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Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors

Exploitable results

A prototype instrument has been developed for continuous and rapid monitoring of the blood chemistry of patients in intensive care. The instrument employs a microdialysis 'mini-shunt' to extract molecules of interest from the bloodstream, and miniaturized flow system to handle very small volumes of fluid, new biosensors to measure small amounts of glucose and lactate, and a computer system to process and display the results in real time. At the heart of the instrument is a biosensor, a device that detects the presence of specific molecules by their interaction with an enzyme placed onto an electrode. By an appropriate choice of enzyme, biosensors can be made sensitive to a variety of molecules including, in this case, glucose or lactate. Microdialysis is used to take a sample of glucose and lactate from the blood. A catheter diverts a small flow of blood around a circuit and back to the body. In one section of the circuit the blood flows through a 'mini-shunt'. This consists of an outer tube, in which the blood flows, surrounding a thin hollow fibre containing a fluid flowing in the opposite direction. The fibre is porous to small molecules such as glucose and lactate but holds back large molecules such as proteins. As the blood flows over the fibre, glucose and lactate molecules pass through into the collecting fluid inside. Rates of fluid flow through the fibre, however, are extremely slow. The instrumentation required to handle this fluid must be correspondingly small if the system is to produce measurements quickly. The answer was to use a 'microflow stack' of 22-mm square silicon wafers. The sample fluid comes in at the top of the stack and then trickles down through holes and channels etched into the wafers until it reaches the biosensors at the bottom. It then passes back up through the stack and is finally collected for disposal. The stack allows calibration solutions to be directed to the sensors and also permits other chemicals to be mixed with the sample fluid where required. The sensors themselves, and the fluid cell containing them, are formed directly on to a printed circuit board by thin-film technology. The combined flow volume of the stack and cell is only 8 microlitres. The entire system is controlled by a laptop computer running software designed at Dublin City University.