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Microfluidics-based isolation of disseminated tumour cells, as the technique for early diagnosis and prognostics of prostate cancer

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thesis
posted on 2022-12-22, 22:42 authored by Alexey Rzhevskiy

Globally, prostate cancer has been the second most frequent cancer occurring in males, being at the same time the second most frequent cancer in terms of mortality. Due to a prolonged progression of the disease, one of the most significant aspects in prostate cancer management is its detection at an early localized stage which allows to perform adequate treatment and decreases the risk of possible cancer-related death. Currently, a screening blood test for prostate specific antigen and 12-core tissue biopsy are necessary diagnostic procedures required to establish the diagnosis of prostate cancer. However, prostate specific antigen level has a relatively low specificity as a prostate cancer biomarker and is often elevated in case of such diseases as benign prostatic hyperplasia and prostatitis. At the same time, tissue biopsy is a highly invasive painful procedure which has a relatively low sensitivity in case of early localized form of prostate cancer and has such possible severe complications as local bleeding and abscesses. Hence, alternative diagnostic and prognostic approaches are highly demanded. One of such approaches, which has been actively investigated during the last decade, is liquid biopsy via isolation of disseminated tumour cells from biological fluids of a human body. Overall, the main goal of the PhD project was to develop liquid biopsy approaches based on the microfluidic label-free isolation of prostate cancer tumour cells from biological fluids of patients with early, non-metastatic form of the disease. In the current work, three biological fluids, including blood, urine, and semen, were analyzed and compared as a source of prostate cancer disseminated tumour cells, using the developed microfluidic techniques. According to the results, biological fluids could have been ranked in terms of the average amount of isolated putative tumour cells in the ascending sequence as follows: blood, urine, and semen. In general, in case of blood, only rare tumour cells could have been isolated from small number of patients; in case of urine, some tumor cells could have been isolated from the majority of patients; in case of semen, large number of the tumor cells could have been isolated from all of the patients. Thus, according to the data presented in Chapter VI, prostate cancer tumour cells could have been isolated from the semen of all 13 (100%) of 13 patients, with the amount of isolated tumor cells varying from 47 to 280.8 units per mL of the semen. Also, strong correlation between the amount of isolated tumour cells and prostate specific antigen serum level was indicated. Consequently, liquid biopsy of prostate cancer via microfluidic enrichment of disseminated tumour cells from semen is the promising technique, which has a potential for being introduced as a diagnostic and prognostic tool into a clinical practice of managing prostate cancer at its localized form. For this purpose, further validation and optimization of the technique is required.

History

Table of Contents

Chapter I General introduction -- Chapter II Liquid biopsy in diagnosis and prognosis of non-metastatic prostate cancer -- Chapter III Rapid and label-free isolation of tumour cells from the urine of patients with localized prostate cancer using inertial microfluidics -- Chapter IV Label-free isolation of tumour cells from the blood of patients with non-metastatic prostate cancer using inertial microfluidics -- Chapter V Rapid and label-free isolation of tumour cells from the semen of patients with localized prostate cancer using inertial microfluidics -- Chapter VI Liquid biopsy via label-free microfluidic isolation of tumour cells from biological fluids in localized prostate cancer. What’s better: blood, urine or semen? -- Chapter VII General discussion and conclusions -- Appendix A -- Appendix B

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

Thesis (PhD), Department of Physics and Astronomy, Faculty of Science and Engineering, Macquarie University

Department, Centre or School

Department of Physics and Astronomy

Year of Award

2021

Principal Supervisor

Andrei Zvyagin

Additional Supervisor 1

David Gillatt

Additional Supervisor 2

Majid Ebrahimi Warkiani

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

English

Extent

172 pages