Inactivation of bacterial endotoxin in water using a pressurized microfluidic ultra-high temperature (UHT) pasteurizer

• Published in: Journal of water process engineering 2022-08, Vol.48, p.102927, Article 102927
• Main Authors: Mohamed, Hussein M.H., Burroughs, Samantha, Summerville, Steven, Kearsley, Keith, Rivas, Logan, Hu, Dean, Waite-Cusic, Joy
• Format: Article
• Language: English
• Subjects: Endotoxin; Heat exchanger; Microfluidics; Turbidometric assay; Ultra-pure water
• ISSN: 2214-7144; 2214-7144
• DOI: 10.1016/j.jwpe.2022.102927

Ultra-pure water is critical for certain medical applications such as preparation of dialysis fluid and formulation of intravenous medications. However, production of ultra-pure water is challenging due to the difficulty of inactivating or removing endotoxins in water. The main objective of this study was to evaluate the ability of a pressurized microfluidic ultra-high temperature (UHT) pasteurizer to inactivate endotoxins (>2 log EU/ml) in water to meet the sterility assurance limit. A solution of Pseudomonas endotoxin (300 EU/ml) was prepared in endotoxin-free water and treated at various temperatures (150 °C–230 °C), pressures (1.65–3.10 MPa) and flow rates (100–400 ml/min). Endotoxin concentrations were determined using the Kinetic Turbidimetric LAL Assay. Endotoxin was effectively heat stable when treated at temperatures between 150 °C and 184 °C. Endotoxin inactivation at 200 °C was significant and was influenced by flow rate; however, even the slowest flow rate (100 ml/min) could not confidently achieve >2 log reduction of endotoxin. Increasing the temperature/pressure (230 °C/3.10 MPa) resulted in >3.8 log EU/ml reduction of endotoxin at all flow rates (100–400 ml/min). This is the first demonstration that microfluidic UHT pasteurization could be an effective process for inactivating endotoxin in water used in medical devices and for other continuous flow applications.