Development of direct ionization sampling methods for point-of-care mass spectrometry analysis
Mass spectrometry (MS) has been the “gold standard” for chemical analysis due to its intrinsic sensitivity and specificity. This is particularly true in clinical settings when extreme accuracy and precision is demanded. In a typical MS analysis, a routine sample preparation and separation is always employed to ensure the optimal analytical performance. The emergence of ambient methods provides an alternative for MS interrogation of complex biological mixtures such as blood, urine and cerebral spinal fluid. A combination of an ambient method and a miniature mass spectrometer (MiniMS) enables MS analysis to be carried out on-site with short turnaround time (TAT). Such combination can potentially bring MS analysis to clinical sites providing rapid diagnostic information and a better combination of clinical testing with therapy. Research efforts have been focused on the development of ambient methods to elevate the analytical performances of MiniMS systems. Based on the knowledge gained from the development of paper spray and nanoelectrospray ionization, a new ambient method, extraction spray (EXS), is developed to improve the quantitative performance of MiniMS. This method has been integrated to a spray cartridge design which is compatible with multiple MS system for clinical screening. Furthermore, a slug flow microextraction device for simple and efficient liquid-liquid extraction of low volume sample (~5µL) was developed. This single-step method has been demonstrated to have a wide range of applications in biofluid analysis including rapid quantitation of therapeutic drugs, real-time chemical derivatization for steroid analysis and direct enzyme activity monitoring. In addition to analyzing samples in microscale, slug flow was also demonstrated as a mean to process samples of relative big amount prior to MS analysis. It has been demonstrated that sampling from large scales benefit the analysis by enhanced sensitivity and quantitation using internal standard without accurate volume measurements. The accomplished studies encourage the future development of disposable cartridges, which function with simple operation to replace the traditional complex laboratory procedures for MS analysis of clinical samples.
Ouyang, Purdue University.
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