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Accumulation of amyloid beta (Abeta) in the extracellular spaces of the cerebral cortex and in blood vessel walls as cerebral amyloid angiopathy is a characteristic of Alzheimer's disease (AD) and the ageing human brain. Studies in animals suggest that Abeta is eliminated from the brain either directly into the blood or along perivascular interstitial fluid drainage channels. The aim of the present study is to define the perivascular route for the drainage of Abeta from the human brain. Smears and paraffin sections of post-mortem cortical tissue from 17 cases of AD and from two controls were stained with thioflavin and for Abeta by immunohistochemistry. Histology and confocal microscopy showed that deposits of Abeta in the cortical parenchyma were continuous with Abeta in capillary walls but Abeta in artery walls was not in continuity with Abeta in brain parenchyma. Quantitative studies supported these observations. The results of this study suggest that when Abeta is eliminated from the extracellular spaces of the human brain by the perivascular route, it enters pericapillary spaces and from there drains along the walls of cortical arteries to leptomeningeal arteries. Factors such as overproduction of Abeta, entrapment of Abeta in drainage pathways and poor drainage of Abeta due to functional changes in ageing arteries might result in the failure of elimination of Abeta from the ageing brain and play a major role in the pathogenesis of AD. Such factors might affect therapies for AD that entail administration of anti-Abeta antibodies to eliminate Abeta from the human brain.

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The design of a novel, microfluidic chip with an integrated micro peristaltic pump and chambers for DNA amplification is described. This chip contains three reaction chambers stable at 90 • C, 72 • C and 55 • C for PCR amplification, a bi-directional peristaltic pump and optical integrated detection of the droplet. A reactant droplet is to be introduced into the device, pumped back and forth between the chambers by the micro peristaltic pump for sample processing. The static behaviour of the micro pump was modelled theoretically in order to evaluate the optimal dimensions for the pump membranes and to obtain the maximum flow rate. Thermal analysis by the finite element method was performed to optimize the location of the heaters and the temperature uniformity over the three reaction chambers. Transient thermal analysis indicates that the reactant droplet can be heated/cooled in the proposed device in less than 1 s to achieve the desired temperatures.

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