We present a versatile, mass-producible, paper-based microchip electrophoresis platform that enables rapid, affordable, decentralized hemoglobin testing at the point-of-care.
BackgroundAn understanding of tooth enamel mineral content using a clinically viable method is essential since variations in mineralization may serve as an early precursor of a dental health issues, and may predict progression and architecture of decay in addition to assessing the success and effectiveness of the remineralization strategies.Material and MethodsTwenty two human incisor teeth were obtained in compliance with the NIH guidelines and site specifically imaged with Raman microscope. The front portion of the teeth was divided into apical, medium and cervical regions and subsequently imaged with Raman microscope in these three locations.ResultsMeasured mineralization levels have varied substantially depending on the regions. It was also observed that, the cervical enamel is the least mineralization as a populational average.ConclusionsEnamel mineralization is affected by a many factors such as are poor oral hygiene, alcohol consumption and high intake of dietary carbohydrates, however the net effect manifests as overall mineral content of the enamel. Thus an early identification of the individual with overall low mineral content of the enamel may be a valuable screening tool in determining a group with much higher than average caries risk, allowing intervention before development of caries. Clinically applicable non-invasive techniques that can quantify mineral content, such as Raman analysis, would help answer whether or not mineralization is associated with caries risk. Key words:Enamel, Raman spectroscopy, mineral content, dental caries.
In developing countries, diagnostic tests for homozygous (HbSS) or compound heterozygous (HbSC or HbS-Beta thalassemia) sickle cell disease (SCD) are not readily available at the point-of-care (POC). Very few infants are screened in Africa for SCD because of the high cost and level of skill needed to run traditional tests. Current methods are too costly and take too much time to enable equitable and timely diagnosis to save lives. The World Health Organization recognizes a crucial need for early detection of SCD in newborns, since it is estimated that 70% SCD-related deaths in Africa are preventable with early cost-effective interventions. The diagnostic barrier can be broken with affordable, POC tools that facilitate early detection immediately after birth. We have developed a mobile micro-electrophoretic device (HemeChip) through which to quickly, accurately, and affordably screen for SCD (Fig. 1A). The HemeChip uses a microfabricated platform housing cellulose acetate electrophoresis to rapidly separate hemoglobin (Hb) types. Less than 5 microliters of blood, which can be obtained through a finger stick or heel stick, is processed on a piece of cellulose paper in alkaline buffer. The HemeChip reliably identifies and discriminates amongst Hb C/A2, S, F and A0. The micro-electrophoresis results were validated against standard clinical hemoglobin screening methods, including high performance liquid chromatography (HPLC), with Pearson Correlation Coefficient (PCC) of ≥0.96 relative to HPLC for all Hb types tested. The receiver Operating-Characteristic (ROC) curves showed more than 0.89 sensitivity and 0.86 specificity for identification of hemoglobin types using the HemeChip, based on the travelling distance from the sample application point (Fig. 1B). We developed a web-based image processing application for automated and objective quantification of HemeChip results at the POC using cloud computing resources (Fig. 1C). This intensity-based mobile phone image quantitation method showed high correlation with HPLC results for tested patient blood samples (PCC=0.95). HemeChip can distinguish between different patient phenotypes, including HbSS (HbS only), transfused HbSS (HbS and HbA), and Hemoglobin SC disease (HbS and HbC). In conclusion, the HemeChip identification and quantification of hemoglobin phenotypes, as a POC technique, were comparable to standard clinical methods. This platform has clinical potential in under-served populations worldwide, in which SCD is endemic. Figure 1. Mobile micro-electrophoretic device (HemeChip) for point-of-care screening for sickle cell disease. ( A) HemeChip prototype is shown with a miniscule blood sample that has been separated into characteristic hemoglobin bands. (B) The receiver Operating-Characteristic (ROC) curves show sensitivity and specificity of HemeChip for differentiating between adjacent hemoglobin bands based on the travelling distance from the sample application point. band traveling distance thresholds are shown: circle=7.5 mm, triangle=10.0 mm, and square=12.5 mm. (C) Web-based image processing application for automated and objective quantification of HemeChip results at the POC using cloud computing resources. Figure 1. Mobile micro-electrophoretic device (HemeChip) for point-of-care screening for sickle cell disease. ( A) HemeChip prototype is shown with a miniscule blood sample that has been separated into characteristic hemoglobin bands. (B) The receiver Operating-Characteristic (ROC) curves show sensitivity and specificity of HemeChip for differentiating between adjacent hemoglobin bands based on the travelling distance from the sample application point. band traveling distance thresholds are shown: circle=7.5 mm, triangle=10.0 mm, and square=12.5 mm. (C) Web-based image processing application for automated and objective quantification of HemeChip results at the POC using cloud computing resources. Disclosures No relevant conflicts of interest to declare.
Paper-based microchip electrophoresis has the potential to bring laboratory electrophoresis tests to the point of need. However, high electric potential and current values induce pH and temperature shifts, which may affect biomolecule electrophoretic mobility thus decrease test reproducibility and accuracy of paper-based microfluidic electrophoresis. We have previously developed a microchip electrophoresis system, HemeChip, which has the capability of providing low-cost, rapid, reproducible, and accurate point-of-care (POC) electrophoresis tests for hemoglobin analysis. Here, we report the methodologies we implemented for characterizing HemeChip system pH and temperature during the development process, including utilizing commercially available universal pH indicator and digital camera pH shift characterization, and infrared camera characterizing temperature shift characterization. The characterization results demonstrated that pH shifts up to 1.1 units, a pH gradient up to 0.11 units/mm, temperature shifts up to 40 °C, and a temperature gradient up to 0.5 °C/mm existed in the system. Finally, we report an acid pre-treatment of the separation media, a cellulose acetate paper, mitigated both pH and temperature shifts and provided a stable environment for reproducible HemeChip hemoglobin electrophoresis separation.
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