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Droplet-based microfluidics is leading the development of miniaturized, rapid, and sensitive version of enzyme-linked immunosorbent assays (ELISAs), a central method for protein detection. These assays involve the use of a functionalized surface able to selectively capture the desired analyte. Using the droplet’s oil water interface as a capture surface requires designing custom-perfluorinated fluorosurfactants bearing azide-containing polar groups, which spontaneously react when forming the droplet with strain-alkyne-functionalized antibodies solubilized in the aqueous phase. In this article, we present our research on the influence of the structure of surfactant’s hydrophilic heads on the efficiency of SPAAC functionalization and on the effect of this antibody grafting process on droplet stability. We have shown that while short linkers lead to high grafting efficiency, long linkers lead to high stability, and that an intermediate size is required to balance both parameters. In the described family of surfactants, the optimal structure proved to be a PEG4linker connecting a polar di-azide head and a per-fluoropolyether tail (Krytox). We also found that grafting an increasing amount of antibody, thus increasing interface coverage, increases droplet stability. It thus appears that such a bi-partite system with a reactive fluoro-surfactant in the oil phase and reactive antibody counterpart in the aqueous phase gives access in situ to novel surfactant construct providing unexplored interface structures and droplet functionality.

The oscillation of shelled microbubbles during exposure to ultrasound is influenced by the mechanical properties of the shell components. The oscillation behavior of bubbles coated with various phospholipids and other amphiphiles has been studied. However, there have been few investigations of how the adsorption conditions of the shell molecules relate to the viscoelastic properties of the shell and influence the oscillation behavior of the bubbles. In the present study, we investigated the oscillation characteristics of microbubbles coated with a poloxamer surfactant, that is, Pluronic F-68, at several concentrations after the adsorption kinetics of the surfactant at the gas–water interface had reached equilibrium. The dilatational viscoelasticity of the shell during exposure to ultrasound was analyzed in the frequency domain from the attenuation characteristics of the acoustic pulses propagated in the bubble suspension. At Pluronic F-68 concentrations lower than 2.0 × 10–2mol L–1, the attenuation characteristics typically exhibited a sharp peak. At concentrations higher than 2.0 × 10–2mol L–1, the peak flattened. The dilatational elasticity and viscosity of the shell were estimated by fitting the theoretical model to the experimental values, which revealed that both the elasticity and viscosity increased markedly at approximately 2.0 × 10–2mol L–1. This suggests that the adsorption properties of Pluronic F-68 strongly affect the oscillation characteristics of microbubbles of a size suitable for medical ultrasound diagnostics.

Graphene oxide (GO), single-walled carbon nanohorn (CNHox), and nitrogen-doped CNH (N-CNH) were functionalized with fluorinated poly(ethylene glycol) (F-PEG) and/or with a fluorinated dendrimer (F-DEN) to prepare a series of assembled nanocomposites (GO/F-PEG, CNHox/F-PEG, N-CNH/F-PEG, N-CNH/F-DEN, and N-CNH/F-DEN/F-PEG) that provide effective multisite O2reservoirs. In all cases, the O2uptake increased with time and saturated after 10–20 min. When graphitic carbons (GO and CNHox) were coated with F-PEG, the O2uptake doubled. The O2loading was slightly higher in N-CNH compared to CNHox. Notably, coating N-CNH with F-DEN or F-PEG, or with both F-DEN and F-PEG, was more effective. The best performance was obtained with the N-CNH/F-DEN/F-PEG nanocomposite. The O2uptake kinetics and mechanisms were analyzed in terms of the Langmuir adsorption equation based on a multibinding site assumption. This allowed the precise determination of multiple oxygen binding sites, including on the graphitic structure and in the dendrimer, F-DEN, and F-PEG. After an initial rapid, relatively limited release, the amount of O2trapped in the nanomaterials remained high (>95%). This amount was marginally lower for the functionalized composites, but the oxygen stored was reserved for longer times. Finally, it is shown that these systems can generate singlet oxygen after irradiation by a light-emitting diode, and this production correlates with the amount of O2loaded. Thus, it was anticipated that the present nanocomposites hierarchically assembled from components with different characters and complementary affinities for oxygen can be useful as O2reservoirs for singlet oxygen generation to kill bacteria and viruses and to perform photodynamic therapy.

Semifluorinated alkanes self-assemble into 30–40 nm-large surface domains (hemimicelles) at the air/water interface. They have been drawing increasing attention to stabilize microbubbles coated with lipids, which are used for enhancing the contrast in sonographic imaging. Although previous studies suggested that semifluorinated alkanes increase the stability of phospholipid membranes, little is known about how semifluorinated alkanes influence phase behaviors and mechanical properties of lipid-coated microbubbles. As a well-defined model of microbubble surfaces, we prepared monolayers consisting of a mixture of phospholipids and semifluorinated alkanes at the air/water interface and investigated the influence of hemimicelles of semifluorinated alkanes on the phase behavior and interfacial viscoelastic properties of phospholipid monolayers. Hemimicelles are phase-separated from phospholipids and accumulate at the phase boundary, which strongly modulates the correlation between solid phospholipid domains. Intringuingly, we found that the mixed monolayer of semifluorinated alkanes and phospholipids possesses linear and nonlinear viscoelastic properties comparable to those of phospholipid monolayers. Since the mixing of semifluorinated alkanes and phospholipids enables one to overcome the intrinsically low stability of pure semifluorinated alkanes against the change in the surface area of microbubbles through the partial dissolution of gas into the aqueous phase, this is a promising strategy for the stable coating of microbubbles in ultrasound diagnosis.

The thermal behavior and phase structure of two series of gemini fluorocarbon/hydrocarbon diblock amphiphiles with the general formula (CnF2n+1CH2)(Cm– 2H2m– 3)CH–CH(CnF2n+1CH2)(Cm– 2H2m– 3), with n= 8, 10 and m= 6, 12, 14, 16, 18, 20 (abbreviated as di(FnHm)), have been investigated by differential scanning calorimetry, polarized optical and freeze–fracture transmission electron microscopies, dilatometry, and small-angle X-ray scattering (SAXS). The various terms of the series exhibit the same thermal behavior, essentially composed of two exothermal transitions, a low-temperature event that corresponds to the melting of the hydrocarbon chains at THand a high-temperature transition associated with the melting of the fluorocarbon chains at TF. Below TH, a disordered plastic rotator phase, MLT, and above TH,a lamellar phase, MHT, were determined by SAXS experiments. Above TF, the compounds eventually clear into the isotropic liquid. In the MHTphase, both the Fnand Hmblocks are segregated from each other, forming sublayers with sharp interfaces, as revealed by the five lamellar orders and remarkable sharpness of the SAXS peaks. In the MLTphase, the partial crystallization of the aliphatic blocks when the temperature is lowered leads to the disruption of the aliphatic sublayers into rows of ribbons arranged according to pseudohexagonal and/or rectangular arrangements with different lattice sizes (p2ggsymmetry). The Fnsegments form the fluorinated continuum. In support of SAXS, molecular packing models of the tetrablocks are proposed on the basis of the temperature/volume variations of di(F10H20) and di(F10H16) in both high- and low-temperature phases, as determined by dilatometry. It is notable that the arrangements found for di(FnHm) are completely different from those previously reported for FnHmdiblocks, revealing the influence of the linker unit on the solid-state behavior of the tetrablocks.

Microbubbles shelled with soft materials are expected to find applications as ultrasound-sensitive drug delivery systems, including through sonoporation. Microbubbles with specific vibrational characteristics and long intravascular persistence are required for clinical uses. To achieve this aim, the kinetics of the microbubble shell components at the gas/liquid interface while being subjected to ultrasound need to be better understood. This paper investigates the vibration characteristics and lifetime of single microbubbles coated with a poloxamer surfactant, Pluronic F-68, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) under ultrasound irradiation. Air- and perfluorohexane (PFH)-filled microbubbles coated with Pluronic F-68 and DMPC at several concentrations (0 to 10–2mol L–1) were produced. An optical measurement system using a laser Doppler vibrometer and microscope was used to observe the radial vibration mode of single microbubbles. The vibrational displacement amplitude and resonance radius of Pluronic- or DMPC-coated microbubbles were found to depend very little on the concentrations. The resonance radius was around 65 μm at 38.8 kHz under all the experimental conditions investigated. The lifetime of the microbubbles was investigated simultaneously by measuring their temporal change in volume, and it was increased with Pluronic concentration. Remarkably, the oscillation amplitude of the bubble has an effect on the bubble lifetime. In other words, larger oscillation under the resonance condition accelerates the diffusion of the inner gas.

Microbubbles have potential for applications as drug and gene delivery systems, in which the release of a substance is triggered by an ultrasonic pulse. In this paper, we discuss the adsorption and desorption of a film of phospholipid on the surface of a single microbubble under ultrasound irradiation. Our optical observation system consisted of a high-speed camera, a laser Doppler vibrometer, and an ultrasound cell; 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) was used as the surfactant. The adsorption of the DMPC molecules onto the surface of the bubble was evaluated by measuring the contact angle between the bubble and a glass plate. A decrease of the contact angle of the bubble indicates desorption of the DMPC molecules from the bubble surface into the surrounding aqueous solution. The amount of DMPC molecules adsorbed on the bubble’s surface is shown to decrease over time after bubble generation. The type and intensity of the pulsed ultrasound waves were varied so as to mimic ultrasound-triggered drug release. Increasing the number of cycles and the amplitude of the sound pressure of the pulsed ultrasound yielded a greater increase of the contact angle. We also measured the radial vibrations of the microbubbles in the ultrasound field. The vibrational characteristics of the microbubbles and the desorption characteristics of the DMPC molecules showed the same variation; namely, a greater sound pressure amplitude induced greater vibrational displacement and a larger amount of molecular desorption under resonance conditions. These results support the possibility of controlling drug release with pulsed ultrasound in a microbubble-based drug delivery system.

Although most phospholipid-shelled microbubbles (MBs) investigated for medical applications are stabilized by a fluorocarbon (FC) gas, information on the interactions between the phospholipid and FC molecules at the gas/water interface remains scarce. We report that the procedure of introduction of perfluorohexane (F-hexane), that is, either in the gas phase above dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC) Langmuir monolayers, or in the aqueous subphase, radically affects the compression isotherms. When introduced in the gas phase, F-hexane is rapidly incorporated in the interfacial film, but is also readily desorbed upon compression and eventually totally expelled from the phospholipid monolayers. By contrast, when introduced in the aqueous phase, F-hexane remains trapped at the interface. These dissimilar outcomes demonstrate that the phospholipid monolayer acts as a barrier that effectively hinders the transfer of the FC across the interfacial film. F-hexane was also found to significantly accelerate the adsorption kinetics of the phospholipids at the gas/water interface and to lower the interfacial tension, as assessed by bubble profile analysis tensiometry. The extent of these effects is more pronounced when F-hexane is provided from the gas phase. The size and stability characteristics of DMPC- and DPPC-shelled microbubbles were also found to depend on how the FC is introduced. As compared to reference MBs prepared under nitrogen only, introduction of F-hexane always causes a decrease in MB mean radius. However, while for DMPC this decrease depends on the F-hexane introduction procedure, it is independent from the procedure and most pronounced (from ∼2.0 μm to ∼1.0 μm) for DPPC. Introducing the FC in the gas phase has the strongest effect on MB half-life (t1/2= ∼1.8 and 6.8 h for DMPC and DPPC, respectively), as compared to when it is delivered through the aqueous phase (∼0.8 and ∼1.7 h). Fluorocarbonless reference DMPC and DPPC bubbles had a half-life of ∼0.5 and 0.8 h, respectively. The effects of F-hexane on MB characteristics are discussed with regard to the interactions between phospholipids and F-hexane and monolayer fluidization effect, as revealed by the Langmuir and tensiometric studies.

In view of preparing effective nitric oxide gas carriers, a fluorinated poly(ethylene glycol) (F-PEG) was noncovalently conjugated with acid-treated graphene oxide (GO) to prepare the composite of F-PEG@GO. When the persistence of NO gas doped on GO and F-PEG@GO was investigated for 3 h, the conserved NO gas decreased from 49.00 ± 7.06 to 2.17 ± 1.36 nmol/mg carrier and from 58.51 ± 6.02 to 4.58 ± 2.22 nmol/mg carrier, respectively. The adsorption of F-PEG on GO and the doping of NO on GO and F-PEG@GO were declarative by the increase of distance between GO sheets, and the NO doping was also clarified by infrared absorption and X-ray photoelectron spectroscopies. The antibacterial effect was higher for NO-conserved F-PEG@GO than for NO-conserved GO and more effective against Staphylococcus aureusthan against Escherichia coli. It is evident that the coating of F-PEG on GO is preferable for advancing the loading efficiency, the stability and the biomedical efficacy of NO gas.

Surfactants containing fluorocarbon chains have been increasingly studied because they self-assemble into a variety of microscopic and mesoscopic domains and tend to form highly ordered patterns at the air/water interface; these patterns are clearly different from those formed by their hydrocarbon analogs. Focusing on the fluorinated surfactants possessing unique physical characteristics, this review describes the relationship between the line tension and dipole interaction, which is the comprehensive principle governing the pattern formation of two-dimensional self-assemblies. This review further discusses several key experimental and analytical techniques that are useful for characterizing the shape, size, correlation, and viscoelasticity of hierarchical self-assemblies on water surfaces. Finally, several biomedical applications, including biomimetic surface coating, multimodal contrast agents in medical diagnostics, and controlled delivery of gases (O2and NO) for oxygenation and antimicrobial effects, are introduced to highlight how the unique physicochemical properties of fluorinated self-assemblies can be applied in materials science.

A series of semifluorinated alkanes (CnF2n+1CmH2m+1diblocks, FnHm, n= 6, 8, 10; m= 16, 18, 20), when cast as films onto solid substrates, were found to form ring-banded or radial spherulites when heated above their isotropic temperature and subsequently cooled down to room temperature, demonstrating that the formation of two-dimensional (2D) spherulites is a general feature of molecular fluorocarbon–hydrocarbon diblocks. These spherulites are not birefringent, a seldom encountered feature for such structures (never, so far, for spherulites made of small molecules). They also provide examples of fluorinated 2D spherulites. Film morphology was analyzed by optical microscopy, interferometric profilometry, atomic force microscopy (AFM), and scanning electron microscopy. Increasing the length of the Fnsegment favors the formation of ring-banded spherulites, whereas short Fnsegments tend to favor extended radial stripes. Variation of the cooling rate provides control over the size and morphology of the spherulites: slow cooling promotes fibers and radial spherulites, whereas fast cooling fosters ring-banded spherulites. The AFM studies of F10H16 films revealed that the latter consist of stacks of regularly spaced lamellae. We also observed that, remarkably, stacked lamellae (repeating distance ∼6 nm) can coexist with a layer of close-packed monodisperse circular self-assembled surface nanodomains of FnHmdiblocks (∼30 nm in diameter); the latter are known to form from such diblocks at interfaces at room temperature. Substrates partially covered with F10H16 contain incomplete ring-banded spherulites and smaller objects in which the lamellae and circular nanodomains coexist.

After a brief reminder of the specific properties of fluorocarbons, fluorinated chains and molecular fluorocarbon-hydrocarbon diblocks (semifluorinated alkanes, CnF2n+1CmH2m+1, FnHm) that account for their exceptional aptitude for self-organization, we review recent advances on the self-assembled surface nanodomains that FnHmdiblocks form on water and solid surfaces, their shape and size characteristics, and their hierarchical organization into structures of higher complexity. Remarkably indeed, FnHmdiblocks, when spread as Langmuir monolayers on water, self-assemble into circular mesoscopic nanodomains that exist even in the absence of lateral pressure, and self-organize into regular hexagonal arrays upon compression. These surface domains can be transferred essentially unchanged onto solid surfaces. They can also be obtained by direct casting or spin coating of solutions of diblocks on solids, or by spontaneous formation on liquid crystals. The nanodomains retain their size, shape and organization upon compression and, amazingly, even beyond the collapse of their Langmuir monolayers. The domain-patterned films display uncommon rheology, with predominantly elastic monolayers, and two-dimensional gels were generated, including at zero surface pressure. The formation and behavior of surface domains from related tri- and tetrablocks have also been reported. A tetrablock afforded the first example of pressure-driven stacking of self-assembled nano-objects. The domain-patterned films constitute attractive templates for organizing nanoparticles in components of electronic devices and sensors, and for fabricating ordered mesoporous solids. Most recently, a novel aggregation mode was found for FnHmdiblocks, namely their crystallization into micron-size polycrystalline two-dimensional radial and/or ring-banded spherulites. Applications in medicine and materials science are being investigated.Numerous studies involving various semifluorinated alkanes, spreading techniques and experimental conditions have determined that formation and ordering of molecular surface nanodomains on water and solid supports (including liquid crystals) are intrinsic properties of fluorocarbon/hydrocarbon diblocks. These domains do not coalesce when compressed and survive beyond monolayer collapse. Formation of two-dimensional radial or ring-banded spherulites has also been observed.

We investigated the effects of a 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (DMPC) molecular film surrounding microbubbles on their collapse under ultrasound irradiation. We defined the ejection of the internal gas from the microbubble (i.e. “daughter” bubbles) as bubble collapse. In particular, we measured the sound-pressure thresholds for microbubble collapse in water and a DMPC solution. Bubbles with the DMPC film had a smaller resonance size than naked bubbles. The measured contact angles of the bubbles were lower after collapse, implying that DMPC molecules on the bubble surface partially desorbed between the processes of vibration and collapse.

Fluorine in bloom: A nonpolar fluorocarbon/hydrocarbon tetrablock self‐assembles into a first monolayer consisting of an array of densely packed discrete circular surface micelles (dark); this layer is surmounted by a second layer of such nano‐objects (light).

Understanding and controlling the molecular organization of amphiphilic molecules at interfaces is essential for materials and biological sciences. When spread on water, the model amphiphiles constituted by CnF2n+1CmH2m+1(FnHm) diblocks spontaneously self‐assemble into surface hemimicelles. Therefore, compression of monolayers of FnHmdiblocks is actually a compression of nanometric objects. Langmuir films of F8H16, F8H18, F8H20, and F10H16 can actually be compressed far beyond the “collapse” of their monolayers at ∼30 Å2. For molecular areas Abetween 30 and 10 Å2, a partially reversible, 2D/3D transition occurs between a monolayer of surface micelles and a multilayer that coexist on a large plateau. For A<10 Å2, surface pressure increases again, reaching up to ∼48 mN m−1before the film eventually collapses. Brewster angle microscopy and AFM indicate a several‐fold increase in film thickness when scanning through the 2D/3D coexistence plateau. Compression beyond the plateau leads to a further increase in film thickness and, eventually, to film disruption. Reversibility was assessed by using compression–expansion cycles. AFM of F8H20 films shows that the initial monolayer of micelles is progressively covered by one (and eventually two) bilayers, which leads to a hitherto unknown organized composite arrangement. Compression of films of the more rigid F10H16 results in crystalline‐like inflorescences. For both diblocks, a hexagonal array of surface micelles is consistently seen, even when the 3D structures eventually disrupt, which means that this monolayer persists throughout the compression experiments. Two examples of pressure‐driven transformations of films of self‐assembled objects are thus provided. These observations further illustrate the powerful self‐assembling capacity of perfluoroalkyl chains.

Liquid perfluorocarbons‐like supercritical CO2‐provide valuable reaction media that can facilitate the separation of reaction products and the recovery of catalysts. Chemistry in fluorous media requires that some of the protagonist molecules, and in particular the catalysts, be grafted with one or more perfluoroalkylated chains. These chains, due to powerful hydrophobic and lipophobic effects, tend to self‐assemble and induce the formation of a variety of nanocompartmented supramolecular architectures and colloids, such as micelles, vesicles, tubules, monolayers, and emulsions, thus generating microheterogenicity in the reaction medium. Fluorinated amphiphiles are, for example, known to generate fibrous gels in fluorous, organic, and aqueous media. Phase separation, nanocompartmentation, and interface‐driven parameters can thus complicate otherwise simple chemistry. Conversely, they can provide useful micro‐ and nanoreactors and templates. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4251–4258, 2006

Fluorocarbon gases (gFCs) were found to inhibit the liquid-expanded (LE)/liquid-condensed (LC) phase transition of dipalmitoyl phosphatidylcholine (DPPC) Langmuir monolayers. The formation of domains of an LC phase, which typically occurs in the LE/LC coexistence region upon compression of DPPC, is prevented when the atmosphere above the DPPC monolayer is saturated with a gFC. When contacted with gFC, the DPPC monolayer remains in the LE phase for surface pressures lower than 38 mN m−1, as assessed by compression isotherms and fluorescence microscopy (FM). Moreover, gFCs can induce the dissolution of preexisting LC phase domains and facilitate the respreading of the DPPC molecules on the water surface, as shown by FM and grazing incidence x-ray diffraction. gFCs have thus a highly effective fluidizing effect on the DPPC monolayer. This gFC-induced fluidizing effect was compared with the fluidizing effect brought about by a mixture of unsaturated lipids and proteins, namely the two commercially available lung surfactant substitutes, Curosurf and Survanta, which are derived from porcine and bovine lung extracts, respectively. The candidate FCs were chosen among those already investigated for biomedical applications, and in particular for intravascular oxygen transport, i.e., perfluorooctyl bromide, perfluorooctylethane, bis(perfluorobutyl)ethene, perfluorodecalin, and perfluorooctane. The fluidizing effect is most effective with the linear FCs. This study suggests that FCs, whose biocompatibility is well documented, may be useful in lung surfactant substitute compositions.

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Control of phospholipid monolayerfluidity: A fluorocarbon gas (gFC) has a highly effective fluidizing effect on a semicrystalline monolayer of dipalmitoylphosphatidylcholine (DPPC, the main component of native lung surfactant), prevents it from crystallizing, and induces the dissolution of pre‐existing liquid‐condensed‐phase domains (see fluorescence micrographs; left: without gFC, right: with gFC). The biocompatible FC may, therefore, prove useful in lung‐surfactant therapy.

We have studied the molecular patterns formed in Langmuir–Blodgett (LB) films of semifluorinated alkanes C_nF_2n+1C_mH_2m+1 (FnHm diblocks, n = 6, 8, 10, m = 14, 16, 18, 20) by atomic force microscopy. All the compounds investigated formed surface micelles whose shape and dimensions varied with the molecular structure of the FnHm diblocks. Except for F6H16 and F8H14, which produced exclusively circular micelles, all of the other diblocks also formed elongated micelles that coexisted with circular micelles. The mean diameter of the circular micelles increased with the length of the hydrogenated segment of the diblocks. By contrast, increasing the length of the fluorinated segments did not have any detectable effect on the diameter. The elongated micelles became more numerous and longer for longer FnHm (both the length of the hydrogenated and of the fluorinated segments had a strong effect). The surface pressure of transfer had an influence on the morphology of the elongated micelles, the latter becoming fewer and shorter for higher surface pressures. A detailed X-ray reflectivity study conducted on F8H16 LB films showed that the hydrogenated segments are directed towards the silicon wafer, while the fluorinated segments point outwards toward the air. A disc-like model is proposed for the surface micelles.

We have studied the molecular patterns formed in Langmuir–Blodgett LB films of semifluorinated alkanes CnF2n1CmH2m1FnHmdiblocks, n  6, 8, 10, m  14, 16, 18, 20 by atomic force microscopy. All the compounds investigated formed surface micelles whose shape and dimensions varied with the molecular structure of the FnHmdiblocks. Except for F6H16 and F8H14, which produced exclusively circular micelles, all of the other diblocks also formed elongated micelles that coexisted with circular micelles. The mean diameter of the circular micelles increased with the length of the hydrogenated segment of the diblocks. By contrast, increasing the length of the fluorinated segments did not have any detectable effect on the diameter. The elongated micelles became more numerous and longer for longer FnHmboth the length of the hydrogenated and of the fluorinated segments had a strong effect. The surface pressure of transfer had an influence on the morphology of the elongated micelles, the latter becoming fewer and shorter for higher surface pressures. A detailed X-ray reflectivity study conducted on F8H16 LB films showed that the hydrogenated segments are directed towards the silicon wafer, while the fluorinated segments point outwards toward the air. A disc-like model is proposed for the surface micelles.

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A new method of detection of perfluorocarbon molecules (PFCs) in blood sample has been established. After an extraction and pre‐concentration step performed by headspace solid‐phase microextraction (HS‐SPME), the PFCs are detected by gas chromatography‐mass spectrometry (GC/MS) with an ion trap mass spectrometer in MS and MS/MS modes. The influence of different parameters on the SPME process is discussed. The limit of detection and the linearity of the procedure have been determined for two PFCs. Copyright © 2001 John Wiley & Sons, Ltd.Abbreviations used:EIelectron impactEPOerythropoietinFDCF‐decalineHS‐SPMEheadspace solid‐phase extractionIOCInternational Olympic CommitteeLODLimit of detectionPDMSpolydimethylsiloxanePFCsperfluorocarbon molecules

A new method of detection of perfluorocarbon molecules (PFCs) in blood sample has been established. After an extraction and pre-concentration step performed by headspace solid-phase microextraction (HS-SPME), the PFCs are detected by gas chromatography-mass spectrometry (GC/MS) with an ion trap mass spectrometer in MS and MS/MS modes. The influence of different parameters on the SPME process is discussed. The limit of detection and the linearity of the procedure have been determined for two PFCs. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: EI electron impact EPO erythropoietin FDC F-decaline HS-SPME headspace solid-phase extraction IOC International Olympic Committee LOD Limit of detection PDMS polydimethylsiloxane PFCs perfluorocarbon molecules

We investigated the effect of a perfluorocarbon emulsion (FC) added to the University of Wisconsin (UW) solution on hypothermic (4°C, 12–72h) preservation of rat small bowel grafts. The FC was 90wv perfluorooctylbromide, 2wv egg yolk phospholipids and 1.4wv mixed fluorocarbon-hydrocarbon molecular dowels. Four groups were defined: [1] UW flush and UW storage; [2] UW flush and FC storage; [3] flush with FC diluted 2 times with UW (FU) and FU storage; [4] FU flush and storage in oxygenated FU. Preservation was estimated with a histological score based on villus epithelium adhesion, on villus sloughing and on crypt cell adhesion to the basal membrane. Antioxidant potential was estimated by measurement of total thiol functions (SH) and activities of glutathione-peroxidase (GSH-P), superoxide dismutase (SOD) and catalase. FC in flush improved preservation during the first 24h (p<0.01). Storage in FC appeared superior to UW for the first 24h (p<0.01). Oxygenation (100 O2) of the storage medium yielded superior results at 12h and 24h (p<0.01 and p<0.001 versus group [1] respectively). After 72h, SOD and catalase activities increased in groups [3] and [4], and SOD decreased in group [1] (p<0.05). SH progressively decreased in group [1] (p<0.05) and GSH-P increased at 24 and 48h in groups [3] and [4] (p<0.01). The increase of O2in the perfusion flush or storage medium ameliorated the preservation status and protected the antioxidant potential of the small bowel.

Anionic glucophospholipids were recently reported as a new family of tubule-forming lipids. We report here investigations on the structure of nanotubules made from a glucophospholipid with a mixed fluorocarbon–hydrocarbon hydrophobe, using freeze fracture and cryo-transmission electron microscopy (TEM) and X-ray and neutron small angle scattering (SAXS, SANS). The hollow and regularly shaped tubules are very thin: they have an external radius of 140 Å and an internal radius of 35 Å on the average. Their 105 Å-thick wall appears to consist in three bilayers in which the glucophospholipid molecules are probably in a tilted and/or interdigitated configuration. Upon heating these nanotubes convert reversibly into vesicles; transformation is complete at 60°C.

Colorimetric determination of the free phospholipids present in concentrated fluorocarbon emulsions indicates that the amount of phospholipids adsorbed at the fluorocarbon/water interface increases when a mixed fluorinated/hydrogenated compound, C₆F₁₃C₁₀H₂₁, is added as a stabilizer. The polar head surface area of the phospholipids in emulsions of C₈F₁₇Br was reduced from ca. 85.8 ± 1.3 Ų to 74.1 ± 1.1 Ų, indicating tighter molecular packing of the surfactant. This effect was not observed when C₁₀F₂₁Br was used as a stabilizer, implying that the fluorocarbon/hydrocarbon compound is located preferentially at the fluorocarbon/water interface rather than dispersed throughout the fluorocarbon phase. The interfacial film structuring effect of the mixed fluorocarbon/hydrocarbon "dowel" molecule is more effective when the dispersed fluorocarbon is linear rather than cyclic. Copyright 1994, 1999 Academic Press

The purpose of the study reported here was to explore a new strategy for the aerobic preservation of transplants using stable concentrated fluorocarbon emulsions as an oxygen delivery system. Fluorocarbons (FCs) are synthetic molecules, chemically and biologically inert, with a high oxygen-dissolving capacity. As they do not mix with water, it is necessary to emulsify them for intra-vascular use. Perfluorooctyl bromide (or perflubron) can be emulsified with egg-yolk phospholipid (EYP), a nontoxic emulsifiant. The recent adjunction of amphiphilic fluorocarbon–hydrocarbon diblock molecules allows the obtaining of stable emulsions. By contrast with hemoglobin, fluorocarbons release oxygen following Henry's linear law rather than Barcroft's sigmoı¨d curve. Release of oxygen by the FCs is only slightly influenced by temperature, which is an advantage for the preservation of organs. We tested a new 90% w/v fluorocarbon stem emulsion (perflubron/EYL/F6H10) diluted to 36% w/v with a hydroelectrolytic solution containing albumin, on four multiple organ blocks (MOBs; heart–lungs, liver, pancreas, kidneys, small intestine) of rats (EMOBs). Five control MOBs were perfused with a 50% v/v mixture of rat-blood and Krebs solution (KBMOBs). The lungs were ventilated with a FiO2 = 100%. In all cases the survival of the MOBs was greater than 210 min, with stable hemodynamics and preserved hydroelectrolytic and acid–base balances. The levels of lactate, amylase, and CK of the EMOBs were inferior (P< 0.05) to those of the KBMOBs between the first and the second hour. The diuresis of the EMOBs was higher (P< 0.05) than that of the KBMOBs (5.65 ± 1.76 vs 1.21 ± 0.28 mg/min). The production of bile, and the AST and ALT levels, were not significantly different. The PaO2 of the EMOBs was higher (P< 0.01) than for the KBMOBs. In normothermy, the maintenance of an aerobic metabolism using the FC emulsion caused less damage to the organs. Aerobic preservation of organs using FC emulsions therefore appears to be an attractive alternative to the presently used cold ischemia.

Fluorocarbons and fluorocarbon-derived materials constitute a vast family of synthetic components that have a range of remarkable properties including exceptional chemical and biological inertness, gas-dissolving capacity, low surface tension, high fluidity, excellent spreading characteristics, unique hydro- and lipophobicity, high density, absence of protons, and magnetic susceptibility close to that of water.These properties lead to a diversity of products and applications as illustrated by those products that are already in advanced clinical trials, which comprise: 1) an injectable oxygen carrier, i.e. blood substitute, consisting of a fluorocarbon-in-water emulsion for use in surgery to alleviate the problems raised by the transfusion of homologous blood; the same emulsion is also being evaluated with cardiopulmonary bypass patients; 2) a neat fluorocarbon for treatment of acute respiratory failure by liquid ventilation; and 3) fluorocarbon-based or stabilized gas bubbles to be used as contrast agents for the assessment of heart function and detection of perfusion defects by ultrasound imaging.Proper selection of the fluorocarbon best suited for the intended application, formulation optimization, and advanced stabilization and processing procedures led to effective, ready-for-use products with minimal side-effects.Further highly fluorinated materials, including amphiphiles and various fluorocarbonbased colloidal systems that have potential as pulmonary, topical and ophthalmological drug delivery agents, and as skin protection barriers, are now being investigated. Such systems include drug-in-fluorocarbon suspensions, reverse water-in-fluorocarbon emulsions, oil-in-fluorocarbon emulsions, multiple emulsions, microemulsions, fluorocarbon gels, fluorinated liposomes, fluorinated tubules and other novel supramolecular systems.

Great caution must be exercised when applying the 1 CF2≈1.5 CH2“rule” for surfactants: when grafted to a fluorinated chain, a hydrocarbon chain does not fully participate in micellization and adsorption processes, so these are controlled primarily by the length of the ‐CF2‐ chain. It is proposed that the hydrocarbon spacer adopts a folded conformation as a result of the difference in cross‐sections between fluorocarbon and hydrocarbon chains.

Dimorpholinophosphates 1, with a single perfluoroalkyl chain, self-aggregate when dispersed in water to give tubular structures which reversibly transform into giant vesicles when heated. Compounds 1 also allow the preparation of stable reverse water-in-fluorocarbon emulsions destined to pulmonary drug delivery. None of this could be achieved with non-fluorinated analogs.

Dimorpholinophosphates 1, with a single perfluoroalkyl chain, self-aggregate when dispersed in water to give tubular structures which reversibly transform into giant vesicles when heated. Compounds 1 also allow the preparation of stable reverse water-in-fluorocarbon emulsions destined to pulmonary drug delivery. None of this could be achieved with non-fluorinated analogs.

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Phospholipids are known to self-organize into bilayer membranes and liposomes. Recently, much attention has also been focussed on highly ordered cylindrical, bilayer-based hollow microstructures usually called tubules, that form, for example, from diacetylenic phosphatidylcholines [1]. However, despite the potential of these new supramolecular architectures in both fundamental and applied area, only few tubule-forming surfactants have been reported yet. We have shown that the driving force required to form and stabilize coiled membranes in water can be brought by fitting amphiphiles with a single fluorinated chain, without need for rigid segments, hydrogen bonding between polar head or chiral centers [2,3].