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Pietro Salvo,1,2 Nicola Calisi,1 Bernardo Melai,1 Valentina Dini,3 Clara Paoletti,1 Tommaso Lomonaco,1 Andrea Pucci,1 Fabio Di Francesco,1 Alberto Piaggesi,4 Marco Romanelli3 1Department of Chemistry and Industrial Chemistry, University of Pisa, 2Institute of Clinical Physiology, National Council of Research, 3Wound Healing Research Unit, Department of Dermatology, University of Pisa, 4Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy Abstract: Foot ulcers account for 15% of comorbidities associated with diabetes. Presently, no device allows the status of foot ulcers to be continuously monitored when patients are not hospitalized. In this study, we describe a temperature and a pH sensor capable of monitoring diabetic foot and venous leg ulcers developed in the frame of the seventh framework program European Union project SWAN-iCare (smart wearable and autonomous negative pressure device for wound monitoring and therapy). Temperature is measured by exploiting the variations in the electrical resistance of a nanocomposite consisting of multiwalled carbon nanotubes and poly(styrene-b-(ethylene-co-butylene)-b-styrene). The pH sensor used a graphene oxide (GO) layer that changes its electrical potential when pH changes. The temperature sensor has a sensitivity of ~85 Ω/°C in the range 25°C–50°C and a high repeatability (maximum standard deviation of 0.1% over seven repeated measurements). For a GO concentration of 4 mg/mL, the pH sensor has a sensitivity of ~42 mV/pH and high linearity (R2=0.99). Keywords: diabetic foot ulcer, wearable sensors, wound temperature, wound pH

Pietro Salvo,1,2 Nicola Calisi,1 Bernardo Melai,1 Valentina Dini,3 Clara Paoletti,1 Tommaso Lomonaco,1 Andrea Pucci,1 Fabio Di Francesco,1 Alberto Piaggesi,4 Marco Romanelli3 1Department of Chemistry and Industrial Chemistry, University of Pisa, 2Institute of Clinical Physiology, National Council of Research, 3Wound Healing Research Unit, Department of Dermatology, University of Pisa, 4Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy Abstract: Foot ulcers account for 15% of comorbidities associated with diabetes. Presently, no device allows the status of foot ulcers to be continuously monitored when patients are not hospitalized. In this study, we describe a temperature and a pH sensor capable of monitoring diabetic foot and venous leg ulcers developed in the frame of the seventh framework program European Union project SWAN-iCare (smart wearable and autonomous negative pressure device for wound monitoring and therapy). Temperature is measured by exploiting the variations in the electrical resistance of a nanocomposite consisting of multiwalled carbon nanotubes and poly(styrene-b-(ethylene-co-butylene)-b-styrene). The pH sensor used a graphene oxide (GO) layer that changes its electrical potential when pH changes. The temperature sensor has a sensitivity of ~85 Ω/°C in the range 25°C–50°C and a high repeatability (maximum standard deviation of 0.1% over seven repeated measurements). For a GO concentration of 4 mg/mL, the pH sensor has a sensitivity of ~42 mV/pH and high linearity (R2=0.99). Keywords: diabetic foot ulcer, wearable sensors, wound temperature, wound pH

Two analytical procedures are presented for the determination of the total content and unbound fraction of both warfarin and warfarin alcohols in human plasma. Chromatographic separation was carried out in isocratic conditions at 25. °C on a C-18 reversed-phase column with a mobile phase consisting of a 70% buffer phosphate 25. mM at pH. = 7, 25% methanol and 5% acetonitrile at a flow rate of 1.2. mL/min. Fluorescence detection was performed at 390. nm (excitation wavelength 310. nm). Neither method showed any detectable interference or matrix effect. Inter-day recovery of the total warfarin and warfarin alcohols at a concentration level of 1000. ng/mL was 89. ±. 3% and 73. ±. 3%, respectively, whereas for their unbound fraction (at a concentration level of 10. ng/mL) was 66. ±. 8% and 90. ±. 7%, respectively. The intra- and inter-day precision (assessed as relative standard deviation) was <10% for both methods. The limits of detection were 0.4 and 0.2. ng/mL for warfarin and warfarin alcohols, respectively. The methods were successfully applied to a pooled plasma sample obtained from 69 patients undergoing warfarin therapy. © 2013 Elsevier B.V