Improved Dried Blood Spot-Based Metabolomics: A Targeted, Broad-Spectrum, Single-Injection Method

Abstract

Dried blood spots (DBS) have proven to be a powerful sampling and storage method for newborn screening and many other applications. However, DBS methods have not yet been optimized for broad-spectrum targeted metabolomic analysis. In this study, we developed a robust, DBS-based, broad-spectrum, targeted metabolomic method that was able to measure over 400 metabolites from a 6.3 mm punch from standard Whatman 903TM filter paper cards. The effects of blood spot volumes, hematocrit, vacutainer chemistry, extraction methods, carryover, and comparability with plasma and fingerstick capillary blood samples were analyzed. The stability of over 400 metabolites stored under varying conditions over one year was also tested. No significant impacts of blood volume and hematocrit variations were observed when the spotted blood volume was over 60 µL and the hematocrit was between 31% and 50%. The median area under the curve (AUC) of metabolites in the DBS metabolome declined by 40% in the first 3 months and then did not decline further for at least 1 year. All originally detectable metabolites remained within detectable limits. The optimal storage conditions for metabolomic analysis were −80 °C with desiccants and without an O2 scavenger. The method was clinically validated for its potential utility in the diagnosis of the mitochondrial disease mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Our method provides a convenient alternative to freezing, storing, and shipping liquid blood samples for comparative metabolomic studies.

A Noninvasive Assessment of Tumor Proliferation in Lung cancer Patients using Intravoxel Incoherent Motion Magnetic Resonance Imaging

“…Differentiating SCLC from NSCLC (large cell carcinoma or basaloid squamous cell carcinoma) using noninvasive methods is essential since the therapeutic strategies and clinical prognoses are significantly different. Several noninvasive blood metabolomic and dynamic multiphase computed tomography (CT) methods have been recently developed to discriminate SCLC and NSCLC [27][28][29][30]. However, blood metabolomic biomarker results that showed the differentiation of SCLC and NSCLC tumor types has not been confirmed with large cohort studies.…”

PKU and COVID19: How the pandemic changed metabolic control

“…As first lockdown in Italy began at the end of February 2020 and finished at the end of May 2020, study periods were identified as March–April-May 2019 (MAM-2019) and March–April-May 2020 (MAM-2020). As dried blood spots (DBS) have been proven to be a powerful sampling method to monitor PKUs metabolic control (in this study identified by mean of blood Phe values during analyzed time periods), they were reviewed and analyzed considering both monitoring frequencies and single obtained Phe value results [ 4 ]. Patients with less than 1 DBS performed per month were excluded due to possible related bias, as suggested by literature.…”

Towards a biochemical approach to occupational stress management

“…This would provide access to metabolic signatures coincident with self-reported psychological and physical state. Blood spot analysis reduces sensitivity so is currently more applicable to MS based methods [ 108 , 109 ].…”