Separation science plays a key role for enhancing the performance of mass spectrometry (MS)-based metabolomic studies. However, sample thoughput is limited when using conventional separation platforms. In addition, major efforts are devoted to quality assurance and data pre-processing to correct for long-term instrumental drift that are time-consuming and/or subject to bias. Recently, we have introduced a new approach for multiplexed analysis based on multi-segment injection (MSI)-CE-MS that enhances sample throughput and overall data fidelity while using an accelerated metabolomics workflow for biomarker discovery. MSI-CE-MS offers the sample throughout analogous to direct injection-ESI-MS while retaining the benefits of a high resolution separation, including greater selectivity and better quantiative reliability for complex biological samples. Confirmatory testing of in-born errors of metabolism will first be presented to showcase the advantages of MSI-CE-MS for high throughput screening of disease biomarkers derived from dried blood spot extracts or sweat specimens. Customized injection configurations and dilution patterning are used to encode information temporally to allow for unambiguous diagnostic testing of rare yet treatable genetic diseases. In addition, time-resolved metabolomic studies will also be presented to examine the putative health benefits of high intensity interval training (HIT) among a group of obese/overweight female subjects as a therapeutic tool for type 2 diabetes prevention. Plasma markers of differential treatment responses to HIT intervention were identified among sub-groups of non-diabetic yet high risk subjects. MSI-CE-MS offers a unprecedented approach for enhancing sample throughput up to an order of magnitude while simplfying data pre-processing requirements that is urgently needed for biomarker discovery and personalized medicine.

Multisegment injection-capillary electrophoresis-mass spectrometry: Multiplexed separations for biomarker discovery in metabolomics

248th National Meeting (2014)

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