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Metabolomics, the study of metabolites present in biological samples, can provide a global view of sample state as well as insights into biological changes caused by disease or environmental interactions. Mass spectrometry (MS) is commonly used for metabolomics analysis given its high-throughput capabilities, high sensitivity, and capacity to identify multiple compounds in complex samples simultaneously. MS can be coupled to separation methods that can handle small volumes, making it well suited for analyzing the metabolome of organoids, miniaturized three-dimensional aggregates of stem cells that model in vivo organs. Organoids are being used in research efforts to study human disease and development, and in the design of personalized drug treatments. For organoid models to be useful, they need to recapitulate morphological and chemical aspects, such as the metabolome, of the parent tissue. This review highlights the separation- and imaging-based MS-based metabolomics methods that have been used to analyze the chemical contents of organoids. Future perspectives on how MS techniques can be optimized to determine the accuracy of organoid models and expand the field of organoid research are also discussed.
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Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples
Abstract The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample volumes. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelectric nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro - cultured human mesenchymal stromal cells. Both test samples are only available in minimum amounts. Experiments show that picoliter-volume spray pulses suffice to generate high-quality spectral fingerprints, which increase the information density produced per unit sample volume. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liquid chromatography-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.
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- Award ID(s):
- 1648035
- PAR ID:
- 10311314
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41467-020-19444-y
