# US 12,007,316 B2 · Pulse-modulated periodic backflush for clearance of fouling layers in dead-end filtration systems > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,007,316 B2 - Document ID: US12007316B2 - Status: Granted - Kind: B2 - Application number: 16/965,111 - Filed: 2019-01-30 - Published: 2020-11-19 - Granted: 2024-06-11 - Earliest claimed: 2018-01-30 - Assignees: Georgia Tech Research Corporation - Applicants: Georgia Tech Research Corporation - Inventors: Aaron C. Enten; Todd Sulchek - Web page: https://patentgrep.com/patent/US12007316B2 ## CPC - G01N 1/34: Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)} - B01D 61/18: Apparatus therefor - B01D 61/22: Controlling or regulating - B01D 63/087: {Single membrane modules} - C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)} - C12M 33/14: {with filters, sieves or membranes} - G01N 1/4005: {by transferring a selected component through a membrane} - B01D 2311/16: Flow or flux control - B01D 2315/08: Fully permeating type; Dead-end filtration - G01N 2001/4088: {filtration} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract Embodiments of the present disclosure relate generally to dead-end filtration systems and, more particularly, to pulse-modulated periodic backflush systems and methods for clearing fouling layers in dead-end filtration systems. In some embodiments, a controller may control the flow of fluid in the system from cycling from a forward flow to a reverse flow. In some embodiments, the controller may cycle from forward to reverse flow based on a volumetric flow ratio. Embodiments of the present disclosure describe optimal volumetric flow ratios for optimizing the break of cake in a dead-end filtration system. Embodiments of the present disclosure describe optimal volumetric flow ratios for optimizing recovery percentages of targeted particles. ## Claims ### Claim 1 A filtration system comprising: a channel having an inlet and an outlet; a membrane positioned within the channel between the inlet and the outlet; and a controller configured to cycle α flow of a volume of fluid based on a volumetric flow ratio from flowing in a forward direction through the membrane at a volume of fluid flow Vf, to flowing in a reverse direction through the membrane at a volume of fluid flow Vr; wherein the forward direction of fluid flow is the direction from the inlet toward the membrane; wherein the reverse direction of fluid flow is the direction from the outlet toward the membrane; and wherein the volumetric flow ratio is equal to V f V f + V r . ### Claim 2 (depends on 1) The filtration system of claim 1 further comprising: a suspension comprising the fluid, first particles, and second particles, the mean size of the first particles larger than the mean size of the second particles; wherein the membrane is configured to allow at least a portion of the fluid and a portion of the second particles of the suspension flowing in the forward direction to permeate through the membrane; and wherein the membrane is configured to prevent at least a portion of the first particles of the suspension flowing in the forward direction to permeate through the membrane. ### Claim 3 (depends on 1) The filtration system of claim 1, wherein the volumetric flow ratio is from between 0.5 and 1.00. ### Claim 4 (depends on 1) The filtration system of claim 1, wherein the volumetric flow ratio is from between 0.55 and 0.80. ### Claim 5 (depends on 1) The filtration system of claim 1, wherein the controller is further configured to perform two or more cycles and to vary at least one of a volumetric flow rate of the fluid in the forward direction or a volumetric flow rate of the fluid in the reverse direction from a first cycle to a subsequent second cycle. ### Claim 6 (depends on 1) The filtration system of claim 1, wherein the controller is further configured to perform two or more cycles and to increase a volumetric flow rate of the fluid in the reverse direction from a first cycle to a subsequent second cycle. ### Claim 7 (depends on 1) The filtration system of claim 1, wherein the membrane comprises at least one of a fibrous membrane, patterned microsieve membrane, pillar membrane, trap membrane, or weir membrane. ### Claim 8 (depends on 1) The filtration system of claim 1, wherein the membrane comprises a tissue. ### Claim 9 (depends on 8) The filtration system of claim 8, wherein the tissue comprises at least one of an extracellular matrix or a bone matrix. ### Claim 10 (depends on 1) The filtration system of claim 1, wherein the controller is further configured to perform two or more cycles and to decrease the volumetric flow ratio in each subsequent cycle. ### Claim 11 (depends on 1) The filtration system of claim 1, wherein the inlet is configured to receive a suspension, the suspension comprising the fluid, first particles, and second particles; and wherein the controller is further configured to perform two or more cycles and to monitor an amount of the second particles permeating through the membrane during flow in the forward direction of a first cycle, and based on the monitored amount, vary during a subsequent second cycle at least one of: the volumetric flow ratio; the flow rate in the forward direction; the flow rate in the reverse direction; a duration of flow in the forward direction; or a duration of flow in the reverse direction. ### Claim 12 (depends on 11) The system of claim 11, wherein the volumetric flow ratio is from between 0.5 and 1.00; wherein the controller is further configured to vary at least one of the volume of fluid flow Vf or the volume of fluid flow Vr from the first cycle to the subsequent second cycle; and wherein in at least one of the cycles, the volume of fluid flow Vf and volume of fluid flow Vr are not the same. ### Claim 13 (depends on 11) The filtration system of claim 11, wherein a first side of the membrane proximate the inlet of the channel comprises a cake layer comprising the first particles and the second particles; and wherein the suspension flowing in the reverse direction is configured to break apart at least a portion of the cake layer. ### Claim 14 (depends on 11) The filtration system of claim 11, wherein the suspension comprises whole blood; wherein the first particles are white blood cells; and wherein the second particles are red blood cells. ### Claim 15 (depends on 14) The filtration system of claim 14, wherein the suspension further comprises a diluting agent. ### Claim 16 (depends on 11) The filtration system of claim 11, wherein the second particles are bacterial cells. ### Claim 17 (depends on 11) The filtration system of claim 11, wherein the first particles are aggregated particulates resulting from a protein conjugation protocol and the second particles are conjugated microspheres. ### Claim 18 (depends on 2) A method of filtering particles comprising: providing the suspension into the inlet of the channel of the filtration system of claim 2; and cycling a flow of the suspension at the volumetric flow ratio through the filtration system between the forward direction and the reverse direction. ### Claim 19 (depends on 18) The method of claim 18, wherein the volumetric flow ratio is from between 0.5 and 1.00. ### Claim 20 (depends on 18) The method of claim 18, wherein the volumetric flow ratio is from between 0.55 and 0.80. ### Claim 21 (depends on 18) The method of claim 18, wherein the volumetric flow ratio decreases in each subsequent cycle. ### Claim 22 (depends on 18) The method of claim 18, wherein the first particles are aggregated particulates resulting from a protein conjugation protocol and the second particles are conjugated microspheres. ### Claim 23 (depends on 18) The method of claim 18 further comprising: monitoring an amount of the second particles permeating through the membrane during flow of the suspension in the forward direction of a first cycle; and varying during a subsequent second cycle, based on the monitored amount, at least one of: the volumetric flow ratio; the flow rate in the forward direction; the flow rate in the reverse direction; a duration of flow in the forward direction; and a duration of flow in the reverse direction. ### Claim 24 (depends on 18) The method of claim 18, wherein the volumetric flow ratio has a linear relationship to a recovery percentage for a portion of the second particles permeating through the membrane; and wherein the method further comprises: calculating the recovery percentage of the second particles permeating through the membrane at a plurality of volumetric flow ratios; identifying a desired permeation amount for a portion of the second particles based on the recovery percentage; calculating a desired volumetric flow ratio based on the linear relationship; adjusting the volumetric flow ratio to equal the desired volumetric flow ratio; and recovering the desired permeation amount for the portion of the second particles. ### Claim 25 (depends on 2) A method of controlling seed density and uniformity comprising: cycling the suspension through the filtration system of claim 2; wherein the filtration system is a profusion bioreactor; wherein the membrane comprises a tissue scaffold; and wherein the first and second particles are cells. ### Claim 26 (depends on 25) The method of claim 25, wherein the tissue scaffold comprises at least one of an extracellular matrix or a bone matrix. ### Claim 27 (depends on 2) A method of delivering molecules into a permeated cell comprising: cycling the suspension through the filtration system of claim 2, wherein the fluid is a cell medium, the first particles are cells, and the second particles are molecules, and wherein the permeation of the permeated cells through the membrane applies a shear stress to the permeated cells; permeabilizing, via the shear stress, the permeated cells that pass through the membrane; and delivering at least one molecule into one of the permeabilized cells. ### Claim 28 (depends on 27) The method of claim 27, wherein the molecules are selected from the group consisting of macromolecules, nanoparticles, sugars, plasmids, mRNA, enzymes, nucleases, DNA, RNP, antibodies, beads, viruses, immune cells, stem cells, stromal cells, and therapeutic cells.