The future of metabolic phenotyping

Data from a parallel, continuous metabolic phenotyping system (black line) vs. a multiplexed system (red line)

The essence of metabolic phenotyping is accurate metabolic measurement. As a matter of convenience, cost and feasibility, practically all metabolic phenotyping systems operate in a multiplexed mode, in which a single gas analysis chain is shared between multiple animals, typically 8, 10, 16 or more. Cycle times between metabolic measurements for a given animal vary widely between systems, ranging (in the case of 16 animals) from 2 minutes for an optimized Promethion-M Multiplexed metabolic phenotyping system to as much as ~45 minutes for its competitors. The result is a heavily sub-sampled data set from which much fine temporal detail is missing or distorted.

The picture above is worth a thousand words. It shows the output of a brand new Promethion-C Continuous, parallel metabolic phenotyping system. Data from one of sixteen animals (mice, strain C57BL/6J) is shown. Eight at a time were measured simultaneously, without multiplexing, and the system is capable of indefinite expansion (one pharmaceutical company has a 24-channel Promethion-C system). Click on the picture to embiggen it. Data on VCO2, food and water uptake, body mass, water loss rate etc. were also acquired synchronously but are not shown. For more on this topic, including an excellent interactive visualizationof the distortions caused by multiplexing, visit this later blog post.

The multiplexed system (red lines) was simulated from the output of the Promethion-C system*, assuming a 30 minute cycle time, which is faster than average. As you can see, the Promethion-C system (black trace) tracks each metabolic excursion by the animal, as it alternates between rest, pedestrian locomotion, and wheel running, with extraordinary fidelity. The data storage interval of the Promethion-C metabolic phenotyping system is one second for all attached sensors.

Now that Promethion-C is available, it is extremely hard to justify acquiring multiplexed metabolic phenotyping systems any longer unless cost is an overriding factor. If that is the case, Promethion-M offers the fastest cycle times available - for example, down to 2 minutes cycle time for a 16-cage system. Like all Promethion systems, Promethion-M also offers the many traceability and transparency benefits of complete raw data retention. Plus, most components of a Promethion-M system can be used in your Promethion-C system if you ever decide to upgrade.

Designing and building a "massively parallel", continuous, multi-animal metabolic phenotyping system is far from easy. This is especially true if the system stores all of the raw data from all sensors - a requirement for good laboratory practice. The bandwidth requirements are formidable, as are the requirements for implementing suitably flexible data analysis protocols. There is no way this massive exercise in coordinated integration will work unless, as with Promethion, the manufacturer has total control over all aspects of the design of all instrumentation comprising the system. This we do. As a result, Promethion-C is up and running, in production, a documented and field-proven product with multiple installations in the field.

As the chief designer of both Promethion systems, it's been a privilege to have the opportunity to turn my knowledge of respirometry and passion for innovation to practical use for the biomedical community!

If you have any questions, contact me.

 -- John Lighton

* Thanks to Thomas Förster, Ph.D., Sable Systems International's expert in-house data analysis and data presentation consultant, for running the simulation and creating the graph.