CHAPTER 22: Endotoxin Monitoring Using Nanomaterials

Endotoxins or lipopolysaccharides (LPS) present on the outer surface of Gram-negative bacteria are highly immunogenic molecules and therefore can pose significant health risks to humans. Endotoxins can also be present in drinking water; hence, inhalation of water vapour is regarded as a primary route of human exposure, resulting in inflammation of alveoli, inhalation fever and gastrointestinal disorders. Medical solutions such as the dialysate used in hemodialysis and recombinant preparations such as vaccines can be contaminated with endotoxins and trigger side effects, such as tissue injury, endotoxic shock and death. Waterborne endotoxin-related illnesses have not been documented frequently, possibly owing to the difficulty of being able to identify the source of the fever by medical and bacterial analysis. The symptoms are short lived and have non-specific symptoms, such as fever, diarrhea and vomiting. Endotoxins cause fever, the most typical symptom experienced, as this is owing to the release of endogenous pyrogens that affect the hypothalamus, which regulates body temperature. However, exposure to higher doses of endotoxins, intravascular coagulation, shock and death can occur. Inhalation of aerosolised water droplets with endotoxin molecules is an important route of human exposure as it can cause inflammation of alveoli and other acute respiratory illnesses, inhalation fever and also gastrointestinal disorder. To detect the endotoxins using the rabbit pyrogen test (RPT) or the Limulus amebocyte lysate (LAL) there is need for a reference endotoxin. A new Lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]) derived from Escherichia coli O:113, Lot EC-6 is now used. The initial endotoxin derived from E. coli group O113:H10:Knegative produced 20 years ago has been depleted and has lost 40–0% activity of original its original potency according to researchers. The reference endotoxin is set at 5 Endotoxin Unit (EU) kg as the threshold and anything above this limit can cause endotoxic side effects, which is tested through the LAL and RPT. Solutions produced by pharmaceutical companies must be below the threshold to pass the process. Several techniques exist for the monitoring and removal of endotoxins, such as ion-exchange chromatography, affinity adsorbents, gel filtration chromatography and ultrafiltration. These techniques are target-specific and cannot be used widely as a standardized method. The success rate is variable and is highly dependent on the properties of the target protein. Nanotechnology provides a great effort and potential for endotoxin monitoring and detection, covering the development of nanomaterials for endotoxins and the use of the technology to provide diagnostic tools for endotoxins. All of these advances in using nanomaterials are to overcome the drawbacks and limitations of current systems while improving the accuracy of the diagnosis, which plays a vital role in diagnostics. This chapter will cover the applications of nanomaterials in the development of rapid diagnostics, such as bio-sensing devices for endotoxin monitoring.