(63a) A Continuous Microfluidic Blood/Plasma Separation Unit with Electrokinetic Stirring and Cross-Flow

Many biomarkers of clinical significance are found in the plasma. However, before the plasma can be analyzed to assay for their presence, the blood cells need to be removed. Many point-of-care diagnostic procedures require that this operation (blood/plasma separation) be performed continuously or intermittently over a sustained duration (at least a few hours) without the need for human intervention and/or replacement of parts. The task is further complicated by the requirement that no more than a few cc of blood can be drawn from the patient per day but diagnostic reading should be made frequently (in some cases, once every 5 minutes) using micro-liter sized samples. The microfluidic device being presented provides a means to achieve this goal.

A conceptually simple technique of removing the blood cells is to filter them out using porous structure such as a monolith. However, in a dead-end filtration mode, the pores get clogged after a very short time, and the device fails. In our system, a porous monolith is placed in the vertical arm of a T-junction network right next to the intersection of the two arms. Through one end of the horizontal arm, suspension (blood with cells) is introduced at a controlled flow rate. Through the other end of the horizontal arm, suspension is withdrawn at a controlled flow rate. The key is that that latter (withdrawal) flowrate is smaller than the former (infusion) flowrate and the balance is made up by the flow of filtrate (plasma) through the porous monolith and down the vertical arm of the T channel network.

This system is able to operate much longer than dead-end filtration systems because the blood cells excluded at the filter are swept away by the cross-flow of the fluid. Additionally, patterned electrodes at the junction are used to induce an AC electro-osmotic flow that drives the cells excluded by the filter towards the center of the cross-flow, and thereby enables the device to operate for hours without failure.