Substantial increase in perfluorocarbons CF4 (PFC-14) and C2F6 (PFC-116) emissions in China.

The perfluorocarbons tetrafluoromethane (CF4, PFC-14) and hexafluoroethane (C2F6, PFC-116) are potent greenhouse gases with near-permanent atmospheric lifetimes relative to human timescales and global warming potentials thousands of times that of CO2. Using long-term atmospheric observations from a Chinese network and an inverse modeling approach (top-down method), we determined that CF4 emissions in China increased from 4.7 (4.2-5.0, 68% uncertainty interval) Gg y-1 in 2012 to 8.3 (7.7-8.9) Gg y-1 in 2021, and C2F6 emissions in China increased from 0.74 (0.66-0.80) Gg y-1 in 2011 to 1.32 (1.24-1.40) Gg y-1 in 2021, both increasing by approximately 78%. Combined emissions of CF4 and C2F6 in China reached 78 Mt CO2-eq in 2021. The absolute increase in emissions of each substance in China between 2011-2012 and 2017-2020 was similar to (for CF4), or greater than (for C2F6), the respective absolute increase in global emissions over the same period. Substantial CF4 and C2F6 emissions were identified in the less-populated western regions of China, probably due to emissions from the expanding aluminum industry in these resource-intensive regions. It is likely that the aluminum industry dominates CF4 emissions in China, while the aluminum and semiconductor industries both contribute to C2F6 emissions. Based on atmospheric observations, this study validates the emission magnitudes reported in national bottom-up inventories and provides insights into detailed spatial distributions and emission sources beyond what is reported in national bottom-up inventories.

[In searching for perfect blood substitute. Creation and application of perftorane]. / V poiskakh ideal'nogo krovezamenitelya. Sozdanie i primenenie perftorana.

The article is devoted to historiography of perfluorocarbons, as well as discoverers of perftorane and their discoveries. There would be no national priority in transfusiology without these discoveries. Perftorane is the only one of the world series of perfluorocarbon emulsion drugs that has passed all phases of clinical trials. Perftorane has been used in clinical medicine for 30 years.

Research Progress in Oxygen Carrier Design and Application.

Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.

Recent advances in micro-sized oxygen carriers inspired by red blood cells.

Supplementing sufficient oxygen to cells is always challenging in biomedical engineering fields such as tissue engineering. Originating from the concept of a 'blood substitute', nano-sized artificial oxygen carriers (AOCs) have been studied for a long time for the optimization of the oxygen supplementation and improvement of hypoxia environments in vitro and in vivo. When circulating in our bodies, micro-sized human red blood cells (hRBCs) feature a high oxygen capacity, a unique biconcave shape, biomechanical and rheological properties, and low frictional surfaces, making them efficient natural oxygen carriers. Inspired by hRBCs, recent studies have focused on evolving different AOCs into microparticles more feasibly able to achieve desired architectures and morphologies and to obtain the corresponding advantages. Recent micro-sized AOCs have been developed into additional categories based on their principal oxygen-carrying or oxygen-releasing materials. Various biomaterials such as lipids, proteins, and polymers have also been used to prepare oxygen carriers owing to their rapid oxygen transfer, high oxygen capacity, excellent colloidal stability, biocompatibility, suitable biodegradability, and long storage. In this review, we concentrated on the fabrication techniques, applied biomaterials, and design considerations of micro-sized AOCs to illustrate the advances in their performances. We also compared certain recent micro-sized AOCs with hRBCs where applicable and appropriate. Furthermore, we discussed existing and potential applications of different types of micro-sized AOCs.

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia.

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.

[Fucoidan-Modified Phase-Transitional Contrast Agent for Ultrasound Imaging and Targeting of Hepatoma Cells].

Objective: To prepare a fucoidan-modified phase-transitional contrast agent (FPCA) and to evaluate its in vitro capabilities for ultrasound imaging and targeting of hepatoma cells. Methods: Nano-liposomes encapsulated with perfluoropentane were prepared using thin-film hydration and ultrasonic emulsification methods. Then, FPCA nanoparticles were prepared through chemical grafting of fucoidan and the characterization of their physical and chemical properties was performed. After applying external stimuli of heating with hot water bath and microwave irradiation, the phase-transition status of FPCA was observed with microscope. The imaging abilities of phase-transited FPCA on two-dimensional ultrasound and contrast-enhanced ultrasound were observed with ultrasonic diagnostic instrument. The ability of FPCA to target at hepatoma cells was evaluated and verified with fluorescence confocal observation and flow cytometry analysis. Results: The FPCA prepared in the study had an average diameter of (222.1±32.5) nm, displaying spherical appearance, good dispersion, good stability, and good biocompatibility. The phase-transition of FPCA was induced by both heating with hot water bath and microwave irradiation. For phase transition, the optimal temperature was found to be 50 ℃ and the preferred microwave power was 1.5 W/cm 2. Moreover, after phase transition, FPCA showed significant imaging enhancement on both two-dimensional ultrasonography and contrast-enhanced ultrasonography. Through fluorescein isothiocyanate (FITC) labeling, FPCA could specifically bind with hepatoma cells at a high binding rate of (96.19±1.62)%, while it rarely bound with normal liver cells, showing a binding rate of less than 10%. Conclusion: A new type of phase-transitional ultrasound contrast agent with good stability and biocompatibility was successfully prepared. It not only could enhance ultrasound imaging through phase transition, but also had specific active hepatoma cell-targeting properties.

Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry.

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (Kd) for each compound were calculated using regression analysis of the dose-dependent changes in HSA melting temperature. Estimated Kd values for HSA binding of octanoic acid, decanoic acid, hexadecenoic acid, ibuprofen, and warfarin agreed with established values. The binding affinities for 24 PFAS that included perfluoroalkyl carboxylic acids (C4-C12), perfluoroalkyl sulfonic acids (C4-C8), mono- and polyether perfluoroalkyl ether acids, and polyfluoroalkyl fluorotelomer substances were determined. These results demonstrate the utility of this differential scanning fluorimetry assay as a rapid high-throughput approach for determining the relative protein-binding properties and identification of chemical structures involved in binding for large numbers of structurally diverse PFAS.

The effect of the perfluorocarbon emulsion Oxycyte™ in an ovine model of severe decompression illness.

Background: The treatment of decompression sickness (DCS) with hyperbaric oxygen (HBO2) serves to decrease intravascular bubble size, increase oxygen (O2) delivery to tissue and enhance the elimination of inert gas. Emulsified perfluorocarbons (PFC) combined with breathing O2 have been shown to have similar effects animal models. We studied an ovine model of severe DCS treated with the intravenous PFC Oxycyte™ while breathing O2 compared to saline control also breathing O2. Methods: Juvenile male sheep (N=67; weight 24.4±2.10kg) were compressed to 257 feet of sea water (fsw) in our multiple large-animal chamber where they remained under pressure for 31 minutes. Animals then were decompressed to surface pressure and randomized to receive either Oxycyte at 5mL/kg intravenously (IV) or 5mL/kg saline IV (both receiving 100% O2) 10 minutes after reaching surface pressure. Mortality was recorded at two hours, four hours, and 24 hours after receiving the study drug. Surviving animals underwent perfusion fixation and harvesting of the spinal cord at 24 hours. Spinal cord sections were assessed for volume of lesion area and compared. Results: There was no significant difference in survival at two hours (p=0.2737), four hours (p=0.2101), or 24 hours (p=0.3171). Paralysis at 24 hours was not significantly different. However, spinal cord lesion area was significantly smaller in the Oxycyte group as compared to the saline group, with median spinal cord lesion areas 0.65% vs. 0.94% (p=0.0107). Conclusion: In this ovine model of severe DCS the intravenous PFC Oxycyte did not reduce mortality but did ameliorate spinal cord injury when used after the onset of DCS.

Perfluorocarbons in Chemical Biology.

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and 19 F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.

Reducing exposure to high levels of perfluorinated compounds in drinking water improves reproductive outcomes: evidence from an intervention in Minnesota.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) have been detected in drinking water supplies around the world and are the subject of intense regulatory debate. While they have been associated with several illnesses, their effects on reproductive outcomes remains uncertain. METHODS: We analyzed birth outcomes in the east Minneapolis-St. Paul metropolitan area from 2002 to 2011, where a portion of the population faced elevated exposure to PFASs due to long-term contamination of drinking water supplies from industrial waste disposal. Installation of a water filtration facility in the highly contaminated city of Oakdale, MN at the end of 2006 resulted in a sharp decrease in exposure to PFASs, creating a "natural experiment". Using a difference-in-differences approach, we compare the changes in birth outcomes before and after water filtration in Oakdale to the changes over the same period in neighboring communities where the treatment of municipal water remained constant. RESULTS: Average birth weight and average gestational age were statistically significantly lower in the highly exposed population than in the control area prior to filtration of municipal water supply. The highly exposed population faced increased odds of low birth weight (adjusted odds ratio 1.36, 95% CI 1.25-1.48) and pre-term birth (adjusted odds ratio 1.14, 95% CI 1.09-1.19) relative to the control before filtration, and these differences moderated after filtration. The general fertility rate was also significantly lower in the exposed population (incidence rate ratio 0.73, 95% CI 0.69-0.77) prior to filtration and appeared to be rebounding post-2006. CONCLUSIONS: Our findings provide evidence of a causal relationship between filtration of drinking water containing high levels of exposure to PFASs and improved reproductive outcomes.

A Bis-Acridinium Macrocycle as Multi-Responsive Receptor and Selective Phase-Transfer Agent of Perylene.

A bis-acridinium cyclophane incorporating switchable acridinium moieties linked by a 3,5-dipyridylanisole spacer was studied as a multi-responsive host for polycyclic aromatic hydrocarbon guests. Complexation of perylene was shown to be the most effective and was characterized in particular by a charge-transfer band as signal output. Effective catch and release of the guest was triggered by both chemical (proton/hydroxide) and redox stimuli. Moreover, the dicationic host was also easily switched between organic and perfluorocarbon phases for applications related to the enrichment of perylene from a mixture of polycyclic aromatic hydrocarbons.

Multicore Liquid Perfluorocarbon-Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking.

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core-shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging.

Dissociation of 19F and fluorescence signal upon cellular uptake of dual-contrast perfluorocarbon nanoemulsions.

OBJECTIVE: Perfluorocarbon nanoemulsions (PFCs) tagged with fluorescence dyes have been intensively used to confirm the in vivo 19F magnetic resonance imaging (MRI) localization of PFCs by post mortem histology or flow cytometry. However, only limited data are available on tagged PFCs and the potential dissociation of fluorescence and 19F label after cellular uptake over time. MATERIALS AND METHODS: PFCs were coupled to rhodamine (Rho) or carboxyfluorescein (Cfl) and their fate was analyzed after in vitro uptake by J774, RAW and CHO cells by flow cytometry and 19F MRI. In separate in vivo experiments, the dual-labelled emulsions were intravenously applied into mice and their distribution was monitored in spleen and liver over 24 h. In a final step, time course of fluorescence and 19F signals from injected emulsions were tracked in a local inflammation model making use of a subcutaneous matrigel depot doped with LPS (lipopolysaccharide). RESULTS: Internalization of fluorescence-labelled PFCs was associated with a substantial whitening over 24 h in all macrophage cell lines while the 19F signal remained stable over time. In all experiments, CflPFCs were more susceptible to bleaching than RhoPFCs. After intravenous injection of RhoPFCs, the fluorescence signal in spleen and liver peaked after 30 min and 2 h, respectively, followed by a successive decrease over 24 h, whereas the 19F signal continuously increased during this observation period. Similar results were found in the matrigel/LPS model, where we observed increasing 19F signals in the inflammatory hot spot over time while the fluorescence signal of immune cells isolated from the matrigel depot 24 h after its implantation was only marginally elevated over background levels. This resulted in a massive underestimation of the true PFC deposition in the reticuloendothelial system and at inflammatory hot spots. CONCLUSION: Cellular uptake of fluorescently tagged PFCs leads to a dissociation of the fluorescence and the 19F label signal over time, which critically impacts on interpretation of long-term experiments validated by histology or flow cytometry.

In vivo 19F MR inflammation imaging after myocardial infarction in a large animal model at 3 T.

OBJECTIVES: Fluorine-19 (19F) MRI with intravenously applied perfluorocarbons allows the in vivo monitoring of infiltrating immune cells as demonstrated in small animal models at high field. Here, we aimed to transfer this approach to a clinical scanner for detection of inflammatory processes in the heart after acute myocardial infarction (AMI) in a large animal model. MATERIALS AND METHODS: Optimization of coil and sequence performance was carried out on phantoms and in vivo at a 3 T Philips Achieva. AMI was induced in Munich mini pigs by 90-min occlusion of the left anterior descending artery. At day 3 after AMI, pigs received a body weight-adjusted intravenous dose of a perfluorooctyl bromide nanoemulsion followed by 1H/19F MRI at day 6 after AMI. RESULTS: A balanced steady-state free precession turbo gradient echo sequence using an ellipsoidal 19F/1H surface coil provided the best signal-to-noise ratio and a superior localization of 19F patterns in vivo. This approach allowed the reliable detection of 19F signals in the injured myocardium within less than 20 min. The 19F signal magnitude correlated significantly with the functional impairment after AMI. CONCLUSION: This study demonstrates the feasibility of in vivo 19F MR inflammation imaging after AMI at 3 T within a clinically acceptable acquisition time.

Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice.

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.

Cardiovascular Sonothrombolysis.

PURPOSE OF REVIEW: This review will provide recent pre-clinical and initial clinical trials exploring the efficacy of sonothrombolysis as an adjunct to current emergent therapies in acute coronary syndromes. RECENT FINDINGS: The initial clinical trials examining the efficacy of short pulse duration diagnostic ultrasound (DUS) high mechanical index impulses in patients with ST segment elevation myocardial infarction (STEMI) have demonstrated that there is improved patency of the infarct vessel, and improved microvascular flow following percutaneous coronary intervention. Subsequent randomized prospective trials have confirmed that in patients with acute STEMI receiving an intravenous microbubble infusion, diagnostic high mechanical index impulses applied in the apical windows pre- and post-percutaneous coronary intervention have reduced myocardial infarction size, as assessed by magnetic resonance imaging at 72 h following presentation, and have been associated with better left ventricular systolic function at 6 month follow-up. Sonothrombolysis has potential for improving early epicardial coronary artery patency and reduce left ventricular remodeling when added to current interventional strategies in STEMI.

Phagocytosis of a PFOB-Nanoemulsion for 19F Magnetic Resonance Imaging: First Results in Monocytes of Patients with Stable Coronary Artery Disease and ST-Elevation Myocardial Infarction.

Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorooctyl bromide-nanoemulsions (PFOB-NE) has proven its feasibility to visualize inflammatory processes in experimental disease models. This approach is based on the properties of monocytes/macrophages to ingest PFOB-NE particles enabling specific cell tracking in vivo. However, information on safety (cellular function and viability), mechanism of ingestion and impact of specific disease environment on PFOB-NE uptake is lacking. This information is, however, crucial for the interpretation of 19F MRI signals and a possible translation to clinical application. To address these issues, whole blood samples were collected from patients with acute ST-elevation myocardial infarction (STEMI), stable coronary artery disease (SCAD) and healthy volunteers. Samples were exposed to fluorescently-labeled PFOB-NE and particle uptake, cell viability and migration activity was evaluated by flow cytometry and MRI. We were able to show that PFOB-NE is ingested by human monocytes in a time- and subset-dependent manner via active phagocytosis. Monocyte function (migration, phagocytosis) and viability was maintained after PFOB-NE uptake. Monocytes of STEMI and SCAD patients did not differ in their maximal PFOB-NE uptake compared to healthy controls. In sum, our study provides further evidence for a safe translation of PFOB-NE for imaging purposes in humans.

Multiple linear regression applied to predicting droplet size of complex perfluorocarbon nanoemulsions for biomedical applications.

Multiple linear regression (MLR) modeling as a novel methodological advancement for design, development, and optimization of perfluorocarbon nanoemulsions (PFC NEs) is presented. The goal of the presented work is to develop MLR methods applicable to design, development, and optimization of PFC NEs in broad range of biomedical uses. Depending on the intended use of PFC NEs as either therapeutics or diagnostics, NE composition differs in respect to specific applications (e.g. magnetic resonance imaging, drug delivery, etc). PFC NE composition can significantly impact on PFC NE droplet size which impacts the NE performance and quality. We demonstrated earlier that microfluidization combined with sonication produces stable emulsions with high level of reproducibility. The goal of the presented work was to establish correlation between droplet size and composition in complex PFC-in-oil-in-water NEs while manufacturing process parameters are kept constant. Under these conditions, we demonstrate that MLR model can predict droplet size based on formulation variables such as amount and type of PFC oil and hydrocarbon oil. To the best of our knowledge, this is the first report where PFC NE composition was directly related to its colloidal properties and MLR used to predict colloidal properties from composition variables.

Multimodal assessment of orbital immune cell infiltration and tissue remodeling during development of graves disease by 1 H19 F MRI.

PURPOSE: To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling. METHODS: To this end, we utilized a murine model of GO induced by immunization with a human thyroid-stimulating hormone receptor A-subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl) immunized with ß-galactasidose plasmid. From these, 17 GO and 12 Ctrl mice were subjected to multimodal MRI at 9.4T, whereas 23 mice only underwent histology. Beyond anatomical hydrogen-1 (1 H) MRI, we employed transverse relaxation time (T2 ) mapping for visualization of edema, chemical exchange saturation transfer (CEST) for detection of hyaluronan, and fluorine-19 (19 F) MRI for tracking of in situ-labeled immune cells after intravenous injection of perfluorcarbons (PFCs). RESULTS: 1 H/19 F MRI demonstrated substantial infiltration of PFC-loaded immune cells in peri and retro-orbital regions of GO mice, whereas healthy Ctrls showed only minor 19 F signals. In parallel, T2 mapping indicated onset of edema in periorbital tissue and adjacent ocular glands (P = 0.038/0.017), which were associated with enhanced orbital CEST signals in GO mice (P = 0.031). Concomitantly, a moderate expansion of retrobulbar fat (P = 0.029) was apparent; however, no signs for extraocular myopathy were detectable. 19 F MRI-based visualization of orbital inflammation exhibited the highest significance level to discriminate between GO and Ctrl mice (P = 0.006) and showed the best correlation with the clinical score (P = 0.0007). CONCLUSION: The present approach permits the comprehensive characterization of orbital tissue and holds the potential for accurate GO diagnosis in the clinical setting. Magn Reson Med 80:711-718, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

A versatile and robust microfluidic device for capillary-sized simple or multiple emulsions production.

Ultrasound-vaporizable microdroplets can be exploited for targeted drug delivery. However, it requires customized microfluidic techniques able to produce monodisperse, capillary-sized and biocompatible multiple emulsions. Recent development of microfluidic devices led to the optimization of microdroplet production with high yields, low polydispersity and well-defined diameters. So far, only few were shown to be efficient for simple droplets or multiple emulsions production below 5 µm in diameter, which is required to prevent microembolism after intravenous injection. Here, we present a versatile microchip for both simple and multiple emulsion production. This parallelized system based on microchannel emulsification was designed to produce perfluorocarbon in water or water within perfluorocarbon in water emulsions with capillary sizes (<5 µm) and polydispersity index down to 5% for in vivo applications such as spatiotemporally-triggered drug delivery using Ultrasound. We show that droplet production at this scale is mainly controlled by interfacial tension forces, how capillary and viscosity ratios influence droplet characteristics and how different production regimes may take place. The better understanding of droplet formation and its relation to applied pressures is supported by observations with a high-speed camera. Compared to previous microchips, this device opens perspectives to produce injectable and biocompatible droplets with a reasonable yield in order to realize preclinical studies in mice.