We have characterized the imbibed horizontal flow of sickle blood into 100-μm-diameter glass capillaries. We find that blood containing sickled cells typically traverses the capillaries between three and four times as slowly as oxygenated cells from the same patient for all genotypes tested, including SS, AS, SC and Sβ+ thalassemia blood. Blood from SS patients treated with hydroxyurea has a viscosity intermediate between the SS and AA values. Blood containing cells that are not rigidified, such as normal red cells or oxygenated sickle cells, follows a simple Lucas-Washburn flow throughout the length of the 3-cm capillary. By fitting the flexible-cell data to the Lucas-Washburn model, a viscosity can be derived that is in good agreement with previous measurements over a range of volume fractions and is obtained using an apparatus that is far more complex. Deoxygenation sickles and thus rigidifies the cells, and their flow begins as Lucas-Washburn, albeit with higher viscosity than flexible cells. However, the flow further slows as a dense mass of cells forms behind the meniscus and increases in length as flow progresses. By assuming that the dense mass of cells exerts a frictional force proportional to its length, we derive an equation that is formally equivalent to vertical imbibition, even though the flow is horizontal, and this equation reproduces the observed behavior well. We present a simple theory using activity coefficients that accounts for this viscosity and its variation without adjustable parameters. In the course of control experiments, we have found that deoxygenation increases the flexibility of normal human red cells, an observation only recently published for mouse cells and previously unreported for human erythrocytes. Together, these studies form the foundation for an inexpensive and rapid point-of-care device to diagnose sickle cell disease or to determine blood viscosity in resource-challenged settings.

We show that the characteristic time for sickled blood to traverse 100 µm-diameter glass capillaries can be used as the foundation for a useful point-of-care diagnosis for sickle cell disease. 3.2 cm long capillaries were inserted into a 5 µL drop of blood, and 1/4 µL was spontaneously drawn into the tube. The rate at which the blood traversed the capillary was significantly changed by deoxygenation only for sickle genotypes, a consequence of the increased viscosity of cells containing sickle fibers. Under these conditions, we find deoxygenation causes the time for sickle blood to traverse the capillary to increase to about 3 times its original value, in contrast to normal blood, where the times are equivalent regardless of state of oxygenation. This corresponds to readily-observed time differences of around 10 s for capillary traversal. Such changes are present for blood from homozygous sickle cell patients, as well as heterozygous patients with hemoglobin AS, SC, and Sβ+ thalassemia. Moreover, we demonstrate that this test is sensitive to sickling therapies that increase the production of fetal Hb. This viscosity-based measurement thus offers the prospect of an assay that is 10 times faster than any current test of which we are aware, at costs that rival the least expensive of any current assays.

Sickle cell disease is a world-wide problem, and its diagnosis remains a challenge in both developed and underdeveloped nations. In Africa, for example, where 300,000 children are born each year with the disease, early identification and elementary care could propel the lifespan from the current 5 years to near the 40 years seen in places such as the US. In places where screening is more nearly universal, issues of diagnosis are more likely to arise when emergency care is required and a patient's sickle cell status is uncertain. Moreover, the possibilities of mass migrations can again confound issues of patient identification that might be simple in a geographically fixed population. We are accordingly developing rapid and inexpensive tests for sickle cell disease. Our most recent device employs a narrow (100 micron) tube, which will draw in blood based on capillary forces. When sickle blood is deoxygenated blood, it will rise more slowly due to the viscosity increment from the rigid cells than its oxygenated counterpart. When the blood does not sickle, the oxygenated and deoxygenated cells have the same viscosity and rise time. Because the patient's own oxygenated blood serves as a control, the method is immune to errors arising from issues such as anemia, polycythemia vera or the presence of malarial parasites. The method is extremely rapid (tens of seconds), robust, and inexpensive. We have developed a simple analytic description of the process, which shows that initially height proceeds as the square root of time, and this is what is observed. The differences in sickle and normal blood are readily observed. Progress in integrating deoxygenation of the blood into the device will also be presented.

The life-span of the 300,000 African newborns with sickle cell disease is typically less than 5 years, and the World Health Organization estimates that "70% of SCD deaths in Africa are preventable with simple, cost-effective interventions such as early identification of SCD patients by newborn screening and the subsequent provision of comprehensive care." In contrast, early and regular care has extended the life-span to around 40 years for the 100,000 total number with SCD in the United States. Present techniques for diagnosing sickle cell disease require resources not necessarily readily available in susceptible areas of the world or fail to give correct response under certain conditions. To address these issues we have developed a capillary-based device to determine the presence of sickle blood. The device, assembled from off-the-shelf components at very low cost, performs the test based on the known rigidity of deoxygenated sickle cells. In the device, a packed bed of glass beads is trapped between two narrow glass capillaries. Capillary action will draw whole blood into the device, but deoxygenated sickle blood, as it occludes the inter-bead spaces, rises into the capillary more slowly than oxygenated sickle blood, which forms the local control for the test. The performance of the device will be described, as well as its potential future use in assessment of the clinical status of patient who have sickle cell disease.

Recent high-precision measurements in a three-slit diffraction experiment [Sinha et al., Science 329, 418 (2010)] have been performed as an explicit test of the validity of Born's rule for quantum probabilities. This experiment aims to establish an upper limit to the possibility of higher-order interference, which, if observed, could support generalization of quantum probability theory. We reproduce this three-slit experiment using position-resolved detection, compare our results to a computational model, and find significant limitations to the normalization scheme proposed by Sinha et al. that influence interpretation. We further show that the dependence of the measurements on detector size and position must be taken into account for proper interpretation of results and meaningful comparison with other experimental schemes.