Magnetic nanoparticles, especially superparamagnetic nanoparticles (SPIONs), have attracted tremendous attention for various biomedical applications. Facile synthesis and functionalization together with easy control of the size and shape of SPIONS to customize their unique properties, have made it possible to develop different types of SPIONs tailored for diverse functions/applications. More recently, considerable attention has been paid to the thermal effect of SPIONs for the treatment of diseases like cancer and for nanowarming of cryopreserved/banked cells, tissues, and organs. In this mini-review, recent advances on the magnetic heating effect of SPIONs for magnetothermal therapy and enhancement of cryopreservation of cells, tissues, and organs, are discussed, together with the non-magnetic heating effect (i.e., high Intensity focused ultrasound or HIFU-activated heating) of SPIONs for cancer therapy. Furthermore, challenges facing the use of magnetic nanoparticles in these biomedical applications are presented.

Thermoregulation is a process that is essential to the maintenance of life for all warm-blooded mammalian and avian species. It sustains a constant core body temperature in the face of a wide array of environmental thermal conditions and intensity of physical activities that generate internal heat. A primary component of thermoregulatory function is the movement of heat between the body core and the surface via the circulation of blood. The peripheral vasculature acts as a forced convection heat exchanger between blood and local peripheral tissues throughout the body enabling heat to be convected to the skin surface where is may be transferred to and from the environment via conduction, convection, radiation, and/or evaporation of water as local conditions dictate. Humans have evolved a particular vascular structure in glabrous (hairless) skin that is especially well suited for heat exchange. These vessels are called arteriovenous anastomoses (AVAs) and can vasodilate to large diameters and accommodate high flow rates. We report herein a new technology based on a physiological principle that enables simple and safe access to the thermoregulatory control system to allow manipulation of thermoregulatory function. The technology operates by applying a small amount of heating local to control tissue on the body surface overlying the cerebral spine that upregulates AVA perfusion. Under this action, heat exchangers can be applied to glabrous skin, preferably on the palms and soles, to alter the temperature of elevated blood flow prior to its return to the core. Therapeutic and prophylactic applications are discussed.

Cryoprotective agents (CPAs) are routinely used to vitrify, attain an amorphous glass state void of crystallization, and thereby cryopreserve biomaterials. Two vital characteristics of a CPA-loaded system are the critical cooling and warming rates (CCR and CWR), the temperature rates needed to achieve and return from a vitrified state, respectively. Due to the toxicity associated with CPAs, it is often desirable to use the lowest concentrations possible, driving up CWR and making it increasingly difficult to measure. This paper describes a novel method for assessing CWR between the 0.4 × 10 and 10 °C/min in microliter CPA-loaded droplet systems with a new ultrarapid laser calorimetric approach. Cooling was achieved by direct quenching in liquid nitrogen, while warming was achieved by the irradiation of plasmonic gold nanoparticle-loaded vitrified droplets by a high-power 1064 nm millisecond pulsed laser. We assume "apparent" vitrification is achieved provided ice is not visually apparent (i.e., opacity) upon imaging with a camera (CCR) during cooling or highspeed camera (CWR) during warming. Using this approach, we were able to investigate CWRs in single CPA systems such as propylene glycol (PG), glycerol, and Trehalose in water, as well as mixtures of glycerol-trehalose-water and propylene glycol-trehalose-water CPA at low concentrations (20-40 wt %). Further, a phenomenological model for determining the CCRs and CWRs of CPAs was developed which allowed for predictions of CCR or CWR of single component CPA and mixtures (within and outside of the regime their constituents were measured in), providing an avenue for optimizing CCR and CWR and perhaps future CPA cocktail discovery.

Irreversible electroporation (IRE), also referred to as nonthermal pulsed field ablation (PFA), is an attractive focal ablation modality for solid tumors and cardiac tissue due to its ability to destroy aberrant cells with limited disruption of the underlying tissue architecture. Despite its nonthermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested as a potential means to limit thermal damage. However, several variables affect TM performance including the pulsing paradigm, electrode geometry, PCM composition, and chosen active cooling parameters, meaning direct comparisons between approaches are lacking. In this study, we developed a computational model of conventional bipolar and monopolar probes with solid, PCM-filled, or actively cooled cores to simulate clinical IRE treatments in pancreatic tissue. This approach reveals that probes with integrated PCM cores can be tuned to drastically limit thermal damage compared to existing solid probes. Furthermore, actively cooled probes provide additional control over thermal effects within the probe vicinity and can altogether abrogate thermal damage. In practice, such differences in performance must be weighed against the increased time, expense, and effort required for modified probes compared to existing solid probes.

This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study. While uniformly distributed nanoparticles can lead to uniform rewarming, and thereby minimize adverse effects associated with ice crystallization and thermomechanical stress, the combined effects of heart anatomy and nanoparticle loading limitations present practical challenges which this study comes to address. Results of this study demonstrate that under such combined effects, nonuniform nanoparticles warming may lead to a subcritical rewarming rate in some parts of the domain, excessive heating in others, and increased exposure potential to cryoprotective agents (CPAs) toxicity. Nonetheless, the results of this study also demonstrate that computerized planning of the cryopreservation protocol and container design can help mitigate the associated adverse effects, with examples relating to adjusting the CPA and/or nanoparticle concentration, and selecting heart container geometry, and size. In conclusion, nanowarming may provide superior conditions for organ recovery from cryogenic storage under carefully selected conditions, which comes with an elevated complexity of protocol planning and optimization.

Nanoparticles (NPs) are promising agents to absorb external energy and generate heat. Clusters of NPs or NP array heating have found an essential role in several biomedical applications, diagnostic techniques, and chemical catalysis. Various studies have shed light on the heat transfer of nanostructures and greatly advanced our understanding of NP array heating. However, there is a lack of analytical tools and dimensionless parameters to describe the transient heating of NP arrays. Here we demonstrate a comprehensive analysis of the transient NP array heating. Firstly, we develop a set of analytical solutions for the NP array heating and provide a useful mathematical description of the spatial-temporal evolution of temperature for 2D, 3D, and spherical NP array heating. Based on this, we introduce the concept of thermal resolution that quantifies the relationship between minimal heating time, NP array size, energy intensity, and target temperature. Lastly, we define a set of dimensionless parameters that characterize the transition from confined heating to delocalized heating. This study advances the understanding of nanomaterials heating and guides the rational design of innovative approaches for NP array heating.

The purpose of this study is to investigate the effect of partial liquefaction (due to ageing) of the vitreous humor on the transport of ocular drugs. In our model, the gel part of the vitreous is treated as a Darcy-type porous medium. A spherical region within the porous part of vitreous is in a liquid state which, for computational purposes, is also treated as a porous medium but with a much higher permeability. Using the finite element method, a time-dependent, three-dimensional model has been developed to computationally simulate (using the Petrov-Galerkin method) the transport of intravitreally injected macromolecules where both convection and diffusion are present. From a fluid physics and transport phenomena perspective, the results show many interesting features. For pressure-driven flow across the vitreous, the flow streamlines converge into the liquefied region as the flow seeks the fastest path of travel. Furthermore, as expected, with increased level of liquefaction, the overall flow rate increases for a given pressure drop. We have quantified this effect for various geometrical considerations. The flow convergence into the liquefied region has important implication for convective transport. One effect is the clear diversion of the drug as it reaches the liquefied region. In some instances, the entry point of the drug in the retinal region gets slightly shifted due to liquefaction. While the model has many approximations and assumptions, the focus is illustrating the effect of liquefaction as one of the building blocks toward a fully comprehensive model.

Sustained ocular drug delivery systems are necessary for patients needing regular drug therapy since frequent injection is painful, undesirable, and risky. One type of sustained-release systems includes pellets loaded with the drug, encapsulated in a porous shell that can be injected into the vitreous humor. There the released drug diffuses while the physiological flow of water provides the convective transport. The fluid flow within the vitreous is described by Darcy's equations for the analytical model and Brinkman flow for the computational analysis while the drug transport is given by the classical convection-diffusion equation. Since the timescale for the drug depletion is quite large, for the analytical model, we consider the exterior surrounding the capsule to be quasi-steady and the interior is time dependent. In the vitreous, the fluid-flow process is relatively slow, and meaningful results can be obtained for small Peclet number whereby a perturbation analysis is possible. For an isolated capsule, with approximately uniform flow in the far field around it, the mass-transfer problem requires singular perturbation with inner and outer matching. The computational model, besides accommodating the ocular geometry, allows for a fully time-dependent mass-concentration solution and also admits moderate Peclet numbers. As expected, the release rate diminishes with time as the drug depletion lowers the driving potential. The predictive results are sufficient general for a range of capsule permeability values and are useful for the design of the sustained-release microspheres as to the requisite permeability for specific drugs.

In order to measure the effective diffusion coefficient of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the "contour method" and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result. By floating the diffusion coefficient, different theoretical contours were constructed and the least-squares best fit to the experimental contours was performed at each time point to get the best fit solution. The approach generated consistent diffusion coefficient values based on the experiments on four rabbit eyes over a period of 3 h each, which gave , and the corresponding theoretical contours matched well with the experimental contours. The quantitative measurement of concentration using optical coherence tomography and fluorescein labeling gives a new approach for the "noncontact" in vivo drug distribution measurement within vitreous.

Describing the hydrodynamics of nanoparticles in fluid media poses interesting challenges due to the coupling between the Brownian and hydrodynamic forces at the nanoscale. We focus on multiscale formulations of Brownian motion and hydrodynamic interactions (HI) of a single flexible polymeric nanoparticle in confining flows using the Brownian Dynamics method. The nanoparticle is modeled as a self-avoiding freely jointed polymer chain that is subject to Brownian forces, hydrodynamics forces, and repulsive interactions with the confining wall. To accommodate the effect of the wall, the hydrodynamic lift due to the wall is included in the mobility of a bead of the polymer chain which depends on its proximity to the wall. Using the example of a flexible polymeric nanoparticle, we illustrate temporal dynamics pertaining to the colloidal scale as well as the nanoscale.

In relation to intravitreal drug delivery, predictive mathematical models for drug transport are being developed, and to effectively implement these for retinal delivery, the information on biophysical properties of various ocular tissues is fundamentally important. It is therefore necessary to accurately measure the diffusion coefficient of drugs and drug surrogates in the vitreous humor. In this review, we present the studies conducted by various researchers on such measurements over the last several decades. These include imaging techniques (fluorescence and magnetic resonance imaging (MRI)) that make use of introducing a contrast agent or a labeled drug into the vitreous and tracking its diffusive movement at various time points. A predictive model for the same initial conditions when matched with the experimental measurements provides the diffusion coefficient, leading to results for various molecules ranging in size from approximately 0.1 to 160 kDa. For real drugs, the effectiveness of this system depends on the successful labeling of the drugs with suitable contrast agents such as fluorescein and gadolinium or manganese so that fluorescence or MR imagining could be conducted. Besides this technique, some work has been carried out using the diffusion apparatus for measuring permeation of a drug across an excised vitreous body from a donor chamber to the receptor by sampling assays from the chambers at various time intervals. This has the advantage of not requiring labeling but is otherwise more disruptive to the vitreous. Some success with nanoparticles has been achieved using dynamic light scattering (DLS), and presently, radioactive labeling is being explored.

Traditionally, the numerical computation of particle motion in a fluid is resolved through computational fluid dynamics (CFD). However, resolving the motion of nanoparticles poses additional challenges due to the coupling between the Brownian and hydrodynamic forces. Here, we focus on the Brownian motion of a nanoparticle coupled to adhesive interactions and confining-wall-mediated hydrodynamic interactions. We discuss several techniques that are founded on the basis of combining CFD methods with the theory of nonequilibrium statistical mechanics in order to simultaneously conserve thermal equipartition and to show correct hydrodynamic correlations. These include the fluctuating hydrodynamics (FHD) method, the generalized Langevin method, the hybrid method, and the deterministic method. Through the examples discussed, we also show a top-down multiscale progression of temporal dynamics from the colloidal scales to the molecular scales, and the associated fluctuations, hydrodynamic correlations. While the motivation and the examples discussed here pertain to nanoscale fluid dynamics and mass transport, the methodologies presented are rather general and can be easily adopted to applications in convective heat transfer.

Heat stress experienced by firefighters is a common consequence of extreme firefighting activity. In order to avoid the adverse health conditions due to uncompensable heat stress, the prediction and monitoring of the thermal response of firefighters is critical. Tissue properties, among other parameters, are known to vary between individuals and influence the prediction of thermal response. Further, measurement of tissue properties of each firefighter is not practical. Therefore, in this study, we developed a whole body computational model to evaluate the effect of variability (uncertainty) in tissue parameters on the thermal response of a firefighter during firefighting. Modifications were made to an existing human whole body computational model, developed in our lab, for conducting transient thermal analysis for a firefighting scenario. In conjunction with nominal (baseline) tissue parameters obtained from literature, and physiologic conditions from a firefighting drill, the Pennes bioheat and energy balance equations were solved to obtain the core body temperature of a firefighter. Subsequently, the uncertainty in core body temperature due to variability in the tissue parameters (input parameters), metabolic rate, specific heat, density, and thermal conductivity was computed using the sensitivity coefficient method. On comparing the individual effect of tissue parameters on the uncertainty in core body temperature, the metabolic rate had the highest contribution (within ±0.20°C) followed by specific heat (within ±0.10°C), density (within ±0.07°C), and finally thermal conductivity (within ±0.01 °C). A maximum overall uncertainty of ±0.23 °C in the core body temperature was observed due to the combined uncertainty in the tissue parameters. Thus, the model results can be used to effectively predict a realistic range of thermal response of the firefighters during firefighting or similar activities.

Our bodies depend on an exquisitely sensitive and refined temperature control system to maintain a state of health and homeostasis. The exceptionally broad range of physical activities that humans engage in and the diverse array of environmental conditions we face require remarkable strategies and mechanisms for regulating internal and external heat transfer processes. On the occasions for which the body suffers trauma, therapeutic temperature modulation is often the approach of choice for reversing injury and inflammation and launching a cascade of healing. The focus of human thermoregulation is maintenance of the body core temperature within a tight range of values, even as internal rates of energy generation may vary over an order of magnitude, environmental convection, and radiation heat loads may undergo large changes in the absence of any significant personal control, surface insulation may be added or removed, all occurring while the body's internal thermostat follows a diurnal circadian cycle that may be altered by illness and anesthetic agents. An advanced level of understanding of the complex physiological function and control of the human body may be combined with skill in heat transfer analysis and design to develop life-saving and injury-healing medical devices. This paper will describe some of the challenges and conquests the author has experienced related to the practice of heat transfer for maintenance of health and enhancement of healing processes.

The main motivation of conducting this work is to present a rigorous analysis and investigation of the potential effect of the heat pipe adiabatic region on the flow and heat transfer performance of a heat pipe under varying evaporator and condenser conditions. A two-dimensional steady-state model for a cylindrical heat pipe coupling, for both regions, is presented, where the flow of the fluid in the porous structure is described by Darcy-Brinkman-Forchheimer model which accounts for the boundary and inertial effects. The model is solved numerically by using the finite volumes method, and a fortran code was developed to solve the system of equations obtained. The results show that a phase change can occur in the adiabatic region due to temperature gradient created in the porous structure as the heat input increases and the heat pipe boundary conditions change. A recirculation zone may be created at the condenser end section. The effect of the heat transfer rate on the vapor radial velocities and the performance of the heat pipe are discussed.

The flow field and heat transfer of a plane impinging jet on a hot moving wall were investigated using one point closure turbulence model. Computations were carried out by means of a finite volume method. The evolutions of mean velocity components, vorticity, skin friction coefficient, Nusselt number and pressure coefficient are examined in this paper. Two parameters of this type of interaction are considered for a given impinging distance of 8 times the nozzle thickness (H/e = 8): the jet-surface velocity ratio and the jet exit Reynolds number. The flow field structure at a given surface-to-jet velocity ratio is practically independent to the jet exit Reynolds number. A slight modification of the flow field is observed for weak surface-to-jet velocity ratios while the jet is strongly driven for higher velocity ratio. The present results satisfactorily compare to the experimental data available in the literature for R ≤ 1.The purpose of this paper is to investigate this phenomenon for higher R values (0 ≤ R ≤ 4). It follows that the variation of the mean skin friction and the Nusselt number can be correlated according to the surface-to-jet velocity ratios and the Reynolds numbers.

In this paper, the scale effects are specifically addressed by conducting experiments with air flow in different microtubes. Three stainless steel tubes of 962, 308, and 83 m inner diameter (ID) are investigated for friction factor, and the first two are investigated for heat transfer. Viscous heating effects are studied in the laminar as well as turbulent flow regimes by varying the air flow rate. The axial conduction effects in microtubes are experimentally explored for the first time by comparing the heat transfer in SS304 tube with a 910 m ID/2005 m outer diameter nickel tube specifically fabricated using an electrodeposition technique. After carefully accounting for the variable heat losses along the tube length, it is seen that the viscous heating and the axial conduction effects become more important at microscale and the present models are able to predict these effects accurately. It is concluded that neglecting these effects is the main source of discrepancies in the data reported in the earlier literature.

A hybrid scheme based on Markovian fluctuating hydrodynamics of the fluid and a non-Markovian Langevin dynamics with the Ornstein-Uhlenbeck noise perturbing the translational and rotational equations of motion of a nanoparticle is employed to study the thermal motion of a nearly neutrally buoyant nanoparticle in an incompressible Newtonian fluid medium. A direct numerical simulation adopting an arbitrary Lagrangian-Eulerian based finite element method is employed in simulating the thermal motion of the particle suspended in the fluid contained in a cylindrical vessel. The instantaneous flow around the particle and the particle motion are fully resolved. The numerical results show that (a) the calculated temperature of the nearly neutrally buoyant Brownian particle in a quiescent fluid satisfies the equipartition theorem; (b) the translational and rotational decay of the velocity autocorrelation functions result in algebraic tails, over long time; (c) the translational and rotational mean square displacements of the particle obeys Stokes-Einstein and Stokes-Einstein-Debye relations, respectively; and (d) the parallel and perpendicular diffusivities of the particle closer to the wall are consistent with the analytical results, where available. The study has important implications for designing nanocarriers for targeted drug delivery.

A visual and thermal experimental investigation of four oscillating heat pipes (OHPs) was conducted to observe fluid flow of liquid plugs and vapor bubbles in the OHP and its effect on the temperature distribution and heat transfer performance in an OHP. These four OHPs consist of an open loop water OHP, an open loop acetone OHP, a closed loop water OHP, and a closed loop acetone OHP. These copper OHPs were constructed identically with all six turns in the same plane. They were constructed out of 1.65 mm inner diameter copper tubing and copper heat spreading plates in the evaporator and condenser regions. The heat pipes were charged at a filling ratio of about 50%. The results show that the acetone OHP at low power performs better than the water OHP, while at high power the water OHP exceeds the acetone OHP. The experimental results show that both the acetone and water closed loop OHPs had reduced movement in the connecting turn between the two sides. However, in the water closed loop OHP, this prevented circulation altogether. Comparing the water closed loop OHP to the water open loop OHP, their flow patterns were similar. Therefore, improving the flow in this turn should increase the closed loop OHP's performance.

Cryogenic and high-temperature systems often require compact heat exchangers with a high resistance to axial conduction in order to control the heat transfer induced by axial temperature differences. One attractive design for such applications is a perforated plate heat exchanger that utilizes high conductivity perforated plates to provide the stream-to-stream heat transfer and low conductivity spacers to prevent axial conduction between the perforated plates. This paper presents a numerical model of a perforated plate heat exchanger that accounts for axial conduction, external parasitic heat loads, variable fluid and material properties, and conduction to and from the ends of the heat exchanger. The numerical model is validated by experimentally testing several perforated plate heat exchangers that are fabricated using microelectromechanical systems based manufacturing methods. This type of heat exchanger was investigated for potential use in a cryosurgical probe. One of these heat exchangers included perforated plates with integrated platinum resistance thermometers. These plates provided in situ measurements of the internal temperature distribution in addition to the temperature, pressure, and flow rate measured at the inlet and exit ports of the device. The platinum wires were deposited between the fluid passages on the perforated plate and are used to measure the temperature at the interface between the wall material and the flowing fluid. The experimental testing demonstrates the ability of the numerical model to accurately predict both the overall performance and the internal temperature distribution of perforated plate heat exchangers over a range of geometry and operating conditions. The parameters that were varied include the axial length, temperature range, mass flow rate, and working fluid.

This paper quantifies the pool boiling performance of R134a, R1234yf, R513A, and R450A on a flattened, horizontal reentrant cavity surface. The study showed that the boiling performance of R134a on the Turbo-ESP exceeded that of the replacement refrigerants for heat fluxes greater than 20 kWm. On average, the heat flux for R1234yf and R513A was 16 % and 19 % less than that for R134a, respectively, for R134a heat fluxes between 20 kWm and 110 kWm. The heat flux for R450A was on average 57 % less than that of R134a for heat fluxes between 30 kWm and 110 kWm. A model was developed to predict both single-component and multi-component pool boiling of the test refrigerants on the Turbo-ESP surface. The model accounts for viscosity effects on bubble population and uses the Fritz (1935) equation to account for increased vapor production with increasing superheat. Both loss of available superheat and mass transfer resistance effects were modeled for the refrigerant mixtures. For most heat fluxes, the model predicted the measured superheat to within ± 0.31 K.