Usability Evaluation of a Point-of-Care Diagnostic Test in the Diagnosis of Sickle Cell Disease and Other Hemoglobinopathies

Sickle cell disease (SCD) is a common and life-threatening hematological disorder¹. It is characterized by a mutation in the beta-globin gene resulting in the production of abnormal hemoglobin called hemoglobin S. Under low-oxygen conditions, hemoglobin S polymerizes, forming sickle-shaped rigid cells which can lead to, anemia, painful episodes, organ damage, and in some cases death^2,3. Early detection of SCD is essential for initiating appropriate interventions and reduce mortality. To this end, several methods have been developed to detect the SCD and the carrier states with high sensitivity and specificity. These methods include screening tests such as complete blood count, and sickling test, confirmatory tests such as hemoglobin separation techniques, and genetic tests⁴. Despite advances in detection of SCD, these methods are cost-prohibitive and need centralized labs and/or highly skilled personnel. Advanced portable point-of-care diagnostics can offer a low-cost, simple, and user-friendly method for detecting SCD.

This abstract introduces a new simpler test for Sickle Cell Disease and Beta Thalassemia diagnosis that can reach more people. It removes the need for an experienced lab tech who can pipette allowing the test to be used much more widely. The test takes the existing Gazelle Hb Variant test and simplifies the process such as removing the need for pipetting and removes several steps requiring skill. The Gazelle Hb Variant test uses a miniaturized version of electrophoresis technology for hemoglobin variant detection⁵. In about 8 minutes, using a small patient sample, the Reader displays the result on the screen, including hemoglobin types and percentages and offer interpretative statements for possible conditions such as sickle cell disease and trait, and beta thalassemia⁵.

Gazelle (current version) is being used in 35+ countries with promising results so far. Gazelle's performance is in concordance with the most commonly used laboratory methods such as HPLC in multiple clinical studies. When compared to HPLC, Gazelle showed 100% sensitivity and specificity for normal vs disease; 100% sensitivity and specificity for disease vs trait; and 100% sensitivity and 98.5% specificity for trait vs disease. The average Pearson correlation coefficient for hemoglobin quantification comparing Gazelle to HPLC is 97.1%.

The new simple version of the cartridge (Gen 2) is a breakthrough invention that uses microfluidics to dramatically simplify sample preparation. Usability studies have been completed with 14 users of low skill level. This study seeks to assess how well end users, using the supplied training materials, can understand the workflow, successfully run the diagnostic, and understand test results. The assessment was done through a simple questionnaire which was designed to assess product usability against key technical product specifications. The Simplified cartridge proved to be much superior for non-lab users than the current test. It also emphasized the fact it is so much easier that average people, without any technical training, can take the test. Usability study showed the following results:

- When compared to Gen 1, Simplified cartridge has fewer steps involved in sample preparation which reduced time significantly (~5min vs. 2min).

- All the users were able to prepare the sample easily without any errors.

- All the users noted that the product is very easy to use and that the process steps involved are easy to learn.

- All the users completed the test successfully in two attempts or less.

- All the users were able to complete the test successfully after reviewing the training video or the IFU once.

The miniatured electrophoresis system is ideal for remote settings. It is rugged, small and no cold chain is necessary. It can work using a finger stick or heel prick of blood sample and has self-contained kits with all the sample preparation supplies needed. Gazelle with simplified cartridge is easy to use and an affordable tool for accurate diagnosis of sickle cell disease and other hemoglobinopathies especially in low resource settings.

References:

1. Kato G.J et al. Nat. Rev. Dis. Primers. 2018;4:1-22.

2. Edelstein S.J et al. Proc. Natl. Acad. Sci. USA. 1973;70:1104-1107.

3. Lipowsky H.H et al. Microcirculation. 1997;4:289-301.

4. Da Fonseca S.F et al; Hematol.Hemoter. 2015;37:296-301.

5. Hasan MN et al. Analyst. 2020 Apr 7;145(7):2525-2542.

Jain:Blue Bird Bio: Other: End point adjudication committee ; NovoNordisk: Speakers Bureau; Sanofi: Speakers Bureau; Hemex Health: Consultancy; Beam Therapeutics: Other: End point adjudication committee. Thota:Hemex Health Inc: Current Employment. Gurkan:XaTek Inc: Patents & Royalties; Hemex Health Inc: Consultancy, Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding; BioChip Labs Inc: Consultancy, Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding; DxNow Inc: Patents & Royalties.