Study of point-of-care microfluidic pumping and blood sample preparation
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The objective of this thesis is to study various micropumping methods and propose a new micropumping method suitable for point-of-care testing (POCT). Then based on that, blood based POCT are studied with emphasis on the blood plasma separation. Finally, concept-of-principle blood analysis is demonstrated by integrating the proposed blood plasma separation device with a paper glucose sensor. Moreover, images taken by smartphone are analysis to demonstrate the portability of the proposed methods. First of all, by utilizing the high gas permeability of poly-dimethylsiloxane (PDMS), a simple syringe-assisted pumping method was introduced. A dead-end microfluidic channel was partially surrounded by an embedded microchamber, with a thin PDMS wall isolating the dead-end channel and the embedded microchamber. A syringe was connected with the microchamber port by a short tube and the syringe plunger was manually pulled out to generate low pressure inside the microchamber. When sample liquid was loaded in the inlet port, air trapped in the dead-end channel would diffuse into the surrounding microchamber through the PDMS wall, creating an instantaneous pumping of the liquid inside the dead-end channel. By only pulling the syringe manually, a constant low flow with a rate ranging from 0.089 nl/s to 4 nl/s was realized as functions of two key parameters: the PDMS wall thickness and the overlap area between the dead-end channel and the surrounded microchamber. This method enabled point-of-care pumping without pre-evacuating the PDMS devices in a bulky vacuum chamber. Second, a blood separation microfluidic device suitable for point-of-care (POC) applications is proposed. By utilizing the high gas permeability of polydimethylsiloxane (PDMS) and phaseguide structures, a simple blood separation device is presented. The device consists of two main parts. A separation chamber with the phaseguide structures, where a sample inlet, a tape-sealed outlet and a dead-end ring channel are connected, and pneumatic chambers, in which manually-operating syringes are plugged. The separation chamber and pneumatic chambers are isolated by a thin PDMS wall. By manually pulling out the plunger of the syringe, a negative pressure is instantaneously generated inside the pneumatic chamber. Due to the gas diffusion from the separation chamber to the neighboring pneumatic chamber through the thin permeable PDMS wall, low pressure can be generated and then the whole blood at the sample inlets starts to be drawn into the separation chamber and separated through the phaseguide structures. Reversely, after removing the tape at the outlet and manually pushing in the plunger of the syringe, a positive pressure will be created which will cause the air to diffuse back into the ring channel, and therefore allow the separated plasma to be recovered at the outlet on demand. In this thesis, we focused on the study of the plasma separation and associated design parameters, such as the PDMS wall thickness, the air permeable overlap area between the separation and pneumatic chambers, and the geometry of the phaseguides. The device required only 2 μL of whole blood but yielding approximately 0.38 μL of separated plasma within 12 minutes. Without any of the requirements of sophisticated equipment or dilution techniques, we can not only separate the plasma from the whole blood for on-chip analysis, but also we can push out only the separated plasma to the outlet for off-chip analysis. Moreover, concept-of-principle blood analysis is demonstrated by integrating the proposed blood plasma separation device with a paper glucose sensor. Images taken by smartphone are analysis to demonstrate the portability of the proposed methods. Last, future works to achieve droplet based microfluidic devices for POCT are discussed. A novel passive method for droplets sorting is studied meanwhile more requirements for the future works are outlined.