Surface chemistry of biochips: fundamental aspects

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Biochips are high-throughput analytical tools for fast, quantitative, and simultaneous detection of multiplex biological samples (DNA, proteins, and peptides). In particular, DNA microarrays (also called DNA chips or gene chips), which were the first to be developed, are used for genetic screening, i.e., to identify the nucleotide sequences of mutated genes associated with human disease. Knowledge of surface chemistry is indispensable for the manufacture of such biochips; many fundamental aspects are common to the different types of these miniaturized devices. For instance, critical factors affecting the detection efficiency of target analytes are the design of probe molecules, their immobilization on the chip, and the sensitivity of the signal read-out method. Our research is currently targeting the DNA microarrays, with the intent of extending it to more challenging systems (e.g., protein and carbohydrate chips) later. The proposed project will initially focus on immobilization strategies of DNA probes on novel substrate materials (gold and silicon) to achieve optimum surface density, chemical stability, and molecular orientation. The next phase will encompass a study of the fundamental thermodynamic and kinetic principles governing biochip design, fabrication, and performance, i.e., we will explore DNA monolayers on gold as model systems to evaluate the effect of temperature, ionic strength, probe layer structure, and base-pair mismatches on the efficiency and rate of on-chip hybridization. This will be followed by the electrochemical and solid-state electrical characterization of DNA -modified silicon surfaces, and by the construction of microelectrode arrays to attach multiple DNA probes for sensitive and cost-effective gene analysis.