## 4 Discussion and Conclusions  
In this study, we developed a device to achieve continuous and rapid ICP-based blood cell lysis. We used concentrated electric fields to create ion depletion regions for efficient lysis at an operating voltage of less than 100 V. Fluorescent particle experiments confirmed that ICP was successfully generated by the developed device and that the particles could only be concentrated when an electric field was applied through the ICP. After injecting diluted blood into the device, we confirmed that the blood cells were rapidly lysed. Using timelapse sequences and videos, we demonstrated that the developed device quickly lysed blood cells within 0.3 s. Image analysis also confirmed that more than 99.4% of the injected blood cells were lysed, demonstrating that the device could electrically dissolve most of the injected blood cells. Compared with other conventional lysis methods, our ICP-based approach demonstrates several practical advantages in terms of speed, efficiency, and operational conditions. Figure 4: Image analysis of the blood cell lysis efficiency. (**a**) Images of the blood cell lysis control group; before 0 V (**left**) and after 0 V (**right**). No voltage was applied to the developed device. (**b**) Images of the blood cell lysis group; before 75 V (**left**) and after 75 V (**right**); a voltage of 75 V was applied to generate the ICP. (**c**) Number of cells before and after applying the electric field to each group. Black arrows in (**a,b**) indicate the direction from before to after applying the voltage. (applied voltage: 75 V, flow rate: 1000 nL/min, exposure time: 100 ms). Mechanical lysis (e.g., sonication or bead beating) can be effective but typically requires bulky equipment and generates cellular debris, which complicates downstream analysis. Thermal lysis methods often involve heating samples to over 60 \({}^{\circ}\)C, which can risk protein denaturation. Chemical lysis using surfactants such as Triton X-100 achieves a high efficiency but introduces reagents that may interfere with subsequent biomolecular assays. Conventional electrical lysis methods generally require high voltages (several hundred volts to kilovolts) to disrupt the membranes of blood cells (-7 \(\upmu\)m), potentially causing bubble formation and electrode degradation. In contrast, our system achieves a 99.4% lysis efficiency within 0.3 s under only 75 V, without the use of chemical reagents or complex mechanical components. This performance demonstrates the effectiveness of ion depletion-based electric field focusing even at modest voltages and short exposure times. While the current device uses diluted blood to reduce hydraulic resistance and improve cell flow within microchannels, this is a common practice across many microfluidic lysis studies and does not constitute a fundamental limitation of our approach. Moreover, the applied flow rate of 1000 nL/min is within a typical range for lab-on-a-chip devices and can be optimized further depending on application needs. Previous studies have explored ICP-based lysis mechanisms for various cell types. Our earlier work [36] demonstrated field focusing via ICP in a micro/nanochannel device using cultured HEK293 cells (-20 \(\upmu\)m), where lower operating voltages were sufficient due to the larger cell size. However, the system operated at extremely low flow rates (-40 nL/min) and used non-physiological buffers (1 mM sodium phosphate) to stabilize the ICP region. In this study, we adapted the ICP-based approach for red blood cells, which are more challenging to lyse electrically. We successfully maintained ion depletion and field localization even in PBS and at a substantially higher flow rate (1 \(\upmu\)L/min), demonstrating the robustness and practical applicability of our design. In contrast to other ICP-based lysis approaches such as [37], which relied on synergistic effects between electric fields and vortex-induced shear forces to disrupt bacterial cells, our platform achieves efficient blood cell lysis using electrical forces alone.