Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

Li, Xiangtang; Hu, He-xuan; Zhao, Shulin; Liu, Yiming

doi:10.1021/acs.analchem.6b00638

Cited by 28 publications

(22 citation statements)

References 44 publications

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“…MS also provides high selectivity, the ability to detect multiple compounds in single scans, and direct detection of compounds without labels. ESI-MS is compatible with continuous flow systems and can be coupled to microfluidic chips [32–38]. All of these properties make ESI-MS well-suited as a general tool for analyzing cell perfusates.…”

Section: Introductionmentioning

confidence: 99%

Monitoring cell secretions on microfluidic chips using solid-phase extraction with mass spectrometry

et al. 2016

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Microfluidics is an enabling technology for both cell biology and chemical analysis. We combine these attributes with a microfluidic device for on-line solid-phase extraction (SPE) and mass spectrometry (MS) analysis of secreted metabolites from living cells in culture on the chip. The device was constructed with polydimethylsiloxane (PDMS) and contains a reversibly-sealed chamber for perfusing cells. A multilayer design allowed a series of valves to control an on-chip 7.5 μL injection loop downstream of the cell chamber with operation similar to a 6-port valve. The valve collects sample and then diverts it to a packed SPE bed that was connected in-line to treat samples prior to MS analysis. The valve allows samples to be collected and injected onto the SPE bed while preventing exposure of cells to added back-pressure from the SPE bed and organic solvents needed to elute collected chemicals. Here, cultured murine 3T3-L1 adipocytes were loaded into the cell chamber and non-esterified fatty acids (NEFAs) that were secreted by the cells were monitored by SPE-MS at 30 min intervals. The limit of detection for a palmitoleic acid standard was 1.4 μM. Due to the multiplexed detection capabilities of MS, a variety of NEFAs were detected. Upon stimulation with isoproterenol and forskolin, secretion of select NEFAs was elevated an average of 1.5-fold compared to basal levels. Despite the 30 min delay between sample injections, this device is a step towards a miniaturized system that allows automated monitoring and identification of a variety of molecules in the extracellular environment.

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Section: Introductionmentioning

confidence: 99%

Monitoring cell secretions on microfluidic chips using solid-phase extraction with mass spectrometry

et al. 2016

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“…Li et al developed a system to study the release of different neurotransmitters in rat pheochromocytoma cell line (PC12) stimulated with a chemical stimulant known to lead to cells depolarization followed by exocytosis, KCl, or alcohol [128]. Their ME-MS system allowed to monitor the DA release from PC-12 cells, which was significantly increased in stimulated cells; the authors were also able to demonstrate an increase in the secretion of serotonin (5-HT) in conjunction with the stop in DA release.…”

Section: Me For Separation and Quantification Of Neurotransmitters Inmentioning

confidence: 99%

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

et al. 2020

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The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. Finally, the integration of microfluidics with recent innovative technologies—such as organoids, organ-on-chip, and 3D printing—for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies.

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“…A three-layered microfluidic chip was fabricated and evaluated for studying the dynamics of neurotransmitter release from PC-12 cells. 60 Neurotransmitter including dopamine (DA), serotonin (5-HT), aspartic acid (Asp), and glutamic acid (Glu) was successfully quantified by this system. Capillary-electrophoresis ESI-MS based on microfluidics has become a very mature method with a large number of related patents and articles.…”

Section: Esi-msmentioning

confidence: 99%

Cell Analysis on Microfluidics Combined with Mass Spectrometry

Zhang

Lin

2020

ANAL. SCI.

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Cell analysis is of great significance for the exploration of human diseases and health. However, there are not many techniques for high-throughput cell analysis in the simulated cell microenvironment. The high designability of the microfluidic chip enables multiple kinds of cells to be co-cultured on the chip, with other functions such as sample preprocessing and cell manipulation. Mass spectrometer (MS) can detect a large number of biomolecules without labelling. Therefore, microfluidic chip coupled with MS has been a major branch of cell analysis during the past decades. Here, we concisely introduce various microfluidic devices coupling with MS used for cell analysis. The main functions of microfluidic devices were first described, followed with different interfaces to different types of MS. Then, their various applications in cell analysis were highlighted, with an emphasis on cell metabolism, drug screening, and signal transduction. Current limitations and prospective trends of microfluidics coupling with MS are discussed at the end.

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Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

Cited by 28 publications

References 44 publications

Monitoring cell secretions on microfluidic chips using solid-phase extraction with mass spectrometry

Monitoring cell secretions on microfluidic chips using solid-phase extraction with mass spectrometry

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

Cell Analysis on Microfluidics Combined with Mass Spectrometry

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