Tiny dishes etched on microscope slides act like ear trumpets A micro-ear could soon help scientists eavesdrop on tiny events just like microscopes make them visible. Initially, researchers will use it to snoop on cells as they go about their daily business. It may allow researchers to listen to how a drug disrupts micro-organisms, in the same way as a mechanic might listen to a car's engine to find a fault. A team from three UK institutions are building the device, which they hope will become standard lab equipment. Institutions involved include the Universities of Glasgow and Oxford as well as the National Institute of Medical Research at Mill Hill. Force feedback The micro-ear is based upon modifying an established technology that uses laser light to create so-called optical tweezers.These are already used to accurately measure tiny forces. They work by suspending very small glass or plastic beads in a beam of laser light. Measuring the movement of these beads as they are jostled by tiny objects allows measurements of tiny forces that operate at molecular scales. Please turn on JavaScript. Media requires JavaScript to play. "We are now using the sensitivity afforded by the optical tweezer as a very sensitive microphone," said Professor Jon Cooper from the University of Glasgow, who is heading the micro-ear project. "The optical tweezer can measure or manipulate at piconewton forces," said Professor Cooper. A piconewton is a millionth of the force that a grain of salt exerts when resting on a tabletop. While many researchers use single beams of laser light to trap single beads, the micro-ear team hopes to use several arranged in a ring that will be able to surround and "listen to" an object of interest. "We can look at a number of objects and watch them wobble," said Prof Miles Padgett. "A wobbling object is like a diaphragm on a microphone." HOW TO MEASURE MICRO-ORGANISMS 1. Scientists are using laser beams to help them measure the sounds created by microscopic organisms. 2. A micro-organism, such as an E-coli bacterium, is placed in the centre of a ring of laser beams each of which traps tiny electrically-charged beads. The beads are one or two microns across - that's 100 times thinner that a human hair. 3. Any sound from the organism will be detected by the beads wobbling and this can be measured by a high-speed camera.

As such, said Professor Padgett, the wobble can be measured and used to turn the wobbles in the fluid surrounding the subject into sound giving an ear to events on the tiniest of scales. By surrounding an object, said Professor Padgett, it should be easier to work out whether what that object does is the result of its own actions or something else. A high-speed camera watches the motion of the ring of beads to determine the source of the motion. Prof Padgett said work on refining the basic elements of what would become the eventual micro-ear was going well. "We can trap and hold the beads and can connect the output to a speaker so we can hear them vibrating," he said. In addition, he said, the team use tiny etched dishes, like a Victorian ear trumpet, to help focus the movements in the fluid surrounding an object and make them easier to pick up. Already the team has been able to listen to Brownian motion - the restless jostling of the atoms and molecules in a fluid. Drug trials Once the device is completed, a team led by Dr Richard Berry, a physicist at the University of Oxford, plans to use it to eavesdrop on flagella - the tiny motor that many bacteria such as E. coli use to move themselves around. "Because this tech is so new and these guys are exploring what's possible the flagellar motor will be a very good test for the technology," said Dr Berry. Currently, the movement of flagella are studied by sticking tiny beads to them and watching them whip around with a high-speed camera. The beads are different to those used in the optical tweezers. To complicate the process further, scientists must genetically engineer the bacteria to allow them to stick the beads on their tails. "We have to make them specifically sticky to what we want to stick to them," said Dr Berry. "There's a biological step which can be very hit and miss." This also means that the bacteria do not necessarily behave in the same way as natural organisms. "We work on extremely genetically engineered subjects, nothing like you would find in the world," he said. The micro-ear makes it possible to listen to a flagella whipping around The micro-ear might mean it is possible to use wild bacteria and many of them to get a much better understanding of what they do. If the work with bacteria is successful the team is also planning to look at other micro-organisms. One candidate could be the human trypanosome parasite which moves in the blood using a different sort of flagellar motor. The parasite is behind sleeping sickness that affects up to 500,000 people a year in sub-Saharan Africa. By listening to this motor, it may be possible to better understand how it works and ultimately investigate the action of new medicines that might stop its motor. "Its truly exploratory in that we expect and hope we will hear something interesting but we really don't know," said Dr Berry.



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