Electrochemical Devices for In-Vitro Detection of Cancer

用於體外癌症檢測的電化學裝置

Student thesis: Doctoral Thesis

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Award date19 Feb 2021

Abstract

There is an ever-growing need for more advanced methods to study the response of cancer cells to new therapies. Conventional methods for detection tumors, such as liquid biopsy, histopathological diagnostic techniques and immunological methods request high analytical costs, complex operation, qualified personnel and high false-positive rates. Moreover, these techniques necessity long experience time to get the confirm results and are difficult to obtain an early diagnosis for tumors. Cancer is a type of complex diseases developed by abnormal cellular growth inside the body and its information are useful for detecting the early diagnosis of cancers. Early diagnosis of cancer is important for the positive treatment of the disease. Highly sensitive techniques are essential for measuring cancer markers that presents at very low levels in early stage of disease. Such techniques should be small, cheaper, and faster (one-step) device for replacing time consuming analyses. Enhancements in molecular technologies have led to a deeper understanding of potential biomarkers that can be used for early-stage cancer diagnosis. In this thesis, we examine the information of single cell- cellular behaviours such as how ions concentration changes before cells death and after cells death. And we studied electrical response of irradiated cell (Single cell) to monitor the in-situ response of individual HeLa cells using a Single Cell Gated Transistor (SCGT). As a cell undergoes apoptotic cell death, it experiences changes in morphology and ion concentrations. This change is well in line with the threshold voltage of the SCGT, which has been verified by correlating the data with the cell morphologies by scanning electron microscopy and the ion-concentration analysis by Inductively coupled plasma mass spectrometry (ICP-MS). This SCGT could replace patch clamps to study single cell activity via direct measurement in real time. In addition, changes in ions concentrations give understanding of cancer markers inside the blood to study the early stage of cancer detection. Detection of cancer marker inside the blood is the advance method for cancer diagnosis. Compared with traditional techniques, electrochemical sensing technique has advantages of rapid detection, high specificity, and sensitivity in the detection of cancer antigens. This technique has not only successful in separating tumor cells from normal cells but has also achieved targeted detection of localized tumor cells. Hence, electrochemical biosensors provide the powerful tool for early diagnosis of tumor in clinical medicine. In this work, we used 50 nm diameter pole size nuclepore track-etched polycarbonate membranes for sensing surface conjunction with specific aptamer, Oligo RNA for detecting the targeted cancer markers, cancer antigen CA72-4, CA 19-9 and Carcinoembryonic antigen (CEA) respectively. Membrane electrochemical sensing device give the sensitivity values 7.029 µAU-1mLcm-2, and 5.54010 µAng-1mLcm-2 for cancer marker CA72-4 and CEA with minimum detection level 4 U/mL and 2 ng/mL respectively.

Further, experimental works targeting to study the detection of cancer markers to specific sequence of Oligo RNA which are immobilized on the nucleopores track-etched polycarbonate sensing membranes. The transmittance spectra of targeted antigens and molecules in single bond, triple bond and double regions were investigated by using Fourier Transformed Infrared Spectroscopy (FTIR) spectroscopy. The surface improvements of sensing membranes were analysed by Raman scattering measurements. The changes of surface sensitive and formation of chemical bonds on the surface of the membranes were studied with the help of X-ray Photoelectron Spectroscopy (XPS). The results of modified nucleopore track-etched polycarbonate membranes are in line with the results of electrical data. It is proved that the antigens, CA72-4, and CEA were binding the corresponding sequence of Oligo RNA on the gold coated membranes. Therefore, our electrochemical sensing device can detect the different concentration of antigens inside the human serum.

    Research areas

  • Single Cell Gated Transistor (SCGT), Inductively coupled plasma mass spectrometry (ICP-MS), Oligo RNA, Cancer antigens CA72-4, CA19-9, Carcinoembryonic antigen (CEA), nuclepore track-etched polycarbonate membrane