(570c) Point-of-Care Diagnosis of Hemoglobin Disorders with a Mobile Electrophoresis Chip

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, time for sample transfer to a central laboratory (2-6 weeks), and level of skill needed to run traditional tests. 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 or at the time of immunization. To address this unmet clinical need, we have developed a mobile electrophoresis platform (HemeChip) for reliable, affordable, and rapid diagnosis of SCD.

The HemeChip uses a microfabricated platform, with a material cost less than $0.87 per device, 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 acetate paper via an applied electric field in alkaline buffer within 10 minutes. We clinically tested and benchmarked HemeChip against standard clinical methods using 51 blood samples from 14 patients.

The HemeChip reliably identifies and discriminates amongst Hb C/A2, S, F and A0. The HemeChip hemoglobin concentration results were correlated (Pearson Correlation Coefficient (PCC) of â?¥0.96 for all Hb types tested) with standard clinical hemoglobin screening methods, including high performance liquid chromatography (HPLC). The agreement between the HemeChip and HPLC results were assessed using the Blandâ??Altman plot, which showed a strong agreement between estimated (HemeChip) and actual (HPLC) hemoglobin percentages. The majority (95.5%) of the differences between actual and estimated hemoglobin percentages were within the limits of agreement. Furthermore, 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 band travelling distance from the sample application point.

We developed a web-based image processing application for automated and objective quantification of HemeChip results at the POC using cloud computing resources. This intensity-based mobile phone image quantitation method showed high correlation with HPLC results for tested patient blood samples (PCC=0.95). Moreover, the Bland-Altman analysis showed strong agreement between the HemeChip results analyzed with the mobile user interface and HPLC. The majority (91%) of the differences between actual (HPLC) and estimated (mobile user interface) were within limits of agreement.

HemeChip technology offers a low-cost, easy to use, rapid approach and an innovative solution to POC diagnosis of SCD and other hemoglobin disorders. HemeChip can distinguish between different patient phenotypes, including HbSS (HbS only), transfused HbSS (HbS and HbA), and Hemoglobin SC disease (HbS and HbC). In summary, 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.