Detecting endotoxin, a lipid-polysaccharide combination that is ground in the outer membranes of many types of bacteria, is a standard way to make the presence ofin a full array of drugs, medical supplies and equipment. The current technology is based on a complex variety of proteins isolated from the line of asays Nicholas Abbott, a professor and the president of chemical andat UW-Madison.
Abbott, an adept in surfaces of delicate materials, knows that liquid crystals have highly useful properties. "An unusual feature of a liquid crystal is that information travels through it over long distances. Many past studies have shown that events at a coat of a liquid crystal, which might touch only one level of molecules, can activate a shift in the order of the liquid crystal that propagates as thick as 100,000 molecules away from the interface."
In a report published Friday, May 20, in Science, Abbott and colleagues showed that concentrations of endotoxin in the picogram/milliliter range were adequate to spark a shift in the appearance of liquid crystalline droplets visible in a . "When we investigated the conduct of endotoxin with the liquid crystalline droplets, we were surprised to discover that we could decrease the concentration of endotoxin to extremely low levels and even see that vary in the order of the liquid crystals."
Abbott initially thinking that the changes in the liquid crystalline droplets would be due to the adsorption of the endotoxin to the surfaces of the droplets, but the density was too low to warrant this explanation. So Abbott and his graduate students I-Hsin Lin and Dan Miller along with colleagues in the NSF-sponsored UW-Madison Materials Research Science and Engineering Center determined that "the passage was not determined by adsorption of endotoxin over the rise of the liquid crystalline droplet, but rather by localization of the endotoxin at defects in the liquid crystal droplets."
The location of impurities to defects is "omnipresent" in material science, Abbott says, "and it appears that a similar phenomenon is occurring here, which then triggers the transition in thedroplet. This is a fundamentally different mechanics that gives boost to a layer of sensibility which is 10,000 to 100,000 higher than surface-driven transitions seen in past studies of liquid crystalline systems, and it suggests the ground for a really high point of sensitiveness in detection." Abbott also comments that "defect-driven ordering transitions in liquid crystalline systems have not been reported previously, and it is also highly surprising that it is so particular to the peculiar structure of endotoxin."
The defect-driven phenomenon that Abbott found could be more generally applicable than endotoxin, but he says "endotoxin in itself is somewhat important. Endotoxin comes from the outer membrane of Gram-negative bacteria, and is considered a key indication of bacterial infection." Animal immune systems themselves are tuned to reply to endotoxin, Abbott says, and the Food and Drug Administration requires testing for endotoxin on equipment used to produce vaccines, drugs, intravenous fluids and many other devices and materials.
The current FDA-approved test for endotoxin is based on the origin of horseshoe crabs, which have evolved to fight infection by clotting their ancestry in the front of endotoxin. Horseshoe crabs are captured, bled and so returned to the water. The horseshoe crab test is the "gold standard assay" for endotoxin, Abbott says, "but our system so far seems a bit more sensitive and does not imply any biological components. The shift in visual appearance of the droplets is rather striking, and it occurs inside a minute."
The find could be the first of a long road to commercialization, but Abbott cautions, "We have found a key phenomenon, but it's a long way to make a validated technology that can replace the horseshoe crab assay."
Horseshoe crabs are about of the most primitive multicellular organisms surviving on Earth, but Abbott believes they would still appreciate not having to donate blood quite so often.
Provided by University of Wisconsin-Madison (news : web)
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