## 5 Leukocyte Adhesion  
The structure of leukocytes is the reason why they are much more resistant to deformation than red blood cells. Consequently, leukocytes flow relatively slowly through capillaries and can stop and affect the distribution of red blood cell flow. Furthermore, the migration of leukocytes into tissue means that they can actively change their structure and therefore their mechanical properties. When leukocytes pass through capillaries narrower than or similar in size to themselves (6-9 \(\upmu\)m), they move slower than red blood cells (RBCs), \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Method/Device** & **Principle/Technique** & **Measured Parameters** & **Key Features/Limitations** & **Applications/ Disease Focus** \\ \hline Bifurcating Microchannel Analysis & Microfluidic channels with bifurcations and flow splitting & CDL width, aggregation intensity & Reveals impact of bifurcations on aggregate size and partitioning; shows plasma & Microvascular flow dynamics, viscosity reduction \\ \hline Flow Cytometry + Laser Tweezers Priezzhev & Measures light scattering and aggregation force after incubation with macromolecules & FSC, SSC, Fagg & HSA increases PS/SSC, SEG slightly, fibrinogen raises Fagg significantly; glutaraldehydehedevedes aggregation & Biochemical effects on aggregation and membrane mechanics \\ \hline Pharmacological Studies & Assesses drug effects (e.g., PDE inhibitors) on RBC rheology in vitro and in vivo & RBC deformability, aggregation reduction (\%) & Vinpocetine and aggregation; relates to improved microvascular flow & \\ \hline \hline \end{tabular}
\end{table} 
Table 5: _Cont._due to the larger size and spherical shape of the leukocytes, compared to the biconcave shape of RBCs [48]. Upon entering larger postcapillary vessels (8-30 um), faster-moving RBCs overtake leukocytes, pushing them toward the vessel wall--a process called force margination. This positioning promotes leukocyte-endothelium interaction, leading to adhesion and the subsequent rolling of leukocytes along the endothelium [49]. RBC aggregation enhances white blood cell (WBC) marginalization and adhesion to vessel walls [48; 49; 50; 51]. WBC marginalization is influenced by flow hydrodynamics, hematocrit, cell elasticity, and cell interactions. While RBC aggregation promotes WBC margination, WBC deformability reduces it. High molecular weight agents and low shear rates in post-capillary venules increase RBC aggregation, leading to more leukocytes being pushed toward the vessel wall and improving their attachment efficiency to the endothelium. Thus, lower shear rates and greater RBC aggregation both enhance WBC margination and adhesion, showing a direct relationship between erythrocyte aggregation and leukocyte-endothelium interactions [52; 53]. The impact of blood rheological properties on leukocyte adhesion in diabetic patients remains poorly studied, especially compared to leukocyte marginalization. Studies have shown that the presence of red blood cells (RBCs) enhances the adhesion of isolated lymphocytes to endothelial cells. In diabetes, increased RBC aggregation correlates with a higher number of rolling leukocytes at low shear rates, due to greater leukocyte marginalization. However, in diabetic patients, the separate contributions of free-flowing, marginalized, and rolling leukocytes have not yet been individually quantified [53; 54]. Leukocyte adhesion is a dynamic process influenced by blood flow conditions. To study it under near-physiological conditions, researchers use a flow microfluidic chamber system, which includes a microcamera, microscope, microfluid pump, and image analysis software [3; 17; 53]. This setup enables cell tracking, morphological analysis, rheological measurements, and leukocyte adhesion studies [3; 17]. In both healthy individuals and type 2 diabetes mellitus (T2 DM) patients, increased cell deformability leads leukocytes to maintain a round shape.