Nano to Micro Scale Coulter Counters.

摘要

As biotechnology advances, personalized medicine has become one of the prominent trends. It can be briefly described as an effort to provide preventative, diagnostic and treatment measures for health problems implemented on an individual basis. Resistive pulse technique is a measurement scheme that has found a wide range of applications in this field. In this dissertation, research on devices that are based on resistive pulse technique from nano to micro scale are presented.;Nanopore sensing, one of the major candidate technologies for next-generation DNA sequencing is an example of nano-scale application of this technique. It is a promising technology due to its potential to provide label-free, robust and rapid DNA sequencing. However, there are several challenges in reaching this ultimate goal. We present an architecture for solving the aggregate base detection problem through ubiquitous, cost-effective CMOS fabrication. We describe the challenges and advantages of this approach.;Beyond DNA sequencing, there are many exciting potential applications of synthetic nanopores, such as sizing and investigating polymer based constructs. Due to its well understood properties, DNA can be used to build functional nano-mechanical structures. However, DNA nano-structures usually lack a robust validation and quality control method, leading to populations that are poorly characterized in terms of shape and size. In this dissertation, the feasibility of utilizing synthetic nanopores to characterize a high volume of DNA nanotubes is investigated.;Next, a micro scale application of resistive pulse technique for cancer diagnosis is explored. Particularly, Circulating Tumor Cells (CTCs) have recently emerged as indicators of cancer metastasis. Thus, efficient detection of CTCs can provide non-invasive biopsy, enable personalized medicine and help understand cancer biology. Currently used immunoassay based CTC detection techniques are inefficient and insufficient to classify extremely heterogeneous CTCs such as Circulating Melanoma Cells (CMCs). Cancer cells have markedly different physical attributes, such as size and stiffness, and can be used to distinguish tumor cells from normal cells. We report a micro-fluidic chip potentially meeting the urgent need to detect individual CTCs in a label-free, fast and inexpensive fashion while maintaining cell viability. We present the design, fabrication and modeling of microfluidic channels that enable the classification of CTCs based on their size and stiffness. We use the device was to classify melanoma (MNT1) and breast cancer (MCF-7) cells both alone and in the presence of blood cells.