## 1 Introduction  
Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia  
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## 1 Introduction  
Sickle cell disease (SCD) is the most common severe inherited red blood cell disorder, affecting millions of people worldwide [1]. Three-quarters of sickle cell cases in the world occur in Africa with an annual incidence of about 250,000-400,000, mainly in sub-Saharan Africa [2; 3]. For example, a WHO report estimated that around 2% of neonates in Nigeria are affected by SCD, giving a total of 150,000 births per year in Nigeria alone [2]. Similarly, in some regions of Africa, more than a quarter of the population carries the SS mutation [2]. The frequency of the sickle cell trait ranges between 15% and 30% in Ghana and Nigeria and from 10% to 40% across equatorial Africa, reaching up to 45% among the Baamba tribe in Uganda and decreasing to 1-2% on the North African coast and less than 1% in South Africa [2]. According to the United States Centers for Disease Control and Prevention, 7.7% (1 in 13) of Black or African American babies are born with the trait, and SCD affects approximately 100,000 Americans [4]. Death from SCD complications occurs mostly in children under five years in Africa, due to the late detection of the condition, inadequate facilities, scarcity of trained personnel, lack of adequate diagnostic tools and insufficient medical care [2]. Sickle Hb (HbS) is due to a mutation resulting in the substitution of thymine for adenine (GAG to GTG) in the sixth codon of the hemoglobin \(\beta\) chain gene. This causes the coding of valine (neutral charge) instead of glutamic acid (negative charge) at position six on the \(\beta\) chain [5; 6]. The alteration in the charge of the HbS molecule accounts for its different mobility abilities under electrophoresis. The loss of a negative charge at this site on the outside of the HbS molecule (cf. normal adult HbA) also enables neighboring molecules to aggregate upon deoxygenation, eventually forming long polymers [7]. Individuals homozygous for HbS (cf. HbA) develop the disease, while heterozygotes (HbAS, or the so-called sickle cell trait), usually lack symptoms, although their RBCs can be induced by sickle ex vivo [8; 9]. In addition to homozygote HbSS disease (sickle cell anemia, SCA), seven other major sickle genotypes have been linked to the disease. These include HbSC, HbS/\(\alpha\)-thalasemia, HbS/\(\beta^{\circ}\)-thalasemia, HbS/\(\beta\)+thalasemia, HbS/hereditary persistence of fetal Hb (S/HPFH), HbS/HbE syndrome, HbS/G6 PD (glucose-6-phosphate dehydrogenase deficiency) and many other rare combinations, such as HbS with HbD Los Angeles, HbO Arab, G-Philadelphia, etc.