Metabolomics-based mass spectrometry methods to analyze the chemical content of 3D organoid models

Abstract

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....

Interrogating Matrix Stiffness and Metabolomics in Pancreatic Ductal Carcinoma Using an Openable Microfluidic Tumor-on-a-Chip

“…This match of technologies is particularly ideal due to operation in the small volume domain where MS detection improves as a result of higher resolving power and sensitivity. This allows the detection of metabolites and small molecules even at very low concentrations, as is the case for analytes that can be extracted from OOC devices. , However, traditional fabrication and assembly techniques still limit sample accessibility in state-of-the-art OOC architectures, thereby restricting feasibility of hyphenation with MS systems for small molecule detection.…”

“…57,58 Neither of these sensing techniques can match the selectivity and sensitivity of MS, which offers a near universal approach to detection of small molecules. 59,60 Samples most commonly ionized by a "soft" ionization method such as electrospray ionization (ESI) 61 are identified with minimal molecular fragmentation based on mass-to-charge ratio. 62 Spectral methods are typically combined with chromatographic methods to obtain nearly pure fractions of chemical components from crude samples.…”

“…Fluorescence detection is usually the method of choice due to the ease with which fluorescence data can be obtained from microscale channel layouts . Electrochemistry also offers tools that are amenable to component miniaturization, but like fluorescence detection, it suffers from a lack of universality in addition to difficulty in decoupling high voltage detection electronics responsible for driving flow. , Neither of these sensing techniques can match the selectivity and sensitivity of MS, which offers a near universal approach to detection of small molecules. , Samples most commonly ionized by a “soft” ionization method such as electrospray ionization (ESI) are identified with minimal molecular fragmentation based on mass-to-charge ratio . Spectral methods are typically combined with chromatographic methods to obtain nearly pure fractions of chemical components from crude samples .…”

Modelling cancer metabolism in vitro: current improvements and future challenges

“…In this respect, MS can be applied to virtually any 3D model. In addition, when combined with separation methods that can analyse small specimens, and/or with imaging‐based MS that allows a better visualization of 3D [47], it can provide considerable knowledge about metabolic dynamics and perturbations. However, this wealth of knowledge needs to be balanced with subregion scale analyses such as single‐cell studies, because a variety of compartmentalized metabolic fluxes within the same tissue (e.g.…”

Mass spectrometry-based quantitation combined with time-dependent metabolomics to discover metabolic features in human neurogenesis using neural constructs generated from neural progenitor cells

“…10 Metabolomics, the profiling of small molecules that are involved in metabolism in a biological system, is a reproducible, accurate and sensitive tool for analyzing metabolic changes. 11,12 Metabolomics offers the closest direct measurement of a cell's physiological activity, and has advanced efforts to characterize cells' fate, identify biomarkers, and investigate metabolic pathways. 13 Recently, analyses of the metabolic changes accompanying maturation of several human in vitro models, such as the liver 14,15 and heart, 16 have been performed to better characterize and understand these organs.…”