Silicone Oil Interface Research Articles

The silicone depletion in combination products induced by biologics

Silicone oil (SO) migration into the drug product of combination products for biopharmaceuticals during storage is a common challenge. As the inner barrel surface is depleted of SO the extrusion forces can increase compromising the container functionality. In this context we investigated the impact of different formulations on the increase in gliding forces in a spray-on siliconized pre-filled syringe upon storage at 2–8 °C, 25 °C and 40 °C for up to 6 months. We tested the formulation factors such as surfactant type, pH, and ionic strength in the presence of one monoclonal antibody (mAb) as well as compared three mAbs in one formulation. After 1 month at 40 °C, the extrusion forces were significantly increased due to SO detachment dependent on the fill medium. The storage at 40 °C enhanced the SO migration process but it could also be observed at lower storage temperatures. Regarding the formulation factors the tendency for SO migration was predominantly dependent on the presence and type of surfactant. Interestingly, when varying the mAb molecules, one of the proteins showed a rather stabilizing effect on the SO layer resulting into higher container stability. In contrast to the formulation factors, those different stability outcomes could not be explained by interfacial tension (IFT) measurements at the SO interface. Further characterization of the mAb molecules regarding interfacial rheology and conformational stability were not adequately able to explain the observed difference. Solely a hydrophobicity ranking of the molecules correlated to the stability outcome. Further investigations are needed to clarify the role of the protein in the SO detachment process and to understand the cause for the stabilization. However, the study clearly demonstrated that the protein itself plays a critical role in the SO detachment process and underlined the importance to include verum for container stability.

Monitoring the Molecular Structure of Fibrinogen during the Adsorption Process at the Buried Silicone Oil Interface In Situ in Real Time

Interfacial proteins play important roles in many research fields and applications, such as biosensors, biomedical implants, nonfouling coatings, etc. Directly probing interfacial protein behavior at buried solid/liquid and liquid/liquid interfaces is challenging. We used sum frequency generation vibrational spectroscopy and a Hamiltonian data analysis method to monitor the molecular structure of fibrinogen on silicone oil during the adsorption process in situ in real time. The results showed that the adsorbed fibrinogen molecules tend to adopt a bent structure throughout the entire adsorption process with the same orientation. This is different from the case of adsorbed fibrinogen on CaF2 with a linear structure or on polystyrene with a bent structure but a different orientation. The method introduced herein is generally applicable for following time-dependent molecular structures of many other proteins and peptides at interfaces in situ in real time at the molecular level.

Computational Fluid Dynamics of Intraocular Silicone Oil Tamponade.

PurposeTo investigate the behavior of silicone oil (SiO) at the steady equilibrium and during saccades and calculate SiO-retina contact, shear stress (SS), and shear rate (SR).MethodsA 24 mm phakic eye mesh model underwent 50°/0.137s saccade. The vitreous chamber compartment was divided into superior and inferior 180° sectors: lens, pre-equator, postequator, and macula. SiO-retina contact was evaluated as a function of fill percentages between 80% and 90% for a standing patient, 45° upward gaze, and supine. SS and SR for 1000 mPa-s (SiO1000) and 5000 mPa-s (SiO5000) silicon oil were calculated.ResultsSiO fill between 80% to 90% allowed 55% to 78% retinal contact. The superior retina always kept better contact with SiO, regardless of the fill percentage (P < 0.01). SiO interface thoroughly contacted the macula only in standing position. SS followed a bimodal behavior and was always significantly higher for SiO5000 compared to SiO1000 (P < 0.01) throughout the saccade. The macula suffered the highest mean SS in standing position, while throughout the saccade the average SS was maximum at the SiO-aqueous interface. SR was significantly higher for SiO1000 compared to SiO5000 (P < 0.001).ConclusionsSS on the retinal surface may instantaneously exceed reported retinal adhesiveness values especially at the SiO-aqueous interface and possibly favor redetachment. Despite 90% SiO fill the inferior retina remains extremely difficult to tamponade.Translational RelevanceAccurate assessment of retina-tamponade interaction may explain recurrent inferior retinal redetachment, silicone oil emulsification, and help to develop better vitreous substitutes.

Oscillatory spontaneous dimpling in evaporating curved thin films

We examine the dynamics of a thin film composed of a non-evaporative silicone oil (high surface tension) with trace amounts of an evaporative silicone oil (low surface tension) over an air bubble. An evaporating thin liquid film is formed atop a capillary-pinned air bubble by squeezing then holding the bubble against the air–silicone oil interface. Despite the simplicity of the system, complex oscillatory dynamical behaviour has been observed. Through interferometric experiments and numerical simulations, we show that as the bubble is moved towards the opposite interface, a dimple forms and during the subsequent holding period the dimple spontaneously oscillates. The evaporation-driven solutal–thermal Marangoni flow thickens the film and capillarity subsequently discharges the dimple. Solutal and thermal Marangoni flows both contribute to film thickening and as the local concentration of the non-evaporative species increases, the strength of the Marangoni flows increases. The oscillation frequency and waveform depend on initial composition and the maximum dimple volume. We suggest that these oscillatory solutions and the associated mechanism are a partial explanation for the film stabilization in multicomponent oils, reported experimentally in a recent publication (Chandran Suja et al., Proc. Natl Acad. Sci., vol. 115, 2018, pp. 7919–7924).

Electrostatic Suppression of the Leidenfrost State on Liquid Substrates.

An applied electric field can fundamentally eliminate the Leidenfrost effect (formation of a vapor layer at the solid-liquid interface at high temperatures). This study analyzes electrostatic suppression of the Leidenfrost state on liquid substrates. Electrostatic suppression on silicone oil and Wood's metal (liquid alloy) is studied via experimentation, high-speed imaging, and analyses. It is seen that the nature of electrostatic suppression can be drastically different from that on a solid substrate. First, the Leidenfrost droplet completely penetrates into the silicone oil substrate and converts to a thin film under an electric field. This is due to the existence of an electric field inside the substrate and the deformability of the silicone oil interface. A completely different type of suppression is observed for Wood's metal and solid substrates, which have low deformability and lack an electric field in the substrate. Second, the minimum voltage to trigger suppression is significantly lower on silicone oil when compared to Wood's metal and solid substrates. Fundamental differences between these transitions are analyzed, and a multiphysics analytical model is developed to predict the vapor layer thickness on deformable liquids. Overall, this study lays the foundation for further studies on electrostatic manipulation of the Leidenfrost state on liquids.

Understanding Protein-Interface Interactions of a Fusion Protein at Silicone Oil-Water Interface Probed by Sum Frequency Generation Vibrational Spectroscopy

Protein adsorbed at the silicone oil-water interface can undergo a conformational change that has the potential to induce protein aggregation on storage. Characterization of the protein structures at interface is therefore critical for understanding the protein-interface interactions. In this article, we have applied sum frequency generation (SFG) spectroscopy for studying the secondary structures of a fusion protein at interface and the surfactant effect on protein adsorption to silicone oil-water interface. SFG and chiral SFG spectra from adsorbed protein in the amide I region were analyzed. The presence of beta-sheet vibrational band at 1635 cm−1 implies the protein secondary structure was likely perturbed when protein adsorbed at silicone oil interface. The time-dependent SFG study showed a significant reduction in the SFG signal of preadsorbed protein when polysorbate 20 was introduced, suggesting surfactant has stronger interaction with the interface leading to desorption of protein from the interface. In the preadsorbed surfactant and a mixture of protein/polysorbate 20, SFG analysis confirmed that surfactant can dramatically prevent the protein adsorption to silicone oil surface. This study has demonstrated the potential of SFG for providing the detailed molecular level understanding of protein conformation at interface and assessing the influence of surfactant on protein adsorption behavior.

YAG Membranotomy for Persistent Postoperative Fibrinous Pupillary Membrane in an Aphakic Patient with Silicone Oil

We report a case of using Nd:YAG laser to perform a membranotomy of a persistent dense fibrinous pupillary membrane at the silicone oil (SO) interface in an aphakic patient following pars plana vitrectomy (PPV), pars plan lensectomy(PPL) with SO placement. Nd:YAG laser was successfully used to create a central opening in the fibrinous membrane at the SO interface which allowed for the proper examination of the posterior segment and improvement in the patient’s visual acuity.

Instability-Induced Mixing of Ferrofluids in Uniform Magnetic Fields

The advantages of ferrofluids in microfluidic lab-on-a-chip applications include remote control of the fluid flow within the chips, e.g., mixing of the species using an external uniform magnetic field. Hence, three-stream flow systems consisting of a ferrofluid core clad by two streams of diamagnetic silicone oil were studied. The instability of the ferrofluid, subjected to an external uniform magnetic field, was also studied. When the strength of this magnetic field was increased to a critical value, the ferrofluid was spread toward the silicone oil and a transient instability developed at the ferrofluid–silicone oil interface. Further increasing magnetic field resulted in periodic instability structures and permanent instability. The effect of magnetic field strength, flow rate, and flow rate ratio were determined. With a higher flow rate ratio, the permanent instability was observed only at the larger magnetic field strength. Our modeling results were consistent with these experimental results. Our work shows that an external uniform magnetic field of only a few millitesla can lead to instability and mixing, thus it is relevant to mixing in practical microfluidic devices.

Perfluorocarbon Liquid–Silicone Oil Interface After Vitreoretinal Surgery: Mirror Image of the Retina

doi: 10.3928/01913913-20XXXXXX-XX A 15-year-old boy was operated on due to a traumatic rhegmatogenous retinal detachment in the left eye. Pars plana vitrectomy (23-gauge), lensectomy, membrane peeling, perfluorocarbon liquid injection, endolaser, fluid–air exchange, and air-silicone oil exchanged were performed. One week after surgery, a perfluorocarbon–silicone oil interface was noted, giving a “mirror” image of the retina. The patient had a second operation to aspirate perfluorocarbon liquid and complete the silicone oil fill of the eye with successful retinal reattachment.

Quantitative assessment of ophthalmic viscosurgical device retention using in vivo confocal microscopy

To develop and apply a new laboratory method for in vivo quantitative assessment of the retention of ophthalmic viscosurgical devices (OVDs) following phacoemulsification. Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Studies of both eyes of New Zealand White rabbits were performed. Six OVDs were evaluated: Provisc and Healon (both sodium hyaluronate 1%), Healon5 (sodium hyaluronate 2.3%), Amvisc Plus (sodium hyaluronate 1.6%), Viscoat (sodium hyaluronate 3%-chondroitin sulfate 4%), and a new viscous-dispersive OVD, DisCoVisc (sodium hyaluronate 3%-chondroitin sulfate 4%). The OVD was injected to fill the anterior chamber and a phacoemulsification needle inserted with the tip positioned just anterior to the lens capsule. Simulated phacoemulsification was performed for 1 minute using flow rates of 20, 40, and 60 mL/min; a vacuum level of 300 mm Hg; and ultrasound power of 60% using a Legacy phacoemulsification unit. The needle was removed, and silicone oil (1000 centistokes) was injected into the anterior chamber. The distance between the corneal endothelium and the OVD-silicone oil interface was measured using in vivo confocal microscopy through-focusing (CMTF). Significant differences in residual thickness were found between the OVDs tested. Specifically, the residual thickness of both DisCoVisc (mean 324.5 microm +/- 163.7 [SD]) and Viscoat (251.4 +/- 100.9 microm) was significantly greater than that of Provisc (9.5 +/- 16.7 microm), Healon (3.8 +/- 11.3 microm), Healon5 (0.6 +/- 2.4 microm), and Amvisc Plus (65.6 +/- 134.0 microm) (P < .05, Dunn test). Ophthalmic viscosurgical device retention was greatest with DisCoVisc; however, there was no statistically significant difference between DisCoVisc and Viscoat in residual thickness. The flow rate did not have a significant effect on the residual thickness (Friedman 2-way analysis of variance by ranks). Residual OVD thickness following simulated phacoemulsification could be quantitatively measured using in vivo CMTF. The results are consistent with human surgical experience in that the dispersive OVD (Viscoat) was better retained than the cohesive compounds. DisCoVisc, a new viscous-dispersive OVD, also showed retention compared with Viscoat under the experimental conditions.

On identifying the appropriate boundary conditions at a moving contact line: an experimental investigation

Over the past decade and a half, analyses of the dynamics of fluids containing moving contact lines have specified hydrodynamic models of the fluids in a rather small region surrounding the contact lines (referred to as the inner region) which necessarily differ from the usual model. If this were not done, a singularity would have arisen, making it impossible to satisfy the contact-angle boundary condition, a condition that can be important for determining the shape of the fluid interface of the entire body of fluid (the outer region). Unfortunately, the nature of the fluids within the inner region under dynamic conditions has not received appreciable experimental attention. Consequently, the validity of these novel models has yet to be tested.The objective of this experimental investigation is to determine the validity of the expression appearing in the literature for the slope of the fluid interface in the region of overlap between the inner and outer regions, for small capillary number. This in part involves the experimental determination of a constant traditionally evaluated by matching the solutions in the inner and outer regions. Establishing the correctness of this expression would justify its use as a boundary condition for the shape of the fluid interface in the outer region, thus eliminating the need to analyse the dynamics of the fluid in the inner region.Our experiments consisted of immersing a glass tube, tilted at an angle to the horizontal, at a constant speed, into a bath of silicone oil. The slope of the air–silicone oil interface was measured at distances from the contact line ranging between O.O13a. and O.17a, where a denotes the capillary length, the lengthscale of the outer region (1511 μm). Experiments were performed at speeds corresponding to capillary numbers ranging between 2.8 × 10-4 and 8.3 × 10-3. Good agreement is achieved between theory and experiment, with a systematic deviation appearing only at the highest speed. The latter may be a consequence of the inadequacy of the theory at that value of the capillary number.

Thermodynamic properties and structure of the water–ethanol silicone oil interface

The interface between the water (1) – ethanol (2) system and silicone oil was studied over the whole composition range of the aqueous mixtures by means of adsorption and ellipticity measurements. The adsorbed layer was treated as a phase and, after derelativization of the relative surface excess, the adsorption isotherm (in term of molar fractions) as well as the activity coefficients of water and ethanol were calculated. From the above results and by analysing the ellipticity coefficient, we calculated the contribution to this latter due to the anisotropy of the adsorbed layer; the resulting "polynomial of anisotropy" was analyzed as a consequence of water and ethanol reorientations as the surface composition is changed.