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使用靶向蛋白质组学对一种专为以患者为中心的干血浆采样设计的新型设备进行定量评估。

Quantitative Assessment of a Novel Device Designed for Patient-centric Sampling of Dried Plasma Using Targeted Proteomics.

作者信息

Hober Andreas, Henricsson Marcus, Ruckh Tim, Davidsson Pia, Challis Benjamin, Miliotis Tasso

机构信息

Translational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.

R&D Digital Health, AstraZeneca, 431 83 Gothenburg, Sweden.

出版信息

Anal Chem. 2025 Jul 1;97(25):12953-12962. doi: 10.1021/acs.analchem.4c05455. Epub 2025 Jun 18.


DOI:10.1021/acs.analchem.4c05455
PMID:40532070
Abstract

Technological advancements have significantly enhanced proteomics by improving the quality, depth, and timeliness of proteomic data, making mass spectrometry a promising tool for personalized medicine. To enable successful longitudinal population-level monitoring, it is essential to have cost-efficient and convenient sample collection methods that yield reliable results. Microsampling performed by patients in their own homes fulfills this requirement. In this study, we evaluate a novel microsampling device that readily prepares a dried plasma sample from blood collected through a finger prick. The device was assessed quantitatively through a targeted proteomics approach, using a selection of stable isotope-labeled protein fragments as standards for plasma proteins spanning a range from 1300 μM to 30 nM. All samples were analyzed using selected reaction monitoring to ensure quantitative robustness. The device was assessed both from a storage perspective and across a group of healthy donors to ensure reliable performance between individuals. The dried plasma obtained from the device shows an excellent quantitative correlation with conventional plasma ( > 0.99) and high quantitative precision, with a coefficient of variance (CV) below 10% for 80% of all peptides quantified in the group of healthy donors. All of the targets that perform well in the microsampling device also show good long-term stability when stored at room temperature for up to 232 days, further showcasing the potential benefits of collecting samples in a dry format.

摘要

技术进步通过提高蛋白质组学数据的质量、深度和及时性,显著增强了蛋白质组学,使质谱分析成为个性化医疗的一种有前景的工具。为了实现成功的纵向人群水平监测,拥有经济高效且便捷的样本采集方法以产生可靠结果至关重要。患者在自己家中进行的微量采样满足了这一要求。在本研究中,我们评估了一种新型微量采样装置,该装置可轻松从通过手指针刺采集的血液中制备干血浆样本。通过靶向蛋白质组学方法对该装置进行了定量评估,使用了一系列稳定同位素标记的蛋白质片段作为血浆蛋白的标准品,其浓度范围从1300 μM到30 nM。所有样本均使用选择反应监测进行分析,以确保定量的稳健性。从储存角度以及在一组健康供体中对该装置进行了评估,以确保个体间的可靠性能。从该装置获得的干血浆与传统血浆显示出极好的定量相关性(> 0.99)和高定量精度,在健康供体组中80%的所有定量肽的变异系数(CV)低于10%。在微量采样装置中表现良好的所有靶标在室温下储存长达232天时也显示出良好的长期稳定性,进一步展示了以干燥形式采集样本的潜在益处。

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本文引用的文献

[1]
Temporal Assessment of Protein Stability in Dried Blood Spots.

J Proteome Res. 2024-8-2

[2]
Patient-Centric Quantitative Microsampling for Accurate Determination of Urine Albumin to Creatinine Ratio (UACR) in a Clinical Setting.

J Appl Lab Med. 2024-3-1

[3]
Patient Centric Microsampling to Support Paxlovid Clinical Development: Bridging and Implementation.

Clin Pharmacol Ther. 2024-1

[4]
Challenges and solutions in clinical research during the COVID-19 pandemic: A narrative review.

Health Sci Rep. 2023-8-6

[5]
Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions.

Trials. 2023-6-22

[6]
Targeted proteomics using stable isotope labeled protein fragments enables precise and robust determination of total apolipoprotein(a) in human plasma.

PLoS One. 2023

[7]
Direct Processing and Storage of Cell-Free Plasma Using Dried Plasma Spot Cards.

ACS Meas Sci Au. 2022-10-19

[8]
Opportunities and Challenges for Decentralized Clinical Trials: European Regulators' Perspective.

Clin Pharmacol Ther. 2022-8

[9]
How the COVID-19 pandemic is changing clinical trial conduct and driving innovation in bioanalysis.

Bioanalysis. 2021-8

[10]
Therapeutic drug monitoring of valproic acid using a dried plasma spot sampling device.

J Mass Spectrom. 2021-4

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