## 4 Methods and Devices for Assessing Erythrocyte (RBC) Aggregation
### Image Analysis Method in a Flow Chamber
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Technique** & **Main Features** & **Performance/Limitations** & **Disease Focus/Applications** \\ \hline \multirow{4}{*}{Viscometric Methods} & Assesses blood viscosity to infer deformability and aggregation (Tk and IAE indices). & Integrates whole-blood rheology; affected by plasma viscosity, hematocrit, shear rate. & Applied in diabetes, hypertension, and malaria; indicates inflammation risk. \\ \hline \multirow{4}{*}{Optical Laser Tweezers (LT)} & Uses focused laser beams to trap/manipulate RBCs; measurements aggregation forces. & Precise force measurements at cellular scale; technically complex. & Differentiates hypertensive vs. healthy blood microrheology. \\ \hline \multirow{4}{*}{Atomic Force Microscopy (AFM)} & Evaluates topography, elasticity, and adhesion at nanoscale. & Very high resolution; limited throughput and physiological relevance. & Studies membrane mechanics in RBCs, granulocytes, and blood cots. \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._ \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Aspect** & **Image-Based Methods** & **Electrical Impedance Methods** & **Optical Trapping/Optical Capture Methods** \\ \hline \multirow{4}{*}{Throughput} & - Generally lower throughput due to labor-intensive image acquisition and processing steps. & - Typically, higher throughput, as electrical signals can be rapidly recorded and processed. & - Usually low to moderate throughput, as manipulation of individual cells is time-consuming. \\ \hline \multirow{4}{*}{Diagnostic Accuracy} & - Requires microscopy and image analysis, sometimes in microfluidic setups, which can be slower per sample. & - Suitable for bulk measurements or high-frequency sampling in flow. & - Focus on single-cell analysis limits the number of cells analyzed in a given time. \\ \hline \multirow{4}{*}{Diagnostic Accuracy} & - Provides rich morphological and dynamic information on RBC aggregation and deformability. & - Good at detecting bulk changes in electrical properties reflecting cell membrane integrity and aggregation. & - High accuracy in measuring biomechanical properties like aggregation forces at single-cell level. \\ \hline \multirow{4}{*}{Diagnostic Accuracy} & - Captures real-time aggregation dynamics and microstructural behavior, and can identify subtle morphological changes. & - Limited in providing detailed morphological data; more indirect measurement. & - Detailed biomechanical and optical properties assessment, but may miss population-wide variability. \\ \hline \multirow{4}{*}{Complexity and Practicality} & - Equipment like microfluidic flow chambers plus advanced imaging required; labor-intensive post-processing. & - Relatively simpler instrumentation, more amenable to clinical settings. & - Requires specialized laser tweezers and optics; high level of expertise needed. \\ \hline \multirow{2}{*}{In Vivo Relevance} & - Microfluidic models closely mimic microcirculatory flow, improving physiological relevance. & - Less directly related to physiological flow, but sensitive to bulk blood properties. & - Usually in vitro, focusing on isolated cells, less representative of whole-blood dynamics. \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Comparison of image-based methods vs. electrical impedance and optical trapping. light the combined influence of hematocrit and flow velocity on aggregation behavior and demonstrate that using multiple quantification methods enhances the characterization of blood's microstructural properties.