NANOPORE STOCHASTIC SENSING OF BIOMARKERS IN HUMAN DISEASE
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By measuring the ionic current modulation generated by analytes’ electro-osmotic flow through a nanoscale sized pore, nanopore stochastic sensing was invented about 20 years ago. Since then, it has been developed as a powerful and versatile tool for the detection of a wide variety of substances, including metal ions, organic molecules, DNA, RNA, peptides, proteins, etc. Compared with other traditional techniques such as immunochemical detection, colorimetric detection, HPLC, and GC/MS, nanopore detection has many advantages. First and foremost, nanopore stochastic sensing does not need to use sophisticated instruments which are convenient for people who do not have professional training in operating a special device. Furthermore, unlike fluorescent methods which rely on fluorophores labeling, nanopore stochastic sensing is a label-free detection method, which is based on the natural characteristics of analytes of interest. Moreover, nanopore sensing does not need complicated pretreatment of samples and can achieve a very low detection limit rapidly. Most importantly, nanopore detection uses only a small amount of sample with a low assay cost. In this dissertation, I summarize my work on nanopore stochastic sensing of proteases and copper ion, i.e., the detection of the HIV-1 protease (HIV-1 PR), trypsin, and copper ion. It is well-known that the HIV-1 protease is a significant biomarker for AIDS, while trypsin for the pancreatic disease. Considerable effort has been devoted to developing highly sensitive and selective sensors for these two important proteases. By taking advantage of nanopore stochastic sensing, two biosensors are constructed where picomolar concentrations of the HIV-1 protease and trypsin can be detected. On the other hand, copper, an essential trace element, is vital to the health of our human being in many ways. For example, the accumulation of cupric ions in human body may explain the origin of Wilson disease; further, the elevated concentration of copper is also pertinent to some symptoms of Alzheimer disease. Hence, the capability to the sensitive and accurate detection of copper ions is crucial to our health and well-being. For this purpose, a real-time and label-free nanopore biosensor is developed for its detection. The successful research efforts in these projects demonstrate the useful application of nanopore stochastic sensing in medical diagnosis, especially in terms of early disease detection. In addition to the high sensitivity and accuracy as well as low assay cost, other advantages of nanopore sensors include instrumental simplicity, ease of use, and extremely rapid data acquisition rates. Such a field-deployable nanopore sensor is useful as a point-of-care device for early disease detection and diagnosis. Just imagine how convenient your medical diagnosis would become with the pocket size nanopore sensor. We can monitor our own health anytime and anywhere: at home, at workplace, or even outside in remote and isolated places.