Acoustic Wave Sensors And Instruments For Detection Of Lung Cancer Markers In Exhaled Breath

The morbidity and mortality of lung cancer increased year by year, early detection and early treatment is the key to increase the survival rate of lung cancer patients. Conventional lung cancer detection methods can not be used in a wide range of high-risk population screening, so a non-invasive, fast and inexpensive diagnostic method for lung cancer is urgently needed. Volatile organic compounds (VOCs) in the breath gas and the exhaled gas condensate (EBC) contain markers which are associated with lung cancer, so non-invasive diagnosis of lung cancer can be achieved through breath test.Based on the laboratory’s existing research on the exhaled lung cancer markers, two kinds of acoustic sensors and analytical instruments were developed for the detection of VOCs in the exhaled breath and carcino-embryonic antigen (CEA) in EBC, and clinical experiments were carried out. The work of this paper has been funded by Key Scientific and Technological Research Project of Science and Technology Department of Zhejiang Province of China, and the instrument specific project of National Natural Science Foundation.The major contents of this thesis are listed below:1) Resonant Rayleigh Wave gas sensor with high sensitivity and low temperature coefficient was designed for the detection of trace VOCs markers in exhaled breath. The mass sensitivity of this sensor is2.667kHz/ng,the turnover temperature is23.36℃, the temperature sensitivity between20℃and40℃is less than365.9Hz/℃, and the temperature coefficient is less than1.4ppm/℃.2) Circuits for Rayleigh Wave gas sensors were designed and optimized. Phase shifter is added into the oscillator, forcing the working frequency of the sensors close to the center frequency, so the stability and the dynamic range of the oscillation circuit are improved. RF noise in the IF output of mixer is reduced by additional filters and attenuators.3) Two kinds of Love Wave sensors with different piezoelectric substrate were developed for the detection of CEA in EBC. Sensors based on LiTaO3have little loss in liquid, but the sensitivity is low. The sensors based on quartz are more suitable for detection of CEA in EBC, which have a high mass sensitivity of-1.208°/ng.4) Two kinds of Polydimethylsiloxane (PDMS) microfluidic chips were designed, because the two kinds of Love Wave sensors have different working characteristics in liquid. A pressure method to combine the love wave sensor with PDMS chip was proposed, realizing reusability of the sensor chips and microfluidic chips. The height of the channel in PDMS chips was optimized. Besides, fast and realtime detection was achieved by dynamic injection mode.5) Combining resonant Rayleigh Wave gas sensors with gas chromatography (GC), instrument for detection of exhaled VOCs lung cancer markers was developed. The limit of detection (LOD) to tridecane and tridecanone is lower than I ppb. Combining Love Wave immunosensors with microfluidics, instrument for detection of CEA in EBC was developed. The LOD to CEA is56.44ng/mL.6)89clinical VOCs samples were test by the VOCs detection instrument, the sensitivity is95.74%and selectivity is69.05%;6clinical EBC samples were test by the EBC detection instrument, CEA was detected in EBC samples of two lung cancer patients.