In the computer
displays of medical equipment in hospitals and clinics, liquid crystal
technologies have already found a major role. But a discovery reported from the
Univ. of Wisconsin-Madison suggests that micrometer-sized droplets of liquid
crystal, which have been found to change their ordering and optical appearance
in response to the presence of very low concentrations of a particular
bacterial lipid, might find new uses in a range of biological contexts.
Detecting
endotoxin, a lipid-polysaccharide combination that is found in the outer
membranes of many types of bacteria, is a standard way to establish the
presence of bacterial contamination in a wide range of drugs, medical supplies,
and equipment. The current technology is based on a complex mixture of proteins
isolated from the blood of a horseshoe crab, says Nicholas Abbott, a professor and the chair of chemical and biological engineering at
UW-Madison.
Abbott knows
that liquid crystals have highly useful properties. “An unusual
characteristic of a liquid crystal is that information travels through it over
long distances. Many past studies have shown that events at a surface of a
liquid crystal, which might affect just one layer of molecules, can trigger a
change in the ordering of the liquid crystal that propagates as deep as 100,000
molecules away from the interface.”
In a paper
published in Science, Abbott and colleagues
showed that concentrations of endotoxin in the picogram/milliliter range were
enough to trigger a change in the appearance of liquid crystalline droplets
visible in a light microscope. “When we investigated the behavior of
endotoxin with the liquid crystalline droplets, we were surprised to find that
we could decrease the concentration of endotoxin to extremely low levels and
still see that change in the ordering of the liquid crystals.”
Abbott initially
thought 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
concentration was too low to justify 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 transition was not driven by adsorption of endotoxin
over the surface of the liquid crystalline droplet, but instead by localization
of the endotoxin at defects in the liquid crystal droplets.”
The localization
of impurities to defects is “ubiquitous” in material science, Abbott
says, “and it appears that a similar phenomenon is occurring here, which
then triggers the transition in the liquid crystal droplet. This is a
fundamentally different mechanism that gives rise to a level of sensitivity
which is 10,000 to 100,000 higher than surface-driven transitions seen in past
studies of liquid crystalline systems, and it suggests the basis for a very
high level of sensitivity 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
specific to the particular structure of endotoxin.”
The defect-driven
phenomenon that Abbott found could be more broadly applicable than endotoxin,
but he says “endotoxin in itself is pretty 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
respond to endotoxin, Abbott says, and the Food and Drug Administration
requires testing for endotoxin on equipment used to make vaccines, drugs,
intravenous fluids and many other devices and materials.
The current
FDA-approved test for endotoxin is based on the blood of horseshoe crabs, which
have evolved to combat infection by clotting their blood in the presence of
endotoxin. Horseshoe crabs are captured, bled and then 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 involve any biological components. The change in optical appearance of the
droplets is quite striking, and it occurs within a minute.”
The discovery
could be the start of a long road to commercialization, but Abbott cautions,
“We have found a fundamental phenomenon, but it’s a long path to have a
validated technology that can replace the horseshoe crab assay.”
Horseshoe crabs
are some of the most primitive multicellular organisms surviving on Earth, but
Abbott believes they would still appreciate not having to donate blood quite so
often.
