## 6 Modeling the Microrheological Deformation Behavior of Blood Cells
\begin{table}
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**Factor** & **Impact on Reliability and Reproducibility** & **Specific Challenges** & **Possible Mitigations** \\ \hline \hline \multirow{7}{*}{\(1\). Channel Fabrication Variability} & Small variations in microchannel dimensions (width, height, and surface roughness) can alter flow profiles, shear stress, and cell interactions, aggregation and deformability measurements. & - Differences in lithography or molding processes - Inconsistent surface coatings affecting cell adhesion - Material variability (PDMS, glass, etc.) & - Implement rigorous fabrication quality control (QC) - Use standardized fabrication protocols and materials - Characterize channels post-fabrication using microscopy or profoimetry - Surface treatment (plasma, coatings) \\ \hline \multirow{7}{*}{\(2\). Blood Sample Preparation} & Variability in sample handling, anticoagulant type/concentration, hematocrit, temperature, and storage time affects RBC behavior and aggregation propensity. & - Inconsistent anticoagulants affecting cell deformability - Variability in dilution or cell concentration - Control hematocrit and cell temperature fluctuations altering viscosity - Time-dependent cell aging or activation & - Define strict sample prep protocols (anticoagulants, timing) - Control hematocrit and cell - Temperature fluctuations altering viscosity - Time-dependent cell aging or activation & - Use high-precision syringe or pressure pumps - Incorporate flow sensors and feedback control - Design bubble traps and cleaning protocols - Regular calibration of flow equipment \\ \hline \multirow{7}{*}{\(3\). Flow Control Precision} & Inaccurate or unstable flow rates and pressures lead to variations in shear stress, influencing cell deformation and aggregation kinetics. & - Pump pulsatility or drift Pressure fluctuations in microfluidic setups - Backpressure variations caused by channel fouling or bubble formation & - Use high-precision syringe or pressure pumps - Incorporate flow sensors and feedback control - Design bubble traps and cleaning protocols - Regular calibration of flow equipment \\ \hline \multirow{7}{*}{\(4\). Measurement and Detection Consistency} & Imaging resolution, frame rate, and illumination consistency impact the accuracy of cell morphology and aggregation metrics. & - Variability in microscope settings - Operator-dependent focusing and image capture - Differences in image analysis software with calibration \\ \hline \multirow{7}{*}{\(5\). Biological Variability} & Intrinsic differences between donor samples or pathological conditions contribute to measurement variability independent of the platform. & - Inter-individual variability in RBC deformability and aggregation - Disease states causing heterogeneity & - Use replicate samples and multiple donors - Establish baseline ranges for normal and pathological states - Incorporate controls in each run \\ \hline \hline \end{tabular}
\end{table} 
Table 6: Reliability and reproducibility of microfluidic platforms: Key considerations. biological samples. Integrating multiple methods--such as hydrodynamic, optical, electromagnetic, and acoustic techniques--enables precise analysis of the physical properties of blood and blood cells. Circulating leukocytes and platelets must adhere to the blood vessel wall to carry out the protective function of immunity for leukocytes and hemostasis for platelets. Given the importance of these adhesive processes, they have been widely analyzed both in vivo, using intravital microscope, and in vitro, using flow-based models. Flow-based studies have revealed that leukocytes and platelets use a multi-step process to achieve control recruitment. It has become increasingly recognized that adhesion is constrained by the local hemodynamic environment and modulated by the rheological properties of the blood. [PERSON] et al.