Periodic Reporting for period 1 - Sencell16 (Lifecare’s Sencell sensor is an implantable micro-sensor for subcutaneous location, long time, continuous, wireless, real time monitoring of interstitial glucose for diabetes management.) Reporting period: 2016-08-01 to 2016-12-31 Summary of the context and overall objectives of the project Summary of the Animal ExperimentThe Sencell device iteration resulting from the first animal experiments were evaluated in another animal experiment in pigs. Implantation of three modified Sencell sensors and one Dexcom® G4 control sensor was performed in the back and the neck area of three pigs (1 female, 2 male), respectively. After two days of equilibration and signal documentation, they received an i.v. glucose load of up to 100 mg/kg of dextrose. Reference measurements from capillary blood samples were performed using the YSI 2300 STAT Plus glucose analyser every 15 min for 5 h. In addition, the Dexcom 4 device was used as interstitial reference method. During the first two days, six Sencell prototype devices were able to track glucose changes paralleling the results of the Dexcom Sensor over extended time periods. An example is shown in the figure below. Neither the Dexcom-Sensor, nor the Sencell sensor were able to reflect the very rapid intravenous blood glucose changes induced during the ivGTT in the plasma. This may rather represent the delayed and blunted glucose dynamics in the interstitial fluid during this time-period than can allow for any performance interpretation of the interstitial sensors. In comparison to the previous results, deduction of movement artefacts as captured by the reference pressure chambers substantially reduced the noise level of the signals. The magnitude of the signals was in a predicted range and working sensors were matching G4 results. Although the body temperatures in the animals within three experimental days partially exceeded 39°C, the activity of ConA was preserved. No external signs of inflammation were observed. In conclusion, improved performance of the actual sensor after recent design modifications could be demonstrated in vivo. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far We revised the Sencell test-device to include a ‘reference chamber’ (buffer) as well as a ‘signal chamber’ (active fluid) to provide cancelation of in-vivo pressure noise In addition we introduced more robust, absolute pressure sensors (one per chamber) and Bluetooth communications to enable data recovery without sedationThese devices were subject to limited (due to the tight timescales) in-vitro evaluation at CC before a second round of pre-clinical trials. Key observations follow:The dual sensor (signal and reference) does provide noise reduction but there is still significant noise after subtraction for in-vivo data which must be filtered and which may limit sensitivityIn the pre-clinical trials, we see some evidence of correlation between Sencell and Dexcom but only for a small subset of devices and for restricted periodsWe suspect that chemistry yield may be the dominant cause of inconsistent behaviour as most implanted Sencell devices provided sensible pressure dataOther factors, as listed later in this presentation may also affect correlation: for example, residual pressure noise, baseline drift and the reliability of the Dexcom referenceWe consider that the pre-clinical results offer promise but also emphasise the need to ensure that chemistry is reliable (as made) and stable (as used) via device independent QA/QC and by extended-testing, in-device and in-vitro (as a pre-requisite for any further in-vivo tests) Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Nothing in particular from the feasabiity study sencell2016.jpg
