WO2024118323A1 - Fluid-dividing lid having one port distributing fluid to a plurality of outlets - Google Patents

Fluid-dividing lid having one port distributing fluid to a plurality of outlets Download PDF

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Publication number
WO2024118323A1
WO2024118323A1 PCT/US2023/079768 US2023079768W WO2024118323A1 WO 2024118323 A1 WO2024118323 A1 WO 2024118323A1 US 2023079768 W US2023079768 W US 2023079768W WO 2024118323 A1 WO2024118323 A1 WO 2024118323A1
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WO
WIPO (PCT)
Prior art keywords
fluid
passages
layer
major surface
dividing
Prior art date
Application number
PCT/US2023/079768
Other languages
French (fr)
Inventor
Lan Bo
Lien-Yu Hung
Original Assignee
Corning Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Corning Incorporated filed Critical Corning Incorporated
Publication of WO2024118323A1 publication Critical patent/WO2024118323A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/12—Well or multiwell plates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/16—Microfluidic devices; Capillary tubes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/38—Caps; Covers; Plugs; Pouring means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/40—Manifolds; Distribution pieces
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/42—Integrated assemblies, e.g. cassettes or cartridges
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/44—Multiple separable units; Modules
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/46—Means for fastening
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Definitions

  • the disclosure relates generally to fluid routing devices and more particularly to a fluid-dividing lid for a fluidic device configured to distribute fluid from a single port to a plurality of outlets.
  • Three-dimensional (3D) cell cultures provide enhanced realism when studying the effect of drugs on cells as compared to two-dimensional (2D) cell cultures, which quickly lose viability.
  • 3D cell cultures require more complex microfluidic-based systems for maintenance and growth of the cell cultures. Often the systems have small channels that make loading the cells into the channels difficult. Such systems are typically driven by syringe pumps, vacuum pumps, and electrical magnetic controllers. Further, each cell growth channel may need its own pump and controller, making the overall fluidic system cumbersome to operate and leading to different volumes pushed to each channel based on variability in pump and controller configuration.
  • a fluid dividing lid comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports.
  • the fluid dividing lid of aspect (1) wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface.
  • the fluid dividing lid of aspect (2) is provided, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
  • the fluid dividing lid of aspect (3) is provided, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
  • the fluid dividing lid of any of aspects (l)-(4) is provided, wherein the plurality of outlet ports comprises at least eight outlet ports.
  • the fluid dividing lid of any of aspects (l)-(5) is provided, further comprising: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer.
  • the fluid dividing lid of aspect (6) wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
  • the fluid dividing lid of aspect (6) or (7) wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
  • the fluid dividing lid of any of aspects (6)-(8) is provided, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
  • the fluid dividing lid of any of the preceding aspects is provided, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
  • the fluid dividing lid of any of the preceding aspects is provided, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ⁇ 40% of an average of the flow of fluid through all of the plurality of outlet ports.
  • a kit comprising: a fluidic device, comprising a plurality of fluid arrays; a fluid dividing lid, comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; wherein the plurality of outlet ports are configured to be in fluid communication with the plurality of fluid arrays.
  • the kit of aspect (12) is provided, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface.
  • the kit of aspect (13) is provided, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
  • the kit of aspect (14) is provided, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
  • the kit of any of aspects (12)-(15) is provided, wherein the plurality of outlet ports comprises at least eight outlet ports and wherein the plurality of fluid arrays is at least eight fluid arrays.
  • the kit of any of aspects (12)-(16) is provided, wherein the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the
  • the kit of aspect (17) wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
  • the kit of aspect (17) or (18) is provided, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
  • the kit of any of aspects (17)-(19) is provided, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
  • the kit of any of aspects (12)-(20) is provided, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
  • the kit of any of aspects (12)-(21) is provided, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ⁇ 40% of an average of the flow of fluid through all of the plurality of outlet ports.
  • the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a microfluidic plate.
  • the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a microplate array.
  • the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a three-dimensional cell culture.
  • a method comprising: arranging a fluid dividing lid over a fluidic device, the fluid dividing lid comprising a first outer surface comprising an inlet port, a second outer surface opposite to the first outer surface and comprising a plurality of outlet ports, and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; and flowing fluid through the fluid dividing lid from the inlet port, through the plurality of passages, and out of the plurality of outlet ports to fluid arrays of the fluidic device.
  • the method of aspect (26) is provided, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface; and wherein flowing further comprises: directing the fluid from the inlet port through the first passages and second passages to the plurality of outlet ports.
  • directing further comprises directing the fluid through at least two layers of the first passages and at least one layer of second passages.
  • the method of aspect (28) is provided, wherein directing further comprises dividing the fluid at least two ways in each of the at least two layers.
  • the method of any of aspects (26)-(29) wherein flowing further comprises flowing the fluid through at least eight outlet ports to inlets of at least eight fluid arrays.
  • the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer; and wherein flowing
  • the method of aspect (31) is provided, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein, prior to arranging, the method further comprises: stacking the first layer and the second layer such that the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
  • the method of aspect (31) or (32) is provided, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein, prior to arranging, the method further comprises: stacking the second layer and the third layer such that the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
  • flowing further comprises dividing the fluid among the plurality of outlet ports such that no outlet port receives more than ⁇ 40% of an average of the flow of fluid through all of the plurality of outlet ports.
  • flowing further comprises flowing a fluid having a viscosity in a range from 10' 4 poise to 100 poise.
  • FIG. 1 depicts a schematic representation of a fluid-dividing lid with a single inlet port distributing to thirty-two outlets, according to an exemplary embodiment
  • FIG. 2 depicts representative layouts of layers of the fluid-dividing lid shown in the schematic of FIG. 1, according to an exemplary embodiment
  • FIG. 3 depicts the assembled layers of the fluid-dividing lid of FIG. 2, according to an exemplary embodiment
  • FIG. 4 depicts the lid of FIG. 3 as positioned over a microplate containing a plurality of wells, according to an exemplary embodiment
  • FIG. 5 depicts a fluid-dividing lid with a single inlet port distributing to sixteen outlets, according to an exemplary embodiment
  • FIGS. 6-9 depict the individual layers of the fluid-dividing lid of FIG. 5, according to an exemplary embodiment
  • FIG. 10 depicts the fluid-dividing lid of FIG. 5 positioned over a fluidic device, according to an exemplary embodiment
  • FIG. 11 depicts a fluid-dividing lid with a single inlet port distributing fluid to eight outlets positioned over a fluidic device, according to an exemplary embodiment
  • FIG. 12 depicts an exploded view of a fluid-dividing lid, according to an exemplary embodiment.
  • FIG. 13 depicts an exploded view of a fluid-dividing lid in which the layers of the lid include complementary channels to form fluid passages, according to an exemplary embodiment.
  • the fluid-dividing lid includes a plurality of layers that divide fluid entering a single port among a plurality of outlets.
  • the fluid-dividing lid only needs one pump and controller for directing fluid to a plurality of fluid arrays of a fluidic device.
  • fluid was directed to the plurality of fluid arrays using a channel plate with one port per outlet, which required multiple pumps and multiple controllers and which lead to inconsistent output from the outlets.
  • the presently disclosed fluid-dividing lid is less cumbersome to set up, and the outlets are provided with more uniform flow.
  • FIG. 1 depicts an embodiment of a lid 20 for a fluidic device.
  • the lid 20 includes a first outer surface 22, and an inlet port 24 for receiving fluid is provided on the first outer surface 22.
  • the lid 20 also includes a second outer surface 26 on an opposite side of the lid from the first outer surface 22.
  • the second outer surface 26 includes a plurality of outlet ports 28.
  • Disposed between the first outer surface 22 and the second outer surface 26 is an intermediate region 30.
  • a plurality of passages 32 are configured to divide the flow of fluid entering the inlet port 24 among the plurality of outlet ports 28.
  • the plurality of passages 32 include first passages 34 and second passages 36.
  • the first passages 34 extend substantially parallel to the length L or width W (shown in FIG. 2) of the first outer surface 22.
  • the second passages 36 extend substantially parallel to a thickness T of the intermediate region 30, the thickness T being defined as the distance between the first outer surface 22 and the second outer surface 26.
  • the intermediate region 30 is divided into a plurality of layers 38 (generally; individual layers will be referred to as 38a, 38b, 38c, . . .).
  • the first passages 34 are intralayer passages in that the first passages 34 direct fluid within the layer 38
  • the second passages 36 are interlayer passages in that the second passages 36 direct fluid to another layer 38.
  • the intermediate region 30 includes at least two layers 38 with first passages 34 that are connected by second passages 36.
  • FIG. 2 depicts a layout for the passages 32 in each of the layers 38 of the lid 20 shown schematically in FIG. 1.
  • each layer 38 includes a first major surface 40 and a second major surface 42 that is opposite to the first major surface 40.
  • the first layer 38a includes the first outer surface 22, which is the first major surface 40a of the first layer 38a.
  • the single inlet port 24 is formed on the first major surface 40a of the first layer 38a.
  • the inlet port 24 is in fluid communication with a first passage 34 formed on the second major surface 42a of the first layer 38a.
  • the first passage 34 divides fluid from the inlet port 24 two ways. Respective terminal ends of the first passage 34 are in fluid communication with two second passages 36 formed in the first major surface 40b of the second layer 38b.
  • the two second passages 36 of the second layer 38b are in fluid communication with midpoints of two first passages 34 formed on the second major surface 42b of the second layer 38b.
  • Each of the two first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the two first passages 34 of the second layer 38b are in fluid communication with four respective second passages 36 formed through the first major surface 40c of the third layer 38c.
  • the four second passages 36 of the third layer 38c are in fluid communication with midpoints of four first passages 34 formed on the second major surface 42c of the third layer 38c.
  • Each of the four first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the four first passages 34 of the third layer 38c are in fluid communication with eight respective second passages 36 formed through the first major surface 40d of the fourth layer 38d.
  • the eight second passages 36 of the fourth layer 38d are in fluid communication with midpoints of eight first passages 34 formed on the second major surface 42d of the fourth layer 38d. Each of the eight first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the eight first passages 34 of the fourth layer 38d are in fluid communication with sixteen respective second passages 36 formed through the first major surface 40e of the fifth layer 38e.
  • the sixteen second passages 36 of the fifth layer 38e are in fluid communication with midpoints of thirty -two first passages 34 formed on the second major surface 42e of the fifth layer 38e. Each of the sixteen first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the sixteen first passages of the fifth layer 38e are in fluid communication with the plurality of outlets 28, which is a total of thirty-two outlets 28.
  • FIG. 3 depicts a top view of the lid 20 with the layers 38a-e assembled.
  • the passages 32 distribute fluid entering the inlet port 24 among the plurality of outlets 28.
  • the first passages 34 divide the fluid within the respective layers 38a-e, and the second passages 36 transport the fluid between the layers 38a-e.
  • FIG. 4 depicts an embodiment of the lid 20 placed over a microplate array 44 having ninety-six wells 46.
  • the lid 20 allows for thirty-two wells 46 to be filled at a time.
  • a microplate array 44 having ninety-six wells 46 can be filled with three operations using the same lid 20 or with a single operation using three lids 20.
  • FIGS. 5-9 depict an embodiment of a lid 20 configured to divide fluid from a single inlet port 24 among sixteen outlets 28.
  • FIG. 5 depicts the assembled lid 20 with the port 24 in fluid communication with a plurality of passages 32 that divide the flow between the plurality of outlets 28.
  • FIGS. 6-9 depict only the fluid dividing passages, namely the first passages 34, and the second passages 36 that transport the fluid between layers 38a-e are not shown.
  • FIG. 6 depicts the first layer 38a with a first passage 34 that divides the fluid from the inlet port 24 two ways. In particular, fluid from the inlet port 24 intersects with the midpoint of the first passage 34, and the fluid flows in opposite directions to two terminal ends of the first passage 34.
  • the terminal ends of the first passage 34 are in fluid communication with two midpoints of two first passages 34 of the second layer 38b as shown in FIG. 7. Fluid in the two first passages 34 of the second layer 38b is divided from respective midpoints in opposing directions to respective terminal ends of each of the two first passages 34.
  • the terminal ends of the two first passages 34 are in fluid communication with four midpoints of four first passages 34 of the third layer 38c as shown in FIG. 8. Fluid in the four first passages 34 of the third layer 38c is divided from respective midpoints in opposing directions to respective terminal ends of each of the four first passages 34.
  • the terminal ends of the of the four first passages 34 are in fluid communication with eight midpoints of eight first passages 34 of the fourth layer 38d as shown in FIG. 9. Fluid in the eight first passages 34 of the fourth layer 38d is divided from the respective midpoints in opposing directions to respective terminal ends of each of the eight first passages 34.
  • the respective terminal ends of each of the eight first passages 34 correspond sixteen outlets 28.
  • FIG. 10 depicts the lid 20 of FIGS. 5-9 positioned over a microfluidic plate 48.
  • the microfluidic plate 48 includes a plurality of fluid arrays 50.
  • the lid 20 divides fluid sixteen ways, such that each fluid array 50 receives two streams of fluid from the lid 20.
  • FIG. 11 depicts an embodiment of a lid 20 positioned over another microfluidic plate 48.
  • the microfluidic plate 48 has eight fluid arrays 50, and thus, the lid 20 is configured to divide fluid eight ways such that each fluid array 50 receives a single stream of fluid from the lid 20.
  • FIGS. 10 and 11 demonstrate that the layouts of the passages can vary to achieve the desired fluid divisions.
  • the second level of fluid passages is perpendicular to the fluid passage in the first level.
  • Each subsequent level of fluid passages is parallel to the fluid passages in the second level.
  • the fluid passages in each level of the lid 20 of FIG. 11 are perpendicular to the fluid passages in the level above and below it (as applicable).
  • the fluid passages in the second level are perpendicular to the fluid passage in the first level
  • the fluid passages in the third level are perpendicular to the fluid passages in the second level.
  • FIGS. 10 and 11 demonstrate that the layout of the passages can be adjusted as necessary to position the desired number of outlets of the lid in the desired location relative to the microfluidic plate 48.
  • FIG. 12 depicts an exploded view of the layers 38a-c of a fluid dividing lid 20.
  • the first layer 38a includes the inlet port 24 extending from the first major surface 40a. Fluid communication is provided through the port 24 to the second major surface 42a of the first layer 38a.
  • the second layer 38b includes two first passages 34 formed on the first major surface 40b of the second layer 38b. As can be seen in FIG. 12, the first passages 34 have open tops. In this regard, the first passages 34 are defined not only by the first major surface 40b of the second layer 38b but by the second major surface 42a of the first layer 38a.
  • the first passages 34 of the second layer 38b are in fluid communication with first passages 34 of the third layer 38c.
  • the first passages of the third layer 38c are formed in the first major surface 40c of the third layer 38c.
  • the first passages 34 of the third layer 38c have open tops such that the second major surface 42b of the second layer 38b encloses the first passages 34 of the third layer 38c.
  • the lid 20 includes outlets 28 formed on the second major surface 42c of the third layer 38c.
  • the first passages 34 can be formed on the first major surface 40 of a layer 38 or the second major surface 42 of a layer 38. Further, the first passages can be defined by the combination of the first major surface 40 of one layer 38 and the second major surface 42 of an adjacent layer 38.
  • FIG. 13 depicts another example embodiment of a fluid-dividing lid 100, and the fluid-dividing lid 100 is shown in combination with a fluidic device 102, in particular a microfluidic device, such as a three-dimensional (3D) cell culture plate.
  • a fluidic device 102 in particular a microfluidic device, such as a three-dimensional (3D) cell culture plate.
  • the fluid-dividing lid 100 includes a first layer 104, which is an outer layer of the fluid-dividing lid 100, and the first layer 104 has a first major surface 106 and a second major surface 108.
  • the second major surface 108 is opposite to the first major surface 106.
  • a port 110 extends from the first major surface 106.
  • the fluid-dividing lid 100 includes a second layer 112, which is an intermediate layer of the fluid-dividing lid 100, and the second layer 112 has a third major surface 114 and a fourth major surface 116.
  • the fourth major surface 116 is opposite to the third major surface 114.
  • a first fluid passage is defined by the first layer 104 and the second layer 112 between the second major surface 108 and the third major surface 114.
  • the fluid-dividing lid 100 includes a third layer 118, which is another outer layer of the fluid-dividing lid 100.
  • the third layer 118 has a fifth major surface 120 and a sixth major surface 122.
  • the sixth major surface 122 is opposite to the fifth major surface 120.
  • a plurality of second fluid dividing passages are defined by the second layer 112 and the third layer 118 between the fourth major surface 116 and the fifth major surface 120. Further, as will be discussed below, a plurality of outlets are formed on the sixth major surface 122.
  • the first layer 104 includes a first fluid dividing channel 124 formed on the second major surface 108.
  • the first fluid dividing channel 124 is in fluid communication with the port 110.
  • the port 110 defines a through bore from the first major surface 106 to the second major surface 108 and into the first fluid dividing channel 124.
  • the first fluid dividing channel 124 is configured to divide fluid entering the port 110 in at least two directions. As shown in FIG. 13, the first fluid dividing channel 124 includes a first initial segment 126 and a second initial segment 128 that divide fluid from the port 110 initially in two, in particular opposing, directions. At the end of each initial segment 126, 128 are respective third terminal segments 130 and fourth terminal segments 132, which further divide the fluid from each initial segment 126, 128 in two further directions. Thus, fluid from the port 110 is divided in four ways by the first fluid dividing channel 124. In one or more other embodiments, the first fluid dividing channel 124 may include a different number of initial segments to divide the fluid from the port 110 in a multitude of different ways.
  • the first fluid dividing channel 124 may include from two to eight initial segments in fluid communication with the port 110. Such segments may be further divided by additional terminal segments. In one or more embodiments, the first fluid dividing channel 124 may include additional intermediate segments that further divide the fluid between the initial segments and the terminal segments. Further, in one or more embodiments, the initial segments are the terminal segments (i.e., the fluid in the initial segments is not further divided by other segments). For example, the first fluid dividing channel 124 could include four initial segments to directly divide the fluid in four ways instead of using two initial segments and four terminal segments. In total, the fluid dividing channel 124 may divide the fluid in a range of ways from two ways to thirty-two ways.
  • the second layer 112 includes a second fluid dividing channel 134 that is formed on the third major surface 114.
  • the second fluid dividing channel 134 complements the first fluid dividing channel 124 to form a first fluid dividing passage. That is, when the first layer 104 is stacked with the second layer 112, the first fluid dividing channel 124 and the second fluid dividing channel 134 cooperate or engage to form a fully enclosed passage through which fluid can travel.
  • the second fluid dividing channel 134 includes a corresponding number of segments (initial, intermediate, and/or terminal) as the first fluid dividing channel 124.
  • the second layer 112 includes through bores 136 that provide fluid communication from the third major surface 114 to the fourth major surface 116.
  • the second layer 112 includes a plurality of third fluid dividing channels 138 that are formed on the fourth major surface 116.
  • the second fluid dividing channel 134 is in fluid communication with the plurality of third fluid dividing channels 138.
  • Each of the third fluid dividing channels 138 further divides the fluid from the second fluid dividing channel 134.
  • the third fluid dividing channels 138 further divide the fluid in two ways. Thus, in the example embodiment depicted in FIG.
  • the fluid having been divided in four ways by the first and second fluid dividing channels 124, 134, is further divided two additional ways for a total of eight fluid divisions.
  • the plurality of third fluid dividing channels 138 may divide the fluid in a range from two ways to four ways, for example.
  • the third layer 118 includes a plurality of fourth fluid dividing channels 140 that are formed on the fifth major surface 120.
  • the plurality of fourth fluid dividing channels 140 complement the plurality of third fluid dividing channels 138 to form a plurality of second flow passages. That is, when the second layer 112 is stacked with the third layer 118, the plurality of third fluid dividing channels 138 cooperate or engage the plurality of fourth fluid dividing channels 140 to form fully enclosed second fluid passages through which fluid can travel.
  • the plurality of fourth fluid dividing channels 140 match the layout of the plurality of third fluid dividing channels 138.
  • the third layer 118 includes a plurality of outlets 142 formed on the sixth major surface 122.
  • the plurality of outlets 142 extend from the sixth major surface 122 to the fifth major surface 120, providing fluid communication with the plurality of fourth fluid dividing channels 140. In this way, fluid from the plurality of fourth fluid dividing channels 140 flows into the outlets 142.
  • fluid from a single port 110 is divided among a plurality of outlets 142 through the first layer 104, the second layer 112, and the third layer 118.
  • embodiments of the fluid-dividing lid 100 depict three layers, other embodiments of the fluiddividing lid 100 can include two layers or more than three layers. Further, the depicted embodiment of the fluid-dividing lid 100 divides fluid from the port 110 among eight outlets 142, but in one or more other embodiments, the fluid-dividing lid 100 could divide the fluid from the port 110 among fewer than eight outlets 142 or more than eight outlets 142, such as up to thirty-two, up to one hundred twenty-eight, or up to five hundred and twelve outlets 142.
  • FIG. 13 also depicts the fluidic device 102.
  • the fluidic device includes a plurality of fluid arrays 144.
  • the fluid arrays 144 may be used for 3D cell cultures.
  • the fluidic device 102 includes eight fluid arrays 144 corresponding to the eight outlets 142 of the fluid-dividing lid 100.
  • fluid from the port 110 is divided in the first fluid passage and the plurality of second fluid passages to the outlets 142, where the fluid flows into the fluid arrays 144 of the fluidic device 102.
  • the first layer 104 is reversibly engageable with the second layer 112, and the second layer 112 is reversibly engageable with the third layer 118.
  • the layers 104, 112, 118 can be disassembled, cleaned, and reassembled for directing fluid to a fluidic device 102.
  • the fluid-dividing lid 100 of FIG. 13 is a multilayer structure.
  • the fluid-dividing lid 100 has layers 104, 112, 118 that are analogous to layers 38a-n of the lid 20.
  • the first layer 104 has a first major surface 106 corresponding to the first outer surface 22 of lid 20, and the third layer 118 has a sixth major surface 122 corresponding to the second outer surface 26 of lid 20.
  • an inlet port 110 is formed on the first major surface 106 like the inlet port 24 of the first outer surface 22 of lid 20, and outlet ports 142 are provided on the sixth major surface 122 like the outlet ports 28 of the lid 20.
  • the intermediate region 30 of the fluid-dividing lid 20 corresponds to the first and second fluid-dividing channels 124, 134 defining the first fluid passage formed between the second and third major surfaces 108, 114 and the third and fourth pluralities of fluid-dividing channels 138, 140 defining the plurality of second fluid passages formed between the fourth and fifth major surfaces 116, 120.
  • a fluid-dividing lid 100 as shown in FIG. 13 was constructed and tested to determine how effectively the fluid-dividing lid 100 was able to distribute fluid entering the single inlet port 110 between the eight outlets 142. Fluid was pumped into the inlet port 110 at a rate of 85 pL/sec for four minutes. The volume pumped through each outlet 142 was measured. Three such tests were conducted, and an average volume of output was taken for each outlet 142. The average for the eight outlets 142 was 1.8 ⁇ 0.9, 1.2 ⁇ 0.7, 2.3 ⁇ 1.6, 2.7 ⁇ 0.6, 2.0 ⁇ 0.9, 1.4 ⁇ 0.5, 1.2 ⁇ 0.5, 2.3 ⁇ 0.9 mL. The average total throughput for all eight outlets 142 was 14.9 mL, and the average per outlet 142 was 1.86 mL. As can be seen from the output of each port, the output of each port was within 40% of the average output per outlet 142. For these volumes, this level of uniformity is an improvement over conventional devices.
  • the fluid could instead be divided in more ways than two in other embodiments.
  • the fluid is divided by at least three, at least four, at least five, at least six, at least seven, or at least eight ways per layer.
  • the number of fluid divisions can be different in different layers (e.g., divided two ways in a first layer and then three ways in a second layer to provide six outlets).
  • the size of the passages 32, 170, 172 can be from 10 pm to 12.7 cm.
  • the designs of the fluid-dividing lid 20, 100 disclosed herein can distribute fluids across a range of viscosities from 10' 4 poise to 100 poise.
  • lids 20, 100 can be assembled from a plurality of layers 38a-//, 104, 112, 118 and adhered or clamped together to provide a customizable fluid distributing system powered by a single pump and controller.
  • Embodiments of the disclosure also relate to a method of dividing fluid through a lid.
  • a fluid dividing lid 20, 100 is arranged over a fluidic device 44, 48, 102.
  • the fluid dividing lid 20, 100 is a lid as described above in relation to FIGS. 1-13.
  • the fluidic device 102 is at least one of a microplate array 44 including a plurality of wells 46, a microfluidic plate 48, or a three- dimensional cell culture, among other possibilities.
  • the fluid dividing lid 20, 100 is arranged such that outlets 28, 142 of the lid 20, 100 are arranged over respective fluid arrays 46, 48, 144 of the fluidic device 44, 48, 102.
  • fluid is flowed through the fluid dividing lid 20, 100 such that the fluid flows from an inlet port 24, 110 to a plurality of outlets 28, 142 and into the fluid arrays 46, 48, 144.
  • the fluid dividing lid 20, 100 includes a single inlet port 24, 110 on the first outer surface 22, 106 that is connected to the plurality of outlets 28, 142 on the second outer surface 26, 122 by a plurality of passages 32 through an intermediate region 30 between the first outer surface 22, 106 and the second outer surface 26, 122.
  • fluid provided to the inlet port 24, 110 may be pumped from a fluid reservoir through tubing connected to the inlet port 24, 110. From the inlet port 24, 110, the passages 32 of the immediate region 30 divide the fluid among the plurality of outlets 28, 142 to provide a substantially uniform amount of fluid to each fluid array 46, 48, 144 of the fluidic device 44, 48, 102.

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Abstract

Embodiments of the disclosure relate to a fluid dividing lid. The fluid dividing lid includes a first outer surface having an inlet port, a second outer surface opposite to the first outer surface and including a plurality of outlet ports. Further, the fluid dividing lid includes an intermediate region between the first outer surface and the second outer surface. The intermediate region includes a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports.

Description

FLUID-DIVIDING LID HAVING ONE PORT DISTRIBUTING FLUID TO A PLURALITY OF OUTLETS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority under 35 U.S.C. §119 of Chinese Patent Application Serial No. 202211 11659.4 filed on November 29, 2022, the content of which is relied upon and incorporated herein by reference in its entirety.
BACKGROUND
[0002] The disclosure relates generally to fluid routing devices and more particularly to a fluid-dividing lid for a fluidic device configured to distribute fluid from a single port to a plurality of outlets.
[0003] Three-dimensional (3D) cell cultures provide enhanced realism when studying the effect of drugs on cells as compared to two-dimensional (2D) cell cultures, which quickly lose viability. However, 3D cell cultures require more complex microfluidic-based systems for maintenance and growth of the cell cultures. Often the systems have small channels that make loading the cells into the channels difficult. Such systems are typically driven by syringe pumps, vacuum pumps, and electrical magnetic controllers. Further, each cell growth channel may need its own pump and controller, making the overall fluidic system cumbersome to operate and leading to different volumes pushed to each channel based on variability in pump and controller configuration.
SUMMARY
[0004] According to aspect (1), a fluid dividing lid is provided. The fluid dividing lid comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports.
[0005] According to aspect (2), the fluid dividing lid of aspect (1) is provided, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface. [0006] According to aspect (3), the fluid dividing lid of aspect (2) is provided, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
[0007] According to aspect (4), the fluid dividing lid of aspect (3) is provided, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
[0008] According to aspect (5), the fluid dividing lid of any of aspects (l)-(4) is provided, wherein the plurality of outlet ports comprises at least eight outlet ports.
[0009] According to aspect (6), the fluid dividing lid of any of aspects (l)-(5) is provided, further comprising: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer.
[0010] According to aspect (7), the fluid dividing lid of aspect (6) is provided, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
[0011] According to aspect (8), the fluid dividing lid of aspect (6) or (7) is provided, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages. [0012] According to aspect (9), the fluid dividing lid of any of aspects (6)-(8) is provided, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
[0013] According to aspect (10), the fluid dividing lid of any of the preceding aspects is provided, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
[0014] According to aspect (11), the fluid dividing lid of any of the preceding aspects is provided, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports.
[0015] According to aspect (12), a kit is provided. The kit comprising: a fluidic device, comprising a plurality of fluid arrays; a fluid dividing lid, comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; wherein the plurality of outlet ports are configured to be in fluid communication with the plurality of fluid arrays.
[0016] According to aspect (13), the kit of aspect (12) is provided, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface.
[0017] According to aspect (14), the kit of aspect (13) is provided, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
[0018] According to aspect (15), the kit of aspect (14) is provided, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
[0019] According to aspect (16), the kit of any of aspects (12)-(15) is provided, wherein the plurality of outlet ports comprises at least eight outlet ports and wherein the plurality of fluid arrays is at least eight fluid arrays. [0020] According to aspect (17), the kit of any of aspects (12)-(16) is provided, wherein the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer.
[0021] According to aspect (18), the kit of aspect (17) is provided, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
[0022] According to aspect (19), the kit of aspect (17) or (18) is provided, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
[0023] According to aspect (20), the kit of any of aspects (17)-(19) is provided, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
[0024] According to aspect (21), the kit of any of aspects (12)-(20) is provided, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
[0025] According to aspect (22), the kit of any of aspects (12)-(21) is provided, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports. [0026] According to aspect (23), the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a microfluidic plate.
[0027] According to aspect (24), the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a microplate array.
[0028] According to aspect (25), the kit of any of aspects (12)-(22) is provided, wherein the fluidic device is a three-dimensional cell culture.
[0029] According to aspect (26), a method is provided. The method comprising: arranging a fluid dividing lid over a fluidic device, the fluid dividing lid comprising a first outer surface comprising an inlet port, a second outer surface opposite to the first outer surface and comprising a plurality of outlet ports, and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; and flowing fluid through the fluid dividing lid from the inlet port, through the plurality of passages, and out of the plurality of outlet ports to fluid arrays of the fluidic device.
[0030] According to aspect (27), the method of aspect (26) is provided, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface; and wherein flowing further comprises: directing the fluid from the inlet port through the first passages and second passages to the plurality of outlet ports.
[0031] According to aspect (28), the method of aspect (27) is provided, wherein directing further comprises directing the fluid through at least two layers of the first passages and at least one layer of second passages.
[0032] According to aspect (29), the method of aspect (28) is provided, wherein directing further comprises dividing the fluid at least two ways in each of the at least two layers.
[0033] According to aspect (30), the method of any of aspects (26)-(29) is provided, wherein flowing further comprises flowing the fluid through at least eight outlet ports to inlets of at least eight fluid arrays. [0034] According to aspect (31), the method of any of aspects (26)-(30) is provided, wherein the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer; and wherein flowing further comprises: flowing the fluid from the inlet port, through the first fluid dividing passage, through the plurality of second fluid dividing passages, and out of the plurality of outlet ports to fluid arrays of the fluidic device.
[0035] According to aspect (32), the method of aspect (31) is provided, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein, prior to arranging, the method further comprises: stacking the first layer and the second layer such that the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
[0036] According to aspect (33), the method of aspect (31) or (32) is provided, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein, prior to arranging, the method further comprises: stacking the second layer and the third layer such that the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
[0037] According to aspect (34), the method of any of aspects (26)-(33) is provided, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
[0038] According to aspect (35), the method of any of aspects (26)-(34) is provided, wherein flowing further comprises dividing the fluid among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports.
[0039] According to aspect (36), the method of any of aspects (26)-(35) is provided, wherein flowing further comprises flowing a fluid having a viscosity in a range from 10'4 poise to 100 poise.
[0040] Additional features and advantages will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from the description or recognized by practicing the embodiments as described in the written description and claims hereof, as well as the appended drawings.
[0041] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary, and are intended to provide an overview or framework to understand the nature and character of the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] The accompanying drawings are included to provide a further understanding and are incorporated in and constitute a part of this specification. The drawings illustrate one or more embodiment(s), and together with the description serve to explain principles and operation of the various embodiments. In the drawings:
[0043] FIG. 1 depicts a schematic representation of a fluid-dividing lid with a single inlet port distributing to thirty-two outlets, according to an exemplary embodiment;
[0044] FIG. 2 depicts representative layouts of layers of the fluid-dividing lid shown in the schematic of FIG. 1, according to an exemplary embodiment;
[0045] FIG. 3 depicts the assembled layers of the fluid-dividing lid of FIG. 2, according to an exemplary embodiment;
[0046] FIG. 4 depicts the lid of FIG. 3 as positioned over a microplate containing a plurality of wells, according to an exemplary embodiment;
[0047] FIG. 5 depicts a fluid-dividing lid with a single inlet port distributing to sixteen outlets, according to an exemplary embodiment;
[0048] FIGS. 6-9 depict the individual layers of the fluid-dividing lid of FIG. 5, according to an exemplary embodiment; [0049] FIG. 10 depicts the fluid-dividing lid of FIG. 5 positioned over a fluidic device, according to an exemplary embodiment;
[0050] FIG. 11 depicts a fluid-dividing lid with a single inlet port distributing fluid to eight outlets positioned over a fluidic device, according to an exemplary embodiment;
[0051] FIG. 12 depicts an exploded view of a fluid-dividing lid, according to an exemplary embodiment; and
[0052] FIG. 13 depicts an exploded view of a fluid-dividing lid in which the layers of the lid include complementary channels to form fluid passages, according to an exemplary embodiment.
DETAILED DESCRIPTION
[0053] Referring generally to the following description and appended figures, various embodiments of a fluid-dividing lid for a fluidic device are provided. As will be described more fully below, the fluid-dividing lid includes a plurality of layers that divide fluid entering a single port among a plurality of outlets. Advantageously, because the fluid-dividing lid only has a single port, the fluid-dividing lid only needs one pump and controller for directing fluid to a plurality of fluid arrays of a fluidic device. In conventional devices, fluid was directed to the plurality of fluid arrays using a channel plate with one port per outlet, which required multiple pumps and multiple controllers and which lead to inconsistent output from the outlets. By using a single port to direct flow through a plurality of outlets, the presently disclosed fluid-dividing lid is less cumbersome to set up, and the outlets are provided with more uniform flow. These and other aspects and advantages of the disclosed multilayer fluid-dividing lid and method of assembling and operating same will be described herein and in relation to the figures. Such exemplary embodiments are provided by way of illustration and not by way of limitation.
[0054] FIG. 1 depicts an embodiment of a lid 20 for a fluidic device. The lid 20 includes a first outer surface 22, and an inlet port 24 for receiving fluid is provided on the first outer surface 22. The lid 20 also includes a second outer surface 26 on an opposite side of the lid from the first outer surface 22. The second outer surface 26 includes a plurality of outlet ports 28. Disposed between the first outer surface 22 and the second outer surface 26 is an intermediate region 30. In the intermediate region 30, a plurality of passages 32 are configured to divide the flow of fluid entering the inlet port 24 among the plurality of outlet ports 28. [0055] As shown in FIG. 1, the plurality of passages 32 include first passages 34 and second passages 36. In one or more embodiments, the first passages 34 extend substantially parallel to the length L or width W (shown in FIG. 2) of the first outer surface 22. In one or more embodiments, the second passages 36 extend substantially parallel to a thickness T of the intermediate region 30, the thickness T being defined as the distance between the first outer surface 22 and the second outer surface 26.
[0056] In one or more embodiments, the intermediate region 30 is divided into a plurality of layers 38 (generally; individual layers will be referred to as 38a, 38b, 38c, . . .). In one or more embodiments, the first passages 34 are intralayer passages in that the first passages 34 direct fluid within the layer 38, whereas the second passages 36 are interlayer passages in that the second passages 36 direct fluid to another layer 38. In one or more embodiments, the intermediate region 30 includes at least two layers 38 with first passages 34 that are connected by second passages 36.
[0057] FIG. 2 depicts a layout for the passages 32 in each of the layers 38 of the lid 20 shown schematically in FIG. 1. In FIG. 2, each layer 38 includes a first major surface 40 and a second major surface 42 that is opposite to the first major surface 40. The first layer 38a includes the first outer surface 22, which is the first major surface 40a of the first layer 38a. The single inlet port 24 is formed on the first major surface 40a of the first layer 38a. The inlet port 24 is in fluid communication with a first passage 34 formed on the second major surface 42a of the first layer 38a. The first passage 34 divides fluid from the inlet port 24 two ways. Respective terminal ends of the first passage 34 are in fluid communication with two second passages 36 formed in the first major surface 40b of the second layer 38b.
[0058] The two second passages 36 of the second layer 38b are in fluid communication with midpoints of two first passages 34 formed on the second major surface 42b of the second layer 38b. Each of the two first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the two first passages 34 of the second layer 38b are in fluid communication with four respective second passages 36 formed through the first major surface 40c of the third layer 38c.
[0059] The four second passages 36 of the third layer 38c are in fluid communication with midpoints of four first passages 34 formed on the second major surface 42c of the third layer 38c. Each of the four first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the four first passages 34 of the third layer 38c are in fluid communication with eight respective second passages 36 formed through the first major surface 40d of the fourth layer 38d.
[0060] The eight second passages 36 of the fourth layer 38d are in fluid communication with midpoints of eight first passages 34 formed on the second major surface 42d of the fourth layer 38d. Each of the eight first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the eight first passages 34 of the fourth layer 38d are in fluid communication with sixteen respective second passages 36 formed through the first major surface 40e of the fifth layer 38e.
[0061] The sixteen second passages 36 of the fifth layer 38e are in fluid communication with midpoints of thirty -two first passages 34 formed on the second major surface 42e of the fifth layer 38e. Each of the sixteen first passages 34 further divide the flow of fluid two additional ways. Terminal ends of each of the sixteen first passages of the fifth layer 38e are in fluid communication with the plurality of outlets 28, which is a total of thirty-two outlets 28.
[0062] FIG. 3 depicts a top view of the lid 20 with the layers 38a-e assembled. As can be seen, the passages 32 distribute fluid entering the inlet port 24 among the plurality of outlets 28. In particular, the first passages 34 divide the fluid within the respective layers 38a-e, and the second passages 36 transport the fluid between the layers 38a-e.
[0063] FIG. 4 depicts an embodiment of the lid 20 placed over a microplate array 44 having ninety-six wells 46. The lid 20 allows for thirty-two wells 46 to be filled at a time. Thus, a microplate array 44 having ninety-six wells 46 can be filled with three operations using the same lid 20 or with a single operation using three lids 20.
[0064] FIGS. 5-9 depict an embodiment of a lid 20 configured to divide fluid from a single inlet port 24 among sixteen outlets 28. FIG. 5 depicts the assembled lid 20 with the port 24 in fluid communication with a plurality of passages 32 that divide the flow between the plurality of outlets 28. FIGS. 6-9 depict only the fluid dividing passages, namely the first passages 34, and the second passages 36 that transport the fluid between layers 38a-e are not shown. FIG. 6 depicts the first layer 38a with a first passage 34 that divides the fluid from the inlet port 24 two ways. In particular, fluid from the inlet port 24 intersects with the midpoint of the first passage 34, and the fluid flows in opposite directions to two terminal ends of the first passage 34. The terminal ends of the first passage 34 are in fluid communication with two midpoints of two first passages 34 of the second layer 38b as shown in FIG. 7. Fluid in the two first passages 34 of the second layer 38b is divided from respective midpoints in opposing directions to respective terminal ends of each of the two first passages 34. The terminal ends of the two first passages 34 are in fluid communication with four midpoints of four first passages 34 of the third layer 38c as shown in FIG. 8. Fluid in the four first passages 34 of the third layer 38c is divided from respective midpoints in opposing directions to respective terminal ends of each of the four first passages 34. The terminal ends of the of the four first passages 34 are in fluid communication with eight midpoints of eight first passages 34 of the fourth layer 38d as shown in FIG. 9. Fluid in the eight first passages 34 of the fourth layer 38d is divided from the respective midpoints in opposing directions to respective terminal ends of each of the eight first passages 34. The respective terminal ends of each of the eight first passages 34 correspond sixteen outlets 28.
[0065] FIG. 10 depicts the lid 20 of FIGS. 5-9 positioned over a microfluidic plate 48. The microfluidic plate 48 includes a plurality of fluid arrays 50. The lid 20 divides fluid sixteen ways, such that each fluid array 50 receives two streams of fluid from the lid 20.
[0066] FIG. 11 depicts an embodiment of a lid 20 positioned over another microfluidic plate 48. The microfluidic plate 48 has eight fluid arrays 50, and thus, the lid 20 is configured to divide fluid eight ways such that each fluid array 50 receives a single stream of fluid from the lid 20.
[0067] From a comparison of FIGS. 10 and 11, it can be seen that the layouts of the passages can vary to achieve the desired fluid divisions. In FIG. 10, the second level of fluid passages is perpendicular to the fluid passage in the first level. Each subsequent level of fluid passages is parallel to the fluid passages in the second level. In contrast, the fluid passages in each level of the lid 20 of FIG. 11 are perpendicular to the fluid passages in the level above and below it (as applicable). Thus, the fluid passages in the second level are perpendicular to the fluid passage in the first level, and the fluid passages in the third level are perpendicular to the fluid passages in the second level. FIGS. 10 and 11 demonstrate that the layout of the passages can be adjusted as necessary to position the desired number of outlets of the lid in the desired location relative to the microfluidic plate 48.
[0068] FIG. 12 depicts an exploded view of the layers 38a-c of a fluid dividing lid 20. The first layer 38a includes the inlet port 24 extending from the first major surface 40a. Fluid communication is provided through the port 24 to the second major surface 42a of the first layer 38a. The second layer 38b includes two first passages 34 formed on the first major surface 40b of the second layer 38b. As can be seen in FIG. 12, the first passages 34 have open tops. In this regard, the first passages 34 are defined not only by the first major surface 40b of the second layer 38b but by the second major surface 42a of the first layer 38a.
[0069] The first passages 34 of the second layer 38b are in fluid communication with first passages 34 of the third layer 38c. The first passages of the third layer 38c are formed in the first major surface 40c of the third layer 38c. Like the first passages 34 of the second layer 38b, the first passages 34 of the third layer 38c have open tops such that the second major surface 42b of the second layer 38b encloses the first passages 34 of the third layer 38c. The lid 20 includes outlets 28 formed on the second major surface 42c of the third layer 38c.
[0070] Thus, as demonstrated by the embodiment of FIG. 12, the first passages 34 can be formed on the first major surface 40 of a layer 38 or the second major surface 42 of a layer 38. Further, the first passages can be defined by the combination of the first major surface 40 of one layer 38 and the second major surface 42 of an adjacent layer 38.
[0071] FIG. 13 depicts another example embodiment of a fluid-dividing lid 100, and the fluid-dividing lid 100 is shown in combination with a fluidic device 102, in particular a microfluidic device, such as a three-dimensional (3D) cell culture plate.
[0072] In one or more embodiments, the fluid-dividing lid 100 includes a first layer 104, which is an outer layer of the fluid-dividing lid 100, and the first layer 104 has a first major surface 106 and a second major surface 108. The second major surface 108 is opposite to the first major surface 106. A port 110 extends from the first major surface 106.
[0073] In one or more embodiments, the fluid-dividing lid 100 includes a second layer 112, which is an intermediate layer of the fluid-dividing lid 100, and the second layer 112 has a third major surface 114 and a fourth major surface 116. The fourth major surface 116 is opposite to the third major surface 114. As will be discussed more fully below, a first fluid passage is defined by the first layer 104 and the second layer 112 between the second major surface 108 and the third major surface 114.
[0074] In one or more embodiments, the fluid-dividing lid 100 includes a third layer 118, which is another outer layer of the fluid-dividing lid 100. The third layer 118 has a fifth major surface 120 and a sixth major surface 122. The sixth major surface 122 is opposite to the fifth major surface 120. As will be discussed more fully below, a plurality of second fluid dividing passages are defined by the second layer 112 and the third layer 118 between the fourth major surface 116 and the fifth major surface 120. Further, as will be discussed below, a plurality of outlets are formed on the sixth major surface 122.
[0075] As can be seen in FIG. 13, the first layer 104 includes a first fluid dividing channel 124 formed on the second major surface 108. The first fluid dividing channel 124 is in fluid communication with the port 110. In particular, the port 110 defines a through bore from the first major surface 106 to the second major surface 108 and into the first fluid dividing channel 124.
[0076] In one or more embodiments, the first fluid dividing channel 124 is configured to divide fluid entering the port 110 in at least two directions. As shown in FIG. 13, the first fluid dividing channel 124 includes a first initial segment 126 and a second initial segment 128 that divide fluid from the port 110 initially in two, in particular opposing, directions. At the end of each initial segment 126, 128 are respective third terminal segments 130 and fourth terminal segments 132, which further divide the fluid from each initial segment 126, 128 in two further directions. Thus, fluid from the port 110 is divided in four ways by the first fluid dividing channel 124. In one or more other embodiments, the first fluid dividing channel 124 may include a different number of initial segments to divide the fluid from the port 110 in a multitude of different ways. For example, the first fluid dividing channel 124 may include from two to eight initial segments in fluid communication with the port 110. Such segments may be further divided by additional terminal segments. In one or more embodiments, the first fluid dividing channel 124 may include additional intermediate segments that further divide the fluid between the initial segments and the terminal segments. Further, in one or more embodiments, the initial segments are the terminal segments (i.e., the fluid in the initial segments is not further divided by other segments). For example, the first fluid dividing channel 124 could include four initial segments to directly divide the fluid in four ways instead of using two initial segments and four terminal segments. In total, the fluid dividing channel 124 may divide the fluid in a range of ways from two ways to thirty-two ways.
[0077] As shown in FIG. 13, the second layer 112 includes a second fluid dividing channel 134 that is formed on the third major surface 114. The second fluid dividing channel 134 complements the first fluid dividing channel 124 to form a first fluid dividing passage. That is, when the first layer 104 is stacked with the second layer 112, the first fluid dividing channel 124 and the second fluid dividing channel 134 cooperate or engage to form a fully enclosed passage through which fluid can travel. Thus, the second fluid dividing channel 134 includes a corresponding number of segments (initial, intermediate, and/or terminal) as the first fluid dividing channel 124.
[0078] At terminal ends of the second fluid dividing channel 134, the second layer 112 includes through bores 136 that provide fluid communication from the third major surface 114 to the fourth major surface 116. In one or more embodiments, the second layer 112 includes a plurality of third fluid dividing channels 138 that are formed on the fourth major surface 116. The second fluid dividing channel 134 is in fluid communication with the plurality of third fluid dividing channels 138. Each of the third fluid dividing channels 138 further divides the fluid from the second fluid dividing channel 134. In one or more embodiments, including the embodiment shown in FIG. 13, the third fluid dividing channels 138 further divide the fluid in two ways. Thus, in the example embodiment depicted in FIG. 13, the fluid, having been divided in four ways by the first and second fluid dividing channels 124, 134, is further divided two additional ways for a total of eight fluid divisions. In one or more other embodiments, the plurality of third fluid dividing channels 138 may divide the fluid in a range from two ways to four ways, for example.
[0079] As shown in FIG. 13, the third layer 118 includes a plurality of fourth fluid dividing channels 140 that are formed on the fifth major surface 120. The plurality of fourth fluid dividing channels 140 complement the plurality of third fluid dividing channels 138 to form a plurality of second flow passages. That is, when the second layer 112 is stacked with the third layer 118, the plurality of third fluid dividing channels 138 cooperate or engage the plurality of fourth fluid dividing channels 140 to form fully enclosed second fluid passages through which fluid can travel. Thus, the plurality of fourth fluid dividing channels 140 match the layout of the plurality of third fluid dividing channels 138.
[0080] In one or more embodiments, the third layer 118 includes a plurality of outlets 142 formed on the sixth major surface 122. The plurality of outlets 142 extend from the sixth major surface 122 to the fifth major surface 120, providing fluid communication with the plurality of fourth fluid dividing channels 140. In this way, fluid from the plurality of fourth fluid dividing channels 140 flows into the outlets 142.
[0081] Accordingly, fluid from a single port 110 is divided among a plurality of outlets 142 through the first layer 104, the second layer 112, and the third layer 118. While embodiments of the fluid-dividing lid 100 depict three layers, other embodiments of the fluiddividing lid 100 can include two layers or more than three layers. Further, the depicted embodiment of the fluid-dividing lid 100 divides fluid from the port 110 among eight outlets 142, but in one or more other embodiments, the fluid-dividing lid 100 could divide the fluid from the port 110 among fewer than eight outlets 142 or more than eight outlets 142, such as up to thirty-two, up to one hundred twenty-eight, or up to five hundred and twelve outlets 142.
[0082] FIG. 13 also depicts the fluidic device 102. As can be seen in FIG. 13, the fluidic device includes a plurality of fluid arrays 144. In one or more embodiments, the fluid arrays 144 may be used for 3D cell cultures. As shown in FIG. 13, the fluidic device 102 includes eight fluid arrays 144 corresponding to the eight outlets 142 of the fluid-dividing lid 100. Thus, fluid from the port 110 is divided in the first fluid passage and the plurality of second fluid passages to the outlets 142, where the fluid flows into the fluid arrays 144 of the fluidic device 102.
[0083] Advantageously, in one or more embodiments, the first layer 104 is reversibly engageable with the second layer 112, and the second layer 112 is reversibly engageable with the third layer 118. In this way, the layers 104, 112, 118 can be disassembled, cleaned, and reassembled for directing fluid to a fluidic device 102.
[0084] Like the fluid-dividing lid 20 of FIGS. 1-12, the fluid-dividing lid 100 of FIG. 13 is a multilayer structure. In particular, the fluid-dividing lid 100 has layers 104, 112, 118 that are analogous to layers 38a-n of the lid 20. The first layer 104 has a first major surface 106 corresponding to the first outer surface 22 of lid 20, and the third layer 118 has a sixth major surface 122 corresponding to the second outer surface 26 of lid 20. Further, an inlet port 110 is formed on the first major surface 106 like the inlet port 24 of the first outer surface 22 of lid 20, and outlet ports 142 are provided on the sixth major surface 122 like the outlet ports 28 of the lid 20. Similarly, the intermediate region 30 of the fluid-dividing lid 20 corresponds to the first and second fluid-dividing channels 124, 134 defining the first fluid passage formed between the second and third major surfaces 108, 114 and the third and fourth pluralities of fluid-dividing channels 138, 140 defining the plurality of second fluid passages formed between the fourth and fifth major surfaces 116, 120.
[0085] A fluid-dividing lid 100 as shown in FIG. 13 was constructed and tested to determine how effectively the fluid-dividing lid 100 was able to distribute fluid entering the single inlet port 110 between the eight outlets 142. Fluid was pumped into the inlet port 110 at a rate of 85 pL/sec for four minutes. The volume pumped through each outlet 142 was measured. Three such tests were conducted, and an average volume of output was taken for each outlet 142. The average for the eight outlets 142 was 1.8±0.9, 1.2±0.7, 2.3±1.6, 2.7±0.6, 2.0±0.9, 1.4±0.5, 1.2±0.5, 2.3±0.9 mL. The average total throughput for all eight outlets 142 was 14.9 mL, and the average per outlet 142 was 1.86 mL. As can be seen from the output of each port, the output of each port was within 40% of the average output per outlet 142. For these volumes, this level of uniformity is an improvement over conventional devices.
[0086] While the depicted embodiments considered passages 32, 170, 172 that divided fluid in two ways, such that each layer divided the fluid by a factor of two, the fluid could instead be divided in more ways than two in other embodiments. In one or more embodiments, the fluid is divided by at least three, at least four, at least five, at least six, at least seven, or at least eight ways per layer. Further, in one or more embodiments, the number of fluid divisions can be different in different layers (e.g., divided two ways in a first layer and then three ways in a second layer to provide six outlets).
[0087] Further, the inventors believe that the designs of the fluid-dividing lid 20, 100 disclosed herein are scalable for use with a variety of different devices. For example, the size of the passages 32, 170, 172 can be from 10 pm to 12.7 cm. Further, the inventors believe that the designs of the fluid-dividing lid 20, 100 disclosed herein can distribute fluids across a range of viscosities from 10'4 poise to 100 poise.
[0088] Such lids 20, 100 can be assembled from a plurality of layers 38a-//, 104, 112, 118 and adhered or clamped together to provide a customizable fluid distributing system powered by a single pump and controller.
[0089] Embodiments of the disclosure also relate to a method of dividing fluid through a lid. In the method, a fluid dividing lid 20, 100 is arranged over a fluidic device 44, 48, 102. In one or more embodiments, the fluid dividing lid 20, 100 is a lid as described above in relation to FIGS. 1-13. In one or more embodiments, the fluidic device 102 is at least one of a microplate array 44 including a plurality of wells 46, a microfluidic plate 48, or a three- dimensional cell culture, among other possibilities. The fluid dividing lid 20, 100 is arranged such that outlets 28, 142 of the lid 20, 100 are arranged over respective fluid arrays 46, 48, 144 of the fluidic device 44, 48, 102.
[0090] After arranging the fluid dividing lid 20, 100 over the fluidic device 44, 48, 102, fluid is flowed through the fluid dividing lid 20, 100 such that the fluid flows from an inlet port 24, 110 to a plurality of outlets 28, 142 and into the fluid arrays 46, 48, 144. In particular, the fluid dividing lid 20, 100 includes a single inlet port 24, 110 on the first outer surface 22, 106 that is connected to the plurality of outlets 28, 142 on the second outer surface 26, 122 by a plurality of passages 32 through an intermediate region 30 between the first outer surface 22, 106 and the second outer surface 26, 122. In one or more embodiments, fluid provided to the inlet port 24, 110 may be pumped from a fluid reservoir through tubing connected to the inlet port 24, 110. From the inlet port 24, 110, the passages 32 of the immediate region 30 divide the fluid among the plurality of outlets 28, 142 to provide a substantially uniform amount of fluid to each fluid array 46, 48, 144 of the fluidic device 44, 48, 102.
[0091] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is in no way intended that any particular order be inferred. In addition, as used herein the article “a” is intended include one or more than one component or element, and is not intended to be construed as meaning only one.
[0092] It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the spirit or scope of the disclosed embodiments. Since modifications combinations, sub-combinations and variations of the disclosed embodiments incorporating the spirit and substance of the embodiments may occur to persons skilled in the art, the disclosed embodiments should be construed to include everything within the scope of the appended claims and their equivalents.

Claims

What is claimed is:
1. A fluid dividing lid, comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports.
2. The fluid dividing lid of claim 1, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface.
3. The fluid dividing lid of claim 2, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
4. The fluid dividing lid of claim 3, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
5. The fluid dividing lid of any one of claims 1-4, wherein the plurality of outlet ports comprises at least eight outlet ports.
6. The fluid dividing lid of any one of claims 1-4, further comprising: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer.
7. The fluid dividing lid of claim 6, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
8. The fluid dividing lid of claim 6, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
9. The fluid dividing lid of claim 6, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
10. The fluid dividing lid of any one of claims 1-4, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
11. The fluid dividing lid of any one of claims 1 -4, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports.
12. A kit, comprising: a fluidic device, comprising a plurality of fluid arrays; a fluid dividing lid, comprising: a first outer surface comprising an inlet port; a second outer surface, the second outer surface being opposite to the first outer surface and the second outer surface comprising a plurality of outlet ports; and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; wherein the plurality of outlet ports are configured to be in fluid communication with the plurality of fluid arrays.
13. The kit of claim 12, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, and wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface.
14. The kit of claim 13, wherein the intermediate region comprises at least two layers of the first passages connected by at least one layer of the second passages.
15. The kit of claim 14, wherein the first passages are configured to divide the flow of fluid at least two ways in each of the at least two layers.
16. The kit of any one of claims 12-15, wherein the plurality of outlet ports comprises at least eight outlet ports and wherein the plurality of fluid arrays is at least eight fluid arrays.
17. The kit of any one of claims 12-15, wherein the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; and wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer.
18. The kit of claim 17, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
19. The kit of claim 17, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
20. The kit of claim 17, wherein the first layer is reversibly engageable with the second layer and the second layer is reversibly engageable with the third layer.
21. The kit of any one of claims 12-15, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
22. The kit of any one of claims 12-15, wherein the flow of fluid from the inlet port is divided among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports.
23. The kit of any one of claims 12-15, wherein the fluidic device is a microfluidic plate.
24. The kit of any one of claims 12-15, wherein the fluidic device is a microplate array.
25. The kit of any one of claims 12-15, wherein the fluidic device is a three-dimensional cell culture.
26. A method, comprising: arranging a fluid dividing lid over a fluidic device, the fluid dividing lid comprising a first outer surface comprising an inlet port, a second outer surface opposite to the first outer surface and comprising a plurality of outlet ports, and an intermediate region between the first outer surface and the second outer surface, the intermediate region comprising a plurality of passages configured to divide a flow of fluid entering the inlet port among the plurality of outlet ports; and flowing fluid through the fluid dividing lid from the inlet port, through the plurality of passages, and out of the plurality of outlet ports to fluid arrays of the fluidic device.
27. The method of claim 26, wherein the plurality of passages comprises first passages and second passages, wherein the first passages extend substantially parallel to a length or width of the first outer surface, wherein the second passages extend substantially parallel to a thickness of the intermediate region between the first outer surface and the second outer surface; and wherein flowing further comprises: directing the fluid from the inlet port through the first passages and second passages to the plurality of outlet ports.
28. The method of claim 27, wherein directing further comprises directing the fluid through at least two layers of the first passages and at least one layer of second passages.
29. The method of claim 28, wherein directing further comprises dividing the fluid at least two ways in each of the at least two layers.
30. The method of any one of claims 26-29, wherein flowing further comprises flowing the fluid through at least eight outlet ports to inlets of at least eight fluid arrays.
31. The method of any one of claims 26-29, wherein the fluid dividing lid further comprises: a first layer comprising a first major surface and a second major surface, the first major surface being the first outer surface and the second major surface being opposite to the first major surface; a second layer comprising a third major surface and a fourth major surface, the fourth major surface being opposite to the third major surface; and a third layer comprising a fifth major surface and a sixth major surface, the sixth major surface being opposite to the fifth major surface and the sixth major surface being the second outer surface; wherein the plurality of passages comprises a first fluid dividing passage formed between the first layer and the second layer; wherein the plurality of passages comprises a plurality of second fluid dividing passages formed between the second layer and the third layer; and wherein flowing further comprises: flowing the fluid from the inlet port, through the first fluid dividing passage, through the plurality of second fluid dividing passages, and out of the plurality of outlet ports to fluid arrays of the fluidic device.
32. The method of claim 31, wherein the first layer comprises a first fluid dividing channel formed on the second major surface, wherein the second layer comprises a second fluid dividing channel formed on the third major surface, and wherein, prior to arranging, the method further comprises: stacking the first layer and the second layer such that the first fluid dividing channel and the second fluid dividing channel cooperate to form the first fluid dividing passage.
33. The method of claim 31, wherein the second layer comprises a plurality of third fluid dividing channels formed on the fourth major surface, wherein the third layer comprises a plurality of fourth fluid dividing channels formed on the fifth major surface, and wherein, prior to arranging, the method further comprises: stacking the second layer and the third layer such that the plurality of third fluid dividing channels and the plurality of fourth fluid dividing channels cooperate to form the plurality of second fluid dividing passages.
34. The method of any one of claims 26-29, wherein the plurality of fluid passages having a maximum cross-sectional dimension in a range from 10 pm to 12.7 cm.
35. The method of any one of claims 26-29, wherein flowing further comprises dividing the fluid among the plurality of outlet ports such that no outlet port receives more than ±40% of an average of the flow of fluid through all of the plurality of outlet ports.
36. The method of any one of claims 26-29, wherein flowing further comprises flowing a fluid having a viscosity in a range from 10'4 poise to 100 poise.
PCT/US2023/079768 2022-11-29 2023-11-15 Fluid-dividing lid having one port distributing fluid to a plurality of outlets WO2024118323A1 (en)

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