# US 2014/0190903 A1 · System and method for particle filtration > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0190903 A1 - Document ID: US20140190903A1 - Status: Published application - Kind: A1 - Application number: 14/209,046 - Filed: 2014-03-13 - Published: 2014-07-10 - Earliest claimed: 2009-12-23 - Assignees: Cytovera Inc. - Applicants: Cytovera Inc. - Inventors: Lotien R. Huang - Web page: https://patentgrep.com/patent/US20140190903A1 ## CPC - B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation} - B01L 3/5021: {Test tubes specially adapted for centrifugation purposes} - B01L 3/50255: {Multi-well filtration} - B01L 2300/042: Caps; Plugs - B01L 2300/0681: Filter - B01L 2300/0829: Multi-well plates; Microtitration plates - B01L 2400/0409: centrifugal forces - B01L 2400/049: vacuum - B33Y 80/00: Products made by additive manufacturing - C12M 47/04: {Cell isolation or sorting (purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04)} - G01N 2015/1006: {for cytology} - G01N 2015/1028: {Sorting particles} - G01N 2015/1029: {Particle size} - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - B33Y: ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING - 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} - 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) ## Abstract Embodiments of the present disclosure feature a filtration system comprising a filtration module for particle filtration and methods of using the device for the isolation of particles (e.g., viable cells). Advantageously, embodiments of the device provide for the high throughput filtration of large volumes of sample while preserving cell viability and providing high yields. ## Claims ### Claim 1 A filtration device including at least one filtration unit, the at least one filtration unit comprising: a first sidewall; a second sidewall; a first fluid inlet defined between the first sidewall and the second sidewall, the first fluid inlet configured to receive a feed comprising a particle population and a fluid; a first row of pillars; a first plurality of pores defined by spacings between adjacent pillars in the first row of pillars, each of the first plurality of pores having an effective pore size smaller than a first physical pore size, the first physical pore size defined by the spacings between the adjacent pillars in the first row of pillars; a first flow chamber defined between the first row of pillars and the second sidewall and including a first flow chamber inlet and a first retentate outlet, the first flow chamber configured to direct a first retentate including at least a portion of the particle population to the first retentate outlet; a second flow chamber defined between the first row of pillars and the first sidewall and including a first filtrate outlet, the second flow chamber configured to direct a first filtrate including at least a portion of the fluid to the first filtrate outlet; wherein a spacing of pillars in the first row of pillars from the first sidewall that are located proximate the first flow chamber inlet being smaller than a spacing of pillars in the first row of pillars from the first sidewall located proximate the first retentate outlet; a second row of pillars; and a second plurality of pores defined by spacings between adjacent pillars in the second row of pillars, each of the second plurality of pores having an effective pore size smaller than a second physical pore size, the second physical pore size defined by the spacings between the adjacent pillars in the second row of pillars. ### Claim 2 (depends on 1) The filtration device of claim 1, further comprising a third flow chamber defined between the second row of pillars and the second sidewall, the third flow chamber including a third flow chamber inlet configured to receive the first retentate and the first filtrate and a second retentate outlet, the third flow chamber configured to direct at least a portion of the particle population to the second retentate outlet, a spacing of pillars in the second row of pillars from the first sidewall located proximate the third flow chamber inlet being smaller than a spacing of pillars in the third row of pillars from the first sidewall located proximate the second retentate outlet. ### Claim 3 (depends on 1) The filtration device of claim 1, including a plurality of filtration units. ### Claim 4 (depends on 1) The filtration device of claim 1, wherein each filtration unit further includes a second fluid inlet disposed substantially equidistant from the first sidewall and the second sidewall. ### Claim 5 (depends on 1) The filtration device of claim 1, wherein each filtration unit further includes a third row of pillars disposed between the first flow chamber and the second sidewall, a spacing of pillars in the third row of pillars from the second sidewall located proximate the first flow chamber inlet being smaller than a spacing of pillars in the third row of pillars from the first sidewall located proximate the first retentate outlet, the third row of pillars configured to direct at least a portion of the particle population to first retentate outlet, and wherein each filtration unit further includes a fourth row of pillars disposed between the third flow chamber and the second sidewall, a spacing of pillars in the third row of pillars from the second sidewall located proximate the third flow chamber inlet being smaller than a spacing of pillars in the third row of pillars from the first sidewall located proximate the second retentate outlet. ### Claim 6 (depends on 5) The filtration device of claim 5, wherein each filtration unit is substantially symmetric about a center line defined substantially equidistant from the first sidewall and the second sidewall, and wherein the first physical pore size and the second physical pore size are substantially identical. ### Claim 7 (depends on 5) The filtration device of claim 5, wherein each of the first row of pillars and the third row of pillars includes an upstream end and a downstream end, a spacing between the downstream end of the first row of pillars and the downstream end of the third row of pillars defining the first retentate outlet, the third flow chamber inlet disposed downstream of the first retentate outlet. ### Claim 8 (depends on 1) The filtration device of claim 1, wherein the effective pore size of the first plurality of pores of the first row of pillars is smaller than at least one particle in the particle population. ### Claim 9 (depends on 1) The filtration device of claim 1, wherein the particle population is a cell population. ### Claim 10 (depends on 1) The filtration device of claim 1, wherein the particle population is stem cells. ### Claim 11 (depends on 1) The filtration device of claim 1, wherein the feed is blood. ### Claim 12 (depends on 1) The filtration device of claim 1, wherein the feed is umbilical cord blood. ### Claim 13 (depends on 1) The filtration device of claim 1, wherein the feed is a stromal vascular fraction. ### Claim 14 A filtration device including at least one filtration unit, the at least one filtration unit comprising: a first sidewall; a second sidewall; a first fluid inlet defined between the first sidewall and the second sidewall, the first fluid inlet configured to receive a feed comprising a particle population and a fluid; a first row of pillars including an upstream end and a downstream end; a first plurality of pores defined by spacings between adjacent pillars in the first row of pillars, each of the first plurality of pores having an effective pore size smaller than a first physical pore size, the first physical pore size defined by the spacings between the adjacent pillars in the first row of pillars; wherein a spacing of pillars in the first row of pillars from the first sidewall located proximate the upstream end of the first row of pillars is smaller than a spacing of pillars in the first row of pillars from the first sidewall located proximate the downstream end of the first row of pillars; a second row of pillars disposed downstream of the upstream end of the first row of pillars; and a second plurality of pores defined by spacings between adjacent pillars in the second row of pillars, each of the second plurality of pores having an effective pore size smaller than a second physical pore size, the second physical pore size defined by the spacings between the adjacent pillars in the second row of pillars; wherein a spacing of pillars in the second row of pillars from the second sidewall located proximate the upstream end of the second row of pillars is smaller than a spacing of pillars in the second row of pillars from the second sidewall located proximate the downstream end of the second row of pillars. ### Claim 15 (depends on 14) The filtration device of claim 14, wherein each filtration unit further includes a second inlet disposed substantially equidistant from the first sidewall and the second sidewall. ### Claim 16 A filtration system comprising: a fluid line configured to receive a liquid suspension of cells comprising a target cell population suspended in a fluid; a first collection chamber; a second collection chamber; and at least one cartridge comprising an cartridge inlet, a first cartridge outlet fluidicly connected to the first collection chamber, a second cartridge outlet fluidicly connected to the second collection chamber, and at least one filtration unit, the at least one filtration unit having a filtration unit inlet fluidicly connected to the cartridge inlet, a first filtration unit outlet fluidicly connected to the first cartridge outlet, a second filtration unit outlet fluidicly connected to the second cartridge outlet, a flow chamber configured to separate the target cell population from at least a portion of the fluid by flow conditions, to direct the target cell population to the first filtration unit outlet, and to direct the at least a portion of the fluid to the second filtration unit outlet, the first collection chamber, the second collection chamber, and the at least one cartridge forming a closed system. ### Claim 17 (depends on 16) The filtration system of claim 16, wherein the flow chamber further includes: a first sidewall; a second sidewall; a flow chamber inlet; a flow chamber outlet; a first row of pillars; and a first plurality of pores defined by spacings between adjacent pillars in the first row of pillars, each of the first plurality of pores having an effective pore size smaller than a first physical pore size, the first physical pore size defined by the spacings between the adjacent pillars in the first row of pillars; a spacing of pillars in the first row of pillars from the first sidewall located proximate the flow chamber inlet being smaller than a spacing of pillars in the first row of pillars from the first sidewall located proximate the flow chamber outlet. ### Claim 18 (depends on 17) The filtration system of claim 17, wherein the at least one filtration unit further includes a second row of pillars, a spacing of pillars in the second row of pillars from the second sidewall located proximate the flow chamber inlet being smaller than a spacing of pillars in the second row of pillars from the second sidewall located proximate the flow chamber outlet. ### Claim 19 (depends on 18) The filtration system of claim 18, wherein each filtration unit is substantially symmetric about a center line defined equidistant from the first sidewall and the second sidewall. ### Claim 20 (depends on 18) The filtration system of claim 18, wherein each filtration unit further includes: a third row of pillars including an upstream end and a downstream end, a spacing of pillars in the third row of pillars from the first sidewall located proximate the upstream end of the third row of pillars being smaller than a spacing of pillars in the first row of pillars from the first sidewall located proximate the downstream end of the third row of pillars, the third row of pillars positioned downstream of the first row of pillars. ### Claim 21 (depends on 16) The filtration system of claim 16, including a plurality of filtration units disposed on a surface in a high module density device. ### Claim 22 (depends on 16) The filtration system of claim 16, comprising a plurality of high module density devices each including a plurality of filtration units. ### Claim 23 (depends on 16) The filtration system of claim 16, wherein the at least one filtration unit further includes at least one carrier fluid inlet distinct from the filtration unit inlet. ### Claim 24 A method for cell processing comprising: introducing a feed sample comprising a viable target cell population and a nonviable cell population suspended in a fluid to a closed filtration system including a plurality of filtration units, each filtration unit including a flow chamber, a first outlet and a second outlet, the first outlet fluidicly connected to a first collection chamber and the second outlet fluidicly connected to a second collection chamber; driving the feed sample through the filtration system; creating flow conditions at each flow chamber to direct at least a portion of the viable target cell population to the first outlet, and to direct at least a portion of the nonviable cell population and at least a portion of the fluid to a second outlet; collecting the viable target cell population in the first collection chamber; and collecting the portion of the nonviable cell population and the portion of the fluid in the second collection chamber. ### Claim 25 (depends on 24) The method of claim 24, wherein the flow chamber further including at least one row of pillars. ### Claim 26 (depends on 24) The method of claim 24, wherein each flow chamber further comprises: a first sidewall; a second sidewall; a first fluid inlet defined between the first sidewall and the second sidewall, the first fluid inlet configured to receive the feed sample; a first row of pillars including an upstream end and a downstream end and configured to direct at least a portion of the target cell population to the first outlet by flow exclusion; a spacing of pillars in the first row of pillars from the first sidewall located proximate the upstream end of the first row of pillars being smaller than a spacing of pillars in the first row of pillars from the first sidewall located proximate the downstream end of the first row of pillars; a second row of pillars including an upstream end and a downstream end and configured to direct at least a portion of the target cell population to the first outlet by flow exclusion; and a spacing of pillars in the second row of pillars from the second sidewall located proximate the upstream end of the second row of pillars being smaller than a spacing of pillars in the second row of pillars from the second sidewall located proximate the downstream end of the second row of pillars. ### Claim 27 (depends on 24) The method of claim 24, wherein the closed filtration system includes at least one high module density device including the plurality of filtration units, the plurality of filtration units disposed on a surface of a high module density device. ### Claim 28 (depends on 24) The method of claim 24, wherein driving the feed sample through the filtration system comprises driving the feed sample through the filtration system under the influence of gravity, and wherein creating the flow conditions comprises creating laminar flow conditions. ### Claim 29 (depends on 24) The method of claim 24, wherein driving the feed sample through the filtration system comprises concurrently driving the feed sample through a plurality of high module density devices, each of the plurality of the high module density devices including a plurality of filtration units. ### Claim 30 (depends on 24) The method of claim 24, wherein creating the flow conditions includes creating gentle flow conditions which provide for about 99% of the target cell population collected in the first collection chamber to be viable. ### Claim 31 (depends on 24) The method of claim 24, wherein collecting the target cell population in the first collection chamber comprises: directing the at least 75% of the target cell population to the first collection chamber; and collecting the target cell population in the first collection chamber in a fluid volume of less than about 25% of the volume of the feed sample in the first collection chamber. ### Claim 32 (depends on 24) The method of claim 24, wherein the target cell population includes blood cells. ### Claim 33 (depends on 24) The method of claim 24, wherein the target cell population includes stem cells. ### Claim 34 (depends on 24) The method of claim 24, wherein the target cell population includes CD34+ cells. ### Claim 35 (depends on 24) The method of claim 24, wherein the target cell population includes cells derived from an adipose tissue. ### Claim 36 (depends on 24) The method of claim 24, wherein the target cell population includes umbilical cord blood cells. ### Claim 37 A method for umbilical cord blood volume reduction, the method comprising: introducing umbilical cord blood having an initial volume, a population of red blood cells and a viable population of a first type of nucleated cells into a filtration device within about six hours from draw, the filtration device including: a device inlet, and a flow chamber configured to separate the first type of nucleated cells from a portion of the population of red blood cells, to direct the first type of nucleated cells towards a first collection chamber, and to direct the portion of the population of red blood cells to a second collection chamber; passing the umbilical cord blood through the filtration device; collecting at least a portion of the population of red blood cells in the second collection chamber, and collecting at least 75% of the first type of nucleated cells in a fluid volume of less than about 25% of the initial volume in the first collection chamber, greater than about 99% of the population of nucleated cells collected in the first collection chamber being viable. ### Claim 38 (depends on 37) The method of claim 37, wherein the filtration device is a closed system. ### Claim 39 (depends on 37) The method of claim 37, further comprising drawing umbilical cord blood into a first receptacle, wherein introducing the umbilical cord blood into the filtration device comprises forming a closed system by connecting the first receptacle to the filtration device. ### Claim 40 (depends on 39) The method of claim 39, wherein the first receptacle contains a fluid. ### Claim 41 (depends on 39) The method of claim 39, wherein the first receptacle contains an additive. ### Claim 42 (depends on 39) The method of claim 39, wherein the first receptacle contains an anticoagulant. ### Claim 43 (depends on 37) The method of claim 37, wherein passing the umbilical cord blood through the filtration device comprises passing the umbilical cord blood through the filtration device under the influence of gravity. ### Claim 44 (depends on 37) The method of claim 37, wherein the first type of nucleated cells are CD34+ cells. ### Claim 45 (depends on 37) The method of claim 37, wherein the first type of nucleated cells is stem cells. ### Claim 46 (depends on 37) The method of claim 37, wherein the first collection chamber is a cryopreservation freezing bag. ### Claim 47 (depends on 37) The method of claim 37, wherein the fluid flow inside the flow chamber is laminar. ### Claim 48 (depends on 37) The method of claim 37, wherein the filtration device includes at least one row of pillars. ### Claim 49 (depends on 37) The method of claim 37, wherein the flow chamber includes a first sidewall; a second sidewall; a flow chamber inlet defined between the first sidewall and the second sidewall, the flow chamber inlet configured to receive the umbilical cord blood; a row of pillars including an upstream end and a downstream end and configured to direct a portion of the first type of nucleated cells to the first collection chamber; and a plurality of pores defined by spacings between adjacent pillars in the row of pillars, each of the plurality of pores having an effective pore size smaller than a physical pore size, the physical pore size defined by the spacings between the adjacent pillars in the row of pillars; and a spacing of pillars in the row of pillars from the first sidewall located proximate the upstream end of the row of pillars being smaller than a spacing of pillars in the row of pillars from the first sidewall located proximate the downstream end of the row of pillars.