monitoring blood lead levels using VAMS

An article by Anthony Breton et al at the Institut National de Sante´ Publique du Que´bec (INSPQ) in Canada published in the January 2023 edition of Bioanalysis, discussed the development of a blood lead level assay using Mitra^® microsampling devices with VAMS^® technology. The paper is entitled “Method development for the quantification of lead levels in whole blood sampled on Mitra^® with VAMS^® tips by inductively coupled plasma-MS/MS.”

This study showed excellent stability of lead in dried blood collected on Mitra devices and minimized any lead contamination of the device tips. The group concluded that devices based on VAMS may be “a useful alternative sampling approach for further research on blood lead analysis and possibly for many other trace elements.” Toxic lead exposure comes from many sources

Lead: A Dangerous Poison That Impacts People Around the Globe 

In August 2022, the World Health Organization (WHO) reported that lead toxicity is one of the top 10 chemical elements of concern and is the underlying cause of 1 million annual deaths globally. They recommended that action was needed to protect children, women of reproductive age, and workers.

Indeed, according to an article published the same year by the United Nations agency UNICEF, in Bangladesh alone, up to 35 million children have blood lead levels (BLL) that are dangerously high, posing a risk of irreparable damage to their health.
Toys can be a source of lead exposure in children

One issue associated with lead exposure is that it is a cumulative heavy metal toxin that is distributed in many parts of the body, including the brain, kidneys, bones and liver. This cumulative effect can lead to several health concerns, including kidney damage and impaired development of the nervous system.

Moreover, because lead accumulates in bones and teeth, the heavy metal is released from the bones during pregnancy, posing an exposure risk to the developing fetus. Indeed, children absorb 4-5 times more lead than adults, which puts them more at risk. Biomonitoring of pregnant women and children for lead exposure is, thus, critically important.

Sources of Lead Exposure 

There are many sources of lead exposure, such as the burning of materials containing the toxic metal and dusts contaminated with lead that may be inhaled. Although the source of the majority of lead exposure or contamination is lead acid batteries, the WHO lists the following additional sources of lead contamination: 

• pigments and paints 
• solder, stained glass, and lead crystal glass ware 
• ammunition
• ceramic glazes
• jewelry
• toys
• some cosmetics, such kohl and sindoor
• traditional medicines used in countries such as India, Mexico, and Vietnam
• drinking water delivered through lead pipes

A Consideration of Less Invasive Blood Collection for Measuring Blood Lead Levels (BLL) 

Like the majority of analytes measured from blood, BLL is currently measured through venipuncture, is collected into specimen tubes by trained phlebotomists. Typically, several mL of blood are collected per tube, however, the majority of this blood is often wasted because modern analyzers in labs require only a tiny amount of blood to conduct the vast majority of clinical tests.   

Moreover, many people find venipuncture blood draws to be uncomfortable and stressful experiences. Further, because the collection of venous blood requires a trained phlebotomist working in a clinical setting, and because wet blood samples typically require cryogenic transport to a laboratory, traditional venipuncture blood collection is not always the most practical or cost-effective choice.   

However, as discussed above, monitoring BLL in populations is critical to mitigate the public health concern posed by lead exposure. It appears that collecting finger-stick capillary blood microsamples for easy shipping and dried blood analysis really is a more practical solution. It also is a far more convenient collection method for use in pediatric studies, of particular importance since children at highest risk for lead exposure and lead poisoning.   

Development and Validation of a BLL Method from VAMS Microsamples 

With these considerations in mind, the research team at INSPQ decided to develop a BLL assay from dried VAMS samples. The reason they chose VAMS was because, as reported by many other research groups, the Mitra devices are based on volumetric absorptive microsampling, so they eliminate certain volumetric biases seen when using conventional dried blood spot cards or filter papers. 

Nevertheless, developing a blood lead assay is not a straightforward venture due to possible environmental contamination of the Mitra microsamplers. Indeed, the INSPQ group commented that the reported thresholds for BLL in children are 0.48 μmol/L and for adults 0.90 μmol/L. Thus, contamination of the microsamplers would be a concern at such low levels and the VAMS tips would need to be as metal-free as possible to minimize any false positives. 

Lead Level Study Methods and Findings 

• A BLL assay, employing inductively coupled plasma–MS/MS (ICP-MS/MS), was fully developed and validated (ISO 17025 guidelines.) for 30 µL Mitra^® devices with VAMS^® technology and then compared to venous blood levels. 

• A matrix matched calibration curve on the VAMS samples was employed. 
  
  
• Good stability for Pb at room temperature was observed on dried blood Mitra-VAMS samples. 
  
  
• Using a novel approach employing nitric acid and sonication, the VAMS tips on the Mitra devices were washed and then dried to minimize any trace element contamination. 
    
• With an initial cohort of 29 volunteers, capillary samples using the washed VAMS tips were compared to simultaneously collected venous samples. The results showed that there was an average 40% higher BLL on the blood samples collected on VAMS tips compared to venous blood samples.  
   
• It was concluded that a possible source contamination may have been from the fingers and the sampling site. Indeed, there are many sources of metal contamination that can contaminate fingers, so the researchers decided to test this by asking the subjects to thoroughly wash their hands with soap and water prior to capillary sampling.   

• A second cohort (N=28) was studied, and thorough handwashing was employed, resulting in a much-reduced bias (>75%). 

Lead Study Authors’ Conclusions 

• Washing the VAMS tips prior to sampling significantly reduced lead contamination.
   
• The developed ICP-MS/MS method gave enough sensitivity for analysis of trace Pb levels from VAMS microsamples. 
  
  
• Stability of the microsamples were excellent, mitigating the need from cryogenically stored and transported venous samples. 

• Future work will be done to develop a multi-element screen. 
  
  
• The authors stated, “The results overall are promising for the use of Mitra-VAMS as an alternative blood sampling approach to venipuncture.” 

Neoteryx Comments  

The work developed at INSPQ showed that it is possible to develop a capillary BLL assay, which minimized environmental lead contamination of the VAMS tips on Mitra devices as well as on fingers.  As a result, the implication is that it is now possible to conduct epidemiological BLL studies to identify most at-risk cohorts.

This work also supplies the data needed to employ measures that remove the source of contamination, allowing for children to develop without the deleterious effects of heavy metals impeding their health and natural growth. 

This article was summarized for our readers by James Rudge, PhD, Technical Director. This is curated content. To learn more about the important research outlined in this blog, visit the original article in Future Science-Bioanalysis.

Image Credits: Shutterstock, Neoteryx, Trajan