small samples, big impact: mitra vs. malnutrition
Lean, low-resource field work poses unique challenges to those involved, whether in research or diagnosis. Mitra® microsampling technology has the potential to meet and overcome some of these challenges.
Recently, Volumetric Absorptive Microsampling (VAMS™) technology helped a group of organ transplant patients summit Mt. Kilimanjaro. Now students and scientists from the biomedical engineering program at Duke University have found another transformative new use case: testing children in Liberia for biomarkers associated with malnutrition.
Over the summer, Daniel Joh, an MD-PhD student at Duke, and his associates touched down in New Kru Town, a neighborhood in the outer reaches of Monrovia, Liberia. They were there to field test diagnostic tools designed to rapidly measure the biomarkers linked to malnutrition. In this low-resourced reigion, they set up shop at Redemption Clinic, and made use of some revolutionary medical innovations to do their work under subprime conditions.
Twenty-five percent of the world's children are believed to suffer from malnutrition. Traditional measures for malnutrition do not always provide a clear and consistent picture of the severity of malnutrition the children are experiencing; therefore, an improved diagnostic method was required. However, to make an efficient diagnostic test, researchers needed a single, easy-to-measure biological target.
Fieldwork in Uganda, undertaken by Michael Freemark M.D. in 2014, examined the metabolic changes in children who were undergoing treatment for malnutrition and identified the role played by the hormone leptin. Leptin is produced by white adipose tissue and is a marker of energy storage.
Children suffering from malnutrition have low amounts of this fatty tissue, which makes it more difficult for them to maintain the energy needed to keep their bodies functioning properly. The hormone also helps stimulate different mechanisms within the immune system, so patients with lower levels of leptin often also develop an immune deficiency, which increases their susceptibility to infections.
The Importance and Challenges of Remote Sampling
However, drawing blood from a patient and shipping it back for testing at Duke University was not feasible. In resource-limited settings, clinicians need to rely on lateral flow tests. These are rapid diagnostic tests, which are highly portable and can provide a diagnosis in five minutes. However, they are not particularly sensitive. Highly sensitive tests, such as ELISA, provide highly accurate analysis but are not rapid or portable. A viable test for a variety of low-resource settings worldwide, where malnutrition is a significant problem, was needed.
The development of a diagnostic test that used a unique non-stick coating, which acted like Teflon for molecules and cells found in blood, had the potential to provide the necessary answer to the problem. The D4 assay was designed to combine the required sensitivity, speed, and portability. However, storing and shipping samples remained problematic in low-resource situations.
Traditionally, biological samples that are collected in the field are transported by a cold chain process, meaning that researchers need to keep the samples refrigerated or frozen to prevent protein degradation. This approach was not feasible, so the team opted to use the Mitra microsampler.
"In order to deploy the D4 assay in larger field studies," said Joh's associate and Duke undergraduate Jay Gupta, "we needed a reliable, low-resource method of collecting and storing patient samples. This is where the Mitra fits in and integrates well with the D4 assay workflow. In our case, the Mitra is used to collect samples in the field in Liberia. Samples are then shipped from Liberia to Duke University. We process the samples in our lab at Duke."
Combating the Challenges
Small-volume sampling with the Mitra device allowed researchers to gather and ship biological samples at room temperature while preserving them and allowing them to be easily reconstituted in the lab. Researchers were able to ship samples back to the US and process them on the D4 chips as they had initially intended.
The project provided crucial data which could be used to answer questions about how the D4 assay performs regarding malnutrition diagnosis, as well as how sampling methods like the Mitra perform in various settings.
Using Mitra and the D4 assay in the field provided opportunities to identify problems, something that would not have been possible if the tests had been carried out in a controlled lab environment. This meant that crucial modifications to the technology could be made leading to greater success in further rounds of field testing.
Photos courtesy of Michaela Kane (Duke BME).