ALBUQUERQUE, N.M. — A biochemical technique being refined at Sandia National Laboratories may soon enable sensors that can in seconds detect the equivalent of one contaminant particle among a billion other molecules in waste streams.
The technique makes use of molecular bundles called “liposomes” that are tailored to react with certain metal ions in solution. A Sandia team is studying ways to entrap these spherical liposomes in porous silica materials called sol-gels – essentially whipped glasses – which may open doors to a variety of practical inventions, from water purity sensors in microchip factories to molecule-sized metal detectors for environmental cleanup operations.
Eventually the technique might enable a family of biosensors that could rapidly and from the convenience of home indicate whether a person has a virus.
Sensors for identifying very low-level concentrations of airborne biological weapons agents, which might be useful for Sandia’s treaty verification work, are among a list of intriguing national security uses for this type of sensor. The technique relies on a biochemical process discovered a few years ago at the California Institute of Technology, where researchers were studying ways to purify protein samples by patterning thin-film materials with liposomes. Depending on the chemical roles assigned to reactive molecular groups on the liposomes’ surfaces, areas on the film could selectively bond with certain proteins and reject others.
Former Caltech post-doc Darryl Sasaki, who now leads the Sandia research, found that when he added copper ions to a liquid solution containing liposomes he had created, the sample’s color emission under a fluorescence spectrophotometer changed from green to blue very rapidly. The researchers surmised that the introduction of charged metal ions prompted the liposomes to scramble their molecular arrangements to incorporate the new ions, thereby altering their fluorescence signal.
“When the reactive head [surface] groups accept the metal ions, they develop equally strong ionic repulsive forces, causing them to disperse across the surface of the liposome,” says Sasaki. “We think the color change results from this dispersion.”
The liposomes reacted to other metals as well manganese, cobalt, calcium, and nickel, among them. Their high sensitivities to metals suggested uses outside the protein-separation arena. “We began to see this as a candidate technology for practical sensors that could rapidly detect heavy metals in nanomolar concentrations,” says Sasaki, who joined Sandia in 1994 and began studying ways to turn the liposomes into practical sensors.
Because the liposomes are chemically fragile, the liposome-bearing solutions had a brief shelf life. Also, the liposomes weren’t very practical for sensor applications when free-floating in a liquid. A solid, dry medium was needed, one that could physically immobilize the liposomes while stabilizing them chemically.
To solve these problems, Sasaki and Sandia team members developed a procedure to entrap the liposomes in sol-gels, a class of solid, lightweight, silica-based materials Sandia has studied for decades as part of its materials science program. The entrapped liposomes reside within cavities in the porous sol-gel matrix but are not chemically attached to the matrix.
Not only did the sol-gel-entrapped liposomes react rapidly to metal ions, their sensitivities were 4 to 50 times greater than those observed for the liposomes in solution in the parts-per-billion range. Sasaki thinks the negatively charged silica surface (a product of sol-gel formation) acts like an ionic sponge, increasing concentrations of positively charged metal ions near the sol-gel material’s surface and the odds that a metal ion will encounter and react with a liposome.
Theoretically, liposomal molecules can be created with parts-per-billion sensitivities to a variety of contaminants commonly found at environmental remediation sites. Such liposomes entrapped in sol-gels could lead to practical sensors for rapidly detecting very low levels of heavy metal or radionuclide contamination in groundwater for site characterization applications. The Sandia team now is working to create liposomal sensors targeted for lead, mercury, and chromium.
Similar in-situ sensors might rapidly detect parts-per-billion concentrations of iron, copper, zinc, nickel, lead, or other contaminants common to process streams at microchip fabrication facilities, a capability that could help chip manufacturers ensure that recycled process water is as contaminant-free as possible. (Ultraclean process water recycling is a major concern in the microelectronics industry as manufacturers strive to reduce water use). One sensor company already has expressed an interest in such a technology.
Other uses for sol-gel entrapped liposomes could include rapid laboratory or in-home virus detectors. “You might put saliva or a blood sample on a strip of this sol-gel material,” he says, “and the sensor’s color would change depending on whether it detected a virus the liposomes were looking for.”
Sandia is working with Lawrence Berkeley National Laboratory researcher Deborah Charych on recognition groups for viral particles, and the team already has created a sol-gel-entrapped liposome that shows high sensitivity to a common influenza (flu) virus. Charych has developed a working sensor targeted for the cholera toxin, which causes a potentially fatal bacterial disease, as well.
For sensor applications, sol-gels have a number of advantages over other materials, Sasaki says. They can be applied as a thin film to a variety of surfaces or cast in bulk form into nearly any shape. They are optically clear, so liposomal color changes would be easy to read. The entrapped liposomes seem impervious to fungal or bacterial attack even after months on a laboratory shelf. And they’re durable – the liposomes remain intact even when the sol-gel structure is damaged.
In addition, says Sasaki, the very few in-situ heavy metal sensors available today typically require minutes to hours to respond definitively in the parts-per-billion range. The liposomes themselves respond in less than a second. The team is experimenting with sol-gel film thicknesses to get response times down when they are entrapped in sol-gel.
“This would be an inexpensive, rapid, highly sensitive detection capability that we hope will soon find use in a variety of sensor applications,” Sasaki says.
The work is funded through the Lab’s Research Foundations program, which identifies and supports the long-range study of promising technologies with possible national security and nondefense applications.
Sandia is a multiprogram Department of Energy laboratory operated by a subsidiary of Lockheed Martin Corp. With main facilities in Albuquerque and Livermore, Calif., Sandia has broad-based research and development programs contributing to national security, energy and environmental technologies, and economic competitiveness.
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Technical contact:
Darryl Sasaki, dysasak@sandia.gov (505) 845-0824