Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve ...efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.
Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized ...that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. Serial in vivo cineCT imaging provided data in hearts from control pigs (n = 3) and data from pigs (n = 5) under baseline conditions before MI induction, post-MI day 3, post-MI day 7, and one hour after intramyocardial delivery of a hyaluronic acid (HA)-based hydrogel with shear-thinning and self-healing properties to the central infarct area. Isolated, excised hearts underwent similar cineCT imaging using an ex vivo perfused heart preparation with cyclic LV pressurization. Deformations were evaluated using nonlinear image registration of cineCT volumes between end-diastole (ED) and end-systole (ES), and 3D Lagrangian strains were calculated from the displacement gradients. Post-MI day 3, radial, circumferential, maximum principal, and shear strains were reduced within the MI region (p < 0.04) but were unchanged in normal regions (p > 0.6), and LV end diastolic volume (LV EDV) increased (p = 0.004), while ejection fraction (EF) and stroke volume (SV) decreased (p < 0.02). Post-MI day 7, radial strains in MI border zones increased (p = 0.04) and dilation of LV EDV continued (p = 0.052). There was a significant negative linear correlation between regional radial and maximum principal/shear strains and percent infarcted tissue in all hearts (R2 > 0.47, p < 0.004), indicating that cineCT strain measures could predict MI location and degree of injury. Post-hydrogel day 7 post-MI, LV EDV was significantly reduced (p = 0.009), EF increased (p = 0.048), and radial (p = 0.021), maximum principal (p = 0.051), and shear strain (p = 0.047) increased within regions bordering the infarct. A smaller strain improvement within the infarct and normal regions was also noted on average along with an improvement in SV in 4 out of 5 hearts. CineCT provides a reliable method to assess regional changes in strains post-MI and the therapeutic effects of intramyocardial hydrogel delivery.
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•Developed novel platform to assess left ventricle deformation in vivo and ex vivo.•Local cardiac strains decreased progressively over 7 days in infarcted regions.•Measured linear correlation between local degree of infarction and strain.•Hydrogel injection improved strain in regions bordering the infarct.•Hydrogel injection resulted in less ventricle dilation and larger ejection fraction.
Hydrogen storage is essential in hydrogen value chains and subsurface storage may be the most suitable large-scale option. This paper reports numerical simulations of seasonal hydrogen storage in the ...Norne hydrocarbon field, offshore Norway. Three different storage schemes are examined by injecting pure hydrogen into the gas-, oil-, and water zones. Implementation of four annual withdrawal-injection cycles followed by one prolonged withdrawal period show that the thin gas zone is a preferred target with a final hydrogen recovery factor of 87%. The hydrogen distribution in the subsurface follow the geological structures and is restricted by fluid saturation and displacement efficiencies. Case studies show that the pre-injection of formation gas as a cushion gas efficiently increases the ultimate hydrogen recovery, but at the cost of hydrogen purity. The injection of 30% hydrogen-formation gas mixture results in a varying hydrogen fraction in the withdrawn gas. An alternative well placement down the dipping structure shows lower storage efficiency.
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•Long-term and large-scale hydrogen storage is examined in a depleted oil and gas field.•A real full-field simulation model with site-specific parameters was used.•Preferred targets for seasonal hydrogen withdrawal were identified.•Effect of the cushion gas nature, its composition and structural geometry were assessed.
•Microfluidics used to observe pore-scale hydrogen flow.•Hydrogen displacement and trapping mechanisms.•Quantification of pore-scale hydrogen dissolution kinetics.•Measurements of static and dynamic ...contact angles and hysteresis.
Underground hydrogen storage (UHS) has been launched as a catalyst to the low-carbon energy transitions. The limited understanding of the subsurface processes is a major obstacle for rapid and widespread UHS implementation. We use microfluidics to experimentally describe pore-scale multiphase hydrogen flow in an aquifer storage scenario. In a series of drainage-imbibition experiments we report the effect of capillary number on hydrogen saturations, displacement/trapping mechanisms, dissolution kinetics and contact angle hysteresis. We find that the hydrogen saturation after injection (drainage) increases with increasing capillary number. During hydrogen withdrawal (imbibition) two distinct mechanisms control the displacement and residual trapping – I1 and I2 imbibition mechanisms, respectively. Local hydrogen dissolution kinetics show dependency on injection rate and hydrogen cluster size. Dissolved global hydrogen concentration corresponds up to 28% of reported hydrogen solubility, indicating pore-scale non-equilibrium dissolution. Contact angles show hysteresis and vary between 17 and 56° Our results provide key UHS experimental data to improve understanding of hydrogen multiphase flow behaviour.
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Implementation of the hydrogen economy for emission reduction will require storage facilities, and underground hydrogen storage (UHS) in porous media offers a readily available large‐scale option. ...Lack of studies on multiphase hydrogen flow in porous media is one of the several barriers for accurate predictions of UHS. This paper reports, for the first time, measurements of hysteresis in hydrogen‐water relative permeability in a sandstone core under shallow storage conditions. We use the steady state technique to measure primary drainage, imbibition and secondary drainage relative permeabilities, and extend laboratory measurements with numerical history matching and capillary pressure measurements to cover the whole mobile saturation range. We observe that gas and water relative permeabilities show strong hysteresis, and nitrogen as substitute for hydrogen in laboratory assessments should be used with care. Our results serve as calibrated input to field scale numerical modeling of hydrogen injection and withdrawal processes during porous media UHS.
Plain Language Summary
Hydrogen storage facilities will need a ramp‐up when the hydrogen share in the future energy mix increase. Large‐scale hydrogen storage can be implemented in empty hydrocarbon fields or ground water reservoirs. Hydrogen storage in such media involve complex interactions with native rocks and fluids, and injection and withdrawal are typically described by flow functions. Relative permeability is one of the key flow functions that describe how easily hydrogen can flow through porous media in the presence of other fluids. In underground storage, hydrogen is cyclically injected and withdrawn multiple times, and its relative permeability may differ between these two processes, described as hysteresis. In this paper, we investigate hydrogen relative permeability in the laboratory and match with results from numerical simulations. We find that hydrogen relative permeability is different for injection and withdrawal and is also different from that of nitrogen. Our results are directly applicable in computer simulators that predict hydrogen storage efficiency.
Key Points
Steady state measurements of hydrogen‐water relative permeability
Numerical history matching needed for extrapolation
Strong hysteresis observed between drainage and imbibition
In this paper, we report the growth pattern and the rate of CH4 hydrate in sandstone pores. A high-pressure, water-wet, transparent micromodel with pores resembling a sandstone rock was used to ...visualize CH4 hydrate formation at reservoir conditions (P = 35–115 bar and T = 0.1–4.9 °C). The CH4 hydrate preferably formed and grew along the gas–water interface until the gas phase was completely encapsulated by a hydrate film. Two different growth rates were identified on the gas–water interface: CH4 hydrate film growth along the vertical pore walls (∼1200 μm/s) was more than 100 times faster than the film growth toward the pore center (∼8 μm/s). CH4 hydrate crystal growth directly in the water phase was slow and the rate was less than 0.5 μm/s. The film growth rate along the gas–water interface was independent of the pore size, gas saturation, and gas distribution, but the pore wall growth rate displayed a power law dependency on the applied subcooling temperature, ΔT, with a power law exponent equal to 2. The results of this study can be used as input to numerical models aiming to simulate pore-scale CH4 hydrate growth behavior.
Long-term and large-scale H2 storage is vital for a sustainable H2 economy. Research in underground H2 storage (UHS) in porous media is emerging, but the understanding of H2 reconnection and recovery ...mechanisms under cyclic loading is not yet adequate. This paper reports a qualitative and quantitative investigation of H2 reconnection and recovery mechanisms in repeated injection-withdrawal cycles. Here we use microfluidics to experimentally investigate up to 5 cycles of H2 injection and withdrawal under a range of injection rates at shallow reservoir storage conditions. We find that H2 storage capacities increase with increasing injection rate and range between ∼10% and 60%. The residual H2 saturation is in the same range between cycles (30–40%), but its distribution in the pore space visually appears to be hysteretic. In most cases, the residually trapped H2 reconnects in the subsequent injection cycle, predominantly in proximity to the large pore clusters. Our results provide valuable experimental data to advance the understanding of multiple H2 injection cycles in UHS schemes.
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•Microfluidics for examination of cyclic hydrogen injections.•Microscopic hydrogen storage capacities up to 60% of the pore space.•Reproducible residual hydrogen saturation between the injection cycles.•Efficient reconnection of residually trapped hydrogen in the next drainage cycle.
Underground hydrogen storage (UHS) in porous media is proposed to balance seasonal fluctuations between demand and supply in an emerging hydrogen economy. Despite increasing focus on the topic ...worldwide, the understanding of hydrogen flow in porous media is still not adequate. In particular, relative permeability hysteresis and its impact on the storage performance require detailed investigations due to the cyclic nature of H2 injection and withdrawal. We focus our analysis on reservoir simulation of an offshore aquifer setting, where we use history matched relative permeability to study the effect of hysteresis and gas type on the storage efficiency. We find that omission of relative permeability hysteresis overestimates the annual working gas capacity by 34 % and the recovered hydrogen volume by 85 %. The UHS performance is similar to natural gas storage when using hysteretic hydrogen relative permeability. Nitrogen relative permeability can be used to model the UHS when hysteresis is ignored, but at the cost of the accuracy of the bottom-hole pressure predictions. Our results advance the understanding of the UHS reservoir modeling approaches.
•Reservoir simulation for investigation of aquifer hydrogen storage.•Measured and history matched relative permeability input including hysteresis.•Nonhysteretic relative permeability significantly overestimates storage efficiency.•Nitrogen relative permeability can be used as proxy for hydrogen.•Hydrogen exhibits similar performance as natural gas storage.
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