Gallium-based liquid metals (LM) have surface tension an order of magnitude higher than water and break up into micro-droplets when mixed with other liquids. In contrast, silicone oil readily mixes into LM foams to create oil-in-LM emulsions with oil inclusions. Previously, the LM was foamed through rapid mixing in air for an extended duration (over 2 hours). This process first results in the internalization of oxide flakes that form at the air-liquid interface. Once a critical fraction of these randomly shaped solid flakes is reached, air bubbles internalize into the LM to create foams that can internalize secondary liquids. Here, we introduce an alternative oil-in-LM emulsion fabrication method that relies on the prior addition of SiO2 micro-particles into the LM before mixing it with the silicone oil. This particle-assisted emulsion formation process provides a higher control over the composition of the LM-particle mixture before oil addition, which we employ to systematically study the impact of particle characteristics and content on the emulsions' composition and properties. We demonstrate that the solid particle size (0.8 µm to 5 µm) and volume fraction (1% to 10%) have a negligible impact on the internalization of the oil inclusions. The inclusions are mostly spherical with diameters of 20 to 100 µm diameter and are internalized by forming new, rather than filling old, geometrical features. We also study the impact of the particle characteristics on the two key properties related to the functional application of the LM emulsions in the thermal management of microelectronics. In particular, we measure the impact of particles and silicone oil on the emulsion's thermal conductivity and its ability to prevent deleterious gallium-induced corrosion and embrittlement of contacting metal substrates.
Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging
Particles in biopharmaceutical products present high risks due to their detrimental impacts on product quality
and safety. Identification and quantification of particles in drug products are important to understand particle formation mechanisms, which can help develop control strategies for particle formation during the formulation development and manufacturing process. However, existing analytical techniques such as microflow imaging and light obscuration measurement lack the sensitivity and resolution to detect particles with sizes smaller than 2 μm. More importantly, these techniques are not able to provide chemical information to determine particle composition. In this work, we overcome these challenges by applying the stimulated Raman scattering (SRS) microscopy technique to monitor the C−H Raman stretching modes of the proteinaceous particles and silicone oil droplets formed in the prefilled syringe barrel. By comparing the relative signal intensity and spectral features of each component, most particles can be classified as protein−silicone oil aggregates. We further show that morphological features are poor indicators of particle composition. Our method has the capability to quantify aggregation in protein therapeutics with chemical and spatial information in a label-free manner, potentially allowing high throughput screening or investigation of aggregation mechanisms.
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- Award ID(s):
- 1846503
- PAR ID:
- 10497548
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Molecular Pharmaceutics
- Volume:
- 20
- Issue:
- 8
- ISSN:
- 1543-8384
- Page Range / eLocation ID:
- 4268 to 4276
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Protein adsorption on surfaces greatly impacts many applications such as biomedical materials, anti-biofouling coatings, bio-separation membranes, biosensors, antibody protein drugs etc. For example, protein drug adsorption on the widely used lubricant silicone oil surface may induce protein aggregation and thus affect the protein drug efficacy. It is therefore important to investigate the molecular behavior of proteins at the silicone oil/solution interface. Such an interfacial study is challenging because the targeted interface is buried. By using sum frequency generation vibrational spectroscopy (SFG) with Hamiltonian local mode approximation method analysis, we studied protein adsorption at the silicone oil/protein solution interface in situ in real time, using bovine serum albumin (BSA) as a model. The results showed that the interface was mainly covered by BSA dimers. The deduced BSA dimer orientation on the silicone oil surface from the SFG study can be explained by the surface distribution of certain amino acids. To confirm the BSA dimer adsorption, we treated adsorbed BSA dimer molecules with dithiothreitol (DTT) to dissociate these dimers. SFG studies on adsorbed BSA after the DTT treatment indicated that the silicone oil surface is covered by BSA dimers and BSA monomers in an approximate 6 : 4 ratio. That is to say, about 25% of the adsorbed BSA dimers were converted to monomers after the DTT treatment. Extensive research has been reported in the literature to determine adsorbed protein dimer formation using ex situ experiments, e.g. , by washing off the adsorbed proteins from the surface then analyzing the washed-off proteins, which may induce substantial errors in the washing process. Dimerization is a crucial initial step for protein aggregation. This research developed a new methodology to investigate protein aggregation at a solid/liquid (or liquid/liquid) interface in situ in real time using BSA dimer as an example, which will greatly impact many research fields and applications involving interfacial biological molecules.more » « less
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Organosulfates (OSs) formed from heterogeneous reactions of organic-derived oxidation products with sulfate ions are an important component of secondary organic aerosol (SOA) mass, primarily in submicron particles with long atmospheric lifetimes. Fundamental understanding of OS evolution in particles, including the formation of new compounds via oxidation, is limited, particularly across relative humidities above and below the deliquescence of typical sulfate aerosol particles. By generating aqueous particulate OSs and other SOA products from the acid-driven reactive uptake of isoprene epoxydiols (IEPOX) onto inorganic sulfate aerosols in a 2-m3 indoor chamber at various relative humidities (30 – 80%) and injecting them into an oxidation flow reactor under the presence of hydroxyl radicals (·OH), we investigate the modification of particle size distributions, extent of inorganic sulfate conversion to organosulfates, and single-particle physicochemical properties. Chemical composition of particle-phase species, as well as aerosol morphological changes, are analyzed as a function of relative humidity and oxidant exposure times to better understand OS formation and destruction mechanisms in the ambient atmosphere.more » « less
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Small scale contact between a soft, liquid-coated layer and a stiff surface is common in many situations, from synovial fluid on articular cartilage to adhesives in humid environments. Moreover, many model studies on soft adhesive contacts are conducted with soft silicone elastomers, which possess uncrosslinked liquid molecules ( i.e. silicone oil) when the modulus is low. We investigate how the thickness of a silicone oil layer on a soft substrate relates to the indentation depth of glass microspheres in contact with crosslinked PDMS, which have a modulus of <10 kPa. The particles indent into the underlying substrate more as a function of decreasing oil layer thickness. This is due to the presence of the liquid layer at the surface that causes capillary forces to pull down on the particle. A simple model that balances the capillary force of the oil layer and the minimal particle–substrate adhesion with the elastic and surface tension forces from the substrate is proposed to predict the particle indentation depth.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.molpharmaceut.3c00391
