Post-Operative Monitoring of Intestinal Tissue Oxygenation Using an Implantable Microfabricated Oxygen Sensor

Figures

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  Figure 1. Sensor design and fabrication. (a): Microscope image of the 3 × 3 microelectrode WE array fabricated on a silicon substrate. The light-coloured circles in the passivation correspond to the active electrode areas. Platinum extends under all the electrodes, and it forms an interconnect track to left of the array. (b): Schematic cross-section of sensor die layer stack (not to scale), showing the aluminium bond pad, interconnect, and passivation windows over platinum electrodes. (c): Photograph of a fully packaged sensor, flexible PCB, and connection lead. (d): Schematic cross-section of the sensor epoxy packaging and pHEMA hydrogel membrane (not to scale). Reproduced with permission from [15].

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  Figure 2. Bench characterisation of sensor performance. (a): Typical CV scans of sensor in PBS saturated with air (red) and PBS degassed by sparging with argon (blue). Similar results were obtained from four sensors. (b): Mean steady-state WE current at −0.5 V measured over a range of oxygen partial pressures in PBS (n = 3 sensors). (c): Sensor response when moved at t = 0 min from argon-sparged PBS (negligible oxygen) to an air-saturated PBS solution. Steady-state currents were normalised between 0% and 100% response for comparison. Grey line at 90% response indicates the threshold for determining response time. Individual responses from four sensors are shown (red lines). (d): Mean steady-state current at −0.5 V in air-saturated PBS over 24 h. Sensor recordings were performed at intervals of either 2 min (red) or 60 min (blue) (n = 3 sensors/condition).

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  Figure 3. Ischaemia and FiO2 challenges. (a): Sensors fixed on intestine serosal surface at (i) the control site, and (ii) the test site (shown after it had been made ischaemic by ligation of the jejunal arteries). Similar placement was used for both pigs. (b): Ischaemic challenge. Mean steady-state current shown at the control and test sites, before (grey) and after (red) the test site was made ischaemic (n = 4 sensors/location, from two pigs). Readings were averaged over the 10 min before the ischaemia surgery, and the 10 min after. (c): FiO2 challenges. Results shown only from sensors on control (non-ischaemic) site (n = 4 sensors, from two pigs). (i) Schematic showing FiO2 changes in each block. (ii) Absolute mean steady-state current within each FiO2 block, averaged over the final 30 min of the block. (iii) Change in mean steady-state current between FiO2 blocks, calculated using values averaged over the final 10 min of the first block, and over the initial 10–20 min of the second block (providing 10 min for tissue oxygenation to stabilise following the change).

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  Figure 4. Continuous colorectal anastomosis monitoring. (a): Intra-operative photographs showing creation of a stapled colorectal anastomosis and sensor placement. (i) Proximal colon with stapler anvil secured by a purse-string suture; (ii) distal colon with transverse staple line and stapler spike protruding at the midpoint; (iii) proximal and distal colon joined by closure and firing of the stapler; (iv) placement of distal sensors (green arrows) at the anastomosis (white arrow). (b): Mean steady-state current from each sensor during the 45 h experiment, averaged over 5 h periods (five sensors, from one pig). (c): Post-mortem positive contrast CT images taken following a colorectal resection and anastomosis. (i) Transverse view. The positive contrast agent (Gastrografin) can be seen filling the rectum and distal colon. The contrast agent ran past the anastomotic site with no evidence of leakage of contrast material outside the intestinal lumen. (ii) Sagittal view. This image was taken through the anastomotic site. Three sensors can be identified surrounding the colon (green arrows). There is no evidence of leakage of contrast material outside the intestinal lumen.

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  Figure 5. Effect of biofouling on sensor sensitivity. (a): In vitro assessment, showing mean steady-state WE current at 0, 24, and 48 h from sensors continuously immersed in either air-saturated PBS alone or air-saturated PBS with 35 mg/mL BSA (n = 3 sensors/condition). (b): In vivo assessment, showing mean steady-state WE current from sensors in air-saturated PBS before and after implantation in pigs A1–A3 (n = 5 sensors/pig).