Surfactant Production Research Articles

Optimization for Production Tert-Butyl Oleyl Glycoside Nonioic Surfactant Using Response Surface Methodology

The development of surfactant production process strongly influenced by the potential use of raw materials and products that are environmentally friendly. For raw materials such as surfactants are carbohydrate-based material utilization example, glucose, which is reacted with tert-butanol, to form tert-butyl glycoside (TBG), then TBG can be esterified with oleic acid forming surfactant tert-butyl oleyl glycoside (TBOG). This study aims to obtain the optimum conditions TBOG production process of esterification reactions TBG and oleic acid catalyst the para toluene sulfonic acid using response surface method to reach optimum yield TBOG. The independent variable used is the mole ratio of TBG with oleic acid, percent of the catalyst and a temperature. Optimization results obtained optimum conditions of mole ratios of 1: 4.096; 2.33 percent of the catalyst and the temperature of 96.04 °C with a TBOG yield of 92.46%, with a TBOG content of 91.72 %. Based on the HLB value of the surfactant TBOG is 3.87, then these surfactants can be used as an emulsifier of water-in-oil.

Optimization for Production Tert-Butyl Glycoside Nonionic Surfactant Using Response Surface Methodology

It is necessary to develop a surfactant production process using environmentally friendly raw materials and products. For raw materials such as surfactants are carbohydrate-based material utilization example, glucose, which is reacted with tert-butanol, to form tert-butyl glycoside (TBG). This study aims to obtain the optimum conditions TBG production process of acetalization reactions, glucose and tert-butanol, catalyst the para toluene sulfonic acid using response surface method to reach optimum yield TBG. The independent variable used is the mole ratio of glucose with tert-butanol, percent of the catalyst and a temperature. Optimization results obtained optimum conditions of mole ratios of 1: 5.06; 2.87 percent of the catalyst and the temperature of 71.21 °C with a TBG yield of 99.13%, with a TBG content of 61.2 %. The optimum process conditions are verified to strengthen the model equations obtained by the response surface method. Based on the Hydrophilic-Lipophilic Balance value of the surfactant TBG is 4.60, then these surfactants can be used as an emulsifier of water-in-oil.

Constructing the phase diagram of sodium laurylethoxysulfate using dissipative particle dynamics

HypothesisSodium Laurylethoxysulfate (SLES) is a fundamental ingredient in a wide range of surfactant products and the mapping of its various mesophases is pivotal in predicting the liquid viscosity. Here we want to show that the use of properly parameterised coarse-grained molecular models can provide structural information of the surfactant solutions not easily achievable through experimental characterization. ExperimentsWe use a novel set of Dissipative Particle Dynamics parameters specifically developed for surfactant molecules to construct the first phase diagram of pure SLES in sodium chloride/water solutions. FindingsWe found that our DPD model is able to reproduce the range of morphologies expected for these types of ionic surfactants and in agreement with recent rheological data and theoretical predictions based on the packing parameter. We calculated the structure factor for various salt concentrations and show that the change from spherical to worm-like micelles can be inferred also looking at the intensity of the peak at intermediate q-values which decreases in intensity as salt concentrations increase. Varying the ethoxyl groups we observe that the additional ethoxyl group increased the micellar radius and affected the micelles’ shape polydispersity in the system. Finally, based on the contour length of worm-like micelles observed at intermediate salt concentrations, a closed mathematical formula is proposed capable of predicting the average micellar contour length given the salt and surfactant concentrations.

The use of Mixed Bacterial Culture to improve the Biodegradation of Diesel Pollution

This study was conducted to evaluate the hydrocarbon biodegradation abilities of Enterobacter cloacae, Staphylococcus aureus, Sphingomonas paucimobilis, and Pentoae species which were isolated from different diesel-contaminated soil samples. The isolates were identified by the Vitek 2 system. Fourier-transform spectroscopy (FT-IR) tested the potential of these isolates to biodegrade the diesel according to the peak areas, a significant decrease in the area of the peaks at 2856-2928 cm−1 corresponds to aliphatic hydrocarbons. The appearance of small peaks at 900-1032 cm−1 refers to substituted benzene derivative compounds. An appearance of some new peaks at 3010- 3030 cm−1 which indicate the presence of alcohol (-OH) and ketones (RC=O). A sharp peak appeared at 1712 cm−1 refers to the carbonyl group (C=O). The potential of biological surfactant production was tested using the Sigma 703D stand-alone tensiometer showed that these isolates were biological surfactant producers. The better results of the surface tension reduction test were obtained when using the mixed bacterial culture which reduced the surface tension of the medium from 66 mN/m to 35.15 mN/m. Single isolates and mixed bacterial culture have investigated their ability to degrade 3.0 % (v/v) of diesel as sole source of carbon and energy in Bushnell- Haas medium. The results demonstrated that the bacterial isolates could be effective in biodegradation of diesel spills individually and showed good biodegradation abilities when they are used together in the mixed bacterial culture.

Enhancement of Lipase CAL‐A Selectivity by Protein Engineering for the Hydrolysis of Erucic Acid from Crambe Oil

AbstractThe aim of this study is to pursue the identification and characterization of different CAL‐A variants displaying higher specificity toward erucic acid than CAL‐A wild type (wt). A careful analysis of the data generated from previously created site‐directed saturation libraries reveals several variants that display a higher preference for the hydrolysis of p‐nitrophenyl (pNP)‐erucate over pNP‐oleate than the wt. The best three candidates (CAL‐A V238D, V238Y, and V286N) are applied in biocatalysis using both Crambe oil and ethyl ester derivatives. When acting on Crambe oil, these CAL‐A variants are as efficient as CAL‐A wt in terms of C22:1 enrichment and product recovery independently of the temperature (enrichment and recovery values between 70–76% and 67–79% at 37 °C, and between 71–73% and 61–75% at 50 °C). In contrast, hydrolysis of Crambe ethyl esters leads to substantially increased accumulations of C22:1 and recovery values (V238Y: 78% enrichment and 92% recovery; V286N: 83% enrichment and 91% recovery) when using CAL‐A V238Y and CAL‐A V286N compared to CAL‐A wt (78% enrichment, 60% recovery) in the free fatty acid fraction.Practical Applications: This study describes the enhancement of lipase CAL‐A selectivity for the isolation and recovery of erucic acid (C22:1) from plant oil or its ethyl ester derivatives. Hence, this approach could represent a more eco‐friendly alternative for its application in processes where the erucic acid is used as building block, such as the production of surfactants or polymers.

Biomass‐based chemical production using techno‐economic and life cycle analysis

AbstractFurfural has been selected as one of the top 30 biomass derived platform compounds by the U.S. Department of Energy based on several indicators including the raw material used for production, estimated processing cost, technical complexity, and market potential. In this work, several high value chemicals such as butadiene, surfactants, jet‐fuels, and lubricants are produced from furfural. The paper proposes the integrated flowsheet to produce those chemical and techno‐economic and life cycle analysis is performed to compare the minimum selling price and environmental impacts of the integrated process. The capital and operating cost for production of lubricants and surfactants is the highest when compared with other products. Production of surfactants performs the best in terms of environmental impacts except in water depletion when compared with other processes while butadiene production performs the worst regarding the environmental effects.

Genetic causes of surfactant protein abnormalities.

Mutations in genes encoding proteins critical for the production and function of pulmonary surfactant cause diffuse lung disease. Timely recognition and diagnosis of affected individuals is important for proper counseling concerning prognosis and recurrence risk. Involved genes include those encoding for surfactant proteins A, B, and C, member A3 of the ATP-binding cassette family, and for thyroid transcription factor 1. Clinical presentations overlap and range from severe and rapidly fatal neonatal lung disease to development of pulmonary fibrosis well into adult life. The inheritance patterns, course, and prognosis differ depending upon the gene involved, and in some cases the specific mutation. Treatment options are currently limited, with lung transplantation an option for patients with end-stage pulmonary fibrosis. Additional genetic disorders with overlapping pulmonary phenotypes are being identified through newer methods, although these disorders often involve other organ systems. Genetic disorders of surfactant production are rare but associated with significant morbidity and mortality. Diagnosis can be made invasively through clinically available genetic testing. Improved treatment options are needed and better understanding of the molecular pathophysiology may provide insights into treatments for other lung disorders causing fibrosis.

Rhamnolipids functionalized with basic amino acids: Synthesis, aggregation behavior, antibacterial activity and biodegradation studies

Rhamnolipids have been intensively studied due to their remarkable properties; however, the biosynthesis of RLs cannot compete commercially with the production of synthetic surfactants. Here, novel cationic rhamnolipids (RLs) derivatives containing arginine and lysine were prepared for the first time using a straightforward synthetic procedure. The RLs used to prepare these new cationic derivatives were produced by Pseudomonas aeruginosa using waste frying oil as carbon source. It was found that the amino acid-based RLs form aggregates at very low concentrations, even below the CMC. Biodegradation studies indicate that these cationic RLs can be classified as readily biodegradable. Interestingly, the RL arginine conjugates exhibited notable DNA binding affinity and good antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, which increases the potential applications of these compounds. Consequently, the use of low-cost substrates and the added value of the final product constitute a more cost-effective rhamnolipid production.

Improvement in the Safety of Use of Hand Dishwashing Liquids through the Addition of Sulfonic Derivatives of Alkyl Polyglucosides

AbstractThe effect of a sulfonic acid derivative of alkyl polyglucosides on the safety of hand dishwashing liquids was assessed. In this study, it was found that an increase in the concentration of the natural origin raw material in samples led to a decrease in the zein number, and reduced changes in the pH level of bovine serum albumin solution, compared to a reference sample formulated without these compounds. These findings suggest a high level of reduction in the skin‐irritation effect after applying hand dishwashing liquids. In addition, the application of this type of anionic surfactants in products decreases their ability to emulsify fats. Consequently, the skin‐drying effect produced by the washing process and removal of protective epidermal lipids may be significantly reduced.

Isolation of Surfactants Synthesized by the Pseudomonas Bacteria and Study of Their Properties

Background. The important problem of biosurfactants production is biosynthesis optimization. But lack of effective isolation methods elaboration with simultaneous new costeffective products is the greatest weaknesses of existing technologies. Objective. The aim of the study is rational technology elaboration for isolation of biosurfactants obtained from strains Pseudomonas sp. PS-17 and P. fluorescens 8573. Investigation of the influence of different acids and temperatures on the efficiency of isolation of the surfactant products, study the properties of the obtained products. Determination of the possible directions of the use of supernatant obtained after precipitation of the biocomplexes (SPL) as a new inexpensive product. Methods. Rhamnolipid surfactant concentrate was precipitated from culture liquid supernatant (CLS) by acidification to pH 3-4 with acid solutions (HCl, H 2 SO 4 , H 3 PO 4 , HNO 3 , CH 3 COOH), kept at 100 °C for 25 min, cooled to room temperature, centrifuged before the phase separation, the supernatant was decanted. The surface tension of the SPL was determined by du Nouy method (with a platinum ring). The emulsification index of biosurfactants was determined regarding mineral oil and sunflower oil. The RLs were isolated from the SPL by extraction with a mixture of ethyl acetate and isopropanol, their composition was determined by thin layer chromatography. Influence on plants was assessed by their morphometric parameters after presowing seed treatment. Results. The rational technology for surfactants isolation from strains Pseudomonas sp. PS-17 and P. fluorescens 8573 was developed It was shown that the suitable method of the isolation of the biosurfactants of Pseudomonas sp. PS-17 and P. fluorescens 8573 is acidic precipitation from CLS with heating. As a result, the product yield was increased by 20%, and the duration of the process was reduced. The physico-chemical properties of the SPLs after the isolation of biosurfactants from the CLS were studied. SPLs have been shown to be effective oil emulsifiers, foaming and wetting agents for various surfaces. It was shown that SPLs (at dilutions 1:10) do not exhibit phytotoxic effects and stimulate the growth of watercress. Conclusions. The new wasteless technology for Pseudomonas strains biosurfactants isolation has been proposed, which provides for the elimination of the extraction stage with solvents, as a result, the yield of the target products has been increased. Thus, the technology has economic and environmental advantages. It was shown that SPLs, being inexpensive and effective products, can be used in environmentally friendly technologies: in agriculture (for stimulation of plant growth), for remеdiation of contaminated soils, production of detergent compositions.

Endothelial Sash1 Is Required for Lung Maturation through Nitric Oxide Signaling

The sterile alpha motif (SAM) and SRC homology 3 (SH3) domain containing protein 1 (Sash1) acts as a scaffold in TLR4 signaling. We generated Sash1-/- mice, which die in the perinatal period due to respiratory distress. Constitutive or endothelial-restricted Sash1 loss leads to a delay in maturation of alveolar epithelial cells causing reduced surfactant-associated protein synthesis. We show that Sash1 interacts with β-arrestin 1 downstream of the TLR4 pathway to activate Akt and endothelial nitric oxide synthase (eNOS) in microvascular endothelial cells. Generation of nitric oxide downstream of Sash1 in endothelial cells affects alveolar epithelial cells in a cGMP-dependent manner, inducing maturation of alveolar type 1 and 2 cells. Thus, we identify a critical cell nonautonomous function for Sash1 in embryonic development in which endothelial Sash1 regulates alveolar epithelial cell maturation and promotes pulmonary surfactant production through nitric oxide signaling. Lung immaturity is a major cause of respiratory distress and mortality in preterm infants, and these findings identify the endothelium as a potential target for therapy.

Microwave‐Assisted Synthesis and Characterization of Stearic Acid Sucrose Ester: A Bio‐Based Surfactant

AbstractSugar esters of fatty acids are bio‐based surfactants that were synthesized by transesterification of table sugar (sucrose) with stearic acid methyl ester (SAME) in high yield and purity using an optimized microwave‐assisted method. The maximum surfactant product yield of 88.2% was obtained by combining reactants with potassium methoxide and irradiating the mixture with microwaves to achieve an ideal reaction temperature of 132 °C over 21 min. The synthetic procedure described herein minimized undesirable sugar pyrolysis as evidenced by retention of white color characteristic of a pure bio‐based surfactant product. The experiment implemented Box–Behnken design for response surface methodology to refine reaction parameters for optimal product yield. The following parameters were augmented: the irradiation time, the mole ratio of catalyst to sucrose, and temperature.

Bioremediation of Petroleum Hydrocarbons Contaminated Soil using Bio piles System

This study was focused on biotreatment of soil which polluted by petroleum compounds (Diesel) which caused serious environmental problems. One of the most effective and promising ways to treat diesel-contaminated soil is bioremediation. It is a choice that offers the potential to destroy harmful pollutants using biological activity.
 Four bacterial strains were isolated from diesel contaminated soil samples. The isolates were identified by the Vitek 2 system, as Sphingomonas paucimobilis, Pentoae species, Staphylococcus aureus, and Enterobacter cloacae. The potential of biological surfactant production was tested using the Sigma 703D stand-alone tensiometer showed that these isolates are biological surfactant producers. The better results of the surface tension reduction test were obtained using the mixed bacterial culture which reduced the surface tension of the medium from 66mN/m to 33.89mN/m. For further evidence of the biodegradation effect of these isolates individually and as a mixed culture, which was supported by the use of Gas-Chromatography technology confirming the occurrence of biodegradation.
 The capability of mixed bacterial culture was examined to remediate the diesel contaminated soil in bio piles system. Two pilot scale bio piles (25 kg soil each) were constructed containing soils contaminated with approximately 2140 mg/kg total petroleum hydrocarbons (TPHs). Both systems were equipped with oxygen to provide aerobic conditions, incubated at ambient temperature and weekly sampling within 35 days (during summer season). Overall 75.71 % of the total petroleum hydrocarbons were removed from the amended soil and 33.18 % of the control soil at the end of study period. The study concluded that the ex-situ bioremediation (bio piles) is a good option for treating the soil contaminated with diesel as economical and environmentally friendly.

Bioremediation of Petroleum Hydrocarbons Contaminated Soil using Bio piles System

This study was focused on biotreatment of soil which polluted by petroleum compounds (Diesel) which caused serious environmental problems. One of the most effective and promising ways to treat diesel-contaminated soil is bioremediation. It is a choice that offers the potential to destroy harmful pollutants using biological activity.
 Four bacterial strains were isolated from diesel contaminated soil samples. The isolates were identified by the Vitek 2 system, as Sphingomonas paucimobilis, Pentoae species, Staphylococcus aureus, and Enterobacter cloacae. The potential of biological surfactant production was tested using the Sigma 703D stand-alone tensiometer showed that these isolates are biological surfactant producers. The better results of the surface tension reduction test were obtained using the mixed bacterial culture which reduced the surface tension of the medium from 66mN/m to 33.89mN/m. For further evidence of the biodegradation effect of these isolates individually and as a mixed culture, which was supported by the use of Gas-Chromatography technology confirming the occurrence of biodegradation.
 The capability of mixed bacterial culture was examined to remediate the diesel contaminated soil in bio piles system. Two pilot scale bio piles (25 kg soil each) were constructed containing soils contaminated with approximately 2140 mg/kg total petroleum hydrocarbons (TPHs). Both systems were equipped with oxygen to provide aerobic conditions, incubated at ambient temperature and weekly sampling within 35 days (during summer season). Overall 75.71 % of the total petroleum hydrocarbons were removed from the amended soil and 33.18 % of the control soil at the end of study period. The study concluded that the ex-situ bioremediation (bio piles) is a good option for treating the soil contaminated with diesel as economical and environmentally friendly.

Phylogenetic Framework and Metabolic Genes Expression Analysis of Bacteria Isolated from Contaminated Marine Environments of Niger Delta

Aims: To explore the phylogenetic framework of bacteria isolated from contaminated marine environments of Niger Delta and the expression of the metabolic genes coding for aromatic hydrocarbon degradation and surfactant production.
 Study Design: Nine treatments designs were set up in triplicates containing 25 mL of sterile modified mineral basal medium supplemented with nine marine hydrocarbon degraders incubated at 24°C for 5 days. Three of the set ups were supplemented each with 1 mg /L of xylene, anthracene and pyrene.
 Place and Duration of Study: Department of Environmental Sciences, University of South Africa, Pretoria, South Africa between September, 2015 to December, 2017.
 Methodology: A laboratory scale study was carried on six composite samples of the sediment and water samples from the three studied areas using enrichment, screening, selection, characterization, and PCR assays to explore the phylogenetic framework and metabolic genes expression of the marine bacteria for aromatic hydrocarbon degradation and surfactant production.
 Results: The findings revealed that there was significant abundance of THB (P = .05) more than TCHUB and more xylene degraders than anthracene and pyrene degraders in the sediment and water samples respectively. The phylogenetic correlational analysis revealed that all the nine selected best degraders out of 48 isolates from the studied area were evolutionary related belonging to the genera: Providencia, Alcaligenes, Brevundimonas, Myroides, Serratia, and Bacillus; able to significantly (P = .05) utilize the all the aromatic hydrocarbons. The existence of catabolic and surfactant genes namely catechol dioxygenase (C23O), rhamnolipid enzyme (rhlB) and surfactin /lichenysin enzyme (SrfA3 /LicA3) genes were detected in only four (4) out of the nine (9) marine aromatic degrading bacteria with 881 base pairs sizes.
 Conclusion: Thus, the study revealed that these bacterial strains especially Serratia marcescens XYL7 might possess metabolic genes for in situ aromatic hydrocarbon degradation and surfactant production.

Heterogeneous Pulmonary Response After Tracheal Occlusion: Clues to Fetal Lung Growth

BackgroundUnderstanding inconsistent clinical outcomes in infants with severe congenital diaphragmatic hernia (CDH) after tracheal occlusion (TO) is a crucial step for advancing neonatal care. The objective of this study is to explore the heterogeneous airspace morphometry and the metabolic landscape changes in fetal lungs after TO. MethodsFetal lungs on days 1 and 4 after TO were examined using mass spectrometry–based metabolomics, fluorescence lifetime imaging microscopy (FLIM), the number of airspaces, and tissue-to-airspace ratio (TAR). ResultsTwo morphometric areas were identified in TO lungs compared with controls (more small airspaces at day 1 and a higher number of enlarged airspaces at day 4). Global metabolomics analysis revealed a significant upregulation of glycolysis and a suppression of the tricarboxylic acid cycle in day 4 TO lungs compared with day 1 TO lungs. In addition, there was a significant increase in polyamines involved in cell growth and proliferation. Locally, FLIM analysis on day 1 TO lungs demonstrated two types of heterogeneous zones—similar to control and with increased oxidative phosphorylation. FLIM on day 4 TO lungs demonstrated appearance of zones with enlarged airspaces and a metabolic shift toward glycolysis, accompanied by a decrease in the FLIM “lipid-surfactant” signal. ConclusionsIn normal fetal lungs, we report a novel temporal pattern of varied morphometric and metabolic changes. Initially, there is formation of zones with small airspaces, followed by airspace enlargement over time. Metabolically day 1 TO lungs have zones with increased oxidative phosphorylation, whereas day 4 TO lungs have a shift toward glycolysis in the enlarged airspaces. Based on our observations, we speculate that the “best responders” to tracheal occlusion should have bigger lungs with small airspaces and normal surfactant production.

Pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by the accumulation of alveolar surfactant and dysfunction of alveolar macrophages. PAP results in progressive dyspnoea of insidious onset, hypoxaemic respiratory failure, secondary infections and pulmonary fibrosis. PAP can be classified into different types on the basis of the pathogenetic mechanism: primary PAP is characterized by the disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling and can be autoimmune (caused by elevated levels of GM-CSF autoantibodies) or hereditary (due to mutations in CSF2RA or CSF2RB, encoding GM-CSF receptor subunits); secondary PAP results from various underlying conditions; and congenital PAP is caused by mutations in genes involved in surfactant production. In most patients, pathogenesis is driven by reduced GM-CSF-dependent cholesterol clearance in alveolar macrophages, which impairs alveolar surfactant clearance. PAP has a prevalence of at least 7 cases per million individuals in large population studies and affects men, women and children of all ages, ethnicities and geographical locations irrespective of socioeconomic status, although it is more-prevalent in smokers. Autoimmune PAP accounts for >90% of all cases. Management aims at improving symptoms and quality of life; whole-lung lavage effectively removes excessive surfactant. Novel pathogenesis-based therapies are in development, targeting GM-CSF signalling, immune modulation and cholesterol homeostasis.

Enzymatic Synthesis of Aliphatic Nitriles at a Substrate Loading of up to 1.4 kg/L: A Biocatalytic Record Achieved with a Heme Protein.

A biocatalytic approach toward linear aliphatic nitriles being widely used as industrial bulk chemicals has been developed that runs at high substrate loadings of up to 1.4 kg/L as demonstrated for the synthesis of n-octanenitrile. This substrate loading is one of the highest ever reported in biocatalysis and to best of our knowledge the highest obtained for a water-immiscible product in aqueous medium. It is noteworthy that the biotransformation at such a high substrate loading was achieved by means of a metalloprotein bearing an iron-containing heme subunit in the active site. In detail, an aldoxime dehydratase from Bacillus sp. OxB-1 was used as a biocatalyst for a dehydration of aldoximes as readily available starting materials due to their easy preparation from aliphatic aldehydes through spontaneous condensation with hydroxylamine as bulk chemical. Excellent conversions toward the nitriles in the two-phase system were achieved and the products are easily separated from the reaction mixture without the need for further purification. Aliphatic nitriles are used in industry as solvents and intermediates for the production of surfactants and life sciences products.

Utilisation of hydrocarbons and production of surfactants by bacteria isolated from plant leaf surfaces.

Leaves are covered by a cuticle composed of long (C11-C20) and very-long chain hydrocarbons (>C20), e.g. alkanes, fatty acids, alcohols, aldehydes, ketones and esters. In addition to these aliphatics, cyclic hydrocarbons may be present. Leaves are colonised by a variety of so-called epiphytic bacteria, which may have adapted to be able to utilise cuticle hydrocarbons. We tested the ability of a wide range of phylogenetically different epiphytic bacteria to utilise and grow on diesel and petroleum benzine and show that out of the 21 strains tested, nine had the ability to utilise diesel for growth. Only one strain was able to utilise petroleum benzine for growth. The ability to utilise hydrocarbons for growth correlated with the ability of the strains to produce surfactants and out of the 21 tested strains, 12 produced surfactants. Showing that 75% of the strains producing surfactants were able to degrade hydrocarbons. Our findings suggest that the ability to degrade hydrocarbons and to produce surfactants is highly prevalent in epiphytic bacteria. It is unclear if epiphytic bacteria utilise hydrocarbons originating from the cuticle of living leaves. The application of surfactant producing, hydrocarbon-utilising, epiphytic bacteria might serve as a method for hydrocarbon bioremediation.

3434 The Study of Fetal Tracheal Occlusion to Treat Congenital Diaphragmatic Hernia in the EXTEND Model

OBJECTIVES/SPECIFIC AIMS: The goal of this project is to study fetal pulmonary vasculature in a CDH animal model, to understand how FETO affects developing vasculature, and to develop a modifiable fetal tracheal occlusive therapeutic device that avoids previously seen sequelae of FETO, like alveolar distension, decreased surfactant production, and decreased Type II Pneumocytes. The primary outcome is lung volume/kilogram. The secondary outcomes are contrast-enhanced ultrasound perfusion metrics (Time to Peak, Mean Transit Time, Wash-in Rate, Wash-in Perfusion Index), pulmonary vascular density, Lung Injury Histology Scores, and Lung Compliance upon ventilation. METHODS/STUDY POPULATION: Congenital diaphragmatic hernias will be modeled by surgical hernia creation via maternal laparotomy and hysterotomy at gestational age 72 - 74 days. The ewe will undergo a second laparotomy at 105 - 115 days gestational age. After a second hysterotomy is made, the fetus will be removed from the amniotic sac, though placental circulation will be maintained (EXIT Procedure). The animal is cannulated via the umbilical vein and arteries onto the pumpless ECMO circuit. The balloon and pressure sensor complex is placed into the trachea via direct laryngoscopy, and the fetus aseptically sealed into the Biobag. The wires of the tracheal occlusive device (balloon catheter and pressure sensor) will egress via the port of the Biobag. The fetus remains in the Biobag for fourteen days, with the tracheal occlusive device in place for ten days, followed by a four day recovery period. Daily contrast-enhanced ultrasounds and pulmonary artery dopplers are performed. Upon study completion, the fetus is intubated and placed on a conventional ventilator. A full necropsy is then performed, with perfusion fixation of the lungs via the pulmonary artery. RESULTS/ANTICIPATED RESULTS: Hypothesis 1: Modifiable Tracheal Occlusion will have statistically different effects on developing lung parenchyma, surfactant production, and abundance of Type II Pneumocytes Hypothesis 2: Modifiable Tracheal Occlusion will have lower levels of pulmonary hypertension than negative control animals, as measured by contrast-enhanced ultrasound (pulmonary artery velocity and washout time). DISCUSSION/SIGNIFICANCE OF IMPACT: This project will provide insight into the development of pulmonary hypertension in the CDH fetus. It will provide insight into the physiology of FETO, a novel therapy for congenital diaphragmatic hernias, and will demonstrate the utility of the EXTEND System for fetal treatments that are not possible in the maternal uterus.