Flow rate modulated periodic backflush to improve dead-end filtration

Abstract

Dead-end filtration using patterned microsieves, fiber meshwork, and membranes of various materials is a standard technique to isolate desired particles of various sizes and is used in clinical and laboratory settings for both therapeutic and diagnostic applications. Both biological and physical suspensions can be filtered to yield high purity and enrichment at a high throughput. Unfortunately, dead-end filters are especially susceptible to fouling, which leads to lower recovery percentage and yield as a direct result. High recovery percentages, enrichment, and throughput determine the success of sorting technologies. A process which could stop fouling, reintegrate the fouling material into the bulk flow, and allow for further processing could be used to improve the recovery percentage of dead-end systems increasing their success and use. The purpose of this research is to determine if novel flow profiles with variable duty cycles can reduce fouling and improve permeate flux without substantial tradeoffs to processing time by controlling forward volume flow rate, reverse volume flow rate, and the time spent in each phase. This objective was accomplished through 1) the development of pulse modulated (PM) periodic backflush using a square wave duty cycle fluid flow control systems to interrupt membrane fouling, 2) the development of a model to better understand how experimental results compare to what might be achievable, 3) the optimization of amplitude and frequency to reduce and minimize costs to throughput by increasing yield, and 4) demonstration that the control algorithms can be applied to important applications of particle purification, cell enrichment, and scaffold seeding. These practical tests also help to define the conditions upon which the developed methods optimally apply. Ultimately, this thesis work established that pulse modulation is an effective technique to interrupt fouling and reintegrate the cake into the bulk flow to improve the recovery percentage of both microparticle and cellular products while minimizing the anticipated costs to throughput. Pulse modulated periodic backflush was shown to be a useful and innovative approach to controlling fluid flow rate that contributes significantly to advancement and revitalization of dead-end filtration systems. Using pulse modulated backflush, dead-end systems are able to outperform cross-flow filtration devices in both recovery percentage and throughput. We have shown that particle redistribution is a result of convective currents during backflush events and that, for square wave-based volume control, detachment and reintegration of the fouling layer is minimally dependent on backflush velocity. Additionally, we show that we can maximize system throughput by modulating the amplitude and frequency of flow rates. Finally, we demonstrate practical use cases in conjugated particle and cellular recovery and apply the technology to scaffold seeding to improve the uniformity and seed density, significantly improving outcomes compared to what is currently available. This thesis serves to prove that pulse modulated backflush of dead-end filtration systems is the key to maximizing recovery percentage of targeted particles in fluidic suspensions and drives the restoration of flux capacity through clearance and reintegration of fouling layers.