U.S. Department of Energy

Pacific Northwest National Laboratory

For Longitudinal Studies, a Comparison of Serum and Dried Blood Spot Samples

Venn diagrams illustrating the number of serum and DBS small molecule identifications and the overlap between the sample types. The small molecules were separated into polar metabolite and lipid identifications and into those statistically significant among the patient groups.

The Science

Longitudinal studies of disease require collecting biofluids, preferentially blood. But acquiring blood samples in the form of serum requires a professional, and storing thousands of such samples at -80 degrees C requires energy and freezer space. These limitations make dried blood spots (DBS) of great interest to researchers because they can be collected non-invasively in remote locations by non-professionals, transported cheaply, and can be stored at room temperature, taking up comparatively limited space. Given the many advantages, the question is: Are DBS useful in longitudinal studies that follow metabolic disease? A new paper led by researchers at the Pacific Northwest National Laboratory (PNNL) compares DBS to serum samples.

The Impact

The limitations of DBS samples are now better understood. Serum samples are needed for longitudinal studies of polar metabolites if DBS samples are stored at room temperature. But DBS samples are adequate for assessing changes in lipids. 


Longitudinal studies help evaluate human disease by determining the occurrence of biological changes that disrupt a system’s stability. Such studies require that biological samples be collected and stored. Blood is preferred since it flows through every organ and is easy to collect.

A paper by lead author Jennifer E. Kyle and Erin S. Baker of PNNL compares the efficacy of serum samples to dried blood spots (DBS) by analyzing overlappingpolar metabolites (64) and lipids (336) from case-control samples collected in 2000-2001.

Triplicate samples from older male patients with high Body Mass Index, triglycerides, and glucose levels and low HDL (high density lipoprotein) were compared to a control group made up of older males with normal levels. The DBS were stored at room temperature after collection and compared to matched serum samples stored at -80C.  Using mass spectrometry, over 400 lipids and polar metabolites were identified. The lipids and metabolites from the DBS were compared to those in serum samples to determine if molecular degradation occurred over time and if the disease signature was preserved in the patient group. 

The findings support evidence that lipids can be analyzed in older DBS samples and can provide important information in longitudinal studies. 

What’s Next?

Future analyses are needed to address questions related to polar metabolites and lipids in fresh DBS and serum samples, and in DBS samples that have been stored at cooler temperatures for long periods of time. 


This work was supported by the Laboratory Directed Research and Development program at the Pacific Northwest National Laboratory (PNNL), the National Institute of Environmental Health Sciences of the NIH, the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of General Medical Sciences.


Kyle, J. E.Casey, C. P.Stratton, K. G.Zink, E. M.Kim, Y.-M.Zheng, X.Monroe, M. E.Weitz, K. K.Bloodsworth, K. J.Orton, D. J.Ibrahim, Y. M.Moore, R. J.Lee, C. G.Pedersen, C.Orwoll, E.Smith, R. D.Burnum-Johnson, K. E., and Baker, E. S.(2017Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studiesRapid Commun. Mass Spectrom.31447456. doi: 10.1002/rcm.7808.

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