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Various formats of miniaturized arrays of cellulose-bound synthetic probe molecules to suit a broad range of technical and assay configurations have been produced by a novel process which we call spotting compound-support conjugates, SC 2 . This process involves parallel chemical assembly of the probe molecules by SPOT-synthesis on a special cellulose membrane, post-synthesis separation of the tethered compound spots, solubilization of the cellulose matrix and spotting of the soluble cellulose-probe conjugates onto various types of planar surfaces. The performance of such arrays are demonstrated using a set of synthetic peptide analogues, assayed with a monoclonal antibody, as well as utilizing a small molecule library of diketopiperazines assayed with fluorescently labelled calmodulin.

A fully automated synthesizer was constructed and designed to perform high speed miniaturized syntheses of compound libraries using the SPOT technique. Utilizing magnetically controlled drop-on-demand ink jet nozzles, an r/phi array format of 2500 spots can be simultaneously dispensed from up to 24 separate reagent valves onto a rotating disc as the solid phase in less than three minutes. In addition, a complete wash station is on board allowing for fully programmable combinatorial syntheses without manual attention. A new carbon black/polypropylene composite solid phase disc was developed and tested for its functionalisation/loading, spot detection, durability and MALDI-TOF target capabilities. The carbon black/polypropylene composite was then successfully employed jointly as the solid phase in the syntheses of short peptide and PNA oligomers and as the target probe holder for MALDI-TOF measurement without transfer of the material. Several protocols for PNA syntheses were also investigated and an optimised PNA methodology for the carbon black/polypropylene composite is reported.

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