Building and Assembling an Indirect Calorimeter Jon Baran Dhaval Desai Kyle Herzog Tim Pearce Client Dr. Dongsheng Cai MD, PhD Department of Physiology Advisors Dr. Ken Gentry PhD Department of Biomedical Engineering Dr. Richard Keesey PhD Professor Emeritus – Department of Psychology Injury Reserve

Metabolism Controlled by intricate biochemical pathways Aberrations in these pathways results in disorders –Obesity –Diabetes Stress and inflammatory pathways in the CNS  impact on metabolism –Genes (mutations, deletions) Source:

Indirect Calorimeter Measure values of VO 2 and VCO 2 –VO 2 : Rate of oxygen consumption –VCO 2 : Rate of carbon dioxide production –Respiratory Exchange Ratio (RER) Monitor fluctuations over time Heat production and energy source

Problem Statement To build and assemble an indirect calorimeter for mice, which has capabilities to monitor O 2 consumption and CO 2 production, measure animal movement, and store these values for further data analysis.

Design Constraints Measurements: –O 2 and CO 2 within 5% error Units should be in mL/hour Measurements should be taken every 5 minutes for 24 to 48 hours – Food and water consumption –Waste excretion –Animal Movement

Design Constraints Construction: –2 identical systems each with 5 cages One set for control mice, the other for experimental mice –Must fit on a rolling cart for transportation around the building (size and weight considerations) –Should cost less than $2000 –Should last 2-5 years

Design Constraints Must use the parts provided Oxygen sensors and analyzers, CO2 sensors and analyzers, air flow controls, mouse chambers, tubing, computer, electronic switches, software, manual instruction

Competition CLAMS –Comprehensive Lab Animal Monitoring System –Can monitor: Activity, food and water consumption, urine and waste produced, O 2 consumed, CO 2 generated. –Uses measurements to calculate the animals’ respiratory exchange ratio VCO 2 /VO 2, as well as heat production. –Data can be imported to a computer with statistical spreadsheet programs for analysis. –Costs about $150,000.

Final Design – Push-Pull System

Overall Design: Pump  Collection Chamber  Manual Valve  Five Cages  Solenoid Valves (Innervated by Relay)  Dehumidifier  Flow Meter  CO 2  O 2  Air Release to Atmosphere

Pros/Cons of Push Pull Pros Allows for accurate flow rates Dehumidifies air with collection tank Maintains constant flow through cages Allows needed amount of air to pass through sensors/analyzers Cons Collection chamber will require more space System must be checked periodically for leaks Large space requirements

Another Alternative – Pull-pull system 5L Pump O2 Sensor/ Analyzer CO2 Sensor/ Analyzer.2L Pump CPU

Another Alternative – “One to one” Cages O 2 sensors & analyzers CO 2 sensors & analyzers CPU O2O2 O2O2 O2O2 O2O2 O2O2 CO L/min Pump Pump

Design Matrix Cost (1-10) Knowledge Base (1-10) Size (1-5) Simplicity (1-5)Total Push- Pull Pull One to One141511

Future Work Test and calibrate all equipment –Purchase additional equipment as needed First build single cage unit –Pump  Cage  CO 2  O 2 Connect 4 additional cages with relay and solenoid values –Allows for switching of cages –Must be built onto moveable cart –2 independent system must be made Connect sensors to DAQ device –Integrate A/D Converters as needed

References Kouyama R, Suganami T, Nishida J, Tanaka M, Toyoda T, Kiso M, Chiwata T, Miyamoto Y, Yoshimasa Y, Fukamizu A, Horiuchi M, Hirata Y, and Ogawa Y. Attenuation of Diet-Induced Weight Gain and Adiposity through Increased Energy Expenditure in Mice Lacking Angiotensin II Type 1a Receptor. Endocrinology (8): Streeper RS, Koliwad SK, Villanueva CJ, and Farese RVJr. Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin. Am J Physiol Endocrinol Metab : E338-E394 Molero JC, Turner N, Thien CBF, Langdon WY, James DE, and Cooney GJ. Genetic Ablation of the c-Cbl Ubiquitin Ligase Domain Results in Increased Energy Expenditure and Improved Insulin Action. Diabetes : Oxymax Lab Animal Monitoring System: CLAMS. Columbus Instruments. Retrieved from on February 20, 2007.

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