Potential of cell tracking velocimetry as an economical and portable hematology analyzer

Abstract

Anemia and iron deficiency continue to be the most prevalent nutritional disorders in the world, affecting billions of people in both developed and developing countries. The initial diagnosis of anemia is typically based on several markers, including red blood cell (RBC) count, hematocrit and total hemoglobin. Using modern hematology analyzers, erythrocyte parameters such as mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), etc. are also being used. However, most of these commercially available analyzers pose several disadvantages: they are expensive instruments that require significant bench space and are heavy enough to limit their use to a specific lab and lead to a delay in results, making them less practical as a point-of-care instrument that can be used for swift clinical evaluation. Thus, there is a need for a portable and economical hematology analyzer that can be used at the point of need. In this work, we evaluated the performance of a system referred to as the cell tracking velocimetry (CTV) to measure several hematological parameters from fresh human blood obtained from healthy donors and from sickle cell disease subjects. Our system, based on the paramagnetic behavior that deoxyhemoglobin or methemoglobin containing RBCs experience when suspended in water after applying a magnetic field, uses a combination of magnets and microfluidics and has the ability to track the movement of thousands of red cells in a short period of time. This allows us to measure not only traditional RBC indices but also novel parameters that are only available for analyzers that assess erythrocytes on a cell by cell basis. As such, we report, for the first time, the use of our CTV as a hematology analyzer that is able to measure MCV, MCH, mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), the percentage of hypochromic cells (which is an indicator of insufficient marrow iron supply that reflects recent iron reduction), and the correlation coefficients between these metrics. Our initial results indicate that most of the parameters measured with CTV are within the normal range for healthy adults. Only the parameters related to the red cell volume (primarily MCV and RDW) were outside the normal range. We observed significant discrepancies between the MCV measured by our technology (and also by an automated cell counter) and the manual method that calculates MCV through the hematocrit obtained by packed cell volume, which are attributed to the artifacts of plasma trapping and cell shrinkage. While there may be limitations for measuring MCV, this device offers a novel point of care instrument to provide rapid RBC parameters such as iron stores that are otherwise not rapidly available to the clinician. Thus, our CTV is a promising technology with the potential to be employed as an accurate, economical, portable and fast hematology analyzer after applying instrument-specific reference ranges or correction factors.

Applications of magnetic and electromagnetic forces in micro-analytical systems

“…In addition, they observed iron storage in circulating monocytes, 34,35 the relation between phosphatidylserine expression and magnetic mobility, 36 enzymatic deoxidation of Hb, 37 iron transport in cancer cells, 38 and showed the possibility of hematology analyzer detection. 39,40 Watarai's group also contributed to the development of analytical techniques utilizing magnetophoresis. They investigated the magnetophoretic velocities of diamagnetic polystyrene microparticles in paramagnetic manganese(II) aqueous solution, i.e., χ p < χ m .…”

“…In addition, they observed iron storage in circulating monocytes, 34,35 the relation between phosphatidylserine expression and magnetic mobility, 36 enzymatic deoxidation of Hb, 37 iron transport in cancer cells, 38 and showed the possibility of hematology analyzer detection. 39,40…”

Iron in blood cells: Function, relation to disease, and potential for magnetic separation

“…For diagnosing anemia, determination of the RBC count, hematocrit (Hct), and Hb is performed (Gómez‐Pastora, Weigand, et al, 2022). Also, Wintrobe's parameters such as MCV, mean corpuscular Hb (MCH), and MCH concentration (MCHC) of RBCs can be helpful to find the etiology of the anemia (Sarma, 1990).…”

“…Under this scenario, the use of magnetophoresis can be a cheaper solution to diagnose anemias since the introduction of powerful and low‐cost neodymium magnets and modern computer imaging technologies enable the development of instruments that can determine the magnetic susceptibility of blood cells, which are related to their Hb and iron content (Chalmers et al, 1999, 2017). For example, recent works have suggested the use of a permanent magnet‐based microsystem referred to as cell tracking velocimetry (CTV) (Chalmers et al, 1999; Kim, Gómez‐Pastora, Gilbert, et al, 2019; Kim, Gómez‐Pastora, Weigand, et al, 2019; R. H. Weigand et al, 2021) as a portable and inexpensive hematology analyzer able to measure traditional RBC indices and novel indices such as the percentage of hypochromic RBCs and the red cell distribution width (Gómez‐Pastora, Weigand, et al, 2022).…”

Novel Approaches Concerning the Numerical Modeling of Particle and Cell Separation in Microchannels: A Review

“…Moreover, downscaling of sorting systems enables less laboratory space, and the integration of multiple tasks and operations within the same device is possible, which not only increases the precision of the analysis but also improves the accuracy, reliability, and reproducibility of sample preparation procedures [14,15]. Thus, controlling the motion and position of these materials within fluids in microchannels possesses great importance in the previous fields, especially for the development of low-cost and portable diagnostic tools that can be used at the point of need [16][17][18].…”