Our CE-marked COMET measurement system non-invasively measures oxygen availability [mmHg] in human skin cells with a high concentration of protoporphyrin IX.

Is there enough oxygen? Are interventions necessary? How effective are they?

Our organ’s cells die without oxygen. Measuring oxygen in these cells reflects the balance of supply and demand: is there enough? A measurement where oxygen is needed is quite different from measurements in blood. We expect that our measurement in cells will enable doctors to guide interventions to prevent organ failure.

That is vital in many situations. Direct and indirect treatments of oxygen supply strive to prevent organ failure. The measurement in the cells should prove useful for patient management (resuscitation) perioperatively and in critical care. Skin is an early warning sensor, so physicians should get time to act. And sometimes the failing organ is the skin itself, so the measurement should be useful to assess the effects of and necessity for (peripheral) interventions and warn of transplant rejections.

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.

Several clinical trials are ongoing or soon starting at four Universities in two countries. Early results were presented by Ubbink as well as Zwaag (see below), more publications will follow. We believe that clinical research on the mitochondrial oxygen availability and consumption in the next years will lead to new insights in several fields and significant changes to the treatment of large groups of patients.

Further information is found in press releases of Erasmus Medical Center in Rotterdam,  Medgadget, Leiden University Medical Center and in the publications at the bottom of this page.

COMET measurement system

The new COMET measurement system determines oxygen availability as partial pressure of oxygen in mmHg. It measures in real time at the bedside and only in the active mitochondria of epidermal cells. It is available as a medical device in Europe for a first indication. It is not yet available outside Europe. It has been used in nine clinical trials at four institutes in 100 volunteers and more than 80 patients. Most results still need to be published, several articles are expected in early 2018.

In a live demonstration at the 2015 meeting of the World Mitochondria Society in Berlin, Dr. Egbert Mik showed how a low dose of cyanide locally and reversibly blocked mitochondrial respiration in his skin. Romers et al. detected the limit of the critical hemoglobin concentration during isovolemic hemodilution in pigs, the skin provided early warning before kidney damage. Harms et al. showed coinciding changes in cellular respiration in rat skin, liver and buccal mucosa after induction of endotoxemia. Van Diemen et al. from the Center for Human Drug Research in Leiden measured increased oxygen utilization in skin cells of 28 human volunteers after 4 weeks of daily intake of statins. In Rotterdam and Leiden clinicians observed the effects of vasoconstriction, vasodilation, fluid administration and red cell transfusion on mitochondrial oxygenation in chronic anemic, surgical and ICU patients.

The measurement in the cells should prove useful for patient management, to direct therapy for resuscitation, to assess the effects of and necessity for interventions, to detect alterations of cellular metabolism and to help develop treatments for metabolic dysfunction.

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 with Dr. Michiel Sinaasappel, developed a practical way to measure oxygen availability and consumption where oxygen is needed: in the tissue cells rather than in the blood. This first in-vivo measurement of mitochondrial oxygen availability is possible by determining the oxygen dependent duration of the afterglow of protoporphyrin IX,  a heme-precursor 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 standard skin sensor collects a signal from several square millimeters of epidermis, providing an average value for the different cells.

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. Dr. Mik called his method the protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) and initiated the steps to make it clinically available.

The technology and its application has been published in:

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.