(Invited) Towards Point of Care Detection of Iron Metabolism Parameters

Abstract

Disorders in iron metabolism are endemic globally, affecting more than several hundred million individuals and often resulting in increased mortality rates or general deterioration of quality of life. To prevent and monitor iron-related disorders, we present a point of care multiplex system to measure four clinically relevant iron biomarkers: blood iron levels (iron bound to transferrin), total iron-binding capacity (TIBC), percent transferrin saturation, and blood ferritin. This system leverages three distinct channels: two colorimetric and one electrochemical emerging from the same sample injection port designed to accommodate 50 ul of whole blood, filter out cellular components, and transport the filtered sample to the three specified channels’ capillary action. The first channel measures iron levels. It uses a membrane impregnated with the working reagents that reduce iron (III) to iron (II) and chelate the reduced iron with ferene forming a blue- complex. A custom smartphone app quantifies the Fe-ferene complex and provides outputs iron levels in whole blood. The second channel measures TIBC. This channel uses the same membrane and detection method that the first channel but requires an extra preconditioning step of saturating the blood sample with iron standard and precipitating excess unbound iron with a specific binding agent (magnesium carbonate). Using the ratio of total iron (output of channel 1) and TIBC (output of channel 2) enables calculating the percentage of transferrin saturation. The two colorimetric channels were created at Forzani’s Team at Arizona State University, while the electrochemical channel is created by Diez-Perez’s Team at King’s College London. The detection of Ferritin consists of a novel method that combines the selectivity of antibodies with the electrochemical properties of Ferritin for high sensitivity detection. The sensor components are all 3D-printed and require a finger-prick sample for complete measurement of these clinically relevant iron biomarkers. Iron biomarkers. Comparative studies of results obtained by the new sensing device and the reference method in actual samples were performed to determine the device’s capacity to detect iron parameters’ concentrations. Correlation plots with a slope of ~ 1 and regression coefficient of higher than 0.82 were obtained for detection of blood iron levels, total iron-binding capacity, and percentage of transferrin saturation. This indicated that the new device is substantially equivalent to the reference method. With detection times of five minutes, fingerpick sample, and sensor cost less than 10 cents; the device shows excellent promise for point care testing of iron disorders.