Title: Analyzing, quantifying and optimizing crossflow microfiltration of fine suspensions
Description: Steady state crossflow microfiltration (CMF) is an important and often necessary means for varying sized particle separation. It has been widely used in both industrial and biomedical processes, including a wearable water removal device intended to maintain end stage renal disease (ESRD) patients euvolemic. For kidney replacement therapies, there are few options available. Kidney transplantation still represents the optimal treatment for ESRD patients, even though it often requires daily post-transplant medication including immunosuppressant drugs to avoid rejection of the transplanted organ. The transplanted kidney itself has an average lifespan of only 10 years. The biggest engineering contribution to the cited problem was made about 60 years ago with the invention of dialysis machines (or some variation thereof). Dialysis still represents the optimal and most widely used therapeutic approach to renal replacement during long waits on a transplant list. The present-day dialysis system is bulky, totally mechanical, and extracorporeal, leading to a widely used therapy that is only effective in extracting water and toxins out of the blood-stream, but still with major drawbacks (i.e. intermittent treatments, 5-hours thrice-weekly, and forcing clinic-centered therapy) that are permanently costly.

These drawbacks pose a major impediment to rehabilitation or any other lifestyle activity such as working or studying. Of all the vital organs, the kidney is both the most subtle in its homeostatic action and the most complex in terms of the structures it uses to accomplish its action. This thesis proposes a single facet of the multiple complexity of this vital organ: filtration. To that effect, CMF of blood suspensions through a microsieve were studied. Experiments, reported here, have correlated macroscopic measurements - filtration rates, transmembrane pressures (TMP), shear rates - during filtration through a photolithographically pored semiconductor membrane with direct observation of erythrocyte behavior at the filtering surface. Erythrocytes, the preponderant particles in blood, are believed to dominate filtration resistance. At low filtration rates (low TMP), erythrocytes roll along the filter, but at higher rates (higher TMP), there is an increasing probability of their sticking to the sieve.

The design of membrane separation processes requires quantitative expressions relating the separation performance to material properties. The factors controlling the performance of CMF have been and continue to be extensively reviewed. There have been a number of influential approaches in CMF. Most have been based on the rate limiting effects of the concentration polarization of rejectate at the sieving surface. Various empirical and intuitive models exist which have been critically assessed in terms of their predictive capability and applicability to CMF from a microfluidic channel. Chapter 1 summarizes this assessment. Chapter 2 takes a closer look at how erythrocytes behave in a microfiltration environment. Maximum steady-state filtration flux has been observed to be a function of wall shear rate, as predicted by any conventional cross-flow filtration theory, but to show weak dependence on erythrocyte concentration, contrary to theory based on convective diffusion. Flux is known to be directly proportional to the TMP; however, since the pressure drop across a channel decreases along the direction of flow, TMP must modulate along the channel (highest at the leading edge of the membrane and lowest at the trailing edge).

As a consequence, an area of stuck particles growing from the inlet (regimen of high TMP) has been observed, leading to a “fouling cascade.” Post-filtration scanning electron micrographs revealed significant capture and deformation of erythrocytes in all filter pores in the range 0.25 to 2 m diameter. This was then found to form a self-assembled partially complete monolayer. Filtration rates through these filters were reported and a largely unrecognized mechanism was proposed, which allows for stable filtration in the presence of substantial cell layering. Chapter 3 proposes a microfiltration model that pertains to non-deformable particles that are large enough to intrude significantly into the shear layer of a microchannel. A stable, stationary multilayer of particles was studied, whose thickness is shear-limited. The structure and parameters in that limit of steady filtration in this environment was then identified. A steady cake-layer thickness was observed and because of the simple geometry afforded by uniform spheres, the force balance, cake resistance, and filtration rate were derived from first principles.

The good fit of the data to the proposed mechanism, provides a firm basis for the semi-quantitative analysis of the behavior of more complex suspensions. Finally, in Chapter 4, a design methodology was imposed to maintain the TMP constant throughout the whole sieving surface by introducing a flow chamber beneath and parallel to the sieve’s main flow. Co-current filtration was found to allow the TMP to remain stable along the membrane surface, enabling the entire sieve to perform optimally, and thus allowing greater stable filtration rates to be achieved. Co-current flow conditions allowed for twice as much filtration flux compared to a conventional CMF modality.