Single rare cell assays and biomarkers detection using microfluidic nanotechnology

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The microfluidics nanotechnology is employed to enable two streams of research: (1) information-rich assays on single rare cells, and (2) high-throughput microarray-based assays for biomarkers (e.g. nucleic acids and proteins). STREAM 1 is to use a single cell chip to identify and measure single tumor cells contained within a nanolitre-sized cell retention chamber. The measured data may provide information for early disease diagnosis and for prognosis during treatment. Cells such as circulating tumor cells (CTCs) found in blood samples are rare. Our single cell biochip is able to measure a rare cell for multiple cellular parameters, such as cell size, intracellular drug concentration, and cell surface biomarker for multidrug resistance (MDR). We will perform drug accumulation measurements on multiple single cells using MDR inhibitors in order to enhance accumulation; we expect to correlate these measurement results with the immunoassay-based MDR biomarker determination. The measured data of drug accumulation on a single cancer cell with or without the MDR inhibitor may provide information for effective chemotherapy such as the use of the appropriate drug-inhibitor combination. STREAM 2 is to conduct analysis of DNA and proteins biomarkers for high throughput diagnosis. The analysis will be conducted on a microfluidic microarray (MMA) chip developed for fungal pathogen detection. We propose to detect DNA biomarkers on the MMA chip, and to increase detection specificity enhanced by using gold nanoparticles. One application is to detect diseases related to salmon health. The MMA chip is also employed to analyze protein biomarkers in human serum samples for disease detection and treatment. We will also perform computer simulation study of the microfluidic liquid flow process for efficient reagent/sample delivery. Both platforms on single rare cell assays and MMA are suitable for incorporation in point-of-care (POC) systems. The novelty of all projects involves the efficient manipulation of inherently low liquid volumes (in sub-nanolitre) within these microfluidic devices, thus demanding less starting materials and generating less wastes, conforming to the notion of green chemistry.