected to non-thermal plasma (NTP) exposure within a packed-bed dielectric barrier discharge reactor. Comparisons of plaque assays before and after NTP treatment found exponentially increasing inactivation of aerosolized MS2 phage with increasing applied voltage. At 30 kV and an air flow rate of 170 standard liters per minute, a greater than 2.3 log reduction of infective virus was achieved across the reactor. This reduction represented ~2 log of the MS2 inactivated and ~0.35 log physically removed in the packed bed. Increasing the air flow rate from 170 to 330 liters per minute did not significantly impact virus inactivation effectiveness. Activated carbon-based ozone filters greatly reduced residual ozone, in some cases down to background levels, while adding less than 20 Pa pressure differential to the 45 Pa differential pressure across the packed bed at the flow rate of 170 standard liters per minute.

Just a few of the promising applications of graphene Corbino J devices include two-dimensional Dirac fermion microscopes, custom programmable quantized resistors, and mesoscopic valley filters. In some cases, device scalability is crucial, as seen in fields like resistance metrology, where graphene devices are required to accommodate currents of the order 100 μA to be compatible with existing infrastructure. However, fabrication of these devices still poses many difficulties. In this work, unusual quantized resistances are observed in epitaxial graphene Corbino junction devices held at the = 2 plateau ( ≈ 12906 Ω) and agree with numerical simulations performed with the LTspice circuit simulator. The formulae describing experimental and simulated data are empirically derived for generalized placement of up to three current terminals and accurately reflects observed partial edge channel cancellation. These results support the use of ultraviolet lithography as a way to scale up graphene-based devices with suitably narrow junctions that could be applied in a variety of subfields.

Measurements of fractional multiples of the = 2 plateau quantized Hall resistance ( ≈ 12906 Ω) were enabled by the utilization of multiple current terminals on millimetre-scale graphene junction devices fabricated with interfaces along both lateral directions. These quantum Hall resistance checkerboard devices have been demonstrated to match quantized resistance outputs numerically calculated with the LTspice circuit simulator. From the devices' functionality, more complex embodiments of the quantum Hall resistance checkerboard were simulated to highlight the parameter space within which these devices could operate. Moreover, these measurements suggest that the scalability of junction fabrication on millimetre or centimetre scales is feasible with regards to graphene device manufacturing by using the far more efficient process of standard ultraviolet lithography.

Graded magnetic materials represent a promising new avenue in modern material science from both fundamental and application points of view. Over the course of the last few years, remarkable results have been obtained in (epitaxial) heterostructures based on thin alloy films featuring diverse compositional depth profiles. As a result of the precise tailoring of such profiles, the exchange coupling, and the corresponding effective or local Curie temperatures can be controlled over tens of nm with an excellent precision. This topical review article reports the most recent advances in this emerging research field. Several aspects are covered, but the primary focus lies in the study of compositional gradients being transferred into depth dependent magnetic states in ferromagnets, while also reviewing other experimental attempts to create exchange graded films and materials in general. We account for the remarkable progress achieved in each sample and composition geometry by reporting the recent developments and by discussing the research highlights obtained by several groups. Finally, we conclude the review article with an outlook on future challenges in this field.

Metal-oxide (MO) semiconductor gas sensors based on chemical resistivity necessarily involve making electrical contacts to the sensing materials. These contacts are imperfect and introduce errors into the measurements. In this paper, we demonstrate the feasibility of using contactless broadband dielectric spectroscopy (BDS)-based metrology in gas monitoring that avoids distortions in the reported resistivity values due to probe use, and parasitic errors (i.e. tool-measurand interactions). Specifically, we show how radio frequency propagation characteristics can be applied to study discrete processes on MO sensing material, such as zinc oxide (i.e. ZnO) surfaces, when exposed to a redox-active gas. Specifically, we have used BDS to investigate the initial oxidization of ZnO gas sensing material in air at temperatures below 200 °C, and to show that the technique affords new mechanistic insights that are inaccessible with the traditional resistance-based measurements.