We present a comprehensive guide to light-sheet microscopy (LSM) to assist scientists in navigating the practical implementation of this microscopy technique. Emphasizing the applicability of LSM to image both static microscale and nanoscale features, as well as diffusion dynamics, we present the fundamental concepts of microscopy, progressing through beam profile considerations, to image reconstruction. We outline key practical decisions in constructing a home-built system and provide insight into the alignment and calibration processes. We briefly discuss the conditions necessary for constructing a continuous 3D image and introduce our home-built code for data analysis. By providing this guide, we aim to alleviate the challenges associated with designing and constructing LSM systems and offer scientists new to LSM a valuable resource in navigating this complex field.

The calculation of the demagnetization field is crucial in various disciplines, including magnetic resonance imaging and micromagnetics. A standard method involves discretizing the spatial domain into finite difference cells and using demagnetization tensors to compute the field. Different demagnetization tensors can result in contributions from adjacent cells that do not approach zero, nor do their differences, even as the cell size decreases. This work demonstrates that in three-dimensional space, a specific set of magnetization tensors produces the same total demagnetization field as the Cauchy principal value when the cell size approaches zero. Additionally, we provide a lower bound for the convergence speed, validated through numerical experiments.

Eddy current shielding by a Faraday cage is an effective way to shield alternating-current magnetic fields in scientific instrumentation. In a strong static magnetic field, however, the eddy current in the conductive shield is subject to the Lorentz force, which causes the shield to vibrate. In addition to mechanical issues (e.g., acoustic noise), such vibration induces motional eddy current in the shield that can dominate the original, electromagnetic eddy current to undermine the conductor's shielding capability. In this work, we investigate a method to control motional eddy current by making cut-out patterns in the conductor that follow the electromagnetic eddy current image. This effectively limits the surface current of the plate to a single mode and prevents the proliferation of uncontrolled motion-induced surface currents that disrupts eddy current shielding. After developing a comprehensive theory of magneto-mechanical interaction in a conductive plate, the proposed method was tested on a flat-geometry testbed experiment inside a 3 T magnetic resonance imaging (MRI) magnet. It was found that the magnetic field generated by the motional eddy current was much more localized in space and frequency for a patterned-copper shield compared to a solid copper. The magnetic field of the patterned shield could be accurately predicted from the impedance measurement in the magnet. Implications of our results for improved shielding of gradient fields in high-field MRI are discussed.

As investigations in the biomedical applications of plasma advance, a demand for describing safe and efficacious delivery of plasma is emerging. It is quite clear that not all plasmas are "equal" for all applications. This Perspective discusses limitations of the existing parameters used to define plasma in context of the need for the "right plasma" at the "right dose" for each "disease system." The validity of results extrapolated from studies to preclinical and clinical applications is discussed. We make a case for studying the whole system as a single unit, . Furthermore, we argue that while plasma-generated chemical species are the proposed key effectors in biological systems, the contribution of physical effectors (electric fields, surface charging, dielectric properties of target, changes in gap electric fields, etc.) must not be ignored.

Directional fluid flow in perivascular spaces surrounding cerebral arteries is hypothesized to play a key role in brain solute transport and clearance. While various drivers for a pulsatile flow, such as cardiac or respiratory pulsations, are well quantified, the question remains as to which mechanisms could induce a directional flow within physiological regimes. To address this question, we develop theoretical and numerical reduced-order models to quantify the directional (net) flow induceable by peristaltic pumping in periarterial networks. Each periarterial element is modeled as a slender annular space bounded internally by a circular tube supporting a periodic traveling (peristaltic) wave. Under reasonable assumptions of a small Reynolds number flow, small radii, and small-amplitude peristaltic waves, we use lubrication theory and regular perturbation methods to derive theoretical expressions for the directional net flow and pressure distribution in the perivascular network. The reduced model is used to derive closed-form analytical expressions for the net flow for simple network configurations of interest, including single elements, two elements in tandem, and a three element bifurcation, with results compared with numerical predictions. In particular, we provide a computable theoretical estimate of the net flow induced by peristaltic motion in perivascular networks as a function of physiological parameters, notably, wave length, frequency, amplitude, and perivascular dimensions. Quantifying the maximal net flow for specific physiological regimes, we find that vasomotion may induce net pial periarterial flow velocities on the order of a few to tens of m/s and that sleep-related changes in vasomotion pulsatility may drive a threefold flow increase.

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density [the amount of power transferred divided by receiver footprint area (length × width)]. Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm, which is over four times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 and 56 mW to 10 and 27-mm ME receivers, respectively. This total power delivery is over five times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices.

When it comes to simulate or calculate an optoelectronic tweezer (OET) response for a microparticle suspended in a given medium, a precise electrical conductivity (later referred to as conductivity) value for the microparticle is critical. However, there are not well-established measurements or well-referenced values for microparticle conductivities in the OET realm. Thus, we report a method based on measuring the escape velocity of a microparticle with a standard OET system to calculate its conductivity. A widely used 6 m polystyrene bead (PSB) is used for the study. The conductivity values are found to be invariant around 2×10 S/m across multiple different aqueous media, which helps clarify the ambiguity in the usage of PSB conductivity. Our convenient approach could principally be applied for the measurement of multiple unknown OET-relevant material properties of microparticle-medium systems with various OET responses, which can be beneficial to carry out more accurate characterization in relevant fields.

Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. We approached Ca spark activation as an emergent phenomenon of an interactive system of release channels. We constructed a weakly lumped Markov chain that applies an Ising model formalism to such release channel clusters and probable open channel configurations and demonstrated that spark activation is described as a system transition from a metastable to an absorbing state, analogous to the pressure required to overcome surface tension in bubble formation. This yielded quantitative estimates of the spark generation probability as a function of various system parameters. We performed numerical simulations to find spark probabilities as a function of sarcoplasmic reticulum Ca concentration, obtaining similar values for spark activation threshold as our analytic model, as well as those reported in experimental studies. Our parametric sensitivity analyses also showed that the spark activation threshold decreased as Ca sensitivity of RyR activation and RyR cluster size increased.

Arterial wall active mechanics are driven by resident smooth muscle cells, which respond to biological, chemical, and mechanical stimuli and activate their cytoskeletal machinery to generate contractile stresses. The cellular mechanoresponse is sensitive to environmental perturbations, often leading to maladaptation and disease progression. When investigated at the single cell scale, however, these perturbations do not consistently result in phenotypes observed at the tissue scale. Here, a multiscale model is introduced that translates microscale contractility signaling into a macroscale, tissue-level response. The microscale framework incorporates a biochemical signaling network along with characterization of fiber networks that govern the anisotropic mechanics of vascular tissue. By incorporating both biochemical and mechanical components, the model is more flexible and more broadly applicable to physiological and pathological conditions. The model can be applied to both cell and tissue scale systems, allowing for the analysis of , traction force microscopy and , isometric contraction experiments in parallel. When applied to aortic explant rings and isolated smooth muscle cells, the model predicts that active contractility is not a function of stretch at intermediate strain. The model also successfully predicts cell-scale and tissue-scale contractility and matches experimentally observed behaviors, including the hypercontractile phenotype caused by chronic hyperglycemia. The connection of the microscale framework to the macroscale through the multiscale model presents a framework that can translate the wealth of information already collected at the cell scale to tissue scale phenotypes, potentially easing the development of smooth muscle cell-targeting therapeutics.

2'-Deoxy-ATP (dATP), a naturally occurring near analog of ATP, is a well-documented myosin activator that has been shown to increase contractile force, improve pump function, and enhance lusitropy in the heart. Calcium transients in cardiomyocytes with elevated levels of dATP show faster calcium decay compared with cardiomyocytes with basal levels of dATP, but the mechanisms behind this are unknown. Here, we design and utilize a multiscale computational modeling framework to test the hypothesis that dATP acts on the sarcoendoplasmic reticulum calcium-ATPase (SERCA) pump to accelerate calcium re-uptake into the sarcoplasmic reticulum during cardiac relaxation. Gaussian accelerated molecular dynamics simulations of human cardiac SERCA2A in the E1 , ATP-bound and dATP-bound states showed that dATP forms more stable contacts in the nucleotide binding pocket of SERCA and leads to increased closure of cytosolic domains. These structural changes ultimately lead to changes in calcium binding, which we assessed using Brownian dynamics simulations. We found that dATP increases calcium association rate constants to SERCA and that dATP binds to SERCA more rapidly than ATP. Using a compartmental ordinary differential equation model of human cardiomyocyte excitation-contraction coupling, we found that these increased association rate constants contributed to the accelerated rates of calcium transient decay observed experimentally. This study provides clear mechanistic evidence of enhancements in cardiac SERCA2A pump function due to interactions with dATP.

Understanding defect creation is central to efforts to comprehend gate dielectric breakdown in metal-oxide-semiconductor-field-effect-transistors (MOSFETs). While gate dielectrics other than SiO are now popular, models develop for SiO breakdown are used for these dielectrics too. Considering that the Si-O bond is very strong, modeling efforts have focused in ways to weaken it so that defect creation (bond-breaking) is commensurate with experimental observations. So far, bond-breaking models rely on defect-precursors to make the energetics manageable. Here it is argued that the success of the percolation model for gate oxide breakdown precludes the role of defect precursors in gate oxide breakdown. It is proposed that defect creation involves "normal" Si-O bonds. This new model relies on the fact that hole transport in SiO is in the form of a small polaron - meaning that it creates a transient local distortion as it travels. It is this transient distortion that enables normal Si-O bonds to be weakened (albeit transiently) enough that breaking the bonds at a rate commensurate with measurements becomes possible without the help of the externally applied field.

A theoretical method is described to analytically calculate a pair of surface current densities, which produce a desired static magnetic field in one region of the space and zero magnetic field in another. The analysis is based on the known relationship between a surface current density and a stream function, the equivalence of stream functions and surface magnetic dipole density, and the scalar potential representation of the associated magnetic field in free space. From these relations, we formulate the magnetostatic problem, which is often treated as a vector field problem, as a scalar field problem in which a two-dimensional scalar field (stream function) is related to a three-dimensional one (magnetic scalar potential) via the differentiation of the electrostatic Green's function 1/|r-r|. It is shown that, in a coordinate system in which a separated form of the Green's function exists (separable coordinate system), there exists a simple relationship between a harmonic component of a stream function and a harmonic component of the magnetic scalar potential. The method is applied to calculate idealized surface current patterns for actively shielded, linear gradient field coils in the Cartesian, cylindrical, and spherical coordinates.

We investigate the use of Raman spectroscopy to measure carrier concentrations in GaSb epilayers to aid in the development of this technique for the nondestructive characterization of transport properties in doped semiconductors. The carrier concentration is quantified by modeling the measured coupled optical phonon-free carrier plasmon mode spectra. We employ the Lindhard-Mermin optical susceptibility model with contributions from carriers in the two lowest GaSb conduction-band minima, the and minima. Furthermore, we evaluate three conduction-band models: (1) both minima parabolic and isotropic, (2) the minimum non-parabolic and isotropic and the minima parabolic and isotropic, and (3) the minimum non-parabolic and isotropic and the minima parabolic and ellipsoidal. For a given epilayer, the carrier concentration determined from the spectral simulations was consistently higher for the ellipsoidal minima model than the other two models. To evaluate the conduction-band models, we calculated the to electron mobility ratio necessary for the electron concentrations from the Raman spectral measurements to reproduce those from the Hall effect measurements. We found that the model with the ellipsoidal minima agreed best with reported carrier-dependent mobility-ratio values. Hence, employing isotropic minima in GaSb conduction-band models, a common assumption when describing the GaSb conduction band, likely results in an underestimation of carrier concentration at room temperature and higher doping levels. This observation could have implications for Raman spectral modeling and any investigation involving the GaSb conduction band, e.g., modeling electrical measurements or calculating electron mobility.

A series of monofilamentary powder-in-tube MgB wires were fabricated with 2 mol. % C doping and co-additions of 0-3 wt. % DyO. Irreversibility fields ( ), upper critical fields ( ), and transport critical currents were measured, and from these quantities, anisotropies and electronic diffusivities were estimated. The addition of 1 wt. % DyO to already optimally C-doped MgB wires produced higher , , and values at 4.2 K. In addition, the critical current density, , increased with DyO concentration up to 1 wt. % where non-barrier reached 4.35 × 10 A/cm at 4.2 K, 10 T. At higher temperatures, for example, 20 K and 5 T, co-additions of 2 mol. % C and 2 wt. % DyO improved non-barrier by 40% and 93% compared to 2 and 3 mol. % C doping, respectively. On the other hand, measurements of showed that C/DyO co-additions increase interband scattering rates at a lower rate than C doping does (assuming C doping levels giving similar levels of low-T increase as co-addition). Comparisons to a two-band model for in MgB allowed us to conclude that the increases in , , and (as well as concomitant increases in high-field ) with DyO addition are consistent with increases primarily in intraband scattering. This suggests C/DyO co-addition to be a more promising candidate for improving non-barrier of MgB at temperatures above 20 K.

Heating magnetic nanoparticles (MNPs) with alternating magnetic fields (AMFs) have applications in biomedical research and cancer therapy. Accurate measurement of the heating efficiency or specific loss power (SLP) generated by the MNPs is essential to assess response(s) in biological systems. Efforts to develop standardized equipment and to harmonize results obtained from various MNP samples and AMF systems have met with little success. Without a standardized magnetic nanoparticle or calorimeter device, objective comparisons of estimated thermal output among laboratories remain a challenge. In addition, the most widely used adiabatic initial slope model fails to account for thermal losses, which are unavoidable. We propose a non-adiabatic method to analyze MNP heating efficiency derived from the Box-Lucas equation, wherein the sample is subjected to several short duration heating pulses. SLP is then estimated from an arithmetic average of the Box-Lucas fitted coefficients obtained from each pulse. Heating experiments were conducted with two identical samples that were placed within vessels having different thermal insulation using the same AMF parameters. Though the samples generated different temperature curves, the pulsed Box-Lucas method produced nearly equivalent SLP estimates. Further, the pulsed test enabled analysis of the heat transfer coefficient providing quantitative measures of sample heat loss throughout the test, with robust statistical confidence. We anticipate this new methodology will aid efforts to standardize measurements of MNP heating efficiency, enabling direct comparison among varied systems.

We present high-resolution magnetic resonance imaging (MRI) at ultra-low field (ULF) with a proton Larmor frequency of around 120 kHz. The key element is a specially designed high-sensitivity sensing coil in the shape of a solenoid with a few millimeter gap between windings to decrease the proximity effect and, hence, increase the coil's quality ( ) factor and sensitivity. External noise is strongly suppressed by enclosing the sensing coil in a copper cylindrical shield, large enough not to negatively affect the coil's factor and sensitivity, measured to be 217 and 0.47 fT/Hz , respectively. To enhance small polarization of proton spins at ULF, a strong pulsed 0.1 T prepolarization field is applied, making the signal-to-noise ratio (SNR) of ULF MRI sufficient for high-quality imaging in a short time. We demonstrate ULF MRI of a copper sulfate solution phantom with a resolution of and SNR of 10. The acquisition time is 6.3 min without averaging. The sensing coil size in the current realization can accommodate imaging objects of 9 cm in size, sufficient for hand, and it can be further increased for human head imaging in the future. Since the in-plane resolution of is typical in anatomical medical imaging, this ULF MRI method can be an alternative low-cost, rapid, portable method for anatomical medical imaging of the human body or animals. This ULF MRI method can supplement other MRI methods, especially when such methods are restricted due to high cost, portability requirement, imaging artifacts, and other factors.

Integrating miniature pumps within microfluidic devices is crucial for advancing point-of-care diagnostics. Understanding the emergence of flow from novel integrated pumping systems is the first step in their successful implementation. A Purcell-like elasto-magnetic integrated microfluidic pump has been simulated in COMSOL Multiphysics and its performance has been investigated and evaluated. An elastic, cilia-like element contains an embedded magnet, which allows for actuation via a weak, uniaxial, sinusoidally oscillating, external magnetic field. Pumping performance is correlated against a number of variables, such as the frequency of the driving field and the proximity of the pump to the channel walls, in order to understand the emergence of the pumping behavior. Crucially, these simulations capture many of the trends observed experimentally and shed light on the key interactions. The proximity of the channel walls in the in-plane direction strongly determines the direction of net fluid flow. This characterization has important implications for the design and optimization of this pump in practical applications.

Photoacoustic imaging is a hybrid imaging approach that combines the advantages of optical and ultrasonic imaging in one modality. However, for comprehensive tissue characterization, optical contrast alone is not always sufficient. In this study, we combined photoacoustic imaging with high-resolution ultrasound and shear wave elastography. The multi-modal system can calculate optical absorption, acoustic reflection, and stiffness volumetrically. We constructed a multi-modal phantom with contrast for each imaging modality to test the system's performance. Experimental results indicate that the system successfully visualizes the embedded structures. We envision that the system will lead to more comprehensive tissue characterization for cancer screening and diagnosis.

Force spectroscopy using magnetic tweezers (MTs) is a powerful method to probe the physical characteristics of single polymers. Typically, molecules are functionalized for specific attachment to a glass surface at one end and a micrometer-scale paramagnetic bead at the other end. By applying an external magnetic field, multiple molecules can be stretched and twisted simultaneously without exposure to potentially damaging radiation. The majority of MTs utilize mobile, permanent magnets to produce forces on the beads (and the molecule under test). However, translating and rotating the permanent magnets may require expensive precision actuators, limit the rate at which force can be changed, and may induce vibrations that disturb tether dynamics and bead tracking. Alternatively, the magnetic field can be produced with an electromagnet, which allows fast force modulation and eliminates motor-associated vibration. Here, we describe a low-cost quadrapolar electromagnetic tweezer design capable of manipulating DNA-tethered MyOne paramagnetic beads with forces as high as 15 pN. The solid-state nature of the generated B-field modulated along two axes is convenient for accessing the range of forces and torques relevant for studying the activity of DNA motor enzymes like polymerases and helicases. Our design specifically leverages technology available at an increasing number of university maker spaces and student-run machine shops. Thus, it is an accessible tool for undergraduate education that is applicable to a wide range of biophysical research questions.

In recent years, interesting materials have emerged which are only available as μm-scale flakes, and whose novel physics might be better understood through broadband microwave spectroscopy; examples include twisted bilayer graphene [Y. Cao S. Fang, K. Watanabe, T. Taniguchi, E. Kaxiras and P. Jarillo-Herrero Nature , 43 (2018).], 2D materials in which many-body phases are observed [S. Chen R. Ribeiro-Palau, K. Yang, T. Taniguchi, J. Hone, M. O. Goerbig and C. R. Dean Physical Review Letters ¸ 026802 (2019)], and artificial lattices for analog quantum simulations [J. Salfi J. A. Mol, R. Rahman, G. Klimeck, M. Y. Simmons, L. C. L. Hollenberg and S. Rogge Nature Communications , 1 (2016)]. Most previous techniques are unfortunately not sensitive for flakes below mm lateral sizes. We propose a simple technique which does not require sophisticated sample preparation nor Ohmic contact and show through theory and simulations that one will be able to qualitatively measure spectral features of interest, and quantitatively measure the frequency-dependent complex conductivity.

The thick gate oxide breakdown mechanism has become an important topic again due to the rising demand for power electronics. The failure of the percolation model in explaining the observed Weibull shape factor, , seriously hampers the establishment of thick gate oxide breakdown models and the ability to project reliability from measurement data. In this work, lifetime shortening by oxide defects are simulated to produce degraded breakdown distributions that match experimentally observed s. The result shows that even a low density of defects with the right energy is enough to greatly degrade for thick oxides. Strong area scaling for thin oxides counters this sensitivity to defects effectively and explains why the percolation model is successful in thin oxides but not in thick oxides. Only defects with the appropriate energy can degrade the breakdown distribution. The required energy is consistent with oxygen vacancy defect after capturing a hole and the concentration required is consistent with very high-quality oxide. This explains the consistent low values for thick oxides universally reported in the literature.