Therapeutic agents intended to reduce dental plaque and prevent tooth decay are often removed by saliva and the act of swallowing before they can take effect. But a team of researchers has developed a way to keep the drugs from being washed away. Dental plaque is made up of bacteria enmeshed in a sticky matrix of polymers—a polymeric matrix—that is firmly attached to teeth. The researchers, led by Danielle Benoit at the University of Rochester and Hyun Koo at the University of Pennsylvania’s School of Dental Medicine, found a new way to deliver an antibacterial agent within the plaque, despite the presence of saliva. Their findings have been published in the journal ("pH-Activated Nanoparticles for Controlled Topical Delivery of Farnesol To Disrupt Oral Biofilm Virulence"). 
Farnesol is released from the nanoparticle carriers into the cavity-causing dental plaque. (Graphic by Michael Osadciw/University of Rochester). (click on image to enlarge) “We had two specific challenges,” said Benoit, an assistant professor of biomedical engineering. “We had to figure out how to deliver the anti-bacterial agent to the teeth and keep it there, and also how to release the agent into the targeted sites.” To deliver the agent—known as farnesol—to the targeted sites, the researchers created a spherical mass of particles, referred to as a nanoparticle carrier. They constructed the outer layer out of cationic—or positively charged—segments of the polymers. For inside the carrier, they secured the drug with hydrophobic and pH-responsive polymers. The positively-charged outer layer of the carrier is able to stay in place at the surface of the teeth because the enamel is made up, in part, of HA (hydroxyapatite), which is negatively charged. Just as oppositely charged magnets are attracted to each other, the same is true of the nanoparticles and HA. Because teeth are coated with saliva, the researchers weren’t certain the nanoparticles would adhere. But not only did the particles stay in place, they were also able to bind with the polymeric matrix and stick to dental plaque. Since the nanoparticles could bind both to saliva-coated teeth and within plaque, Benoit and colleagues used them to carry an anti-bacterial agent to the targeted sites. The researchers then needed to figure out how to effectively release the agent into the plaque. A key trait of the inner carrier material is that it destabilizes at acidic—or low pH—levels, such as 4.5, allowing the drug to escape more rapidly. And that’s exactly what happens to the pH level in plaque when it’s exposed to glucose, sucrose, starch, and other food products that cause tooth decay. In other words, the nanoparticles release the drug when exposed to cavity-causing eating habits—precisely when it is most needed to quickly stop acid-producing bacteria. The researchers tested the product in rats that were infected with - a microbe that causes tooth decay. “We applied the test solutions to rats’ mouths twice daily for 30 seconds, simulating what a person might do using a mouth rinse morning and night,” said Hyun Koo, a professor in the Department of Orthodontics and co-senior author of the work. “When the drug was administered without the nanoparticle carriers, there was no effect on the number of cavities and only a very small reduction in their severity. But when it was delivered by the nanoparticle carriers, both the number and severity of the cavities were reduced.” Plaque formation and tooth decay are chronic conditions that need to be monitored through regular visits to the dental office. The researchers hope their results will someday lead to better—and perhaps permanent—treatments for dental plaque and tooth decay, as well as other biofilm-related diseases.
Farnesol is released from the nanoparticle carriers into the cavity-causing dental plaque. (Graphic by Michael Osadciw/University of Rochester). (click on image to enlarge) “We had two specific challenges,” said Benoit, an assistant professor of biomedical engineering. “We had to figure out how to deliver the anti-bacterial agent to the teeth and keep it there, and also how to release the agent into the targeted sites.” To deliver the agent—known as farnesol—to the targeted sites, the researchers created a spherical mass of particles, referred to as a nanoparticle carrier. They constructed the outer layer out of cationic—or positively charged—segments of the polymers. For inside the carrier, they secured the drug with hydrophobic and pH-responsive polymers. The positively-charged outer layer of the carrier is able to stay in place at the surface of the teeth because the enamel is made up, in part, of HA (hydroxyapatite), which is negatively charged. Just as oppositely charged magnets are attracted to each other, the same is true of the nanoparticles and HA. Because teeth are coated with saliva, the researchers weren’t certain the nanoparticles would adhere. But not only did the particles stay in place, they were also able to bind with the polymeric matrix and stick to dental plaque. Since the nanoparticles could bind both to saliva-coated teeth and within plaque, Benoit and colleagues used them to carry an anti-bacterial agent to the targeted sites. The researchers then needed to figure out how to effectively release the agent into the plaque. A key trait of the inner carrier material is that it destabilizes at acidic—or low pH—levels, such as 4.5, allowing the drug to escape more rapidly. And that’s exactly what happens to the pH level in plaque when it’s exposed to glucose, sucrose, starch, and other food products that cause tooth decay. In other words, the nanoparticles release the drug when exposed to cavity-causing eating habits—precisely when it is most needed to quickly stop acid-producing bacteria. The researchers tested the product in rats that were infected with - a microbe that causes tooth decay. “We applied the test solutions to rats’ mouths twice daily for 30 seconds, simulating what a person might do using a mouth rinse morning and night,” said Hyun Koo, a professor in the Department of Orthodontics and co-senior author of the work. “When the drug was administered without the nanoparticle carriers, there was no effect on the number of cavities and only a very small reduction in their severity. But when it was delivered by the nanoparticle carriers, both the number and severity of the cavities were reduced.” Plaque formation and tooth decay are chronic conditions that need to be monitored through regular visits to the dental office. The researchers hope their results will someday lead to better—and perhaps permanent—treatments for dental plaque and tooth decay, as well as other biofilm-related diseases.
Growth of a quantum crystal: The thicker blue dots are giant atoms in the Rydberg state which form a quantum crystal. The geometry of the growing crystal changes stepwise from left to right with every Rydberg atom added. The largest quantum crystal with eight atoms can be seen on the right. (Image: Science 2015 / Max Planck Institute of Quantum Optics) Normal magnetism, as occurs in iron, for example, resembles the situation on an estate of terraced houses during a soccer World Cup match. The live broadcast is being watched in every home and as soon as the national team scores a goal, collective roars of delight can be heard through the open windows. In crystalline solids, which include normal magnets, the atoms contributing to the magnetism are ordered in a way which resembles rows of terraced houses. Specific electrons in these atoms align in one direction like tiny compass needles. They join together to form a collective magnetism, just as the shouts of joy from the houses swell to a mighty collective roar. This familiar magnetism is called ferromagnetism, after the Latin word ferrum for iron. There are other forms as well: in antiferromagnetism, adjacent electronic compass needles align themselves in opposite directions. This corresponds to an estate of terraced houses in which every other neighbour is a supporter of the other football team – and the match ends in a draw. Physicists learn a great deal when they tinker with quantum systems There are many other intermediate forms of magnetism between these two magnetic extremes. Moreover, these collective quantum effects play an important role in other physical phenomena as well, for example in superconductivity: a state in which some materials conduct electricity without resistance at low temperatures. This is the reason why investigating these effects is so important. But real crystals whose atoms are connected permanently with each other have several disadvantages: it is difficult to look deep into them in experiments, and gigantic numbers of atoms and electrons are always involved. Above all, researchers can exert very little influence on the interactions which lead to a collective phenomenon such as magnetism. Yet it is precisely this tinkering around with quantum systems that enables physicists to learn a great deal about the quantum world. This is why scientists are putting their hope in artificial crystals with a manageable number of atoms which are easily accessible. Above all, the interactions between them can be wonderfully manipulated. Christian Groß’s team in Garching is working with such a system. It consists of a cloud of between 250 and 700 rubidium atoms which are frozen at very low temperatures. The individual atoms are easy to trap, as they move relatively slowly. The particles are trapped by a lattice of laser beams: one atom is caught at each crossing point, creating an order resembling a crystal. And most importantly: by cleverly irradiating the crystal with additional laser light, the physicists can now manipulate the interactions between the atoms – and even the atoms themselves. “This is a very tidy system in which we can study the individual processes at the quantum level in detail,” says Christian Groß. This new quantum tool is so flexible and powerful that it has already set itself apart from the pure simulation of real solid state crystals. This especially applies to the latest research work of the team headed by the postdoc. Magnetic interactions as vuvuzela collective Together with the theoretical physicists in Thomas Pohl’s Group at the Max Planck Institute for the Physics of Complex Systems in Dresden, the Garching-based researchers asked themselves the following question: What would happen if the interaction between magnetic atoms in the quantum collective was very long range? With normal magnetism, this interaction is limited to short distances: it is primarily the immediate neighbours that have a mutual effect on each other. Returning to our hypothetical estate of terraced houses, a long range would correspond to a situation where every tenth neighbour had a vuvuzela which they could use to join together for a particularly loud noise collective across the intervening houses. If, however, the neighbours in between were now also to reach for their vuvuzelas, the peace would be shattered so lastingly that it would no longer be possible to establish order on the estate. The quantum system with which Groß and his team have now formed a completely new type of magnetic crystal behaves in a very similar way. To this end, the researchers in Garching irradiated the atoms trapped in the light lattice with a special laser light. With its energy, they pumped up some of the atoms – in simple terms – so they became exotic, giant atoms. Like those with vuvuzela on the estate, these Rydberg atoms are able to affect other atoms across many neighbouring atoms. “A giant atom of this type is a thousand times bigger than a normal atom,” explains Groß. Its outermost electron is extremely far away from the nucleus and turns the giant atom into a kind of antenna. It can thus affect other Rydberg atoms, which also act as antennas, so that they form a common, crystalline order – just like the vuvuzela owners joining up for coordinated tooting across many houses. “The atoms remain in the Rydberg state for only a few millionths of a second,” explains Groß: “But in the quantum world, this is an extremely long time.” It is sufficient for an attractive order. Giant atoms form a magnetic crystal Similar to baking cookies, the Garching-based researchers cut out either elongated or circular shapes from the cloud of several hundred rubidium atoms trapped in the light lattice, and in these shapes they pump up individual atoms with their laser to turn them into Rydberg atoms. The elongated shapes gave rise to one-dimensional chains of giant atoms that together formed a magnetic crystal; the circular disks produced two-dimensional crystals of up to eight Rydberg atoms. It turned out here that the size of this cut-out determined how many giant atoms were involved in the magnetism. The distance between them always remained the same and corresponded approximately to ten atoms of the light lattice. With the one-dimensional cut-out, two, then three, finally four Rydberg atoms formed a quantum crystal in stages. It is also important to be aware that normal magnetism knows only two states on the quantum level of individual electrons in solids: like rotary switches, the electrons can only click into place when they are parallel or antiparallel to the magnetic field applied. In the Garching system, Rydberg atoms represent the switching state of parallel to the magnetic field; antiparallel, in contrast, corresponds to the rubidium atoms in the light lattice when they are not excited to giant atoms. The special laser light enables the physicists to switch specifically between these two quantum states. The researchers in Garching are thus in perfect control of their system. They have thereby created a tool which they can use to investigate the collective behaviour of these quantum systems in more detail. The aim is not only to obtain a deeper understanding of magnetism: in principle, this tool can reproduce the behaviour of many complex quantum systems. As “quantum simulators”, they can perhaps even help to answer fundamental questions in other fields, such as particle physics for example.
The plasmonic phase modulator is an inverted, nanoscale speed bump. Gold strands are stretched side by side across a gap just 270 nanometers above the gold surface below them. Incoming plasmons travel though this air gap between the bridges and the bottom gold layer. Incoming plasmons travel though this air gap between the bridges and the bottom gold layer. Lowering the "bump" with a control voltage squeezes the gap and makes the device function like a plasmon switch. (Image: Dennis/Rutgers and Dill/NIST) The team, which included researchers from Rutgers, the University of Colorado at Colorado Springs, and Argonne National Laboratory, fabricated their device using commercial nanofabrication equipment at the NIST NanoFab. Small enough to serve in existing and future computer architectures, this technology may also enable electrically tunable and switchable thin optical components. Their findings were published in ("Compact nano-mechanical plasmonic phase modulators"). The plasmonic phase modulator is effectively an inverted, nanoscale speed bump. Eleven gold strands are stretched side by side like footbridges across a 23-micrometer gap just 270 nanometers above the gold surface below them. Incoming plasmons, created by laser light at one end of the array, travel though this air gap between the bridges and the bottom gold layer. When a control voltage is applied, electrostatic attraction bends the gold strands downwards into a U shape. At a maximum voltage--close to the voltages used in today's computer chips--the gap narrows, slowing the plasmons. As the plasmons slow, their wavelength becomes shorter, allowing more than an extra half of a plasmonic wave to fit under the bridge. Because it's exactly out of phase with the original wave, this additional half wavelength can be used to selectively cancel the wave, making the bridge an optical switch. At 23 micrometers, the prototype is relatively large, but according to NIST researcher Vladimir Aksyuk, their calculations show that the device could be shortened by a factor of 10, scaling the device's footprint down by a factor of 100. According to these calculations, the modulation range can be maintained without increase in the optical loss, as the length and the size of the gap are reduced. "With these prototypes, we showed that nanomechanical phase tuning is efficient," says Aksyuk. "This effect can be generalized to other tunable plasmonic devices that need to be made smaller. And as they get smaller, you can put more of them on the same chip, bringing them closer to practical realization."