Sniffing Out Bladder Cancer: Utilizing an E-nose Based on Eco-Friendly PANI Thin Films

Abstract

BlC is the seventh most common cancer and ni­nth leading cause of cancer related death. The current standard procedure for BIC detection and monitoring tumor progression and recurrence involves urine cytology, cystoscopy, and biopsy. However, its an expensive, low sensitivity, invasive and painful test. ^[1] Thus, new diagnostic approaches that will improve the diagnostic accuracy, less expensive, noninvasive and safe screening of BIC are needed. ^[2,3]

E-nose has been successfully used for diagnosis of health conditions via detection and classification of VOCs associated with related disease in the human body, including exhaled breath, skin/sweat, urine, saliva, feces and intestinal gas.^[4] This subject has been dealt in a more modern context of biomedical research. The VOCs in fluids emerge at very early stages of the cancer so their isolation and detection could serve as a pathway for early detection of the cancer. Of these body fluids, urine is one of the most useful VOC sources for monitoring body chemistry or state of health. Bladder urine is normally sterile and thus the presence of pathogenic bacteria in urine is indicative of a urinary tract infection. ^[5] Matsumura et al., established the feasibility of using urinary volatiles to detect lung cancer for the first time. ^[6] Roine et al., proved that both malignant and nonmalignant prostate cell lines have distinct smell prints.^[7] Asimakopoulos et al., reported a potential role of the e-nose in identifying prostate cancer by smelling urine samples with high specificity.^[8] In the field of BIC, this study trained dogs to dentify people with BIC based on urine odour with powerful results.^[9] The main success of this study was the demonstration that BIC gives an odor signature to the urine. Bernabei et al., performed an e-nose based on eight quartz crystal microbalance (QCM) gas sensors to prove the possibility of diagnosing urinary tract cancers. ^[10] Simian et al., outlined a simple fluorometric optical sensor system to detect VOCs of BIC in patients, and also achieved 66.67% sensitivity and 75.00% specificity for classification of high-grade and low-grade bladder cancer patients. ^[11] However, the selective and cross-reactive sensing of BIC VOCs have no reported and the sensitivity, accuracy and specificity needed improved furthermore.

In this work, an e-nose based on eco-friendly polyaniline (PANI) thin films is successfully applied to noninvasive diagnosis of BIC from urine sources. An e-nose is fabricated by 10 kinds of PANI thin films on the glass substrate covered with a pair of fluorine-doped tin oxide (FTO) interdigitated electrode, and exhibits cross-reactive sensing for 11 types of BlC biomarkers. Using urine samples are collected from BIC patients and healthy controls, then feature extracted from origin response curves to select useful information and realize the effective pattern recognition. The support vector machine (SVM) analysis shows excellent discrimination between the BIC patients and healthy controls 100 % sensitivity and 100 % accuracy. Overall, this study paves the way to use e-nose for simple, inexpensive, portable, and noninvasive diagnosis of urological diseases.  Figure 1 is the scheme illustrating the main experimental procedure.