Reality Check: Bioreactor H&C System Power

After mathematically modeling and experimentally determining the heating and cooling (H&C) requirements of our bioreactor, a Peltier- or thermal-electric-based heat exchange system was built to control the temperature inside the bioreactor. Tests were performed to determine the H&C system’s actual heating and cooling performance. Herein are described the experimental setup, data acquired, and results of those tests. The heat exchange system was built with the top-performing commercially-available 40 x 40 mm2 Peltier. The Peltier was expected to provide approximately 180 Watts of cooling power, according to supplier data. Yet, the outcomes from these experiments do not agree with the Peltier’s marketed performance.

Experimental Goals

1) Determine the actual heating and cooling power of the system. 2) Determine if the water pump was heating the water. 3) determine the relationship between the temperature difference (between the inlet and outlet ports on the water block) and the current delivered to the Peltier. To determine at which current the Peltier efficiency is at maximum.

Procedure

The H&C system was used to cool (or heat) a known volume of water, while the water’s temperature was measured periodically. The heat capacity of water was used to calculate the change in the waters thermal energy. The time, recorded with each temperature reading, was used to calculate the cooling (or heating) power (energy/time) that was delivered to cause the change in water temperature. Heat was transferred to and from the water using two methods:Coiling Tubing for Heat Xfer copy (1) Copper tubing was coiled and placed inside a water filled glass bioreactor (13.9 L). Prior to placement in the bioreactor, one end of the copper tubing was connected to the H&C system. Through one open end of the heat exchange system water was rapidly forced in, to pump out air bubbles, using a water hose. The system was then closed off and the water was re-circulated. Thus, heat was exchanged to (or from) water inside the glass bioreactor across the copper tubing from (or to) the H&C System. Bucket Test Method copy(2) Similarly, water inside a bucket or measuring cup was heated or cooled directly (without copper tubing) by the H&C system. A smaller volume of water is used to cause rapid temperature changes and quickly determine the systems heat-transfer power. To test if the pump was a heat source, water was re-circulated through the H&C system with the Peltier turned off (no heating or cooling). To determine the Peltier’s optimum efficiency temperature probes placed at the inlet and outlet to the heat exchange system, to measure the difference and decide at which point the Peltier hot side becomes too hot and reduces the effectiveness of the cold side.

Results

Actual Heating and Cooling Power

Cooling Power In Bucket and ReactorData indicated that the system has about 40 W of average cooling power. The two test methods, described above, had similar results: 42 W and 38 W average cooling power. In the chart above one can see that the system does not provide constant cooling power. As the water temperature approaches the temperature of the cold side of the Peltier, there is less thermal heat transfer “driving force”, so the rate of heat transfer decreases. In this case, the H&C systems cooling power is about 50 W when it is first started but decreases to about 25 W after about 20 minutes of use. Since, the temperature in the bioreactor is not meant to go below 15 °C, we can anticipate that the Peltier can provide 40 W of cooling power. Heating Power Montage In Bucket and BioreactorIn comparison, the system is much better at heating (as seen in the above graph) – with 180 W, average, heating power!

Pump Heats Water

The pump actually heats water. When the pump is at the maximum voltage/speed (19V), 8W of heat are added to the water. This reduces the systems ability to cool. Therefore, the pumping speed should be decreased to reduce the heat produced by the pump. In these, test the lowest the voltage pump would run at was 5V. This should cut down on the heat delivered to the system. This requires modifications to the electrical control board and would be a nice improvement for future generations of the bioreactor.

Optimal Peltier Operating Voltage Not Easily Determined

The temperature difference between the inlet and outlet to the heat exchange system did not provide conclusive data. Therefore, the Peltier should be run as the supplier suggests: 70-80% of maximum voltage for maximum cooling ability.

Conclusion

According to manufactures specification the system should be able to provide 180 Watts of cooling power. Initial tests indicated that the Peltier could produce 120 Watts of cooling. However, after more careful scrutiny, the Peltier had an average cooling power of about 40W. Therefore, when deciding to use the “best in class” 40 x 40 mm2 thermal electric cooler, the developer/engineer should know that the Peltier delivers 75 to 90 % less cooling power than marketed by the vendor. In this case, the Peltier was expected to provided, at minimum, 130 W of cooling, to cool a 14 L bioreactor at a rate of 6°C/hr. However, the Peltier-based system had less cooling power providing a much slower cooling rate: 40 W and 1.7 °C/hr respectively. Even though the cooling power was disappointing it should be sufficient to keep a 14 L bioreactor from warming up due to heat from growth lights. In our experiments, a water-filled 14 L glass vessel gained 30 W of heat from 4 illuminating growth lights surrounding the vessel. Thus, the system is capable of counteracting enough heat to maintain a setpoint temperature. Reactor heating, on the other hand, will work as planned because the Peltier system can transfer approximately 140 W, of heat to the contents of a 14 L bioreactor. Therefore, if the bioreactor is filled with cold growth media, the media can be warmed up and maintained at a temperature appropriate for cell seeding.

Future Plans

It would take 4 to 6 times as long to cool the reactor (compared to the original design) to a set point temperature. This is fine for long experiments or observations. However, when one wishes to experiment with the effect of temperature fluctuations on culture growth or productivity, the approach must be changed. Why might you want to experiment with temperature? You might be able to control proliferation and increased yield through changes in temperature. For example, reduced operating temperatures were shown to increase the production of desired proteins (biologics) in CHO cells [1]. Here, as in other engineering based projects, iteration is an important step in improving a design or process. Therefore, consider what can be done with this current open-source bioreactor H&C system. One could work with a smaller volume to achieve a faster cooling rate. For example, the targeted rate of cooling, 6 °C/hr, could be achieved – scaling down linearly – in a volume of approximately 3 L. Thus, 3 L in a partially filled reactor or a smaller bioreactor vessel could be regulated at the initially designed heating and cooling rates.

References

1. Kumar, N., P. Gammell, and M. Clynes. “Proliferation Control Strategies to Improve Productivity and Survival During Cho Based Production Culture : A Summary of Recent Methods Employed and the Effects of Proliferation Control in Product Secreting Cho Cell Lines.” Cytotechnology 53, no. 1-3 (2007): 33-46.     (function(i,s,o,g,r,a,m){i[‘GoogleAnalyticsObject’]=r;i[r]=i[r]||function(){ (i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o), m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m) })(window,document,’script’,’https://www.google-analytics.com/analytics.js’,’ga’); ga(‘create’, ‘UA-81033630-1’, ‘auto’); ga(‘send’, ‘pageview’);