In-capillary microextraction for direct mass spectrometry analysis of biological samples

Ren, Yaoyu; Zhang, Wenpeng; Lin, Ziqing; Bushman, Lane R.; Anderson, Peter L.; Ouyang, Zheng

doi:10.1016/j.talanta.2018.07.027

Cited by 15 publications

(11 citation statements)

References 29 publications

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“…4C), where a water-immiscible bridge solvent was placed between the biofluid and polar extraction solvent plugs. 50 In a typical three-phase SFME system of biofluid-hexanemethanol/water, salts, cell debris and proteins in biofluid were blocked by the hexane, while polar analytes could be transferred into the extraction solvents cycle-by-cycle. By coupling with direct MS analysis, LODs of 2 ng/mL were obtained for amino acids in urine samples (Fig.…”

Section: Slug-flow Microextraction (Sfme)-liquid-liquid Extraction Ismentioning

confidence: 99%

Direct sampling mass spectrometry for clinical analysis

Chiang

Zhang

et al. 2019

Analyst

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Section: Slug-flow Microextraction (Sfme)-liquid-liquid Extraction Ismentioning

confidence: 99%

Direct sampling mass spectrometry for clinical analysis

Chiang

Zhang

et al. 2019

Analyst

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“…NanoESI‐MS, using a capillary spray tip with an ultralow flow rate of about 20 nL min −1 , has been demonstrated to have higher sensitivity, higher salt tolerance, and lower sample consumption than the conventional ESI‐MS, which is suitable for the detection of microliter level biofluid in clinical analysis . For the direct MS analysis of raw biofluids with high concentration of salts, high efficient liquid–liquid extraction inside the capillary named as slug‐flow microextraction (SFME) was applied prior to NanoESI‐MS . The movement of the immiscible solvent and biofluid plugs within the capillary introduced a turbulence that facilitated the transfer of analytes to the extraction solvent.…”

Section: Ms Analysis Of Clinical Biomoleculesmentioning

confidence: 99%

Mass Spectrometry Methods for In Situ Analysis of Clinical Biomolecules

Liu

et al. 2019

Small Methods

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past few decades, great efforts and substantial progress have been made in this field, and various methods, such as colorimetric screening, [3] enzyme-linked immunosorbent assay (ELISA), [4] fluorescence, [5] polymerase chain reaction (PCR), [6] and electrochemical assays, [7] have been extensively performed in clinical laboratory tests. Although with efficiency and robustness, the majority of these methods still lack sufficient accuracy, sensitivity, and specificity for clinical diagnostic applications.The inevitable complexity and challenges of clinical biomolecules detection have encouraged researchers to continuously devote great effort to the development of new methods with accuracy, rapidity, and simplicity. Relying on its high throughput and accuracy, great sensitivity and versatility, reliable qualitative and quantitative ability, and multiplexed detection capability, mass spectrometry (MS) is exceptionally suitable for clinical analysis and blooming in modern healthcare industry in recent years. [8][9][10] MS coupled to liquid chromatography (LC) and gas chromatography (GC) is regarded as gold standards for quantitative analysis of various compounds and have been conventionally used in clinical applications such as toxicology, [11] therapeutic drug monitoring, [12] inborn error of metabolism (IEM), [13] and steroid hormone testing [14] for decades. IEMs cause high morbidity and mortality in children, and the utilization of GC-MS and LC-MS expands newborn IEMs screening from single-screening assays to simultaneously screening of various analytes (e.g., amino acids, organic acids, carnitine, and acylcarnitine) in a single run using one sample from the patient. Some reviews have summarized a number of excellent works about applications of GC-MS and LC-MS in clinical chemistry. [15,16] These hyphenated MS methods provide accurate quantification data and abundant information of clinical biomolecules, which facilitates biological behavior understanding, biomarker discovery, and prognosis evaluation. However, in most cases, these methods are conducted by using lysis of cells or tissues, which fail to provide real-time information and spatial distribution of biomolecules in their native states. On the other hand, tedious sample pretreatment (separation, purification, and redissolution) is inevitable. These series of labor intensive and time-consuming procedures may cause unpredictable sample loss and undervaluation of biomolecules. Therefore, chromatography-based MS methods are limited to achieve high-throughput, in situ, and visual clinical applications. The development of emerging Due to the significant role of clinical biomolecules in mediating biological activities and disease progressions, in situ analysis provides a great opportunity for understanding the molecular mechanisms of biological functions, facilitating medical diagnosis, clinical treatment, and prognosis. Among all the analysis methods, mass spectrometry (MS) methodologies exhibit unique features that make them exceptionally suitable for clinica...

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“…Liquid phase extractions that can be performed in-line or online with analytical techniques or detection methods are attractive for increased automation and throughput. This goal has led to the development of hollow fiber based microextractions, − single drop microextractions, , liquid–liquid–liquid microextractions, , and electromembrane extractions. , Besides facilitating coupling to analytical techniques, these methods also allow for reduction of sample and extraction solvent volumes to the hundreds of microliter range rather than the milliliters typical for LLE and can reduce extraction time to minutes. Even further improvements can be obtained by using microfluidics.…”

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confidence: 99%

High-Throughput Liquid–Liquid Extractions with Nanoliter Volumes

Wells

Kennedy

2020

Anal. Chem.

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Current methods for liquid–liquid extractions generally require microliter to milliliter volumes of solvents and sample, long equilibration times, and manual procedures. Extraction methods for samples in microfluidic systems have been limited as this tool is difficult to implement on the nanoliter or smaller scale. We have developed slug-flow nanoextraction (SFNE), a method based on droplet microfluidics that allows multiple liquid–liquid extractions to be performed simultaneously in a capillary tube, using only 5 nL of sample and extraction solvent per extraction. Each two-phase slug is segmented from the others by immiscible carrier fluid. We found rapid extractions (<5 s), partition coefficients matching those achieved at larger scale extractions, and potential to preconcentrate samples through volume manipulation. This method was used to accurately and rapidly determine octanol–water partition coefficients (K ow), determining identical K ow as the shake-flask method for acetaminophen, K ow = 2.48 ± 0.02. The measurement, along with calibration and 12 replicates, was complete within 5 min, consuming under 150 nL of solvent and sample. The method was also applied to extract analytes from complex biological samples prior to electrospray ionization-tandem mass spectrometry (ESI-MS/MS) at a rate of 6 s per sample, allowing for simultaneous determination of five different drugs spiked into human plasma, synthetic urine (SU), and artificial cerebral spinal fluid (aCSF) using ethyl acetate as the extraction phase. The signal-to-noise (S/N) for analytes improved up to 19-fold compared to direct ESI-MS of single-phase droplets (aqueous plugs segmented by carrier fluid), with limits of detection down to 7 nM (35 amol).

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In-capillary microextraction for direct mass spectrometry analysis of biological samples

Cited by 15 publications

References 29 publications

Direct sampling mass spectrometry for clinical analysis

Direct sampling mass spectrometry for clinical analysis

Mass Spectrometry Methods for In Situ Analysis of Clinical Biomolecules

High-Throughput Liquid–Liquid Extractions with Nanoliter Volumes

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