Our organ’s cells need oxygen to function. Organs fail when cells lack oxygen.

Do the cells have enough oxygen? Are interventions necessary? How effective are they? In many situations only signs of damage allow physicians to answer these questions with confidence – when it is too late.

Now there finally is a way to measure oxygen inside active cells. This is quite different from current measurements in blood. Only in the cells themselves can it be determined if there is enough oxygen or if cells are hypoxic – and also if cells can’t use the oxygen they receive.

COMET measurement system

The CE-marked COMET measurement system determines oxygen availability as partial pressure of oxygen [mmHg]. It non-invasively measures oxygen in human skin cells with a high concentration of protoporphyrin IX – in real time at the bedside and only in the mitochondria of active cells.

The COMET measurement system and its prototypes have been used in 16 clinical trials at seven institutes in two countries, in intensive care patients as well as during and after cardiopulmonary bypass and other major surgeries. The effects of hemoglobin, temperature, flow, blood pressure management and other interventions on cellular oxygenation are visible in real time. Studies demonstrated how cellular oxygen provides more relevant information than previously available measures like lactate, regional saturation or blood pressure. Additional clinical trials are expected to start enrolling soon.

We expect that the measurement of oxygen in the cells will enable doctors to guide the many interventions to ensure oxygen delivery to cells and that this will make care easier, safer and cheaper.  Skin is regarded as an early warning sensor, so should give physicians time to prevent lasting damage. Preclinically, transfusion need was detected two hours before kidney failure. Monitoring cellular oxygen in skin should therefore provide early warning of complications and allow doctors to assess the necessity for interventions and follow their effects in real time. It should also facilitate decisions before and during peripheral interventions and be useful to detect alterations of cellular metabolism  and help develop treatments for metabolic dysfunction. Measurements have also been performed in the gut of volunteers and preclinically in other organs. So far, a CE marked sensor is only available for the skin. Eventually, images of cellular oxygen distributions in organs should help assess tissue function for diagnosis, interventions or wound care.

Use the COMET measurement system as a low-burden adjunct to your studies and improve patient safety. Contact us for a quote (Europe only).

The science of cellular monitoring

Anesthesiologist Dr. Egbert Mik, building on his invention made together with Dr. Michiel Sinaasappel, developed the protoporphyrin IX triplet state lifetime technique (PpIX-TSLT). It is the first practical way to clinically measure oxygen availability and consumption where oxygen is needed: in the tissue cells rather than in the blood. It uses the oxygen dependent duration of the ‘glow-in-the-dark’ of the precursor to heme. This protoporphyrin IX is metabolized in epidermal mitochondria after local priming with aminolevulinic acid used in photodynamic therapy or diagnosis. The signal therefore originates only in active mitochondria and reflects the balance between oxygen supply and demand. The COMET’s skin sensor collects a signal from several square millimeters of epidermis, providing an average value for the different cells. In a preclinical trial the oxygenation of cells in the gut has been measured with an endoscopic sensor. Ultimately, interstitial probes, even imaging, should be feasible with this technology. Oxygen should be measured where it is needed so doctors can treat what matters.

Editors of Anesthesiology summarized a publication of research results with a prototype of the COMET and wrote that directly measuring tissue oxygenation “would be a major advance for perioperative medicine.” O’Brien and Schmidt wrote in a separate editorial for Anesthesiology (July 2016):A reliable measure of oxygen tension at the level of the mitochondria might significantly refine transfusion practice…  Indeed, any clinical scenario where cellular oxygenation might be compromised could potentially benefit… If mitochondrial PO2 can be measured reliably in humans, the potential value of this technique is hard to overestimate.

A range of cellular oxygen availability is expected for different cells depending on their positions along capillaries and their distances from them (the Krogh model and its refinements  e.g., here or here, provide theoretical explanations). Intense perfusion can result in average epidermal mitoPO2 values only slightly below the arterial oxygen tension.  Temporary local pressure stops microvascular blood flow in the measurement region. Repeated measurements during and after pressure allow determination of cellular oxygen utilization and analysis of re-perfusion.

The technology and its application has been published in or presented at:

Eurostars supported the development and testing of the COMET measurement system (project E!7294). Photonics Healthcare collaborates with AMC, Erasmus Medical Center, Leiden University, Sanquin Blood Supply and Unitron.

Further information is found in press releases of Erasmus Medical Center in Rotterdam,  Medgadget, Leiden University Medical Center.