A solvent-free matrix application method for matrix-assisted laser desorption/ionization imaging of small molecules

Matrix application continues to be a critical step in sample preparation for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). Imaging of small molecules such as drugs and metabolites is particularly problematic because the commonly used washing steps to remove salts are usually omitted as they may also remove the analyte, and analyte spreading is more likely with conventional wet matrix application methods. We have developed a method which uses the application of matrix as a dry, finely divided powder, here referred to as dry matrix application, for the imaging of drug compounds. This appears to offer a complementary method to wet matrix application for the MALDI-MSI of small molecules, with the alternative matrix application techniques producing different ion profiles, and allows the visualization of compounds not observed using wet matrix application methods. We demonstrate its value in imaging clozapine from rat kidney and 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylic acid from rat brain. In addition, exposure of the dry matrix coated sample to a saturated moist atmosphere appears to enhance the visualization of a different set of molecules.

Computer-assisted production scheduling, planning and control in foundries

The present study describes a pragmatic approach to the implementation of production planning and scheduling techniques in foundries of all types and looks at the use of `state-of-the-art' management control and information systems. Following a review of systems for the classification of manufacturing companies, a definitive statement is made which highlights the important differences between foundries (i.e. `component makers') and other manufacturing companies (i.e. `component buyers'). An investigation of the manual procedures which are used to plan and control the manufacture of components reveals the inherent problems facing foundry production management staff, which suggests the unsuitability of many manufacturing techniques which have been applied to general engineering companies. From the literature it was discovered that computer-assisted systems are required which are primarily `information-based' rather than `decision based', whilst the availability of low-cost computers and `packaged-software' has enabled foundries to `get their feet wet' without the financial penalties which characterized many of the early attempts at computer-assistance (i.e. pre-1980). Moreover, no evidence of a single methodology for foundry scheduling emerged from the review. A philosophy for the development of a CAPM system is presented, which details the essential information requirements and puts forward proposals for the subsequent interactions between types of information and the sub-system of CAPM which they support. The work developed was oriented specifically at the functions of production planning and scheduling and introduces the concept of `manual interaction' for effective scheduling. The techniques developed were designed to use the information which is readily available in foundries and were found to be practically successful following the implementation of the techniques into a wide variety of foundries. The limitations of the techniques developed are subsequently discussed within the wider issues which form a CAPM system, prior to a presentation of the conclusions which can be drawn from the study.