Injectable Phosphorescence-based Oxygen Biosensors Identify Post Ischemic Reactive Hyperoxia

Abstract

Novel injectable biosensors were used to measure interstitial oxygenation before, during, and after transient ischemia. It is well known that reactive hyperemia occurs following a period of ischemia. However, increased blood flow does not necessarily mean increased oxygen tension in the tissue. Therefore, the purpose of this study was to test the hypothesis that tissue reactive hyperoxia occurs following release of hind-limb tourniquet occlusions. Rats were injected with bilateral hind-limb biosensors and were simultaneously subjected to a unilateral femoral vessel ligation. After approximately one and three months, the rats underwent a series of oxygenation challenges, including transient hind-limb tourniquet occlusion. Along with the biosensors, near infrared spectroscopy was used to measure percent oxyhemoglobin in capillaries and laser Doppler flowmetry was used to measure blood flow. Post-occlusion reactive hyperemia was observed. It was accompanied by tissue reactive hyperoxia, affirming that the post-occlusion oxygen supply must have exceeded the expected increased oxygen consumption. The measurement of the physiologic phenomenon of reactive hyperoxia could prove clinically beneficial for both diagnosis and optimizing therapy.

Long-Term In Vivo Oxygen Sensors for Peripheral Artery Disease Monitoring

“…Microsensors were injected subcutaneously, and signal was non-invasively measured with a custom NIR reader [10–12]. Data are expressed as a Lumee Oxygen Index (LOI), which is the micromolar concentration of oxygen as calculated from the phosphorescent lifetime (τ) and temperature, using standard phosphorescent quenching calibrations [13].…”

Injectable Biomedical Devices for Sensing and Stimulating Internal Body Organs

“…Most subcutaneous regions across the body are accessible for relatively large devices to be implanted and removed effortlessly without damaging the tissues. Moreover, numerous classes of injectable electronics, including RFID chips, implantable loop recorders and biosensors were implanted under the skin with little or no surgery 47,226–228. The key to achieving such minimally invasive implantation can be attributed to the high aspect ratio structures of the implants, as opposed to large area, planar format electronic devices, as well as injection tools based on sharp and long shafts, inducing negligible damage to the surrounding tissue upon and after implantation.…”

“…i) Sensor phosphorescence changes depending on oxygen concentration. Reproduced under the terms of the Creative Commons CC BY 4.0 License 227. Copyright 2017, the Authors.…”

“…A purely passive form of injectable subcutaneous sensor was achieved using phosphorescence‐based hydrogel, capable of sensing oxygen concentration of the surrounding tissue 227. The biosensor was shaped into a high aspect ratio structure (0.5 × 5 mm) in order to utilize conventional injection needle (18 gauge), as shown in Figure 10g.…”

Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association

“…85 Injectable biosensor technology has been shown to efficaciously measure reactive hyperoxia in the hind limbs of rats subjected to a series of oxygenation challenges and may be more sensitive to fluctuations in relative tissue oxygenation than near-infrared spectroscopy. 39 This device has also been shown to safely and effectively measure local tissue oxygen levels in the feet of 10 human subjects with CLI during surgical intervention, as well as postoperatively for 28 days. 85 Larger studies are still needed to validate this device and its utility for perioperative limb perfusion assessment.…”