Overall Device Functionality
We will place our four channel device within a flow system. Where fluid with cell nutrients (“Cell Gatorade~water”) will be pumped through the four channel device, creating shear stress and pressure across the ECs. Shear stress is caused by the flow which is regulated by a pump, and pressure is regulated by the deformation valves.
Four Channel Device Layout
Figure 1: Depicts our entire device, consisting of main body and deformation valve
Figure 2: Depicts the physical setup of our entire device
Our four channel device consists of two main components, main body and deformation valve. The main body consists of four channels in series, while the device has three electronically controlled deformation valves. They will regulate pressure drop between channels in order to vary pressure in each channel. Further, each valve will have a tube holder to ensure the appropriate bend of tubing. In addition, a fourth deformation valve is used. However, this valve will go between the four channel device and reservoir.
Component 1: Main Body
Figure 3: Depicts just the main body of our device
Figure 4: Depicts the branching tubing connecting to the pressure sensors
The main body consists of a top and bottom, as shown in figure 3 above. This contains 4 channels connected in series through subsequent inlets and outlets. There are 2 cover slips per channel (8 in total), each containing ECs. One coverslip per channel serves as the control experiment to validate result. A small piece of tubing is located at the outlets of every channel that leads to a pressure sensor that is used to estimate pressure over the ECs. This can be seen in Figure 4 above. On another note, in order to properly seal the device, latches and O-rings are used.
Component 2: Deformation Valves
Figure 5: Depicts just the deformation valve
Figure 6: Depicts the cam used. It changes from 33mm to 35.5mm over the entire rotation of the cam. This gives a deformation of 3mm to 5.5mm but the servo limits the final deformation to 5mm
The pressure is controlled through self-designed valves as shown in figure 5 above. These servos have a rotation limit of 270O and are used to turn a cam depicted in figure 6 above. We found that deforming the tube from 1-3mm did not cause any change in the resistance of the valve and so, to increase the resolution of the valve, the cam was changed accordingly. This cam at 0O deforms the tube 3mm, the smallest point where we saw changes in the resistance of the valve, which slowly turns to 5mm over the 270O of the servo. The additional 0.5mm in the cam at the end is not utilized due to the limits of the servo.This constriction causes the pressures within the channels to change. The final layout of the device during use is shown in figure 1 and 2 above.
Component 3: Electronics Box
Figure 8: Depicts the layout of the completed system
Our device will be part of a flow system consisting of pump, reservoir, and microfluidic device. The ECs, which will be placed on the coverslips that go inside the device, can only be kept alive in ideal conditions. Therefore, the reservoir and microfluidic device will be placed inside an incubator. The incubator will regulate the environment parameters to maintain the ideal conditions. The pulsatile pump will be placed outside of the incubator due to it being too large to fit inside the incubator. Furthermore, the electronics of the device will be controlled by an electronics box that will be placed outside the system. That way the technician who uses the device will be able to control the position of the valves and read the approximate pressure of the channels outside the incubator, further ensuring that the ECs will not be contaminated and die. The fluid through the will cell medium (“Cell Gatorade”), which will contain all the nutrients needed to keep the cells alive. This setup is depicted in figure 8 above.
Performance Results
Figure 7: Depicts the schematics of the electronics used in the system
The deformation valves are connected to an electronics box to turn the servo in order to constrict the tubing. The electronic box also reads and displays the pressures within each channel through an LCD screen while also having the ability to control the motors. Users are able to turn knobs (potentiometers) to change the position of the motors which changes the pressure within each channel all while having the device within the incubator. How everything is connected is seen in figure 7 above. Through the manufacturer's recommendation, capacitors were used with the pressure sensors in order to reduce the noise.
Flow System Layout
Figure 9: Valve Configuration With Non-uniform Pressure Drop
Figure 10: Valve Configuration With Uniform Pressure Drop
Due to unexpected circumstances, channel 4 was cracked during the process of testing. As such, this channel and valve 3 were left out of the final experiment in order for the leak to not affect the performance of the device. Overall, the team were able to vary pressures within the device as shown in figure 9 and figure 10. These figure shows each channel at different pressure values; furthermore, the total pressure drop does not exceed 70mmHg. In addition, the team was able to control the inlet pressure to be 50mmHg using a master valve at the request of our sponsor. Figure 9 shows an uneven pressure drop. In experiments that the sponsor would like to perform, the pressure drop across the channels should be even. By using the deformation valves, the team was able to achieve even pressure drop across each channel (fig.10). Since the pump is a centrifugal pump, the flow rate inside the device varies depending on the valve configuration. The varying flow rate across valve configurations affects the pressure drop. This effect is seen in the last channel (yellow line) of both valve configurations in figure 9 and figure 10. Intuitively, since the last valve is exposed to the reservoir with a small height difference, the pressure value in channel 3 should always be near 0 mmHg (gage pressure). However, it is clear to see that the pressure of channel 3 is approximately 10 mmHg higher in figure 10 than in figure 9. This is due to the flow inside the tubes being in transition flow(flow state in between laminar and turbulent; Re is calculated to be approximately 3800), resulting in different and unpredictable pressure drops from the tubing. However, due to the small height of the channel, the ECs will still be under laminar flow. With a pulsatile pump, such issues will not exist due to the pulsatile pump's ability to provide constant flow rate regardless of head loss. As such, a pulsatile pump is required to realize independent pressure control.
Recommendations
While the team was able to successfully vary the pressures within the channels within the specified parameters, due to the COVID-19 situation, the original objective could not be met. Therefore, the team has some recommendations for future developments of this design:
Change sensors if they end up being problematic
No more than 5 channels should be in series to maintain the desired pressure range
Redesign the channel if a smaller pressure drop is needed
Currently they have a projected pressure drop of 12.6mmHg at maximum flow rate
Re-fabricate the main body of the device due to the previous one being cracked
Retesting of the device utilizing a pulsatile pump at maximum flow rate
Fabricate a reservoir for the flow system
Solder all the electronic components and fabricate an electronics box
Insulate any tubing that will be placed out of the incubator