Development of a gas chromatography silicon-based microsystem in clinical diagnostics

The accurate determination of biological parameters by means of rapid, on-line measurements at low-concentrations is an important task within the fields of pharmaceutical screening and medical diagnostic. Nevertheless, in biological samples, the analytes of interest are present as minor components in complex mixtures and with interfering species. Biosensors are the best candidates for these applications providing a direct solution to this need of accuracy, but their intrinsic selectivity often excludes all the other components in the sample. A separation step introduced prior to the sensing component could allow both the increase of selectivity with respect the interfering species and the identification of a large spectrum of molecular components in the sample. This work reports the development of a silicon-based integrated separation microsystem for gas chromatography aimed to biomedical applications, with particular emphasis to monitor the homovanillic acid (HVA) and vanillylmandelic acid (VMA) ratios in mass population screening for neuroblastoma diagnosis and prognosis. The miniaturised system consists of two main modules: (i) a metal oxide semiconductor detector and (ii) a micromachined separation capillary column. As first step, the metal oxide semiconductor capability to detect HVA and VMA has been demonstrated. Then, a technology for a silicon separation capillary microcolumn including the on-chip gas sensor housing has been proposed and a first prototype has been developed. The proposed microsystem is an analytical device with biosensing capabilities for diagnostic and biomedical applications, which yield an electronic signal proportional to the concentration of a specific analyte or group of analytes. (c) 2004 Elsevier B.V. All rights reserved.