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In numerous developing countries, the lower cost of subsidized liquid fuels such as kerosene compared to market-rate fuels often results in fuel adulteration. Such misuse of kerosene is hard to detect with conventional detection technologies because they are either time consuming, expensive, not sensitive enough or require well-equipped analytical laboratories. In this work, we developed an inexpensive and easy-to-use device for rapid and onsite detection of fuel adulteration. The working principle of our fuel adulteration detection is sensing changes in the mobility of fuel droplets on non-textured (i.e., smooth) and non-polar solid surfaces. Using our device, we demonstrated rapid detection of diesel (market-rate fuel) adulterated with kerosene (subsidized fuel) at concentrations an order of magnitude below typical adulteration concentrations. We envision that our inexpensive, easy-to-use, and field-deployable device as well as the design strategy will pave the way for novel fuel quality sensors.
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Cavitation can occur when liquids are exposed to pressure waves of sufficient amplitude, producing rapidly expanding and collapsing gas bubbles that generate localized regions of high energy dissipation. When vials containing insulin were subjected to mechanical shock or when ultrasound was applied to the vials, the resulting cavitation events induced formation of insulin amyloid fibril nuclei that were detected by transmission electron microscopy and quantified by fluorescence spectroscopy following staining with the amyloid-sensitive dye thioflavin-T. Dropping insulin solutions in glass vials produced only minute amounts of insulin fibril nuclei, which could be detected by allowing the nuclei to grow. Cavitation-induced formation of amyloid aggregates may be relevant for iatrogenic insulin deposition disease, where insulin fibrils formed in vitro prior to administration to patients could serve as nuclei for growing fibril deposits in vivo.
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Amiloide , Insulina , Humanos , Microscopía Electrónica de Transmisión , Espectrometría de FluorescenciaRESUMEN
Therapeutic proteins are among the most widely prescribed medications, with wide distribution and complex supply chains. Shipping exposes protein formulations to stresses that can trigger aggregation, although the exact mechanism(s) responsible for aggregation are unknown. To better understand how shipping causes aggregation, we compared populations of aggregates that were formed in a polyclonal antibody formulation during live shipping studies to populations observed in accelerated stability studies designed to mimic both the sporadic high g-force and continuous low g-force stresses encountered during shipping. Additionally, we compared the effects on aggregation levels generated in two types of secondary packaging, one of which was designed to mitigate the effects of large g-force stresses. Aggregation was quantified using fluorescence intensity of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) dye, size exclusion high performance liquid chromatography (SECHPLC), and flow imaging microscopy (FIM). FIM was also combined with machine learning methods to analyze particle morphology distributions. These comparisons revealed that the morphology distributions of aggregates formed during live shipping resemble distributions that result from low g-force events, but not those observed following high g-force events, suggesting that low g-force stresses play a predominant role in shipping-induced aggregation.
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Anticuerpos , Proteínas , Aprendizaje Automático , Agregado de ProteínasRESUMEN
This work reports the ability of hydrogel coatings to protect therapeutic proteins from cavitation-induced aggregation caused by mechanical stress. Here, we show that polyacrylamide hydrogel coatings on container surfaces suppress mechanical shock-induced cavitation and the associated aggregation of intravenous immunoglobulin (IVIg). First, crosslinked polyacrylamide hydrogels were grown on the surfaces of borosilicate glass vials. Treatment with ultrasound showed that these hydrogel surfaces suppressed cavitation events to levels below those found for unfunctionalized borosilicate glass. Next, IVIg solutions were loaded into these vials and subjected to tumbling, horizontal shaking, and drop testing. Aggregation was quantified by bisANS fluorescence staining and particle counting by flow imaging microscopy (FIM). In all cases, the presence of polyacrylamide hydrogels on the vial surfaces reduced the amount of IVIg aggregation and the number of particulates. In addition, the polyacrylamide appeared to have a protective effect that prevented additional aggregates from forming at extended tumbling times. Finally, drop test studies showed that the polyacrylamide coatings suppressed detectable cavitation. This work reveals how even a simple hydrogel vial coating can have a profound effect on stabilizing protein therapeutics.
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Inmunoglobulinas Intravenosas , Agregado de Proteínas , Hidrogeles , Estrés MecánicoRESUMEN
This work reports the development of a mechanochemistry activated covalent conjugation (MACC) reaction that shows areas of interfacial failure in soft hydrogels. Hydrogels are prone to delamination from rigid substrates due to the competition between swelling and adhesion, which can lead to bonding failure in a mechanism similar to crack propagation in harder materials. In this work, reductive amination was shown to occur when a ketone-bearing fluorescein derivative was bonded to an amine-functionalized hydrogel, as both of these moieties were found to be necessary for covalent conjugation into the gel network. For thin, circular polyacrylamide hydrogels, wrinkle patterns and regions of subsequent delamination at the edge of the gel were found to be selectively tagged by the dye. This reaction was then used to explore the effect of gel properties on patterns of interfacial failure. As cross-linker loading increased, the propagation of the delamination front and the area fraction of delamination were both found to increase, as shown by fluorescence images of gels. Increasing the thickness of the gel increased the fraction of delaminated area but did not change its propagation toward the center of the gel. This MACC reaction shows how mechanochemical reactions can be used for fluorescence tagging without incorporating mechanophores into the polymer gel matrix.
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Aggregation of therapeutic proteins can result from a number of stress conditions encountered during their manufacture, transportation, and storage. This work shows the effects of two interrelated sources of protein aggregation: the chemistry and structure of the surface of the container in which the protein is stored, and mechanical shocks that may result from handling of the formulation. How different mechanical stress conditions (dropping, tumbling, and agitation) and container surface passivation affect the stability of solutions of intravenous immunoglobulin are investigated. Application of mechanical shock causes cavitation to occur in the protein solution, followed by bubble collapse and the formation of high-velocity fluid microjets that impinged on container surfaces, leading to particle formation. Cavitation was observed after dropping of vials from heights as low as 5 cm, but polyethylene glycol (PEG) grafting provided temporary protection against drop-induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates after repeated dropping events, most likely by reducing protein adsorption to container surfaces. These studies enable the development of new coatings and surface chemistries that can reduce the particulate formation induced by surface adsorption and/or mechanical shock.
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Embalaje de Medicamentos , Inmunoglobulinas Intravenosas , Adsorción , Estrés MecánicoRESUMEN
Mechanical shock may cause cavitation in vials containing liquid formulations of therapeutic proteins and generate protein aggregates and other particulates. To test whether common formulation components such as protein molecules, air bubbles, or polysorbate 20 (PS20) micelles might nucleate cavitation, a high-speed video camera was used to detect cavitation in vials containing antibody formulations after application of controlled mechanical shock using a shock test. Higher concentrations of subvisible particles were found in formulations where cavitation had occurred. Bubbles trapped on vial surfaces were a primary site for cavitation nucleation; other potential cavitation nuclei were ineffective. The incidence of cavitation events observed after application of mechanical shock was lower in type I glass vials than in cyclic olefin polymer vials or in SiOPlas™ cyclic olefin polymer vials and correlated with the surface roughness of the different vials. To reduce the incidence of cavitation and the adsorption of mAb on glass-water and silicone oil-water interfaces and thus minimize protein damage due to cavitation, PS20, a common nonionic surfactant, was added to formulations. Addition of PS20 to formulations in glass and silicone oil-coated glass vials significantly reduced both incidence of mechanical shock-induced cavitation and the particle formation that resulted from cavitation events.
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Polisorbatos , Proteínas , Adsorción , VidrioRESUMEN
The need to improve blood biocompatibility of medical devices is urgent. As soon as blood encounters a biomaterial implant, proteins adsorb on its surfaces, often leading to several complications such as thrombosis and failure of the device. Therefore, controlling protein adsorption plays a major role in developing hemocompatible materials. In this study, the interaction of key blood plasma proteins with superhemophobic titania nanotube substrates and the blood clotting responses was investigated. The substrate stability was evaluated and fibrinogen adsorption and thrombin formation from plasma were assessed using ELISA. Whole blood clotting kinetics was also investigated, and Factor XII activation on the substrates was characterized by an in vitro plasma coagulation time assay. The results show that superhemophobic titania nanotubes are stable and considerably decrease surface protein adsorption/Factor XII activation as well as delay the whole blood clotting, and thus can be a promising approach for designing blood contacting medical devices.
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Materiales Biocompatibles/farmacología , Proteínas Sanguíneas/química , Factor XII/genética , Titanio/farmacología , Adsorción/efectos de los fármacos , Materiales Biocompatibles/química , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/genética , Proteínas Sanguíneas/genética , Ensayo de Inmunoadsorción Enzimática , Factor XII/química , Fibrinógeno/química , Fibrinógeno/genética , Humanos , Cinética , Nanotubos/química , Adhesividad Plaquetaria/efectos de los fármacos , Propiedades de Superficie/efectos de los fármacos , Titanio/químicaRESUMEN
Virtually all blood-contacting medical implants and devices initiate immunological events in the form of thrombosis and inflammation. Typically, patients receiving such implants are also given large doses of anticoagulants, which pose a high risk and a high cost to the patient. Thus, the design and development of surfaces with improved hemocompatibility and reduced dependence on anticoagulation treatments is paramount for the success of blood-contacting medical implants and devices. In the past decade, the hemocompatibility of super-repellent surfaces (i.e., surfaces that are extremely repellent to liquids) has been extensively investigated because such surfaces greatly reduce the blood-material contact area, which in turn reduces the area available for protein adsorption and blood cell or platelet adhesion, thereby offering the potential for improved hemocompatibility. In this review, we critically examine the progress made in characterizing the hemocompatibility of super-repellent surfaces, identify the unresolved challenges and highlight the opportunities for future research on developing medical implants and devices with super-repellent surfaces.
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Due to their unique functionality, superomniphobic surfaces that display extreme repellency toward virtually any liquid, have a wide range of potential applications. However, to date, the mechanical durability of superomniphobic surfaces remains a major obstacle that prevents their practical deployment. In this work, a two-layer design strategy was developed to fabricate superomniphobic surfaces with improved durability via synergistic effect of interconnected hierarchical porous texture and micro/nano-mechanical interlocking. The improved mechanical robustness of these surfaces was assessed through water shear test, ultrasonic washing test, blade scratching test, and Taber abrasion test.
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Bacterial infections are a serious issue for many implanted medical devices. Infections occur when bacteria colonize the surface of an implant and form a biofilm, a barrier which protects the bacterial colony from antibiotic treatments. Further, the anti-bacterial treatments must also be tailored to the specific bacteria that is causing the infection. The inherent protection of bacteria in the biofilm, differences in bacteria species (gram-positive vs. gram-negative), and the rise of antibiotic-resistant strains of bacteria makes device-acquired infections difficult to treat. Recent research has focused on reducing biofilm formation on medical devices by modifying implant surfaces. Proposed methods have included antibacterial surface coatings, release of antibacterial drugs from surfaces, and materials which promote the adhesion of non-pathogenic bacteria. However, no approach has proven successful in repelling both gram-positive and gram-negative bacteria. In this study, we have evaluated the ability of superhydrophobic surfaces to reduce bacteria adhesion regardless of whether the bacteria are gram-positive or gram-negative. Although superhydrophobic surfaces did not repel bacteria completely, they had minimal bacteria attached after 24â¯h and more importantly no biofilm formation was observed.
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Antibacterianos/química , Antibacterianos/farmacología , Nanotubos/química , Titanio/química , Bacterias/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Superomniphobic surfaces (i.e., surfaces that are extremely repellent to both high surface tension liquids like water and low surface tension liquid like oils) can be fabricated through a combination of surface chemistry that imparts low solid surface energy with a re-entrant surface texture. Recently, surface texturing with lasers has received significant attention because laser texturing is scalable, solvent-free, and can produce a monolithic texture on virtually any material. In this work, we fabricated nanostructured omniphobic and superomniphobic surfaces with a variety of materials using a simple, inexpensive and commercially available CO2 laser engraver. Further, we demonstrated that the nanostructured omniphobic and superomniphobic surfaces fabricated using our laser texturing technique can be used to design patterned surfaces, surfaces with discrete domains of the desired wettability, and on-surface microfluidic devices.
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In this study, we explore how blood-material interactions and hemodynamics are impacted by rendering a clinical quality 25 mm St. Jude Medical Bileaflet mechanical heart valve (BMHV) superhydrophobic (SH) with the aim of reducing thrombo-embolic complications associated with BMHVs. Basic cell adhesion is evaluated to assess blood-material interactions, while hemodynamic performance is analyzed with and without the SH coating. Results show that a SH coating with a receding contact angle (CA) of 160° strikingly eliminates platelet and leukocyte adhesion to the surface. Alternatively, many platelets attach to and activate on pyrolytic carbon (receding CA = 47), the base material for BMHVs. We further show that the performance index increases by 2.5% for coated valve relative to an uncoated valve, with a maximum possible improved performance of 5%. Both valves exhibit instantaneous shear stress below 10 N/m2 and Reynolds Shear Stress below 100 N/m2. Therefore, a SH BMHV has the potential to relax the requirement for antiplatelet and anticoagulant drug regimens typically required for patients receiving MHVs by minimizing blood-material interactions, while having a minimal impact on hemodynamics. We show for the first time that SH-coated surfaces may be a promising direction to minimize thrombotic complications in complex devices such as heart valves.
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Plaquetas/metabolismo , Prótesis Valvulares Cardíacas/efectos adversos , Hemodinámica , Leucocitos/metabolismo , Ensayo de Materiales , Trombosis/metabolismo , Plaquetas/patología , Adhesión Celular , Humanos , Leucocitos/patología , Resistencia al Corte , Trombosis/etiología , Trombosis/fisiopatologíaRESUMEN
The hemocompatibility of superhemophobic surfaces is investigated and compared with that of hemophobic surfaces and hemophilic surfaces. This analysis indicates that only those superhemophobic surfaces with a robust Cassie-Baxter state display significantly lower platelet adhesion and activation. It is envisioned that the understanding gained through this work will lead to the fabrication of improved hemocompatible, superhemophobic medical implants.
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Plaquetas/metabolismo , Ensayo de Materiales , Adhesividad Plaquetaria/efectos de los fármacos , Titanio/química , Titanio/farmacología , Plaquetas/citología , Humanos , Propiedades de SuperficieRESUMEN
Fabrication of most superomniphobic surfaces requires complex process conditions or specialized and expensive equipment or skilled personnel. In order to circumvent these issues and make them end-user-friendly, we developed the free-standing, flexible, superomniphobic films. These films can be stored and delivered to the end-users, who can readily attach them to virtually any surface (even irregular shapes) and impart superomniphobicity. The hierarchical structure, the re-entrant texture, and the low solid surface energy render our films superomniphobic for a wide variety of liquids. We demonstrate that our free-standing, flexible, superomniphobic films have applications in enhanced chemical resistance and enhanced weight bearing.
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We used FDA-approved, edible materials to fabricate superhydrophobic coatings in a simple, low cost, scalable, single step process. Our coatings display high contact angles and low roll off angles for a variety of liquid products consumed daily and facilitate easy removal of liquids from food containers with virtually no residue. Even at high concentrations, our coatings are nontoxic, as shown using toxicity tests.