Continuous oxygen monitoring to enhance ex-vivo organ machine perfusion and reconstructive surgery.

Continuous oxygenation monitoring of machine-perfused organs or transposed autologous tissue is not currently implemented in clinical practice. Oxygenation is a critical parameter that could be used to verify tissue viability and guide corrective interventions, such as perfusion machine parameters or surgical revision. This work presents an innovative technology based on oxygen-sensitive, phosphorescent metalloporphyrin allowing continuous and non-invasive oxygen monitoring of ex-vivo perfused vascularized fasciocutaneous flaps. The method comprises a small, low-energy optical transcutaneous oxygen sensor applied on the flap's skin paddle as well as oxygen sensing devices placed into the tubing. An intermittent perfusion setting was designed to study the response time and accuracy of this technology over a total of 54 perfusion cycles. We further evaluated correlation between the continuous oxygen measurements and gold-standard perfusion viability metrics such as vascular resistance, with good agreement suggesting potential to monitor graft viability at high frequency, opening the possibility to employ feedback control algorithms in the future. This proof-of-concept study opens a range of research and clinical applications in reconstructive surgery and transplantation at a time when perfusion machines undergo rapid clinical adoption with potential to improve outcomes across a variety of surgical procedures and dramatically increase access to transplant medicine.

Versatile, in-line optical oxygen tension sensors for continuous monitoring during ex vivo kidney perfusion.

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.

Development and in-vivo validation of a portable phosphorescence lifetime-based fiber-optic oxygen sensor.

Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e. the amount of molecular oxygen present in the tissue is a direct result of supply (perfusion) and consumption. Thus, measurement of [Formula: see text] is an effective method to monitor tissue viability. However, tissue oximetry sensors commonly used in clinical practice instead rely on measuring oxygen saturation ([Formula: see text]), largely due to the lack of reliable, affordable [Formula: see text] sensing solutions. To address this issue we present a proof-of-concept design and validation of a low-cost, lifetime-based oxygen sensing fiber. The sensor consists of readily-available off-the shelf components such as a microcontroller, a light-emitting diode (LED), an avalanche photodiode (APD), a temperature sensor, as well as a bright in-house developed porphyrin molecule. The device was calibrated using a benchtop setup and evaluated in three in vivo animal models. Our findings show that the new device design in combination with the bright porphyrin has the potential to be a useful and accurate tool for measuring [Formula: see text] in tissue, while also highlighting some of the limitations and challenges of oxygen measurements in this context.

Calculation of Tissue Oxygenation via an Inverse Boundary Problem for Transcutaneous Oxygenation Wearable Applications.

In this article, we present a toolset to fully leverage a previously developed transcutaneous oxygenation monitor (TCOM) wearable technology to accurately measure skin oxygenation values. We describe numerical models and experimental characterization techniques that allow for the extraction of precise tissue oxygenation measurements. The numerical model is based on an inverse boundary problem of the parabolic equation with Dirichlet boundary conditions. To validate this model and characterize the diffusion of oxygen through the oxygen sensing materials, we designed a series of control/calibration experiments modeled after the device's clinical application using oxygenation values in the physiological range expected for healthy tissue. Our results demonstrate that it is possible to obtain accurate tissue pO2 measurements without the need for long equilibration times with a small wearable device.

Phosphorescent Microneedle Array for the Measurement of Oxygen Partial Pressure in Tissue.

The knowledge of the exact oxygen partial pressure in tissue is crucial for patient care and in the treatment of ischemic medical conditions. However, current methods to assess oxygen partial pressure in tissue suffer from a variety of disadvantages, including complex equipment and procedures that necessitate trained personnel. Additionally, the barrier function of the stratum corneum reduces oxygen exchange and can consequently hamper surface measurements of rapidly changing oxygen partial pressure in tissue. To overcome these challenges, a novel, easy-to-use technique to monitor the oxygen partial pressure in tissue using microneedle arrays (MNAs) has been developed. The MNAs can be made from poly(ethyl methacrylate) and poly(propyl methacrylate) and overcome the skin's barrier function to measure oxygen in the capillary bed and interstitial fluid of the skin. The MNAs' tips are embedded with an oxygen-sensitive phosphorescent metalloporphyrin, where the oxygen partial pressure inversely correlates to changes in both emission intensity and phosphorescence lifetime of the in-house developed red emitting Pt-core porphyrin. It was demonstrated that the oxygen-sensing MNAs are sufficiently robust to puncture human skin via rupture of the stratum corneum, and that the MNAs can detect changes in oxygen partial pressure in skin within the physiologically relevant range (0-160 mmHg). Additionally, the MNAs can be combined with a wearable wireless optical readout system, making these oxygen-sensing MNAs a novel wearable and portable method for user-friendly monitoring of oxygen partial pressure in skin.

A Patient-Ready Wearable Transcutaneous CO2 Sensor.

Continuously monitoring transcutaneous CO2 partial pressure is of crucial importance in the diagnosis and treatment of respiratory and cardiac diseases. Despite significant progress in the development of CO2 sensors, their implementation as portable or wearable devices for real-time monitoring remains under-explored. Here, we report on the creation of a wearable prototype device for transcutaneous CO2 monitoring based on quantifying the fluorescence of a highly breathable CO2-sensing film. The developed materials are based on a fluorescent pH indicator (8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt or HPTS) embedded into hydrophobic polymer matrices. The film's fluorescence is highly sensitive to changes in CO2 partial pressure in the physiological range, as well as photostable and insensitive to humidity. The device and medical-grade films are based on our prior work on transcutaneous oxygen-sensing technology, which has been extensively validated clinically.

Quantitative Luminescence Photography of a Swellable Hydrogel Dressing with a Traffic-Light Response to Oxygen.

Sensor-integrated wound dressings are emerging tools applicable to a wide variety of medical applications from emergency triage to at-home monitoring. Uncomfortable, unnecessary wound dressing changes may be avoided by providing quantitative insight into tissue characteristics related to wound healing such as tissue oxygenation, pH, and exudate/transudate volume. Here, a simple cost-effective methodology for quantifying oxygen and pH in a swellable hydrogel dressing using a single photograph is presented. The red and green luminescence of a novel dendritic polyamine Pt-porphyrin and fluorescein conjugate quantitatively responds to oxygen and pH, respectively, and enables robust sensing. The porphyrin conjugate, when combined with a four-arm star polyethylene glycol (PEG) amine polymer, rapidly crosslinks at room temperature with an N-hydroxysuccinimide (NHS)-PEG crosslinker to form a color-changing hydrogel dressing with tunable swelling capabilities applicable to a variety of wound environments. An inexpensive digital single-lens reflex (DSLR) camera modified with bandpass filters captures the hydrogel luminescence using simple macroscopic photography, and conversion to HSB colorspace allows for intensity-independent image analysis of the hydrogels' dual modality response. The hydrogel formulation exhibits a robust and validated visible red-orange-green "traffic light" spectrum in response to oxygen changes, regardless of swelling state, pH, or autofluorescence from skin, thereby enabling the clinician friendly naked-eye feedback.

Portable Oxygen-Sensing Device for the Improved Assessment of Compartment Syndrome and other Hypoxia-Related Conditions.

Measurement of intramuscular oxygen could play a key role in the early diagnosis of acute compartment syndrome, a common condition occurring after severe trauma leading to ischemia and long-term consequences including rhabdomyolysis, limb loss, and death. However, to date, there is no existing oxygen sensor approved for such a purpose. To address the need to improve the assessment of compartment syndrome, a portable fiber-optic device for intramuscular oxygen measurements was developed. The device is based on phosphorescence quenching, where the tip of an optical fiber was coated with a poly(propyl methacrylate) (PPMA) matrix containing a brightly emitting Pt(II)-core porphyrin. The optoelectronic circuit is highly portable and is based on a microspectrometer and a microcontroller readout with a smartphone. Results from an in vivo tourniquet porcine model show that the sensor is sensitive across the physiological oxygen partial pressure range of 0-80 mmHg and exhibits an appropriate and reproducible response to changes in intramuscular oxygen. A commercial laboratory oxygen sensor based on a lifetime measurement did not respond as expected.

A paintable phosphorescent bandage for postoperative tissue oxygen assessment in DIEP flap reconstruction.

Flaps are common in plastic surgery to reconstruct large tissue defects in cases such as trauma or cancer. However, most tissue oximeters used for monitoring ischemia in postoperative flaps are bulky, wired devices, which hinder direct flap observation. Here, we present the results of a clinical trial using a previously untried paintable transparent phosphorescent bandage to assess the tissue's partial pressure of oxygen (pO2). Statistical analysis revealed a strong relationship (P < 0.0001) between the rates of change of tissue oxygenation measured by the bandage and blood oxygen saturation (%stO2) readings from a standard-of-care ViOptix near-infrared spectroscopy oximeter. In addition, the oxygen-sensing bandage showed no adverse effects, proved easy handling, and yielded bright images across all skin tones with a digital single-lens reflex (DSLR) camera. This demonstrates the feasibility of using phosphorescent materials to monitor flaps postoperatively and lays the groundwork for future exploration in other tissue oxygen sensing applications.

Wearable device for remote monitoring of transcutaneous tissue oxygenation.

Wearable devices have found widespread applications in recent years as both medical devices as well as consumer electronics for sports and health tracking. A metric of health that is often overlooked in currently available technology is the direct measurement of molecular oxygen in living tissue, a key component in cellular energy production. Here, we report on the development of a wireless wearable prototype for transcutaneous oxygenation monitoring based on quantifying the oxygen-dependent phosphorescence of a metalloporphyrin embedded within a highly breathable oxygen sensing film. The device is completely self-contained, weighs under 30 grams, performs on-board signal analysis, and can communicate with computers or smartphones. The wearable measures tissue oxygenation at the skin surface by detecting the lifetime and intensity of phosphorescence, which undergoes quenching in the presence of oxygen. As well as being insensitive to motion artifacts, it offers robust and reliable measurements even in variable atmospheric conditions related to temperature and humidity. Preliminary in vivo testing in a porcine ischemia model shows that the wearable is highly sensitive to changes in tissue oxygenation in the physiological range upon inducing a decrease in limb perfusion.

Humidity-Insensitive Tissue Oxygen Tension Sensing for Wearable Devices†.

Quantification of tissue oxygen partial pressure (pO2 ) at the skin surface is crucial for diagnostic applications in burns, reconstructive surgeries, diabetic ulcers, etc. Further, current advances in wearable and communications technologies have widened the use of transcutaneous oxygen monitors (TCOM) for home care or even enhance athletic performance. For TCOM technology to find widespread use, devices must function reliably yet independently of changes in environmental conditions, humidity in particular. To this end, we have explored the incorporation of an oxygen-sensing metalloporphyrin within different host matrix materials of different compositions with the goal of overcoming the humidity sensitivity of previously explored oxygen-sensing materials. We developed a tetraethyl orthosilicate (TEOS)-based, highly breathable, oxygen-sensing metalloporphyrin polymer film which responds to changes in oxygenation independent of humidity.