Anemia 2013 July-3


A simple, rapid, low-cost diagnostic test for sickle cell disease.

Lab Chip. 2013 Apr 21; 13(8):1464-7.

Yang X, Kanter J, Piety NZ, Benton MS, Vignes SM, Shevkoplyas SS.

Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118, USA. E-mail:



Background: Sickle cell disease (SCD) is a common inherited blood disorder associated with significant lifetime morbidity and premature mortality.  The analytical assays used to diagnose SCD in current clinical practice are too expensive, slow, and complex for most resource-limited settings.  Here we report on implementation of the hemoglobin (Hb) solubility assay in paper as a simple, rapid, and low-cost test for definitive diagnosis of SCD.

Methods: Blood samples from healthy volunteers (Hb AA, n = 3), sickle cell trait (SCT) carriers (Hb AS, n = 3), and SCD patients (Hb SS, n = 6; Hb Sβ, n = 1; Hb SC, n = 4) were collected at Tulane University and the Sickle Cell Center of Southern Louisiana.  To perform the paper-based SCD test, we deposited a 20 µL droplet of blood mixed with the components of the standard Hb solubility assay onto a paper-fluidic device, a patterned patch of chromatography paper.  The resulting blood stain was digitized with a portable flatbed scanner, and the pattern of the stain was analyzed.

Findings: The overall pattern of the blood stain consisted of a darker red spot in the center (produced by the entanglement of polymerized deoxy-Hb S and cellular debris by the fibers of the paper substrate), and a lighter pink ring (produced by the wicking of the soluble forms of Hb through the paper substrate towards the periphery).  The difference between the blood stains produced by Hb AA, Hb AS, and Hb SS samples was visually obvious: nearly identical color of the center spot and the peripheral ring for Hb AA, a much darker center spot and lighter ring for Hb AS, and a dark center spot with virtually no visible ring for Hb SS.  The difference in the SCD index (defined as the normalized color intensity at 5 mm from the center of blood stain) between normal (Hb AA) and SCT (Hb AS), and between normal (Hb AA) and SCD (Hb SS, Hb Sβ, Hb SC) samples was large and highly significant (p<0.001).  The difference between SCT (Hb AS) and the two most severe forms of SCD (Hb SS, Hb Sβ) was similarly large and highly significant (p<0.001).  The difference between SCT (Hb AS) and the least severe form of SCD (Hb SC) was smaller than for the other forms of SCD tested, but it was also significant (p<0.05).

Interpretation: This initial study provides a proof-of-concept for a paper-based Hb solubility assay that can conclusively differentiate between normal Hb, SCT, and SCD samples using the characteristic blood stain patterns produced by each sample on the paper substrate.  The ability to distinguish between normal Hb, SCT, and SCD samples and diagnose SCD so simply, quickly, and inexpensively represents a major breakthrough towards effective treatment of SCD, and will be particularly useful for universal SCD screening in resource-limited settings, such as Africa.  This test will also be very useful in the emergency room setting in high-income countries to enable healthcare professionals to objectively confirm suspected SCD at the bedside.


Sergey Shevkoplyas-1

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