Control Of Magnetic Field Distribution On The Microscale In Microfluidic Chip And Its Applications

In recent years, microfluidic chip has attracted a great amount of interests in researches with its unique advantages, such as speed analysis, portability, reagent-saving, flexible integrating of multiple analytical functional units and so on. Magnetic beads, owing to well-controlled surfaces, large surface-to-volume ratio, flexible modification and easy manipulation by external magnetic field, were widely used in various fields of biology, chemistry and medicine. The assay based on magnetic beads can easily achieve the goal of efficient separation and enrichment of the target species. It is possible to develop high sensitivity detection methods if we can integrate microfluidic technology and magnetic beads and combine their advantages together.However, it was difficult to control the magnetic field distribution precisely in the microchannel by common permanent magnets or electromagnets. Because of the low magnetic field gradients in the microchannel induced by permanent magnets or electromagnets, the magnetic beads can not be captured at high flow velocities and applied for high throughput assays. Therefore, it is significant to develop simple and practical approaches to control the magnetic field distribution precisely. Then the magnetic beads can be captured in the microchannel at high flow velocities by using these methods thus generating magnetic bead patterns for biology and chemistry assays. Meanwhile, it is possible to combine other physical field-based microfluidic chip technology with magnetic field controllable microfluidic chip technology when the magnetic field in the microchannel was accurately controlled. At last, it was possible to develop high efficient, time-saving methods based on magnetic beads in microfluidic chip for multiple detections simultaneously in the magnetic field controllable microfluidic chips.The major work in this dissertation includes:1. An approach of controlling the magnetic field distribution on the micrometer by nickel pattern in microfluidic chip was developed. When the nickel pattern was magnetized in the external magnetic field, high magnetic field gradients were induced around them, so the magnetic field distribution in the microchennel was changed. This method was used to capture the magnetic beads at high velocities and generate fluorescent magnetic bead patterns. We also use this approach to form magnetic-cell arrays in the microfluidic chip. We belive this method could be applied for high throughput assays based on magnetic beads in microchips. 2. Basing on the work in chapter one, we designed and fabricated a magnetic field controllable microfluidic chip with multiple branch channels to capture different modified magnetic beads in branch channels for multiple protein detection. The magnetic bead patterns could be kept stable at high flow velocities continuous washing which could remove the non-specifical adsorption better than the bath washing. Our approach had a good anti-interference capability. We use this method to detect two kinds of cancer biomarkers (AFP and CEA) simultaneously in this microfluidic chip. The detection limits were3.5ng/mL for CEA and3.9ng/mL for AFP respectively. The linear ranges of CEA and AFP were from10.0ng/mL to800.0ng/mL. And the RSDs were5.4%for CEA and4.6%for AFP (n=8), respectively. The recoveries were101.5-108.6%for AFP and103.5-108.8%for CEA in serum samples.3. We designed and fabricated nickel powder doped PDMS pillars in the microfluidic chip and used them to tailor the magnetic field distribution in the microchannels. We used the magnetic bead capture experiments and simulated method to prove the possibility of control the magnetic field distribution in the microfluidic chips. Under two kinds of different external magnetic fields, there were two different magnetic bead patterns generated (Here we use the fluorescent magnetic beads for patterns). The reseason of generating different magnetic bead patterns was discussed and proved by the simulated method. At last, we use this method to capture the magnetic bead-yeast cells and generate magnetic bead-yeast cell arrays. We believe that this magnetic bead-yeast cell arrays could be practical to environmental toxic test.In summary, we established two kinds of methods to control the magnetic field distribution in the microchannel based on nickel pattern and nickel powder doped PDMS pillars. When they were magnetized under external magnetic field, there would be induced high magnetic field gradients around them which we could be applied for tailoring the magnetic field distribution. The simulated method and magnetic bead capture experiments were used to prove the possibility of controlling the magnetic field distribution in the microchannel. And by using this method, the magnetic bead patterns were easily generated and applied for multiple detections of proteins. Also, the nickel powder doped PDMS pillars in microfluidic chips were used to capture the magnetic bead-yeast cells and generate magnetic bead-yeast cell arrays.