Antibiotic resistance is a $55 billion-a-year problem in the United States, and all signs point to it getting worse.
Researchers at the University of Houston are on the case.
Their work suggests a potential solution that is quick and doesn’t require a lot of power, meaning it’s more likely to be used in the real world. A paper published last spring outlined their process of killing even heat-resistant bacteria within seconds by using light to heat porous gold nanodisks.
The prototype builds on work Wei-Chuan Shih, associate professor of electrical and computer engineering, has pursued for several years, including his 2013 discovery that porous gold nanoparticles can reach high temperatures through light absorption. The fact that the nanodisks were highly porous—which increased the surface area—improved the heating efficiency without jeopardizing stability.
That triggered the effort to find potential uses for the technique.
Shih knew hospital-acquired infections and antibiotic resistance were big problems, and he thought his discovery could help. “It was important that we could develop a method that was fast and that didn’t require a large amount of power,” Shih said. “Those qualities are what make this something that will be very useful to people.”
Antibiotics and similar drugs—known as antimicrobial agents—have been the go-to response to bacterial infections since the 1940s, saving untold numbers of lives. But their very success is also their downfall: the infectious organisms that antibiotics once routinely wiped out have adapted, making the drugs less effective. In the United States alone, at least 2 million people become infected with antibiotic-resistant bacteria, according to the Centers for Disease Control and Prevention. At least 23,000 people die each year as a result.
The most alarming news yet came in May, when researchers with the U.S. Department of Defense reported that for the first time they had found a person in the United States carrying bacteria resistant to the antibiotic of last resort, colistin. Top public health officials said society could be entering a post-antibiotic world, with no drugs to treat an increasing number of infections.
It is against that backdrop that Shih and his colleagues—Debora Rodrigues, associate professor of civil and environmental engineering, post-doctoral fellows Greggy M. Santos and Felipe Ibañez de Santi Ferrara and doctoral student Fusheng Zao—published their findings in Optical Materials Express last March. In a world hungry for good news in the battle against infectious disease, the work proposing a new method of sterilization drew immediate attention.
Hospitals and other settings already use heat to sterilize equipment, but those methods, usually involving an autoclave or dry oven, can take minutes or even hours to work. Shih’s method works within seconds.
And it can be used repeatedly.
“NPGD (nanoporous gold disk) arrays can undergo multiple photothermal cycles without the loss of efficiency, a critical feature for preventing recurring bacterial proliferation in situ,” the researchers wrote. “The NPGD array can also be employed as a fixed antibacterial substrate for disinfecting contaminated liquid flow systems. Hence, these characteristics make it a robust and rapid antibacterial platform suitable for various biomedical applications.”
Shih and his lab, the NanoBioPhotonics Group, had been exploring the reaction of gold nanoparticles to light for a while.
“When you shine a light on it, you can excite the electrons,” he said. “When you shine a light at the right wavelength, they move in concert.” That makes for an effective photothermal device, or a device that works through light-activated heat.
Separately, Shih works to harness the oscillation of electrons for sensing applications. He has filed for a patent to use the material for both applications.
Rodrigues, whose own research focuses on bio- and nanotechnologies to reduce energy costs in water and wastewater treatment, provided bacteria samples and contributed work on cell viability testing. Researchers worked with E. coli, a common bacterium that frequently spreads in hospitals, as well as two other strains of bacteria, B. subtilis and Exiguobacterium.
Each strain was prepared and deposited on surfaces coated with an array of nanoporous gold disks, then tested after being exposed to near-infrared light at 5, 10, 15, 20, 25 and 30 second intervals.
E. coli proved most vulnerable—the researchers reported 100 percent of the bacteria were killed within five seconds. It took 25 seconds to kill all B. subtilis and Exiguobacterium.
More light—such as that emitted by a microwave oven—can deliver more heat, but it also can damage biological tissues, Shih said.
“There is a window for light-based biotechnologies, and this fits within it,” he said. “If you want to illuminate something implanted in the body, you can’t use infrared light, because it is too hot. These gold nanoparticles can absorb light within the useable window.”
The key, he reported earlier, is the additional surface area afforded by the porous nature of the particles. The particles themselves are tiny, between 400 and 500 nanometers in diameter. That’s about 0.00002 inches, far too small to be seen with the eye or with a light microscope. At that size, Shih said, nanoparticles normally aren’t very efficient at converting light to heat. But because the particles designed by his lab are porous, they have a larger surface area and are able to convert at a much higher ratio.
The particles are created in the Nanofabrication Lab at UH, starting as an alloy of gold and silver. The silver is removed after an acid treatment, and Shih said the gold self-assembles into a porous network.
Why gold instead of silver or another metal? Shih said the chemical properties of specific metals determine what happens when the electrons are “excited,” or stimulated to move through the use of light. The electrons in gold are compatible with a safe wavelength of light.
And gold is also biocompatible, safe to use for health care applications, he said. “Gold is inert. It won’t degrade or react with anything else.”
That, along with the rapid sterilization, makes the technique potentially game-changing. Shih offers one example for its potential use: Many hospital-acquired infections are caused by urinary catheters, which currently must be removed and disassembled to clean. The nanodisks could be applied as a coating, allowing the catheter to be cleaned within seconds with a blast of light.
The nanodisks could also be sprayed or injected into an infected wound, he said.
Work to refine the technology is on-going, and Shih said the lab hopes to develop it for use in diagnosis and cancer treatment.
A tool that could offer immediate information about bacteria levels or even the presence of cancer cells would be useful for health care professionals, he said. It also might be possible to attach a nanoparticle to a tumor, allowing doctors to treat the cancer by shining a light and generating heat.
And it all starts with the porous gold nanodisks. “The patterning step is critical,” Shih said. “We have done the most work in the world on this.”