# Modeling of Integrated Nanoneedle-Microfluidic System for Single Cell Temperature Measurement
## 2 Proposed Nanoneedle-Microfluidic System
### Simulation Analysis Setup
The mechanical characterization was performed to examine the nanoneedle behavior when exposed to external forces. The displacement of the nanoneedle was obtained to identify the bending it will undergo before failure when forces are applied. The damage and strain energy outputs were studied to obtain the maximum force the nanoneedle could withstand before breakage. The third stage in the modelling was to study the performance of the nanoneedle and its response after penetrating a cell. Two steps were done to assess the performance correctly: electrical measurement on the cell, and the response to temperature change to obtain temperature versus current. The electrical measurement was done to determine the effect of the cell conductivity on  
Figure 4: (**a**) Thermal/electric characterization simulation setup; (**b**) Simulation setup of the nanoneedle mechanical. Figure 3: (**a**) Cross-sectional area to be studied; (**b**) The nanoneedle position on a 4 μm yeast cell model. the nanoneedle. According to the literature, single cell viability could be detected by measuring the current flow inside a cell using dual nanoprobes made of tungsten [2]. This triggered the possibility that the cell conductivity could affect the temperature measurement. Therefore, the dependency of the nanoneedle conductivity on cell conductivity had to be clearly attained. In the simulation setup, two main components were used: the nanoneedle and yeast cell model. The simulation setup proposed was mimicking the situation that would happen after the penetration (Figure 5a). The nanoneedle was assembled and merged with the cell model into one part defined using a 4-node linear coupled thermal-electric element definition. A constant voltage value of 1 volts was applied at one surface of the electrodes and ground to the other, as shown in Figure 5b. The simulation was defined at room temperature and the output current density was obtained and compared to the value from the nanoneedle characterization. The fourth stage of developing the nanoneedle-microfluidic system was to design the microfluidic channel and analyze the water behavior in the channel. The microfluidic system was designed to have two major components, the Polydimethylsiloxane (PDMS) channel and an external pump to control the fluid flow rate. These components were studied and constructed in a way to achieve single cell penetration and thermal characterization. Fluid flow rate inside the microfluidic channel was designed to play a crucial role in the proposed nanoneedle-microfluidic system. It is responsible to push the cells towards the nanoneedle and create the required force for successful penetration. The integrated nanoneedle-microfluidic system required microchannel height optimization and velocity optimization to have the range at which successful penetration could be achieved. The microfluidic channel required height optimization due to the disturbance in the water flow caused by the nanoneedle electrodes after the integration. Water flowed in the opposite direction and backward velocity was observed that disturbed the water distribution throughout the microchannel and the penetration process. This happened to be causing cell damage as well (Figure 6). Thus, the channel height had to be optimized at first with the aims of achieving full cell penetration, minimum cell damage, and least backward velocity. The channel width was maintained at 7 \(\upmu\)m in order to minimize the number of cells entering the channel. The analysis was done using a 6 \(\upmu\)m yeast cell, nanoneedle, microchannel (Figure 7a) and water. The water was defined as a eulerian EC3 DR model with a 4-node linear eulerian brick element definition. Density, equation of state, and viscosity of water were defined and 0.2 hexahedron meshing size was used. The parameter under study was the microchannel height by varying its value between 7 to 9 \(\upmu\)m (Figure 7b) and maintaining the velocity constant at 6.5 \(\upmu\)m/s.