Abstract
We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2′-Fucosyllactose (2’FL) is an HMO associated with infant growth, cognitive development, and protection from infectious diarrhea, one of the major causes of infant death worldwide. Due to genetic variation, the milk of some women (non-secretors) contains no or very little 2′FL with potential implications for infant health and development. However, there is currently no technology to analyze the presence and concentration of HMOs in human milk at the point-of-care (POC). The lack of such technology represents a major impediment to advancing human milk research and improving maternal-infant health. Towards this unmet need, we report an impedimetric assay for HMOs with an α-1,2 linkage, the most abundant of which is 2′FL. The sensor uses a lectin for affinity, specifically Ulex europaeusagglutininI (UEA), with electrochemical readout. In spiked studies, the sensor exhibited a high degree of linearity (R2 = 0.991) over 0.5 to 3.0 μM with a 330-nM detection limit. The sensor performance was clinically validated using banked human milk samples and correctly identified all secretor vs. non-secretor samples. Furthermore, despite the short 35-min assay time and low sample volume (25 μL), the assay was highly correlated with HPLC measurements. This bedside human milk testing assay enables POC, “sample-to-answer” quantitative HMO measurement, and will be a valuable tool to assess milk composition.Graphical abstract
Highlights
Human milk is widely accepted as the best source of nutrients for healthy term newborns [1, 2], and the composition is strongly correlated with maternal-infant health and developmental outcomes [3, 4]
The peak current was reduced with the subsequent addition of cystamine (Au/cystamine dihydrochloride (Cys)), inhibiting electron transfer, which indicated that the electrode conductivity was decreased by the covalent bond formed between Cys and Au (Au-S bonding)
The sensor is read out using an electrochemical impedimetric assay where 2′FL selectively binds to Ulex europaeus agglutinin I (UEA) and decreases the charge transfer resistance
Summary
Human milk is widely accepted as the best source of nutrients for healthy term newborns [1, 2], and the composition is strongly correlated with maternal-infant health and developmental outcomes [3, 4]. Higher 2′FL concentration has been associated with improved infant growth [13, 14], improved memory and learning in rodent models, and improved infant cognitive development at 24 months in human cohorts [15, 16]. While these and other studies highlight the importance of HMOs in human milk, no point-ofcare (POC) technology is currently available to quantify the amount of 2′FL in human milk
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