Session: 803. Emerging Tools, Techniques and Artificial Intelligence in Hematology: Poster II
Hematology Disease Topics & Pathways:
Research, Translational Research, Thalassemia, Hemoglobinopathies, Diseases
Here, we present the first POC diagnostic test for β-thalassemia. We have leveraged the World Health Organization (WHO) listed (WHO Essential In Vitro Diagnostics) Hb electrophoresis test and developed a POC electrophoresis microchip system, Gazelle (Fig. 1A). Gazelle-Multispectral enables sensitive detection and accurate identification of Hb types under ultraviolet (UV 410nm) light illumination. We hypothesized that the high absorbance of Hb around 410 nm wavelength would enhance the limit of detection and allow the accurate quantification of Hb types in blood that are at both higher concentration (e.g., Hb A, Hb F) and lower concentration (e.g., HbA2).
Methods: To test this hypothesis, we have developed customized learning-based algorithm for accurate quantification of HbA2 in addition to our existing algorithm for accurate quantification of HbA, HbF, and HbS. Briefly, a space-time plot is generated to extract the information contained in the 8-minutes long electrophoresis test (Fig. 1B). Specific frames are then selected according to the space-time plot for quantifying HbA2 based on the band total intensity in that frame (Fig. 1B, dashed redline). Other Hb variants including HbA, HbF, and HbS are quantified and reported (Fig. 1C). In this study, we have conducted clinical testing over 372 subjects under age range of 4 – 63 years at Apple Diagnostics lab in Ghatkopar, Mumbai, India, under local IRB-approved study protocol. Additionally, 30 blood samples were prepared to mimic β-thalassemia intermediate and β-thalassemia major samples. In total, 402 tests were conducted in this study (372 patient samples and 30 prepared blood samples).
Results and Discussion: The relative percentage of HbA2 was obtained by comparing to other dominant Hb variants. Subjects with 6-40% HbA, 60-80% HbF, and 0-10% HbA2 were categorized to have β-thalassemia intermedia; subjects with 0-20% HbA, 80-100% HbF, 0-9% HbA2 were categorized to have β-thalassemia major or intermedia; and subjects with 90-100% HbA and >3.5% HbA2 were categorized to have β-thalassemia trait. Following the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines, 393 out of 402 (97.8%) tests were recognized as ‘Valid’, while 9 out of 402 (2.2%) tests were recognized as ‘Inconclusive’. Within the 393 valid tests, subjects with β-thalassemia major or intermedia were identified with 100% sensitivity and specificity against healthy subjects and subjects with β-thalassemia. Subjects with β-thalassemia trait were identified with 100% sensitivity and 98.0% specificity with respect to healthy subjects (Fig. 1 Table).
Conclusion: In summary, Gazelle-Multispectral algorithm allowed accurate detection and quantification of HbA2 in addition to other Hb types including HbA, HbF, and HbS, enabling accurate detection of β-thalassemia carriers. These results suggest that Gazelle is the first accessible, accurate POC diagnostic test for affordable (~$2/test) and rapid (<8 minutes/test) diagnosis of β-thalassemia.
Disclosures: Avanaki: Hemex Health: Current Employment. Thota: Hemex Health: Current Employment. Nemade: Hemex Health: Consultancy. Mehta: Hemex Health: Consultancy. Gurkan: Dx Now Inc.: Patents & Royalties; Xatek Inc.: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Biochip Labs: Patents & Royalties.
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