A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots

Abstract

Background Dried blood spot (DBS) sampling is a simple, cost-effective, and minimally invasive alternative to venipuncture for measuring exposure biomarkers in public health and epidemiological research. DBS sampling provides advantages in field-based studies conducted in low-resource settings and in studies involving infants and children. In addition, DBS samples are routinely collected from newborns after birth (i.e., newborn dried blood spots, NDBS), with many states in the United States permitting access to archived NDBS samples for research purposes. Objectives We review the state of the science for analyzing exposure biomarkers in DBS samples, both archived and newly collected, and provide guidance on sample collection, storage, and blood volume requirements associated with individual DBS assays. We discuss recent progress regarding analytical methods, analytical sensitivity, and specificity, sample volume requirements, contamination considerations, estimating extracted blood volumes, assessing stability and analyte recovery, and hematocrit effects. Methods A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted in March 2022. DBS method development and application studies were divided into three main chemical classes: environmental tobacco smoke, trace elements (including lead, mercury, cadmium, and arsenic), and industrial chemicals (including endocrine-disrupting chemicals and persistent organic pollutants). DBS method development and validation studies were scored on key quality-control and performance parameters by two members of the review team. Results Our search identified 47 published reports related to measuring environmental exposure biomarkers in human DBS samples. A total of 28 reports (37 total studies) were on methods development and validation and 19 reports were primarily the application of previously developed DBS assays. High-performing DBS methods have been developed, validated, and applied for detecting environmental exposures to tobacco smoke, trace elements, and several important endocrine-disrupting chemicals and persistent organic pollutants. Additional work is needed for measuring cadmium, arsenic, inorganic mercury, and bisphenol A in DBS and NDBS samples. Significance We present an inventory and critical review of available assays for measuring environmental exposure biomarkers in DBS and NDBS samples to help facilitate this sampling medium as an emerging tool for public health (e.g., screening programs, temporal biomonitoring) and environmental epidemiology (e.g., field-based studies).

Emerging Microfluidic Devices for Sample Preparation of Undiluted Whole Blood to Enable the Detection of Biomarkers

“…Traditional methods of DNA extraction with phenol-chloroform, spin-columns, and magnetic beads can be time-consuming and expensive and need to be performed by trained personnel in a laboratory setting . Dried blood spot (DBS) samples, such as FTA Whatman and plasma separation cards, are newer low-cost alternatives where dried lysis and storage reagents on paper are activated upon sample spotting, thus eliminating the cell lysis step and simplifying sample preparation as well as improving sample storage and transportation for RLS. − The cards allow between 40 and 140 μL volume of blood per spot; however, previous reports have shown that volumes of 50–100 μL could lead to inaccurate detection of viral pathogens and so larger sample volumes might be required to ensure optimal performance. − Moreover, the uncontrolled flow of blood through the paper can cause the heterogeneous distribution of analytes within the sample spot, leading to variable results obtained from punching different areas of the DBS card. , The NA extraction protocol using these cards requires multiple washing steps to remove inhibitors prior to amplification. , A simpler method involves the addition of prelysed blood to a Whatman No. 1 filter paper disk, which, after a washing step, is added directly to the polymerase chain reaction (PCR) mix for amplification without removing the disk .…”

Volumetric Absorptive Microsampling Technique in the LC-MS Determination of Direct Oral Anticoagulants

“…The sample processing involves using a sample collection card and blood lancet. Briefly, after a finger-prick (or prick of the heel in infants) with the lancet, several drops of blood are absorbed onto the sample collection card, followed by drying, storage, shipping, and extraction steps before the analysis [12]. The shipping and storing conditions are simple and might be performed under ambient temperature and humidity in most applications [13].…”

Translation of nutrigenomic research for personalised and precision nutrition for cancer prevention and for cancer survivors

“…The use of dried blood spot cards is gaining traction as a less invasive means to sample blood with advantages that include smaller sample volume, lower researcher burden (self-collection without the need for a phlebotomist), and lower costs for transport (ambient temperatures) and storage (does not require freezing) [ 135 ]. Blood collected in this way can be used for a wide range of analyses including quantification of nutrients [ 136 ] and application of targeted and untargeted metabolomics [ 137 ] approaches.…”