Blood Extraction and Cell Sorting Integrated on Single MEMS Device

Résumé du document

A Lab-on-chip using MEMS fabrication technology concepts, has been the focus of many different research groups in the past decades. This research topic has been investigated extensively to identify the many advantages that a lab-on-chip device can potentially offer to the medical field. MEMS devices stand to reduce the sampling sizes required to perform medical analysis, which in turn will minimize the impact biological sampling will have on patients. Because lab-on-chip devices are portable, unlike most traditional lab systems, they reduce chances of contamination and human error, and increase turn around time of medical analysis. The research done in this area has produced many promising advances in the extraction of biological tissues and fluids and the analysis of these tissues and fluids. However, one important aspect remains fairly uninvestigated. That is, how to bridge the gap from direct extraction to analysis, taking raw samples and converting them into useable specimens for analysis. Cellular analysis using MEMS devices typically uses presorted, pre-stained, or pre-cultured samples. The processing to do these preliminary steps is done with traditional lab equipment.

Extraits

[...] The entrance into the cell sorting chambers was designed to spread fluid flow evenly, injecting blood into the chamber at opposite corners . Figure Columns in proposed design have an area of 30x30μm2 and are 110 μm high to allow blood, a higher viscous fluid than suspended leukocytes to flow freely. Figure Cross section of sorting chambers' exits, each exit has a width of 164 μm and a height of 110 μm. The exit from the two sorting chambers directs flow into either of two channels (figure X). [...]

[...] The trenches are etched about 32 μm deep. Deep boron diffusion creates the highly p-doped silicon as deep as 20 μm from the exposed wafer surface, shown in figure Xc. The chevron shapes are then closed up with a directional e-beam deposition of silicon oxide, figure Xd. Excess oxide is removed from the wafer surface and then a second DRIE etch is performed to etch the area surrounding the length of the needle, seen in figure X. This DRIE etch should be at least 60 μm deep. [...]

[...] Once clear applications for this apparatus are defined and extensive testing has modeled the behavior of fluid and leukocytes flowing through the device, clear and specific instruction manuals will be created to outline its operation. Conclusions In conclusion, the following proposal presents the idea of integrating two MEMS fabrication concepts onto one silicon device that is easily packaged. The concepts used to create the device are proven by the work of previous research groups. These concepts are straightforward and based on biological reactions that occur regularly in animal and human circulatory systems. [...]

[...] Figure Basic movement of leukocytes through sorting chamber The leukocyte will then from the trailing edge of one square post to the leading edge of the next square post, then the leukocyte proceeds to roll to the trailing edge of the next square post, and the process is repeated. The dimensions of the sorting chamber cause fluid flow between the trailing edge of one square post and the leading edge of the next square post to be greatly reduced, as seen from figure X. Figure Velocity plot of measured velocity field in sorting chamber This reduction in flow speed in between the square posts reduces the speed of the leukocytes once they have been captured even more significantly than cell adhesion alone would reduce the leukocytes' movement. [...]

[...] The concept that the selected cell sorting design uses is based on biological phenomena that happen regularly in blood vessels. When the body is attacked by pathogens, blood vessels in this area produce different protein molecules that adhere to specific types of white blood cells. The family of proteins that white blood cells react to is called selectin, and these proteins bond to the white blood cell's cytoskeleton. This bonding does not typically paralyze the cell's vascular movement. Because of shear forces caused by fluid flow in the vein, white blood cells will along the surface of the vein, moving at significantly slower speeds than free flowing cells. [...]