Electrochemical multi-sensors for biomedical applications

In this thesis, pH and potassium all-solid-state ISE based on potentiometry and bioimpedance sensors were designed, fabricated and integrated in a miniaturized array for its application in endoscopic surgery for in vivo ischemia detection inside the stomach. To achieve this goal, the developed array withstood the low pH and corrosive condition in the gastric juice of the stomach, by modifying the surface with a conductive Ag/AgCl ink containing hydrophilic and hydrophobic groups. That creates a stable and robust candidate for low pH applications. However, these sensors have to demonstrate besides stability, high sensitivity, and selectivity. For this purpose, different ionophores specific to a single ion were tested. Octadecyl isonicotinate was the one that shown better results as pH ionophore and valinomycin, bis [(benzo-15-crown-4)-4-ylmethyl] pimelate for potassium detection. All these ionophores were embedded in PVC polymer membrane containing also plasticizers such as 2-nitrophenyl octyl ether, bis (1-butylpentyl) adipate (BBPA) and liphophilic anionic additives such as potassium tetrakis (4-chlorophenyl) borate (KTpClPB). The specific compositions of membranes to detect potassium or pH were optimized for the better performance of the sensors. pH ISE sensor shows a nernstian behavior (-54,38 mV/pH) at low pH and a nearly nernstian behavior at physiological pH (-34,899 mV/pH). Bioimpedance sensor was tested and optimized in vitro with different solutions of ions concentration to mimic ischemia detection and with different kinds of tissues from different nature. For this purpose, chicken fat and breast tissues were taken as a model for mimicking non-ischemic and ischemic states respectively. The effect of electrodes insulation as well as the pressure applied on the tissue was studied. The dependence of the impedance response with different pressure applied to the sensor was overcome by applying magnetic field attachment. The sensor array was modified with ring magnets which were attracted by an external magnet, giving stable and reliable signal discarding mechanical motion. The shape and size of the sensor array were designed for being adapted to the commercially available gastroendoscopes. Round shaped cylinder of 7 mm diameter was fabricated with 12 electrodes pin of 600 µm diameter, containing 3 RE, 3 pH and 2 potassium all-solid-state sensors and 4 electrodes in a row for impedance measurements. The sensor array was successfully integrated in commercial endoscope and inserted inside the pig stomach. The blood flow of certain area of the stomach was interrupted by ligating or crossclamping vessels and organ wall. Ischemia and reperfusion steps were sensed successfully with potassium and pH sensors. These results also indicate that information about hypoxic tissue damage can be collected with this array. Ischemia was also sensed on small intestine tissue by opening the abdominal part of the body and getting the sensor array in contact with the intestine. By crossclamping of mesenteric artery by tourniquets and scissors, ischemic and reperfusion states were controlled. Results proved that ischemia and reperfusion can be monitored by our integrated sensor array. As a conclusion, a novel all-solid-state potentiometric, miniaturized, low cost and mass producible pH, potassium all-solid-state ISE and impedance sensors integrated in an array was successfully fabricated for detecting ischemia inside the stomach by means of endoscopic techniques and also on small intestine. This array was tested in vitro and vivo giving reproducible and reliable results. The developed all-solid-state pH sensors permit low pH sensing from 0.7-2.5, which is the only example in the literature that allows so low pH detection, and so make this sensor a unique device for stomach detection.