Mark Wefers Bettink

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level 3 49 photomultiplier tube. Users can interact via a multi-touch 12” TFT-LCD screen. Apart from the main switch to turn on the device, the COMET has no physical buttons. If a USB storage device is inserted in the USB-port on the rear panel the data is exported in a comma separated file format for further processing in programs like MS Excel. The COMET can be used on a flat surface or be mounted on a trolley or arm through a VESA 75/100 compatible adapter plate. 2.3.2 Software Lifetimes of the raw data are calculated on an embedded control board. The embedded calculation software is written in C code to simplify the development process as per IEC 62304 as required for certification. The user interface (UI) is running on a separate Linux based operating system to enhance device usability experience. There are three different types of measurement to distinguish, shown in table 1. Table 1 The COMET different measurement types. Single measurement One measurement per activation of the touchscreen non physical button. Interval measurement The COMET will measure in a set interval: At the start of the interval a measurement is done, and the interval time can be chosen (60 min, 20 min, 5 min, 1 min) Dynamic measurement The COMET can conduct a series of up to 120 measurements, one measurement per second. 2.4 Location of the measurement The COMET measures oxygen tension in mitochondria by measuring the triplet-state lifetime of PpIX. Under normal (non-sensitized) conditions PpIX is present in very low concentrations in the human skin and not detectable with the COMET. This can be overcome by the exogenous administration of ALA that leads to higher concentrations of PpIX in the mitochondria. ALA synthase is the first and the rate-limiting enzyme of the porphyrin synthetic pathway. Under normal conditions the level of heme synthesis and the intracellular concentration of PpIX are mainly regulated by heme control of the ALA synthase activity. As a small molecule, ALA penetrates the stratum corneum [22]. Exogenously provided ALA bypasses the negative feedback controls in the heme biosynthetic pathway and leads to overproduction of PpIX [23].