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O rats! An oxygen microsensor implanted in rat brains and chew more, increasing regional cereIn the laboratory of Pier Andrea Serra at shape reduces the amount of damage done to the brain. The final sensor meabral blood flow and oxygen levels. Inthe University of Sassari (Italy), rats go sured just ⬃250 m in length and had a duced grooming (i.e., misting the rats about their usual ratty lives. But these with water) had the same effect. animals differ in a significant way from tip ⬍25 m in diameter. Other studies with the rats included ordinary lab rats: they have an oxygenOnce the sensor design was done, induced hyperoxia and hypoxia (adding sensing electrode implanted in their the researchers turned to building the O2 and N2, respectively, to the heads. Serra and colleagues have designed this device so that they rats’ environment) and exposure can directly monitor the oxygen to acetazolamide, a carbonic anconcentration in the brains of hydrase inhibitor known to infreely moving rats. The researchcrease the level of brain oxygen. ers describe this device in a recent In all cases, the sensor’s readings AC paper (DOI 10.1021/ correlated with previous meaac802390f). surements obtained by another The most common method method, the implanting of for monitoring concentrations of “wired” carbon-paste sensors. small analytes in the extracellular Serra and colleagues have big (a) The biotelemetric device affixed to a rat’s head, and (b) a fluid within brain tissue is miplans for their device. First, they microphotograph of the conical oxygen microsensor. crodialysis. In this technique, a would like to experiment with probe with a semipermeable sensor design. “The next step membrane is inserted into the tissue and biotelemetric device. Serra says that the would be to develop a new kind of biogroup tried a new approach during this allowed to equilibrate. The dialysate sensor using this same shape and this project: rather than trying to fit the senwithin the probe is then analyzed by same approach but changing the matesor into an existing electronics system, HPLC or CE. Microdialysis, although rial of the transducer,” Serra says. They useful, is relatively slow and is difficult to they instead designed the electronics are also set to try out the sensors in huaround the sensor. “First, the sensor and mans. “We hope to start very soon with use to obtain an absolute concentration the neurochemistry, then the electronics of analytes within the brain. some preliminary clinical studies, not in Serra and colleagues therefore set out adapted to itOthis is the best solution the brain, unfortunately, at the moment, to reduce cost and have a very clever to make an implantable sensor that but in the peripheral tissues,” Serra says. device,” Serra explains. could report oxygen concentration in “For example, during major aortic surSerra says that the interdisciplinary the extracellular fluid in real time. “We gery...we can study oxygen in the leg.” —Jennifer Griffiths need new tools for obtaining a new kind nature of his group helped pull the project together. “We first developed of information from the brain,” Serra the sensor in the classical mannerOin says. “The first thing is the real-time a classical analytical chemistry lab,” he readings of the oxygen, and the second says. “After that, we integrated the thing is the separation between brain electronics. ... Then we adapted first a oxygen and brain blood flow.” prototype [of the electronics] to the The desire to study oxygen within sensor.” Finally, the whole setup was brain tissue but not within brain blood miniaturizedOthe final device weighed vessels greatly influenced the design of just 9.6 gOand integrated with the the sensor. It couldn’t be too big or too group’s in vivo work. smallOit had to be just right. “We preThat’s where the rats come in. The fer a large-size sensor to prevent the imresearchers neurosurgically implanted the plantation of the microsensor in a blood vessel,” Serra explains. But the larger the device into the rats and let the animals recover for 12⫺24 hours. After recording sensor, the more tissue damage it will a baseline oxygen level, they applied varicause during implantation. This problem led the group to design ous stimuli to the otherwise freely moving rats and measured how brain oxygen levels a unique, conical carbon microsensor. changed. A tail pinch (i.e., a paper clip on “We need to implant it in the brain tisthe tail) caused the rats to move around sue directly,” says Serra, and the conical 2416
ANALYTICAL CHEMISTRY /
APRIL 1, 2009
10.1021/AC900197Z 2009 AMERICAN CHEMICAL SOCIETY
Published on Web 02/17/2009
