# US 11,027,474 B2 · Fluidic systems, devices and methods for inducing anisotropy in polymeric materials > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,027,474 B2 - Document ID: US11027474B2 - Status: Granted - Kind: B2 - Application number: 15/748,036 - Filed: 2016-07-22 - Published: 2018-08-02 - Granted: 2021-06-08 - Earliest claimed: 2015-07-27 - Assignees: Beth Israel Deaconess Medical Center, Inc.; The Governing Council of the University of Toronto - Applicants: The Governing Council of the University of Toronto; Beth Israel Deaconess Medical Centre, Inc. - Inventors: Lian Leng; Stephanie Grainger; Elliot L. Chaikof; Axel Guenther; David Miranda Nieves; Shashi Malladi; Richard Cheng - Web page: https://patentgrep.com/patent/US11027474B2 ## CPC - B29C 48/2556: {provided in or in the proximity of dies (B29C48/302, B29C48/31, B29C48/325 take precedence)} - B29C 48/002: {combined with surface shaping} - B29C 48/022: {characterised by the choice of material} - B29C 48/08: flexible, e.g. films - B29C 48/92: Measuring, controlling or regulating - C08J 3/24: Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K) - C08J 5/18: Manufacture of films or sheets - C12N 5/0661: {Smooth muscle cells} - B29C 48/28: Storing of extruded material, e.g. by winding up or stacking - B29K 2089/00: Use of proteins, e.g. casein, gelatine or derivatives thereof, as moulding material - B29K 2105/0073: {Solution} - B29K 2105/243: {Partially cured} - B29K 2995/0044: Anisotropic - B29L 2007/002: {Panels; Plates; Sheets} - C08J 2389/00: Characterised by the use of proteins; Derivatives thereof - C08J 2489/00: Characterised by the use of proteins; Derivatives thereof - C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)} - C12M 23/20: {Material Coatings (immunocoatings C12M25/00)} - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS - B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES - 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 Systems, devices and methods are provided for fabricating anisotropic polymer materials. According to various embodiments, a fluidic device is employed to distribute a polymer solution and a flow-confining solution in order to generate a layered flow, where the layered flow is formed such that a polymer liquid sheet is sheathed on opposing sides by flow-confining liquid sheets. The fluidic device includes first and second fluid conduits, where the first fluid conduit receives the layered flow. The second fluid conduit has a reduced height relative to the first fluid conduit, such that the layered flow is constricted as it flows through the second fluid conduit. The constriction formed by the second flow conduit causes hydrodynamic focusing, reducing the thickness of the polymer liquid sheet, and inducing molecular alignment and anisotropy within the polymer liquid sheet as it is hardened and as strain is applied during extrusion of the sheet. ## Claims ### Claim 1 A fluidic device for forming a polymer sheet from a polymer liquid while applying flow constriction thereto, comprising: a polymer distribution fluidic network comprising a plurality of polymer distribution microfluidic or mesofluidic channels, said polymer distribution microfluidic or mesofluidic channels comprising laterally arrayed outlets arranged to form the polymer solution liquid sheet when a polymer solution is provided to a proximal inlet of said polymer distribution fluidic network; a first flow-confining distribution fluidic network comprising a plurality of first flow-confining microfluidic or mesofluidic channels, said first flow-confining microfluidic or mesofluidic channels comprising laterally arrayed outlets arranged to form a first flow-confining liquid sheet when a flow-confining solution is provided to a proximal inlet of said first flow-confining distribution fluidic network; a second flow-confining distribution fluidic network comprising a plurality of second flow-confining microfluidic or mesofluidic channels, said second flow-confining microfluidic or mesofluidic channels comprising laterally arrayed outlets arranged to form a second flow-confining liquid sheet when the flow-confining solution is provided to a proximal inlet of said second flow-confining distribution fluidic network; a first flow conduit having an inlet in flow communication with said laterally arrayed outlets of said polymer distribution fluidic network, said laterally arrayed outlets of said first flow-confining distribution fluidic network and said laterally arrayed outlets of said second flow-confining distribution fluidic network, wherein distal portions of said polymer distribution fluidic network, said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network are arranged in a stacked configuration along a stacking direction, such that a layered flow is formed within said first flow conduit when the flow-confining solution is provided to said proximal inlets of said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network, the layered flow comprising the polymer solution liquid sheet, contacted and sheathed on opposing sides thereof by the first flow-confining liquid sheet and the second flow-confining liquid sheet; and a second flow conduit having an inlet in flow communication with an outlet of said first flow conduit, said second flow conduit having a height, as determined along the stacking direction, that is less than the height of said first flow conduit, and said second flow conduit having a cross-sectional area, perpendicular to a flow direction, that is less than a cross-sectional area of said first flow conduit, the second flow conduit thereby forming a flow constriction suitable for reducing a thickness of the polymer liquid sheet via hydrodynamic focusing as the layered flow flows into and through said second flow conduit. ### Claim 2 (depends on 1) The fluidic device according to claim 1 wherein the height of the first flow conduit is greater than an initial thickness of the layered flow. ### Claim 3 (depends on 1) The fluidic device according to claim 1 wherein said polymer distribution fluidic network, said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network are provided in a microfluidic device; and wherein said first flow conduit and said second flow conduit are provided in a flow-focusing unit that is interfaced to said microfluidic device. ### Claim 4 (depends on 1) The fluidic device according to claim 1 wherein said polymer distribution fluidic network, said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network are provided in a microfluidic device; and wherein said first flow conduit and said second flow conduit are provided in a flow-focusing unit that is integrally formed with said microfluidic device. ### Claim 5 (depends on 1) The fluidic device according to claim 1 further comprising a third flow conduit in flow communication with said second flow conduit, wherein a height of said third flow conduit is greater than the height of the second flow conduit. ### Claim 6 (depends on 1) The fluidic device according to claim 1 wherein the height of said second flow conduit decreases from a proximal region thereof to a distal region thereof. ### Claim 7 (depends on 1) A method of forming an anisotropic polymer material, the method comprising: providing a fluidic device according to claim 1; flowing the polymer solution into said polymer distribution fluidic network at a first controlled rate; flowing the flow-confining solution into the first flow-confining distribution fluidic network and the second flow-confining distribution fluidic network at a second controlled rate; wherein a composition of the polymer solution is selected such that at least an outer portion of the polymer solution liquid sheet is hardened as the polymer solution liquid sheet flows through the second flow conduit, thereby forming a polymer sheet; and extracting the polymer sheet under applied tension, wherein the applied tension and confinement provided by the second flow conduit are selected such that the collected polymer sheet exhibits anisotropic properties. ### Claim 8 (depends on 7) The method according to claim 7 wherein the flow-confining solution is selected such that the polymer solution is cross-linked upon contact therewith. ### Claim 9 (depends on 8) The method according to claim 8 wherein the polymer solution is a collagen solution, and wherein the polymer sheet is an aligned collagen sheet. ### Claim 10 (depends on 9) The method according to claim 9 wherein the flow-confining solution is a polyethylene glycol solution. ### Claim 11 (depends on 9) The method according to claim 9 further comprising: collecting the aligned collagen sheet on a rotating collection device in the absence of overlap of the aligned collagen sheet; seeding the aligned collagen sheet with smooth muscle cells and culturing the smooth muscle cells on the aligned collagen sheet; and collecting the seeded aligned collagen sheet onto a rotating mandrel. ### Claim 12 (depends on 9) The method according to claim 9 further comprising: collecting the aligned collagen sheet on a rotating collection device in the absence of overlap of the aligned collagen sheet; employing the fluidic device to deposit a second collagen layer onto the aligned collagen sheet, the second collagen layer comprising smooth muscle cells, thereby forming a collagen bilayer; and collecting the collagen bilayer onto a rotating mandrel. ### Claim 13 (depends on 12) The method according to claim 12 wherein the second collagen layer is deposited onto the aligned collagen sheet while the aligned collagen sheet is retained on the rotating collection device. ### Claim 14 (depends on 12) The method according to claim 12 further comprising contacting the aligned collagen sheet with a fibril incubation buffer and drying the aligned collagen sheet prior to depositing the second collagen layer onto the aligned collagen sheet. ### Claim 15 (depends on 9) The method according to claim 9 wherein the first controlled rate and the second controlled rate are selected such that collagen fibrillogenesis occurs within at least the outer portion of the polymer solution liquid sheet within the second flow conduit. ### Claim 16 (depends on 8) The method according to claim 8 wherein the polymer solution liquid sheet is cross-linked by one of photochemical cross-linking, ionic cross-linking, and thermal cross-linking. ### Claim 17 (depends on 7) The method according to claim 7 wherein the polymer sheet emerges from the fluidic device onto the surface of a liquid provided within a liquid reservoir, and wherein the polymer sheet is extracted and tensioned by passage thereof over a rotating cylinder partially submerged within said liquid without collecting the polymer sheet on the rotating cylinder. ### Claim 18 (depends on 7) The method according to claim 7 wherein the polymer sheet is collected on a rotating collection device. ### Claim 19 (depends on 18) The method according to claim 18 wherein the rotating collection device is one of a rotating mandrel and a rotating open frame. ### Claim 20 (depends on 19) The method according to claim 19 wherein the rotating collection device is translated during collection of the polymer sheet, such that the polymer sheet is collected in a spiral pattern without overlap. ### Claim 21 (depends on 20) The method according to claim 20 wherein the rotating collection device is configured to collect the polymer sheet with overlap. ### Claim 22 (depends on 18) The method according to claim 18 wherein a rotation axis of the rotating collection device is directed at angle relative to an extrusion direction of the polymer sheet. ### Claim 23 (depends on 22) The method according to claim 22 wherein the angle is between 45 degrees and 120 degrees. ### Claim 24 (depends on 7) The method according to claim 7 wherein the polymer sheet passes between a pair of counter-rotating cylinders after emerging from the fluidic device. ### Claim 25 (depends on 24) The method according to claim 24 wherein one or both of pair of counter-rotating cylinders has a surface pattern configured to induce crimping. ### Claim 26 (depends on 24) The method according to claim 24 wherein the polymer sheet is collected on a rotating collection device. ### Claim 27 (depends on 26) The method according to claim 26 wherein a tangential velocity of the rotating collection device is less than a tangential velocity of the pair of counter-rotating cylinders, such that the polymer sheet is crimped. ### Claim 28 (depends on 26) The method according to claim 26 wherein the rotating collection device is translated during collection of the polymer sheet, such that the polymer sheet is collected in a spiral pattern without overlap. ### Claim 29 (depends on 7) The method according to claim 7 wherein an extrusion velocity of the polymer sheet is VP, a flow rate of the polymer solution is QM, a flow rate of the flow-confining solution is QF, the cross-sectional area of the second flow conduit is A, and the total velocity of the working fluids is VT=(QM+QF)/A, and wherein QM, QF and VP are controlled such that V*>2, where V*=(VP−VT)/VT. ### Claim 30 (depends on 29) The method according to claim 29 wherein QM, QF and VP are controlled such that V*>4. ### Claim 31 (depends on 7) The method according to claim 7 wherein a thickness of said polymer sheet emerging from the second flow conduit is less than 100 microns. ### Claim 32 (depends on 7) The method according to claim 7 wherein a thickness of said polymer sheet emerging from the second flow conduit is less than 10 microns. ### Claim 33 (depends on 7) The method according to claim 7 wherein a thickness of said polymer sheet emerging from the second flow conduit is less than 3 microns. ### Claim 34 (depends on 1) A method of forming an anisotropic polymer material, the method comprising: providing a fluidic device according to claim 1; flowing the polymer solution into said polymer distribution fluidic network at a first controlled rate; flowing the flow-confining solution into the first flow-confining distribution fluidic network and the second flow-confining distribution fluidic network at a second controlled rate; the polymer solution being provided at a flow rate such that the combination of flow-focusing and shear generated within the second flow conduit reduces a thickness of the polymer sheet to a thickness less than 10 microns. ### Claim 35 (depends on 1) A system for forming an anisotropic polymer material, the system comprising: a fluidic device according to claim 1; a polymer solution dispensing device in flow communication with said proximal inlet of said polymer distribution fluidic network for providing the polymer liquid thereto at a first controlled flow rate; a flow-confining solution dispensing device in flow communication with said proximal inlets of said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network for providing the flow-confining solution thereto at a second controlled flow rate; and an extraction device configured to apply tension to a polymer sheet produced by the fluidic device as the polymer sheet emerges from the fluidic device. ### Claim 36 (depends on 35) The system according to claim 35 further comprising a liquid reservoir for receiving the polymer sheet on a liquid surface when the polymer sheet emerges from the fluidic device; and a rotating cylinder configured to be partially submerged by a liquid provided within said liquid reservoir for applying tension to the polymer sheet when the polymer sheet is passed over said rotating cylinder. ### Claim 37 (depends on 35) The system according to claim 35 wherein said extraction device is a rotating collection device configured to collect the polymer sheet as the polymer sheet emerges from the fluidic device. ### Claim 38 (depends on 37) The system according to claim 37 wherein said rotating collection device is one of a rotating mandrel and a rotating open frame. ### Claim 39 (depends on 37) The system according to claim 37 wherein said rotating collection device is translated during collection of the polymer sheet, such that the polymer sheet is collected in a spiral pattern without overlap. ### Claim 40 (depends on 39) The system according to claim 39 wherein said fluidic device is further configured to deposit one or more additional layers onto the polymer sheet when the polymer sheet is retained on said rotating collection device, the system further comprising: a rotating mandrel configured to collect the polymer sheet from said rotating collection device after deposition of the one or more additional layers. ### Claim 41 (depends on 37) The system according to claim 37 wherein a rotation axis of said rotating collection device is directed at a fixed or time-variable angle relative to an extrusion direction of the polymer sheet. ### Claim 42 (depends on 41) The system according to claim 41 wherein the angle is between 45 degrees and 120 degrees. ### Claim 43 (depends on 35) The system according to claim 35 wherein said extraction device is a pair of counter-rotating cylinders configured to receive the polymer sheet. ### Claim 44 (depends on 43) The system according to claim 43 wherein one or both of pair of counter-rotating cylinders has a surface pattern configured to induce crimping. ### Claim 45 (depends on 43) The system according to claim 43 further comprising a rotating collection device configured to collect the polymer sheet after the polymer sheet passes between said pair of counter-rotating cylinders. ### Claim 46 (depends on 45) The system according to claim 45 wherein said rotating collection device is configured to rotate a rotation rate that is less than a rotation rate of said pair of counter-rotating cylinders. ### Claim 47 (depends on 46) The system according to claim 46 wherein said rotating collection device is translated during collection of the polymer sheet, such that the polymer sheet is collected in a spiral pattern without overlap. ### Claim 48 (depends on 35) The system according to claim 35 wherein an extrusion velocity of the polymer sheet is VP, a flow rate of the polymer solution is QM, a flow rate of the flow-confining solution is QF, the cross-sectional area of the second flow conduit is A, and the total velocity of the working fluids is VT=(QM+QF)/A, and wherein QM, QF and VP are controlled such that V*>2, where V*=(VP−VT)/VT. ### Claim 49 (depends on 48) The system according to claim 48 wherein QM, QF and VP are controlled such that V*>4. ### Claim 50 (depends on 1) A system for forming an anisotropic polymer material, the system comprising: a fluidic device according to claim 1; a polymer solution dispensing device in flow communication with said proximal inlet of said polymer distribution fluidic network for providing the polymer liquid thereto at a first controlled flow rate; a flow-confining solution dispensing device in flow communication with said proximal inlets of said first flow-confining distribution fluidic network and said second flow-confining distribution fluidic network for providing the flow-confining solution thereto at a second controlled flow rate; wherein the first controlled flow rate is controlled such that the combination of flow-focusing and shear generated within the second flow conduit produces anisotropy with the polymer sheet.