Using an RTIL-Based Electrochemical Sensor Platform for Trace Detection of Heptane As Biomarker for Lung Cancer (2021)

Lung cancer is one the most common diseases worldwide with more than 1.6 million dead since 2012 [1]. The survival rate for lung cancer is also very low as the disease is generally diagnosed only at an advanced stage when the treatment is not possible as significant damage has been done [2]. Hence, there is a need for an early and timely non-invasive method for the diagnosis of lung cancer. Previous studies have shown the use of endogenously produced volatile organic compounds (VOCs) as target analytes for the detection of lung cancer. Endogenous VOCs are produced in the bloodstream as result of cellular metabolic pathways involved in maintaining homeostasis[3]. Subsequently, the VOCs diffuse into the alveolar air in the blood-gas interface quickly in the lung because of their low solubility in the blood and they are exhaled out of the lung[4]. Therefore, detection of VOC levels in exhaled breath can be used to study the biochemical pathways that have been altered as a result of tumorigenesis. A breathomics device can be developed and used as a tool for non-invasive, sensitive, and specific detection of lung cancer. Moreover, the presence of lung cancer tumor is not masked by other diseases since every disease has its own volatiles fingerprint[5] , thereby making the detection mechanism specific in nature. Electrochemical sensors are gaining widespread interest as they are robust in nature, have faster response time, and specific and sensitive signal response. Electrochemical gas sensors usually involve a two or three electrode setup that causes change in signal as a function of the output current/potential. Electrochemical sensors require an electrode, a transducer, and an electrolyte. A good electrolyte should have high chemical and electrochemical stability, should be stable at elevated temperatures and have high charge transfer ability. Room temperature ionic liquids (RTIL) are being explored as suitable electrolytes for gas sensing applications as they follow all these parameters. There is an increasing interest in the field of non-invasive disease diagnosis, primarily using breath as a sample for monitoring the presence of various metabolites. Breath alkanes such as heptane can be used as a signature target analyte to differentiate the healthy subjects from lung cancer patients. Levels of heptane in breath for a healthy individual are within 50 ppb-200 ppb range. Concentrations greater than 400 ppb are found in breath as a result of altered metabolic pathways. We demonstrate the proof of concept of an electrochemical VOC sensor specific and sensitive for the detection of heptane up to 400 ppb toward developing a handheld breath analyzer for on-site applicability (Scheme 1). We use RTIL as a transducer and the inherent redox properties of these VOCs such as heptane make them a suitable candidate for electrochemical detection. Moreover, RTILs allow easy removal of VOCs by joule heating and prevent fouling of the system, thereby increasing the shelf life of the sensor. For this study, RTIL Triethylsulfonium Bis(trifluoromethanesulfonyl)imide with over 98 percent purity and used as received without any further purification. Trace Source™ disposable permeation tube for Heptane was purchased from KINTEK analytical. Chronoamperometry was used as transduction principle for detection and voltage applied was set within the electrochemical window of the RTIL. An electrochemical sensing platform is developed for the detection of heptane in vapor phase. The sensing platform can be used to monitor the presence of heptane in breath upto 400 ppb (LOD). The sensor showed dose dependent response for the concentrations ranging from 400 ppb to 5 ppm. Scheme 1- Schematic illustration of the sensing strategy used for the development of the electrochemical RTIL-based sensor Figure 1-Chronoamperometry scan was performed at −0.6 V for 60 s RTIL-modified interdigitated electrode (IDE) for the target analytes. Calibrated dose response chronoamperograms were observed for heptane, which varies with concentration. References J.-L. Tan, Z.-X. Yong, C.-K. Liam, J Thorac Dis , 8 (2016) 2772–2783. R.L. Siegel, K.D. Miller, A. Jemal, CA Cancer J Clin , 65 (2015) 5–29. W. Cao, Y. Duan, Clin Chem , 52 (2006) 800–811. A.G. Dent, T.G. Sutedja, P. V Zimmerman, J Thorac Dis , 5 Suppl 5 (2013) S540-50. G. Peng, M. Hakim, Y.Y. Broza, S. Billan, R. Abdah-Bortnyak, A. Kuten, U. Tisch, H. Haick, Br J Cancer , 103 (2010) 542–551. Figure 1