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Improved Dried Blood Spot-Based Metabolomics: A Targeted, Broad-Spectrum, Single-Injection Method
Kefeng Li1,2, Jane C Naviaux1,3, Jonathan M Monk2
1The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego, CA 92103, USA.
Metabolites
|March 4, 2020
Summary
Dried blood spots (DBS) offer a convenient method for broad-spectrum metabolomic analysis, measuring over 400 metabolites. This optimized DBS method is stable for one year and clinically validated for diagnosing conditions like MELAS.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Clinical Diagnostics
Background:
- Dried blood spots (DBS) are widely used for newborn screening but require optimization for broad-spectrum targeted metabolomic analysis.
- Existing DBS methods lack standardization for comprehensive metabolite profiling.
- Liquid blood sample handling presents logistical challenges in storage and shipping.
Purpose of the Study:
- To develop and validate a robust, DBS-based method for broad-spectrum targeted metabolomic analysis.
- To assess the impact of various pre-analytical factors on DBS metabolomic data quality.
- To evaluate the long-term stability of metabolites stored on DBS cards.
Main Methods:
- Developed a DBS method to measure over 400 metabolites from a 6.3 mm punch of Whatman 903 filter paper.
- Investigated effects of blood volume, hematocrit, vacutainer chemistry, and extraction techniques.
- Assessed metabolite stability under various storage conditions for one year.
- Clinically validated the method for diagnosing mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
Main Results:
- The method successfully quantified over 400 metabolites from a small DBS sample.
- Blood volume (>60 µL) and hematocrit (31-50%) had no significant impact on metabolite detection.
- Metabolite levels showed a median 40% decline in the first 3 months, stabilizing thereafter for up to one year.
- Optimal storage conditions identified as -80 °C with desiccants, excluding O2 scavengers.
- Method demonstrated clinical utility in MELAS diagnosis.
Conclusions:
- A robust and optimized DBS method enables broad-spectrum targeted metabolomic analysis.
- The DBS method is stable for at least one year under recommended storage conditions.
- This approach offers a practical alternative to liquid blood sampling for metabolomic studies and clinical diagnostics.
