In vivo application of an implantable tri-anchored methylene blue-based electrochemical pH sensor.

The development of robust implantable sensors is important in the successful advancement of personalised medicine as they have the potential to provide in situ real-time data regarding the status of health and disease and the effectiveness of treatment. Tissue pH is a key physiological parameter and herein, we report the design, fabrication, functionalisation, encapsulation and protection of a miniaturised, self-contained, electrochemical pH sensor system and characterisation of sensor performance. Notably for the first time in this environment the pH sensor was based on a methylene blue redox reporter which showed remarkable robustness, accuracy and sensitivity. This was achieved by encapsulation of a self-assembled monolayer containing methylene blue entrapped within a Nafion layer. Another powerful feature was the incorporation, within the same implanted device, of a fabricated on-chip Ag/AgCl reference electrode - vital in any electrochemical sensor, but often ignored. When utilised in vivo, the sensor allowed accurate tracking of externally induced pH changes within a naturally occurring ovine lung cancer model, and correlated well with single point laboratory measurements made on extracted arterial blood, whilst enabling in vivo time-dependent measurements. The sensors functioned robustly whilst implanted, and maintained in vitro function once extracted and together, these results demonstrate proof-of-concept of the ability to sense real-time intratumoral tissue pH changes in vivo.

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research.

Lung cancer represents a major worldwide health concern; although advances in patient management have improved outcomes for some patients, overall 5-year survival rates are only around 15%. In vitro studies and mouse models are commonly used to study lung cancer and their use has increased the molecular understanding of the disease. Unfortunately, mouse models are poor predictors of clinical outcome and seldom mimic advanced stages of the human disease. Animal models that more accurately reflect human disease are required for progress to be made in improving treatment outcomes and prognosis. Similarities in pulmonary anatomy and physiology potentially make sheep better models for studying human lung function and disease. Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease is endemic in many countries throughout the world and has several features in common with human lung adenocarcinomas, including histological classification and activation of common cellular signaling pathways. Here we discuss the in vivo and in vitro OPA models that are currently available and describe the advantages of using pre-clinical naturally occurring OPA cases as a translational animal model for human lung adenocarcinoma. The challenges and options for obtaining these OPA cases for research purposes, along with their use in developing novel techniques for the evaluation of chemotherapeutic agents or for monitoring the tumor microenvironment in response to treatment, are also discussed.

In Vivo Characterization of a Wireless Telemetry Module for a Capsule Endoscopy System Utilizing a Conformal Antenna.

This paper describes the design, fabrication, packaging, and performance characterization of a conformal helix antenna created on the outside of a capsule endoscope designed to operate at a carrier frequency of 433 MHz within human tissue. Wireless data transfer was established between the integrated capsule system and an external receiver. The telemetry system was tested within a tissue phantom and in vivo porcine models. Two different types of transmission modes were tested. The first mode, replicating normal operating conditions, used data packets at a steady power level of 0 dBm, while the capsule was being withdrawn at a steady rate from the small intestine. The second mode, replicating the worst-case clinical scenario of capsule retention within the small bowel, sent data with stepwise increasing power levels of -10, 0, 6, and 10 dBm, with the capsule fixed in position. The temperature of the tissue surrounding the external antenna was monitored at all times using thermistors embedded within the capsule shell to observe potential safety issues. The recorded data showed, for both modes of operation, a low error transmission of 10-3 packet error rate and 10-5 bit error rate and no temperature increase of the tissue according to IEEE standards.