Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells

Abstract

Iron deficiency anemia (IDA) is a nutritional disorder that impacts over one billion people worldwide, it causes permanent cognitive impairment in children, fatigue in adults, and suboptimal outcomes in pregnancy. IDA can be diagnosed by detection of red blood cells (RBCs) that are characteristically small (microcytic) and deficient in hemoglobin (hypochromic), typically by examining the results of a complete blood count performed by a hematology analyzer. These instruments are expensive, not portable, and require trained personnel; they are therefore, unavailable in many low-resource settings. This paper describes a low-cost and rapid method to diagnose IDA using aqueous multiphase systems (AMPS)-thermodynamically stable mixtures of biocompatible polymers and salt that spontaneously form discrete layers having sharp steps in density. AMPS are preloaded into a microhematocrit tube and used with a drop of blood from a fingerstick. After only two minutes in a low-cost centrifuge, the tests (n = 152) were read by eye with a sensitivity of 84% (72-93%) and a specificity of 78% (68-86%), corresponding to an area under the curve (AUC) of 0.89. The AMPS test outperforms diagnosis by hemoglobin alone (AUC = 0.73) and is comparable to methods used in clinics like reticulocyte hemoglobin concentration (AUC = 0.91). Standard machine learning tools were used to analyze images of the resulting tests captured by a standard desktop scanner to 1) slightly improve diagnosis of IDA-sensitivity of 90% (83-96%) and a specificity of 77% (64-87%), and 2) predict several important red blood cell parameters, such as mean corpuscular hemoglobin concentration. These results suggest that the use of AMPS combined with machine learning provides an approach to developing point-of-care hematology.

Magnetic Levitation in Chemistry, Materials Science, and Biochemistry

“…The container (the solid phase) in (H) is acuvette made of PMMA. Sources:Images (A), [130] (B), [118] (C), [131] and (D-H). [94] 3.3.6.…”

“…Form ost density-based applications,w eu se standards of known density to calibrate the system to determine the coefficients (a, b)and then calculate the density of the sample from its measured levitation height. (The Supporting Information to this article contains am uch more thorough theoretical analysis,i ncluding both qualitative and quantitative description of MagLev.I ta lso describes methods of [f] and Gd-BOPTA [g] in water [67,69,70,73] Mammalian cell lines mm1 .03-1.10 NdFeB 0.4 Gadobutrol [f] in water [69] Frog cm -S uper-conducting electromagnet [118,[130][131][132] measuring densities using "absolute" (e.g., not based on empirical calibration) methods). In general, most practical measurements of density use Equation 2;E quation (1) is useful in understanding the method.…”

Magnetische Levitation in Chemie, Materialwissenschaft und Biochemie

“…(iv) AMPSs können biokompatibel gemacht werden. Die Abbildungen 3 B und 3 C zeigen die Verwendung von AMPSs zur Trennung von Retikulozyten von reifen roten Blutkörperchen [118] und zur Trennung weniger dichter roter Blutkörperchen von dichteren, gesunden roten Blutkörperchen zur Diagnose einer Eisenmangelanämie [131] . Tabelle 6 fasst die Verwendung von AMPS sowohl für biologische als auch für nicht‐biologische Anwendungen zusammen.…”

Maximising benefits and minimising adverse effects of micronutrient interventions in low- and middle-income countries

“…Targeting micronutrient interventions, although programmatically challenging, should be considered whenever possible. To this end, recent advances in point of care diagnostics such as the Cornell Nutriphone ( 66 ) and the density-based fractionation of erythrocytes ( 67 ) hold promise for a minimally-invasive screening tool with potential application in-field. Closer monitoring of appropriate fortification of foods and any possible risk with overlapping interventions is also needed.…”