MICROFLUIDIC PLATFORMS TOWARDS VIRUS DETECTION AND CANCER DIAGNOSIS BASED ON TUMOR CELLS. PDF Download

Author: Yiqiu Xia
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Languages : en
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Book Description
As a major healthcare concern, highly pathogenic viral infection can spread globally with modern transportation. Viral infectious diseases have caused some of the deadliest pandemics and heavily damaged global economy in recorded human history. As we prepare for the next major emerging viral infectious disease outbreak, there is an urgent need for the development of new techniques that can rapidly detect viruses and perform surveillance of viral infectious diseases at any location. On the other and, cancer is a major disease in human society nowadays, leading to the second most deaths worldwide. Circulating tumor cell (CTC) has been established as a liquid biopsy marker, however, there are demands of fast and accurate CTC detection. Microfluidics has the advantages of high throughput, high sensitivity, accurate flow rate control and low cost, allowing it well suited for virus and cancer diagnosis. Besides, the geometry of microfluidics allows precisely controlling of the physical, chemical, biological, and physiological environment at the cellular level or even at the molecular level for fundamental studies of cancers.My major works can be classified into two categories, microfluidic devices for virus diagnosis and microfluidic platforms towards cancer diagnosis. For the virus diagnosis, one microfluidic device for size-based virus isolation and another one for immunoaffinity-based virus detection are developed, respectively. In the first device, inter-wire size-tunable porous silicon nanowire forest is embedded inside the microfluidic channel to trap avian influenza viruses based on their size and then release trapped viruses by nanowire degradation. About 50% of virus can be captured and 60% of trapped virus can be released for culture and further analysis. In the second device, immunoassay is employed inside the channels to capture and detect virus in only ~1.5 hours. Colorimetric reaction with gold nanoparticles and silver enhancer allow detection with naked eyes with about one order of magnitude better than conventional fluorescent enzyme-linked immunosorbent assay (ELISA). Simply by introducing an optical detection scheme with a smartphone detection system, the sensitivity can be 30 times better than conventional fluorescent ELISA. Two microfluidic platforms were developed toward cancer diagnosis. The first microfluidic platform aims to study the process of CTC size-based microfiltration and cancer cell translocating through micro constrictions by mimicking the microfiltration process and in vivo micro-constrictions inside a microfluidic device. It is found that the deformability and size of nucleus instead of the whole cell dominate cellular translocation through micro constrictions under the normal physiological pressure range used by CTC microfiltration. The result is consistent with the size-based enrichment of white blood cells and CTCs from peripheral blood of metastatic cancer patients using a CTC microfilter previously developed in my group. It indicates that the size and deformability of cell nucleus play a critical role in CTC size-based microfiltration and potentially cancer cell translocating micro constrictions in vivo. The second microfluidic platform can measure the Youngs modulus of cells in a high throughput fashion by applying a micropipette aspiration model in an array of micro constrictions. Using this device, a subtype of cancer cells with a softer mechanical phenotype can be enriched. This subtype of cancer cells shows enhanced invasive-related properties and can be used for further study of metastasis and cancer cell heterogeneity.