Articles and methods for fluid introduction into fluidic systems

Abstract

Syringes, fluidic assemblies, kits, and associated methods are generally provided. Some syringes that are described herein may comprise two plungers, each positioned in a separate barrel, that are mechanically coupled to a linear actuator by a connector. Such syringes may advantageously be particularly suitable for delivering fluids from each barrel simultaneously and / or in controllable relative amounts. Some fluidic assemblies and / or kits described herein may comprise a syringe and a fluidic element (e.g., a fluidic chip, a fluidic cartridge) that are configured to be mechanically coupled together, such as via a barrel of the syringe and a port on the fluidic element (e.g., a port on the fluidic chip, a port on the fluidic cartridge). Such fluidic assemblies and / or kits may beneficially allow for fluid to be supplied from the syringe barrel to the fluidic element (e.g., the fluidic chip, the fluidic cartridge) in a manner that reduces and / or eliminates the amount of fluid lost via spillage and / or due to back pressure. Some methods described herein may comprise employing a syringe, a fluidic assembly, and / or a kit described herein. This may be accomplished by delivering a mechanical signal to a connector mechanically coupled to a plunger positioned in a syringe barrel.

Description

[0001] ARTICLES AND METHODS FOR FLUID INTRODUCTION INTO FLUIDIC SYSTEMS

[0002] RELATED APPLICATIONS

[0003] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63 / 587,958, filed October 4, 2023, and entitled “Articles and Methods for Fluid Introduction into Fluidic Systems,” which is incorporated herein by reference in its entirety for all purposes.

[0004] FIELD

[0005] Syringes, kits, and associated methods are generally described.

[0006] BACKGROUND

[0007] Syringes may be employed to dispense fluids into fluidic chips. However, such syringes may be of limited use when precise delivery of multiple fluids is required.

[0008] Accordingly, new syringes, kits, and methods that address this concern would be beneficial.

[0009] SUMMARY

[0010] The present disclosure generally describes syringes, kits, and methods. The subject matter described herein involves, in some cases, interrelated products, alternative solutions to a particular problem, and / or a plurality of different uses of one or more systems and / or articles.

[0011] Paragraph 1: In some embodiments, a fluidic assembly is provided. The fluidic assembly comprises a syringe and a fluidic element. The syringe comprises a first barrel and a component configured to draw fluid into and / or expel fluid from the first barrel. The fluidic element comprises a first port. The first barrel and the first port are configured to be mechanically coupled.

[0012] Paragraph 2: In some embodiments, a kit is provided. The kit comprises a syringe and a fluidic element. The syringe comprises a first barrel and a component configured to draw fluid into and / or expel fluid from the first barrel. The fluidic element comprises a first port. The first barrel and the first port are configured to be mechanically coupled.

[0013] Paragraph 3: In some embodiments, a syringe is provided. The syringe comprises a first barrel, a first plunger positioned within the first barrel, a second barrel, a second plunger positioned within the second barrel, and a connector. The connector is configured to mechanically couple the first and second plungers to a linear actuator.

[0014] Paragraph 4: In some embodiments, a method of operating a syringe is provided. The method comprises delivering a mechanical signal to a connector. The connector is mechanically coupled to a first plunger and a second plunger. The first plunger is positioned within a first barrel. The first barrel comprises an end comprising a first opening. The second plunger is positioned within a second barrel. The second barrel comprises an end having a second opening. The mechanical signal causes the first and second plungers to raise. The raising of the first plunger causes a first fluid to flow through the first opening and into the first barrel. The raising of the second plunger causes a second fluid to flow through the second opening and into the second barrel.

[0015] Paragraph 5: In some embodiments, a method of operating a syringe comprises delivering a mechanical signal to a connector. The connector is mechanically coupled to a first plunger and a second plunger. The first barrel comprises an end comprising a first opening. The second plunger is positioned within a second barrel. The second barrel comprises an end having a second opening. The mechanical signal causes the first and second plungers to lower. The lowering of the first plunger causes a first fluid to flow through the first opening and out of the first barrel. The lowering of the second plunger causes a second fluid to flow through the second opening and out of the second barrel.

[0016] Paragraph 6: In some embodiments, a method of dispensing fluid from a syringe into a fluidic element is provided. The method comprises delivering a first fluid from a first barrel into a first port. The syringe comprises the first barrel. The fluidic element comprises the first port. While the first fluid is being delivered, the first barrel is mechanically coupled to the first port.

[0017] Paragraph 7: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the syringe further comprises a second barrel and a component configured to draw fluid into and / or expel fluid from the second barrel, the fluidic element comprises a second port, and the second barrel and the second port are configured to be mechanically coupled.

[0018] Paragraph 8: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, further comprising delivering a second fluid from a second barrel into a second port, wherein the syringe comprises the second barrel, wherein the fluidic element comprises the second port, and wherein, while the first and second fluids are being delivered, the first barrel is mechanically coupled to the first port and the second barrel is mechanically coupled to the second port.

[0019] Paragraph 9: In some embodiments a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the component configured to draw fluid into and / or expel fluid from the first barrel is a first plunger.

[0020] Paragraph 10: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the component configured to draw fluid into and / or expel fluid from the second barrel is a second plunger.

[0021] Paragraph 11: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the syringe further comprises a connector, and wherein the connector is configured to mechanically couple the first and second plungers to a linear actuator.

[0022] Paragraph 12: In some embodiments, a fluidic assembly comprising the syringe as in any preceding paragraph is provided.

[0023] Paragraph 13: In some embodiments, a kit comprising the syringe as in any preceding paragraph is provided.

[0024] Paragraph 14: In some embodiments, a fluidic assembly or a kit as in any preceding paragraph is provided, wherein the fluidic assembly or the kit comprises a fluidic element.

[0025] Paragraph 15: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element comprises a first port and a second port.

[0026] Paragraph 16: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element comprises a third port.

[0027] Paragraph 17: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first barrel and the first port are configured to be mechanically coupled, and the second barrel and the second port are configured to be mechanically coupled.

[0028] Paragraph 18: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, further comprising delivering a mechanical signal to the connector.

[0029] Paragraph 19: In some embodiments a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical signal causes the first and second plungers to raise. Paragraph 20: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical signal causes the first and second plungers to lower.

[0030] Paragraph 21: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first barrel comprises an end comprising an opening.

[0031] Paragraph 22: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first barrel and the second barrel each comprise an end comprising an opening.

[0032] Paragraph 23: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first barrel comprises an open end.

[0033] Paragraph 24: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first barrel and the second barrel each comprise an open end.

[0034] Paragraph 25: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, further comprising delivering a first fluid from the first barrel into a first port and a second fluid from the second barrel into the second port.

[0035] Paragraph 26: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the syringe comprises the first and second barrels.

[0036] Paragraph 27: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the syringe further comprises the first and second plungers and the connector.

[0037] Paragraph 28: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein a fluidic element comprises the first and second ports.

[0038] Paragraph 29: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein, while the first and second fluids are being delivered, the first barrel is mechanically coupled to the first port and the second barrel is mechanically coupled to the second port.

[0039] Paragraph 30: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the connector is mechanically coupled to the first and second plungers such that, upon receipt of a first mechanical signal from the linear actuator, it delivers a second mechanical signal to both the first and second plunger. Paragraph 31: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second mechanical signal is a linear displacement.

[0040] Paragraph 32: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the connector is mechanically coupled to the first and second plungers such that, upon receipt of a first mechanical signal from the linear actuator, it displaces the first and second plungers by the same amount.

[0041] Paragraph 33: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the connector is integrally connected to the first and second plungers.

[0042] Paragraph 34: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first and the second barrels have the same diameter.

[0043] Paragraph 35: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any one of paragraphs 1-33 is provided, wherein the first barrel has a different diameter than the second barrel.

[0044] Paragraph 36: In some embodiments a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first plunger is positioned within the first barrel such that it forms an air-tight seal with the first barrel.

[0045] Paragraph 37: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second plunger is positioned within the second barrel such that it forms an air-tight seal with the second barrel.

[0046] Paragraph 38: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first plunger is positioned within the first barrel such that it forms a fluid-tight seal with the first barrel.

[0047] Paragraph 39: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluid-tight seal is effectuated by an o- ring. Paragraph 40: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second plunger is positioned within the second barrel such that it forms a fluid-tight seal with the second barrel.

[0048] Paragraph 41: In some embodiments, a syringe, kit, or method as in any preceding paragraph is provided, wherein the fluid-tight seal is effectuated by an o-ring.

[0049] Paragraph 42: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein raising the first plunger causes the pressure in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger to decrease.

[0050] Paragraph 43: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein raising the first plunger causes fluid to flow through the first opening into a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger.

[0051] Paragraph 44: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein raising the second plunger causes the pressure in a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger to decrease.

[0052] Paragraph 45: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein raising the second plunger causes fluid to flow through the second opening into a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger.

[0053] Paragraph 46: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein lowering the first plunger applies a pressure to fluid positioned in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger.

[0054] Paragraph 47: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein lowering the first plunger causes fluid positioned in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger to flow through the first opening and out of the first barrel.

[0055] Paragraph 48: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein lowering the second plunger applies a pressure to fluid positioned in a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger.

[0056] Paragraph 49: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein lowering the second plunger causes fluid positioned in a volume internal to the second barrel and positioned between the open end of the second barrel and the second plunger to flow through the second opening and out of the second barrel.

[0057] Paragraph 50: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein receipt by the connector of a first mechanical signal from the linear actuator causes a first volume of fluid to flow through the first opening and out of the first barrel and a second volume of fluid to flow through the second opening and out of the second barrel.

[0058] Paragraph 51: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first volume is the same as the second volume.

[0059] Paragraph 52: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any one of paragraphs 1-50 is provided, wherein the first volume is different from the second volume.

[0060] Paragraph 53: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein receipt by the connector of a second mechanical signal from the linear actuator causes a third volume of fluid to flow through the open end of the first barrel and into the first barrel and a fourth volume of fluid to flow into through the open end of the second barrel and into the second barrel.

[0061] Paragraph 54, In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the third volume is the same as the fourth volume.

[0062] Paragraph 55: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any one of paragraphs 1-53 is provided, wherein the third volume is different from the fourth volume.

[0063] Paragraph 56: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first fluid is a liquid and / or comprises a liquid.

[0064] Paragraph 57: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first fluid is a gas and / or comprises a gas.

[0065] Paragraph 58: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second fluid is the same type of fluid as the first fluid.

[0066] Paragraph 59: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any one of paragraphs 1-57 is provided, wherein the second fluid is a different type of fluid than the first fluid. Paragraph 60: In some embodiments, a syringe, kit, or method as in any preceding paragraph is provided, wherein the syringe is mechanically coupled to a device comprising the linear actuator.

[0067] Paragraph 61: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the device is a pipette.

[0068] Paragraph 62: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the linear actuator is motor-driven, and / or piezo-driven, and / or pressure driven.

[0069] Paragraph 63: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the syringe is a pipette tip.

[0070] Paragraph 64: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first port is surrounded by an elastic material, and wherein the mechanical coupling between the first barrel and the first port comprises an elastic expansion of the elastic material around the first barrel.

[0071] Paragraph 65: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second port is surrounded by an elastic material, and wherein the mechanical coupling between the second barrel and the second port comprises an elastic expansion of the elastic material around the second barrel.

[0072] Paragraph 66: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is formed from the elastic material.

[0073] Paragraph 67: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the elastic material is and / or comprises PDMS.

[0074] Paragraph 68: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical coupling between the first barrel and the first port comprises a fluid-tight seal.

[0075] Paragraph 69: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical coupling between the second barrel and the second port comprises a fluid-tight seal.

[0076] Paragraph 70: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical coupling between the first barrel and the first port comprises an air-tight seal. Paragraph 71: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the mechanical coupling between the second barrel and the second port comprises an air-tight seal.

[0077] Paragraph 72: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the pipette tip further comprises a third barrel and a third plunger positioned within the third barrel.

[0078] Paragraph 73: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the connector is configured to mechanically couple the third plunger to the linear actuator.

[0079] Paragraph 74: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first fluid is different from the second fluid.

[0080] Paragraph 75: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first fluid comprises a lipid stock solution.

[0081] Paragraph 76: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second fluid comprises an aqueous nucleic acid solution.

[0082] Paragraph 77: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip, and further comprising forming lipid nanoparticles in the fluidic chip.

[0083] Paragraph 78: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the lipid nanoparticles comprise lipids originating from the first fluid.

[0084] Paragraph 79: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, further comprising simultaneously performing the method of any preceding claim with two or more syringes and two or more fluidic elements.

[0085] Paragraph 80: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip, and wherein the first port supplies fluid to a first channel positioned in the fluidic chip.

[0086] Paragraph 81: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the first channel forms a spiral. Paragraph 82: In some embodiments, a fluidic assembly, a kit, a syringe, or a method is provided, wherein the first channel is bounded by a plurality of walls, and wherein one or more of the walls in the plurality of walls comprises a plurality of topological features.

[0087] Paragraph 83: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip, and wherein the second port supplies fluid to a second channel positioned in the fluidic chip.

[0088] Paragraph 84: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second channel divides into two or more subchannels.

[0089] Paragraph 85: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the second channel and / or the subchannels therein intersects the first channel at a junction.

[0090] Paragraph 86: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein, downstream from the junction, fluid flowing into the junction from the first channel is sheathed by fluid flowing into the junction from the second channel and / or one or more of its subchannels.

[0091] Paragraph 87: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip, and wherein the fluidic chip further comprises a reservoir configured to receive fluid from the first channel.

[0092] Paragraph 88: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element further comprises a mixing element.

[0093] Paragraph 89: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip, and wherein the fluidic chip is a microfluidic chip.

[0094] Paragraph 90: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic chip.

[0095] Paragraph 91: In some embodiments, a fluidic assembly, a kit, a syringe, or a method as in any preceding paragraph is provided, wherein the fluidic element is a fluidic cartridge.

[0096] Paragraph 92: In some embodiments, a fluidic cartridge is provided. The fluidic cartridge comprises a first port configured to receive a first fluid, a channel configured to receive the first fluid from the first port, and a second port configured to receive the first fluid from the channel. The channel forms a spiral. Paragraph 93: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the fluidic cartridge comprises a third port configured to receive a second fluid, and wherein the channel is configured to receive the second fluid from the third port.

[0097] Paragraph 94: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the fluidic cartridge comprises a fourth port configured to receive fluid flowing out of the channel.

[0098] Paragraph 95: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the channel is configured to mix two fluids supplied thereto via two different ports.

[0099] Paragraph 96: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the channel is configured to perform inertial separation on a fluid flowing therethrough.

[0100] Paragraph 97: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the first port is configured to be mechanically coupled to a syringe barrel.

[0101] Paragraph 98: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the channel is bounded by a plurality of walls, and wherein one or more of the walls in the plurality of walls comprises a plurality of topological features.

[0102] Paragraph 99: In some embodiments, a fluidic assembly, a kit, a syringe, a fluidic cartridge, or a method as in any preceding paragraph is provided, wherein the topological features are protrusions.

[0103] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, then the document having the later effective date shall control.

[0104] BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

[0105] FIG. 1 shows an exemplary syringe, in accordance with some embodiments;

[0106] FIG. 2A shows an exemplary syringe, in accordance with some embodiments;

[0107] FIG. 2B shows an exemplary syringe comprising barrels having open ends, in accordance with some embodiments;

[0108] FIG. 2C shows an exemplary syringe comprising a connector that is configured to mechanically couple plungers to a linear actuator, in accordance with some embodiments;

[0109] FIGs. 3A-3B show two non-limiting embodiments of kits comprising a syringe and a fluidic chip, in accordance with some embodiments;

[0110] FIGs. 4A-4B show two non-limiting embodiments of kits comprising a syringe and a fluidic cartridge, in accordance with some embodiments;

[0111] FIG. 5 shows a non-limiting embodiment of a kit comprising a syringe and a fluidic chip, in accordance with some embodiments;

[0112] FIGs. 6 and 7 show two non-limiting embodiments of methods, in accordance with some embodiments;

[0113] FIG. 8 shows one non-limiting example of an exemplary fluidic cartridge, in accordance with some embodiments;

[0114] FIG. 9 depicts an exemplary syringe, in accordance with some embodiments;

[0115] FIGs. 10-13 depict exemplary kits comprising a syringe and a fluidic chip, in accordance with some embodiments;

[0116] FIG. 14 depicts an exemplary fluidic chip, in accordance with some embodiments;

[0117] FIG. 15 depicts an exemplary syringe, in accordance with some embodiments;

[0118] FIG. 16 depicts an exemplary syringe barrel mechanically coupled to an exemplary fluidic channel, in accordance with some embodiments;

[0119] FIG. 17 depicts the 3D printing of two exemplary fluidic cartridges, in accordance with some embodiments;

[0120] FIG. 18 depicts two exemplary, 3D-printed fluidic cartridges, in accordance with some embodiments; FIGs. 19 and 20 are mechanical drawings showing the internal channel structure of the two 3D-printed fluidic cartridges shown in FIG. 18, in accordance with some embodiments;

[0121] FIGs. 21 and 22 are mechanical drawings showing a spiral channel including protrusions, in accordance with some embodiments;

[0122] FIGs. 23 and 24 are mechanical drawings showing a straight channel including protrusions, in accordance with some embodiments;

[0123] FIG. 25 depicts an exemplary kit comprising a syringe and a fluidic cartridge and further depicts a pipettor, in accordance with some embodiments;

[0124] FIG. 26 depicts the pipettor, syringe, and fluidic cartridge shown in FIG. 25 after assembly, in accordance with some embodiments;

[0125] FIG. 27 is a chart showing the Z-average diameter and PDI of lipid nanoparticles, in accordance with some embodiments; and

[0126] FIG. 28 depicts a syringe and a fluidic cartridge, in accordance with some embodiments.

[0127] DETAILED DESCRIPTION

[0128] Syringes, fluidic assemblies, kits, and associated methods are generally provided.

[0129] Some syringes that are described herein may comprise two plungers, each positioned in a separate barrel, that are mechanically coupled to a linear actuator by a connector. Such syringes may advantageously be particularly suitable for delivering fluids from each barrel simultaneously and / or in controllable relative amounts.

[0130] Some fluidic assemblies and / or kits described herein may comprise a syringe and a fluidic element (e.g., a fluidic chip, a fluidic cartridge) that are configured to be mechanically coupled together, such as via a barrel of the syringe and a port on the fluidic element (e.g., a port on the fluidic chip, a port on the fluidic cartridge). Such fluidic assemblies and / or kits may beneficially allow for fluid to be supplied from the syringe barrel to the fluidic element (e.g., the fluidic chip, the fluidic cartridge) in a manner that reduces and / or eliminates the amount of fluid lost via spillage and / or due to back pressure.

[0131] Some methods described herein may comprise employing a syringe, a fluidic assembly, and / or a kit described herein. This may be accomplished by delivering a mechanical signal to a connector mechanically coupled to a plunger positioned in a syringe barrel. In some embodiments, a mechanical signal is delivered to a connector mechanically coupled to two plungers, each positioned in a separate syringe barrel. Some methods described herein may be particularly suitable for forming lipid nanoparticles. For instance, they may be reproducible, reliable, and / or eliminate the need for vortexing and pipetting up and down. Additionally, such methods may be relatively simple because they may be capable of being performed without the use of pumps and / or may be capable of being scaled up via connection to automated liquid handlers.

[0132] Some syringes, fluidic assemblies, kits, and methods described herein may provide for a facile way to screen reagents and / or conditions for forming lipid nanoparticles. In some embodiments, such syringes, fluidic assemblies, kits, and / or methods may be provided as disposables, which may reduce the potential for contamination, allow for end-users to employ with common lab practices, and / or allow for facile integration with liquid handlers for high- throughput screening. It is also possible for such syringes, fluidic assemblies, kits, and / or methods to allow for a reduction in capital expenses during early research and development.

[0133] In some embodiments, a syringe, fluidic assembly, kit, or method described herein is capable of performing and / or configured to perform one or more of the following functions: mixing two or more fluids, separating particles and / or cells, and / or generating droplets (e.g., droplets comprising spheroids and / or organoids, droplets present in an emulsion).

[0134] FIG. 1 shows an exemplary syringe. In FIG. 1, the syringe 100 comprises a first barrel 102 and a first plunger 104 positioned within the first barrel.

[0135] FIG. 2A shows another exemplary syringe. In FIG. 2A, the syringe 200 comprises a first barrel 202, a first plunger 204 positioned within the first barrel, a second barrel 206, a second plunger 208 positioned within the second barrel 206, and a connector 210. Syringes comprising two barrels, like that shown in FIG. 2A, may comprise two barrels that have the same diameter or may comprise two barrels having differing diameters.

[0136] As shown in FIGs. 1 and 2A, a barrel that is positioned within the syringe may be positioned such that a portion of the plunger is positioned within the barrel and a portion of the plunger is positioned external to the barrel. It is also possible for a plunger to be positioned entirely within a barrel (not shown). Similarly, a plunger that is positioned within a barrel may occupy the entirety of a length of the barrel (i.e., it may extend from one end of the barrel to an opposing end of the barrel; not shown) or it may occupy only a portion of the length of the barrel (e.g., as shown in FIGs. 1 and 2A). It is also possible for a plunger to be movable with respect to a barrel. In such instances, the amount of the plunger positioned within the barrel and / or the amount of the length of the barrel occupied by the plunger may be adjustable. As shown in FIGs. 1 and 2A, in some embodiments, a barrel positioned in a syringe comprises an end having an opening. The opening may place a volume internal to the barrel in fluidic communication with an environment external to the barrel. This may facilitate fluid flow into or out of the volume internal to the barrel (e.g., through the opening) and / or into or out of the environment external to the barrel, such as upon displacement of a plunger positioned therein. For instance, with respect to FIG. 2A, the first barrel 202 has an end 212 having an opening 214 and the second barrel 206 has an end 216 having an opening 218. In some embodiments, the opening occupies the entirety of the end of the barrel in which it is positioned. In other words, in some embodiments, a barrel has an open end. This is shown schematically in FIG. 2B, in which the barrels 202 and 206 of the syringe 200 have opens ends 220 and 222, respectively.

[0137] In some embodiments, a plunger is positioned within a barrel such that it forms an airtight seal and / or a fluid-tight seal with the barrel. This may be accomplished by use of a rubber and / or elastic sealing element, which may be stretched and / or slid into a groove positioned on the plunger (e.g., an o-ring). It is also possible for the plunger to comprise a tip that is formed from (and / or that consists of and / or consists essentially of) a rubber, an elastic polymer, and / or a non-elastic polymer. When the plunger forms an air-tight seal with the barrel, the volume internal to the barrel may be divided into a first volume positioned between the plunger and the end of the barrel having an opening and a second volume positioned on the opposing side of the plunger. References herein to volumes internal to a barrel should be understood to refer to the first volume or both the first and the second volumes together.

[0138] The presence of an air-tight and / or fluid tight seal between a plunger and a barrel may have a number of advantages. For instance, it may advantageously allow for the raising of the barrel to cause the pressure in the first volume internal to the barrel to decrease, causing a localized vacuum within the first volume internal to the barrel. This pressure reduction may facilitate fluid flow into this first volume (e.g., through an opening positioned in an end of the barrel and into this first volume and / or from an environment external to this first volume). Such seals may also allow for the lowering of the barrel to apply pressure to fluid positioned in this first volume, facilitating the above-described fluid flow out of this first volume (e.g., through an opening positioned in an end of the barrel and out of this first volume and / or to an environment external to this first volume). Such seals may also facilitate the retention of fluid in a first volume internal to the barrel by providing a pressure that counters the force of gravity on the fluid positioned in this first volume. Moreover, such seals may prevent contamination of any components of the syringe positioned in the second volume internal to the barrel by such fluid.

[0139] In some embodiments, a connector positioned within a syringe is configured to mechanically couple a plunger to a linear actuator and / or to mechanically couple two plungers to a linear actuator. In some instances, the connector may also mechanically couple two plungers to each other. With reference to FIG. 2C, the syringe 200 depicted therein comprises a connector 210 that is configured to mechanically couple the plungers 204 and 208 to a linear actuator 224. The mechanical coupling may take the form of integral connection (i.e., the connector may be integrally connected to the linear actuator and / or one or both of the plungers), fastening (i.e., the connector may be fastened to the linear actuator and / or one or both of the plungers), or any other suitable manner for mechanically coupling components together. In some embodiments, one or both plungers and / or the connector are rigid.

[0140] In some embodiments, the connector is mechanically coupled to a first plunger such that, upon receipt of a first mechanical signal from the linear actuator, it delivers a mechanical signal to the first plunger. In some such embodiments, the connector is mechanically coupled to the first and second plungers such that, upon receipt of a first mechanical signal from the linear actuator, it delivers a second mechanical signal to both the first and second plunger. This second signal may be a linear displacement. When two plungers are present, the linear displacement may be the same for both the first and second plunger. For instance, the first and second plungers may be displaced by the same amount upon receipt of a mechanical signal from a linear actuator.

[0141] It should also be noted that a syringe may comprise more than two barrels and may further comprise plungers positioned within some or all of such barrels in excess of two. In such instances, the numbers of barrels in excess of two and / or the plungers in excess of two may be understood to have some or all of the properties described herein with respect to the barrel and plunger shown in FIG. 1 and / or the two barrels and plungers shown in FIGs. 2A- 2C and described elsewhere herein (e.g., the presence of an open end, mechanical coupling to a linear actuator via a connector, mechanical coupling to other plungers via a connector, etc.).

[0142] In some embodiments, a syringe is provided with a kit and / or a fluidic assembly that further comprises a fluidic element, such as a fluidic chip and / or a fluidic cartridge. FIGs. 3A and 3B show exemplary kits comprising fluidic chips and FIGs. 4A and 4B show exemplary kits comprising fluidic cartridges. FIG. 3A shows one non-limiting embodiment of a kit 326. The kit 326 shown in FIG. 3 A comprises a syringe 300 and a fluidic chip 328. In some embodiments, a fluidic assembly is assembled from a kit, such as a kit having one or more of the features shown in FIG. 3A.

[0143] FIG. 3B shows another non-limiting embodiment of a kit 326. The kit 326 shown in FIG. 3B comprises a syringe 300 and a fluidic chip 328. In some embodiments, a fluidic assembly is assembled from a kit having one or more of the features shown in FIG. 3B.

[0144] FIG. 4A shows one non-limiting example of a kit 426. The kit 426 shown in FIG. 4A comprises a syringe 400 and a fluidic cartridge 434. In some embodiments, a fluidic assembly is assembled from a kit having one or more of the features shown in FIG. 4A.

[0145] FIG. 4B shows one non-limiting example of a kit 426. The kit 426 shown in FIG. 4B comprises a syringe 400 and a fluidic cartridge 434. In some embodiments, a fluidic assembly is assembled from a kit having one or more of the features shown in FIG. 4B.

[0146] In some embodiments, like the embodiments shown in FIGs. 3A and 3B and 4A and 4B, a syringe provided with a kit and / or a fluidic assembly may have a design having one or more of the features shown in FIGs. 1 and / or 2A-2C. It is also possible for a syringe to differ from such designs in one or more ways. In some embodiments, a syringe provided as part of a kit and / or a fluidic assembly comprises a first barrel and a second barrel and first and second components configured to draw fluids into the first and second barrels and / or expel fluids from the first and second barrels. The fluids may be configured to be drawn into and / or expelled from volumes internal to the first and second barrels (e.g., first such volumes and / or from an environment external thereto). The components configured to do the fluid drawing and / or expelling may be plungers (e.g., as described above with respect to FIGs. 1 and 2A-2C) or may have a different design.

[0147] A fluidic chip provided with a kit and / or a fluidic assembly may comprise a port, such as the port 330 in FIG. 3. It is also possible for such a fluidic chip to comprise first and second ports, such as the ports 330 and 332 shown in FIG. 3B. Similarly, a fluidic cartridge may comprise one or more ports, such as the port 436 in FIG. 4A and the ports 436 and 438 in FIG. 4B. Such ports may allow for the introduction of fluid into the fluidic chip and / or cartridge and / or for the removal of fluid from the fluidic chip and / or cartridge. In some embodiments, a port on a fluidic chip and / or cartridge provided as part of a kit and / or a fluidic assembly is configured to be mechanically coupled to a barrel of a syringe provided as part of the same kit and / or the same fluidic assembly. For instance, a first port on a fluidic chip and / or cartridge may be configured to be mechanically coupled to a first barrel of a syringe and a second port on the fluidic chip and / or cartridge may be configured to be mechanically coupled to a second barrel of a syringe. The mechanical coupling may comprise compression and / or sealing (e.g., the port may compress and / or seal around a barrel to which it is mechanically coupled). The sealing may be fluid- and / or air-tight. In some embodiments, a port is surrounded by an elastic material, and the mechanical coupling between a barrel and the port comprises an elastic expansion of the elastic material around the barrel. It is also possible for the mechanical coupling to take a different form (e.g., the mechanical coupling may comprise mating, fastening, and / or the interaction between components on the port and the syringe that serve to mechanically couple them to each other).

[0148] It should also be noted that although FIGs. 3 A and 4A show one port and FIGs. 3B and 4B shows two ports, it is also possible for a fluidic chip or a fluidic cartridge to comprise three or more ports. For instance, the two ports shown in FIG. 3B may be employed to supply fluid to the fluidic chip via the syringe (e.g., from volumes internal to first and second barrels positioned therein, such as first such volumes) and the fluidic chip may further comprise a third port through which fluid can be removed from the fluidic chip. As another example, the two ports shown in FIG. 3B may be employed to remove fluid from the fluidic chip via the syringe (e.g., to volumes internal to first and second barrels positioned therein, such as first such volumes) and the fluidic chip may further comprise a third port through which fluid can be supplied to the fluidic chip. It is also possible for a fluidic chip or a fluidic cartridge to have three or more ports through which fluid may be supplied thereto and / or three or more ports through which fluid may be removed therefrom. In some such embodiments, the kit and / or fluidic assembly also comprises a syringe comprising three barrels or more barrels, and each barrel is configured to be mechanically coupled to a port.

[0149] FIG. 5 shows one non-limiting embodiment of a kit comprising a fluidic chip having this design. The kit 526 shown in FIG. 5 comprises a syringe 500 and a fluidic chip 528. The syringe comprises three barrels, each having a plunger positioned therein. The fluidic chip 528 comprises three ports 530, 532, and 540. In some embodiments, a fluidic assembly is assembled from a kit having one or more of the features shown in FIG. 5.

[0150] As noted above, some embodiments relate to methods. Some methods may be related to operating syringes, such as flowing fluid into a syringe (e.g., into one or more barrels therein) and / or expelling fluid from a syringe (e.g., from one or more barrels therein). FIG. 6 shows one non-limiting example of a method. In FIG. 6, the method 642 comprises the step 644 of delivering a mechanical signal to a connector. This method may be employed to operate a syringe comprising the connector to which the mechanical signal is delivered. The syringe may have one or more of the features described elsewhere herein (e.g., it may comprise a plunger positioned in a barrel comprising an end comprising an opening, it may comprise two plungers, each positioned within a barrel comprising an end comprising an opening, and / or it may comprise a linear actuator, etc.). In some embodiments, a linear actuator is employed to deliver the mechanical signal to the connector.

[0151] Receipt of the mechanical signals described herein by a connector (e.g., from a linear actuator) may cause a displacement of one or more components of the syringe, such as one or more plungers therein, and / or may cause fluid to flow into and / or out of one or more barrels in the syringe (e.g., through one or more openings). In some embodiments, a mechanical signal causes one or more plungers positioned within one or more barrels to raise (e.g., first and second plungers positioned within first and second barrels to raise). It is also possible for the mechanical signal to cause one or more plungers positioned within one or more barrels to lower (e.g., first and second plungers positioned within first and second barrels to lower).

[0152] Raising a plunger may cause fluid to flow into a barrel in which the plunger is positioned (e.g., to a volume internal to the barrel, such as a first volume). For instance, raising first and second plungers may cause one or two types of fluids to flow through openings in first and second barrels in which the first and second plungers are positioned into the first and second barrels (e.g., the same fluid may flow into each barrel or different types of fluids may flow into the different barrels). Lowering a plunger may cause fluid to flow out of a barrel in which the plunger is positioned (e.g., from a volume internal to the barrel, such as a second volume). As another example, lowering first and second plungers may cause one or two types of fluids to flow through first and second openings in first and second barrels in which the first and second plungers are positioned out of the first and second barrels (e.g., the same fluid may flow out of each barrel or different types of fluids may flow out of the different barrels).

[0153] As noted above, in some embodiments, a method comprises delivering mechanical signals to two plungers positioned in two barrels via a common connector, causing fluid flow into each barrel (e.g., by flowing through an opening in an end of the barrel into a volume internal to the barrel, such as a first volume). In such embodiments, the volume of fluid flowed into each of the two barrels may be determined by the magnitude and / or rate of the mechanical signal (e.g., the rate at which the mechanical signal causes the plungers positioned in the barrels to raise or lower) and the area of the barrel cross-section perpendicular to the direction of the mechanical signal (e.g., the direction in which the plunger is moved). Accordingly, it may be possible for the volume of fluid that is flowed and rate of fluid flow into and / or out of a barrel to be controlled by controlling the magnitude and rate of the mechanical signal and the geometry of the barrel. Additionally, it is possible for the same or different volumes of fluid may be flowed into different barrels depending on mechanical signals received by the plungers and the geometries of the barrels in which they are positioned. In some embodiments, two plungers are subject to an equal amount of displacement upon receipt of a mechanical signal from the connector. In such instances, if the barrels in which they are positioned have the same diameter, the volumes of fluid flowed into each barrel may be the same. Similarly, in such instances, if the barrels in which they are positioned have different diameters, the volumes of fluid flowed into each barrel may be different.

[0154] As also noted above, in some embodiments, a method comprises delivering mechanical signals to two plungers positioned in two barrels via a common connector, causing fluid to flow out of each barrel (e.g., by flowing through an opening in an end of the barrel out of a volume internal to the barrel, such as a first volume). In such embodiments, the volume of fluid flowed out of each of the two barrels may be the same or different volumes of fluid may be flowed out of different barrels. In some embodiments, two plungers are subject to an equal amount of displacement upon receipt of a mechanical signal from the connector. In such instances, if the barrels in which they are positioned have the same diameter, the volumes of fluid flowed out of each barrel may be the same. Similarly, in such instances, if the barrels in which they are positioned have different diameters, the volumes of fluid transported out of each barrel may be different.

[0155] It is also possible for a method to comprise two or more steps in which a mechanical signal is delivered to a connector. For instance, a method may comprise delivering one mechanical signal that causes first and second plungers positioned within first and second barrels to raise and then delivering a second mechanical signal that causes these first and second plungers to lower. The first mechanical signal may be employed to cause fluid to flow into the first and second barrels (e.g., by flowing the fluid thereinto through first and second openings) and the second mechanical signal may be employed to dispense fluid from the first and second barrels (e.g., by flowing fluid out of the first and second barrels through the first and second openings). The fluid may flow into and / or out of volumes internal to the barrels (e.g., first such volumes) and / or may flow into and / or out of to an environment external to the barrels.

[0156] Some embodiments relate to methods of dispensing fluid from a syringe into a fluidic chip, such as the syringes and fluidic chips described elsewhere herein. One example of such a method is shown in FIG. 7. In FIG. 7, the method 746 comprises the step 748 of delivering a first fluid from a first barrel into a first port (e.g., from a volume positioned within the first barrel). It further comprises the optional step 750 of delivering a second fluid from a second barrel into a second port (e.g., from a volume positioned within the second barrel). The first and second barrels may be positioned in syringes, such as the syringes described elsewhere herein. The first and second ports may be positioned in fluidic elements, such as the fluidic chips and / or fluidic cartridges described elsewhere herein. In some embodiments, the delivery of the first and second fluids may be performed while the first barrel is mechanically coupled to the first port and the second barrel is mechanically coupled to the second port. As noted above, this may assist with reducing and / or eliminating spillage and / or fluid loss due to back pressure. In some embodiments, the delivery of the first and second fluids may be performed simultaneously (e.g., by lowering plungers in first and second barrels by delivering a mechanical signal to a connector connecting the first and second barrels).

[0157] In some embodiments, fluids may be dispensed from a syringe into a fluidic element (e.g., a fluidic chip, a fluidic cartridge) without the presence of an air gap. This may be beneficial when the fluids are to be mixed together in a precise manner on the fluidic chip.

[0158] In some embodiments, the methods shown in FIGs. 6 and 7 may be performed together. For instance, the delivery of the fluids shown in FIG. 7 may comprise delivering a mechanical signal to a connector that causes first and second plungers positioned in first and second barrels to lower. The flowing of the fluid(s) out of the first and second barrels effectuated by the mechanical signal may result in the delivery of the fluid(s) to the first and second ports.

[0159] The syringes and plungers described herein may be formed from a variety of suitable materials. In some embodiments, a plunger comprises one or more parts formed from a plastic. For instance, as described above, a plunger may comprise an end and / or a seal formed from an elastic polymer. It is also possible for a plunger to comprise an end and / or a stem that is formed from a non-elastic polymer, such as polyethylene and / or polypropylene.

[0160] Plungers may have a variety of suitable shapes. In some embodiments, a plunger has a conically shaped tip.

[0161] The syringes described herein may comprise barrels having aspiration volumes (i.e., volumes into which fluid can be drawn) of a variety of suitable sizes. In some embodiments, a syringe described herein comprises one or more barrels having an aspiration volume of between 1 mL and 5 mL. As noted above, some embodiments relate to linear actuators that are configured to be mechanically coupled to syringes and / or are mechanically coupled to syringes. Such linear actuators may be present in a syringe, present in a device comprising the syringe (e.g., a pipette system of which the syringe forms one or more tips), or external to the syringe and any device comprising the syringe. In some embodiments, a device comprising a linear actuator is also mechanically coupled to a syringe to which the linear actuator is mechanically coupled (e.g., separately from the coupling between the linear actuator and the syringe and / or a connector therein). As one example, the linear actuator may present in a pipette and the syringe may take the form of one or more pipette tips to which the pipette is coupled (e.g., separately from the linear actuator). For instance, each barrel and plunger present in a syringe may together form a positive-displacement pipette tip. In some embodiments, the linear actuator is a pipettor, such as a positive-displacement pipettor.

[0162] The coupling between a syringe and a device comprising a linear actuator may take a variety of forms. For instance, it may comprise compression and / or sealing (e.g., one or more portions of the syringe, such as one or more barrels therein, may compress and / or seal around a device comprising a linear actuator or may be compressed and / or sealed by a device comprising a linear actuator). The sealing may be fluid- and / or air-tight. It is also possible for the mechanical coupling to take a different form (e.g., the mechanical coupling may comprise mating, fastening, and / or the interaction between components on the device comprising the linear actuator and the syringe that serve to mechanically couple them to each other). In some embodiments, a linear actuator present in a pipette is mechanically coupled to plungers present in a syringe and the barrels of the syringe are also separately mechanically coupled to a different portion of the pipette (e.g., to a housing encasing the linear actuator).

[0163] A variety of suitable linear actuators may be employed. For instance, linear actuators may be motor-driven, piezo-driven, and / or pressure-driven.

[0164] The fluidic chips described herein may be formed from a variety of suitable materials. In some embodiments, a fluidic chip is formed from and / or comprises a polymer, such as an elastic material. When the fluidic chip is formed from an elastic material, it may facilitate coupling of syringe barrels to ports positioned therein via expansion of the elastic material around the barrel. One non-limiting example of a suitable elastic material is PDMS. It is also possible for a fluidic chip to be formed from and / or comprise a non-elastic polymer. In such instances, it is possible for the fluidic chip to further comprise one or more portions formed from an elastic material. Such portions may, for instance, surround one or more ports present in the fluidic chip.

[0165] The fluidic chips described herein may have a variety of suitable designs. In some embodiments, a fluidic chip comprises one or more channels. It is also possible for a fluidic chip to comprise one or more channels that further divide into two or more subchannels. Such channels and subchannels may be in fluidic communication with one or more ports, may be configured to receive fluid from one or more ports, and / or may be configured to supply fluid to one or more ports. Exemplary fluidic chips may further comprise one or more mixing elements and / or one or more reservoirs to receive fluid from one or more fluidic channels.

[0166] In some embodiments, a fluidic chip has a design particularly suitable for forming lipid nanoparticles. In such embodiments, the fluidic chip comprises first and second ports configured to receive first and second fluids from first and second syringe barrels and supply these fluids to first and second channels. In such embodiments, the second channel supplied by the syringe divides into two subchannels, which both intersect the first channel on opposite sides at a junction. This may cause fluid flowing downstream from the junction in the first channel to be sheathed by fluid supplied to the junction by the first and second subchannels of the second channel. In some such embodiments, the fluidic chip further comprises a fluidic reservoir downstream from the junction configured to receive this sheathed fluid.

[0167] In some embodiments, a fluidic chip described herein may have a design that allows it to be stored on a rack container (e.g., vertically). It is also possible for a fluidic chip and / or a plurality of fluidic chips to be supplied on a rack container.

[0168] In some embodiments, a fluidic chip described herein is a microfluidic chip. In some embodiments, a fluidic chip described herein is a mesoscale fluidic chip.

[0169] In some embodiments, a kit and / or a fluidic assembly comprises a fluidic cartridge, a syringe is configured to be mechanically coupled to a fluidic cartridge, and / or a method comprises operating a syringe that is mechanically coupled to a fluidic cartridge. It is also possible for a fluidic cartridge to be provided on its own and / or without a syringe.

[0170] In some embodiments, a fluidic cartridge comprises two ports and a channel. One of the ports may be configured to receive fluid. The channel may be configured to receive the fluid from that port, and the second port may be configured to receive the fluid from the channel. One non-limiting example of a fluid cartridge comprising such features is shown in FIG. 8. In FIG. 8, the fluidic cartridge 834 comprises a first port 836, a second port 838, and a channel 852 that is configured to receive a fluid from the first port 836. The channel 852 is also configured to supply the fluid to the second port 838. In some embodiments, a channel like the channel 852 shown in FIG. 8 places two ports in fluidic communication (e.g., a port from which it is configured to receive a fluid and a port configured to receive a fluid from it).

[0171] When present, the mechanical coupling between a port present in a fluidic cartridge and a syringe may comprise compression and / or sealing (e.g., the fluidic cartridge may compress and / or seal around a barrel present in the syringe to which it is mechanically coupled). The sealing may be fluid- and / or air-tight. In some embodiments, a fluidic cartridge comprises an elastic material, and the mechanical coupling between the syringe and the fluidic cartridge comprises an elastic expansion of the elastic material around a component of the syringe (e.g., around one or more barrels therein). It is also possible for the mechanical coupling to take a different form (e.g., the mechanical coupling may comprise mating, fastening, and / or the interaction between components on the fluidic cartridge and the syringe that serve to mechanically couple them to each other).

[0172] In some embodiments, and as described above, a fluidic cartridge comprises a port (e.g., exactly one port). The port may be configured to receive fluid from a barrel of a syringe and / or may be configured to be mechanically coupled to a barrel of a syringe. In some embodiments, a fluidic cartridge comprises two or more ports. Some such ports may each be configured to receive fluids from different barrels of a syringe and / or may be configured to be mechanically coupled to different barrels of a syringe. In some embodiments, two such ports may both be configured to supply a channel with a fluid received thereby (e.g., each of the two such ports may be configured to receive a different fluid and supply a different fluid to the channel). In such embodiments, both such ports may be in fluidic communication with the channel. Upon introduction of such fluids into the channel, they may undergo mixing.

[0173] As noted below, it is also possible for a fluidic cartridge to comprise one or more ports through which fluid may flow out of the fluidic cartridge (e.g., two or more such ports). Such port(s) may receive fluid from the channel (e.g., fluid that has undergone mixing in the channel, fluid that has undergone inertial separation in the channel). In embodiments in which a fluidic cartridge comprises two or more ports through which fluid may flow out of the fluidic cartridge, the two such ports may be configured to supply fluid flowing out of the fluidic cartridge to different locations (e.g., one such port may supply fluid flowing out of it to a container for further analysis and another such port may supply fluid flowing out of it to waste). Fluidic cartridges may be configured to mix the fluid received from the barrel(s) of the syringe and / or to perform inertial separation of particles present in one or more such fluids. This may be accomplished by the presence of a channel that is configured to receive fluid from one or more of the port(s). Fluid flowing through the channel may be mixed and / or may be subject to inertial separation as it flows therethrough.

[0174] Channels present in the fluidic cartridges described herein may have a variety of suitable designs, such as being straight and / or forming a spiral. In some embodiments, a channel forming a spiral (i.e., a spiral channel) can be particularly suitable for performing inertial separation of particles (e.g., cells) present in a fluid supplied thereto and / or flowing therethrough. In some embodiments, one port may supply a spiral channel with a sheath fluid and another port may supply the spiral channel with a fluid comprising particles to be separated. It is also possible for a spiral channel to be supplied by exactly one port.

[0175] Spiral channels described herein may have any suitable orientation with respect to gravity, the net direction of fluid flow through the fluidic channel, and / or the net direction of fluid flow through the fluidic cartridge. In some embodiments, a spiral channel comprises one or more portions in which fluid flows therethrough in a direction 180° opposite to the net direction of fluid flow through the fluidic cartridge and / or through the channel. In some embodiments, a spiral channel comprises one or more portions in which fluid flows therethrough in a direction that is the same as the net direction of fluid flow through the fluidic cartridge and / or through the channel. In some embodiments, a spiral channel comprises one or more portions in which fluid flows therethrough in a direction that is 180° opposite to the direction of gravity. In some embodiments, a spiral channel comprises one or more portions in which fluid flows therethrough in a direction that is the same as the direction of gravity.

[0176] Fluid flowing through a fluidic cartridge described herein may flow out of the fluidic cartridge through one or more ports (and / or a fluidic cartridge may be configured for such flow). In some embodiments, a fluidic cartridge is configured such that fluid is mixed by the fluidic cartridge and the mixed fluid flows out of the fluidic cartridge through exactly one port. In some embodiments, a fluidic cartridge is configured such that a fluid undergoes inertial separation in the fluidic cartridge and separated portions of the fluid flow out of the fluidic cartridge through two or more different ports (e.g., one portion comprising particles, such as cells, separated via inertial separation flows out through one port and one portion comprising waste flows out through another port). In some embodiments, a fluidic cartridge is configured to be positioned such that fluid flow therethrough occurs the same direction and / or has a component that is in the same direction as the direction that fluid flows out of the syringe thereinto. As one example, a fluidic cartridge may have a design such that it can receive fluid vertically from a syringe (e.g., in the direction of gravity) and then the fluid received vertically from the syringe will flow vertically therethrough (e.g., in the direction of gravity) and / or will flow therethrough in a direction that has a vertical component (e.g., that has a component that is in the direction of gravity).

[0177] In some embodiments, a method comprises flowing fluid into a syringe described herein (e.g., into a barrel positioned therein by raising a plunger positioned therein), subsequently mechanically coupling a fluidic cartridge to the syringe, and then flowing fluid out of the syringe and into and / or through the fluidic cartridge (e.g., out of one or more barrels positioned therein by lowering the plunger(s) positioned therein). The fluid flowing out of the fluidic cartridge may be dispensed into a container, such as a well in a multi-well plate.

[0178] The channels present in the fluidic chips and cartridges described herein may have a variety of suitable dimensions. In some embodiments, such channels may have a width and / or a height of several hundred microns (e.g., between 100 microns and 10 mm, between 100 microns and 1 mm). Such channels may have a cross-sectional shape (i.e., perpendicular to the direction of fluid flow therethrough) that is rectangular, square, or another suitable shape.

[0179] Channels present in the fluidic chips and cartridges described herein may, in some embodiments, be bounded partially or fully by a plurality of walls. Such walls may include one or more topological features therein. Such topological features may create obstacles for the flow of fluid through the channel, which may cause chaotic mixing of fluid flowing therethrough. In some embodiments, a channel wall comprises one or more topological features that extend into the channel, such as one or more pillars that extend into the channel, one or more baffles that into the channel, and / or one or more protrusions that extend into the channel. Pillars or baffles may extend through an entirety of a channel thickness (e.g., from one wall to an opposing wall) and / or may extend only partially through a channel thickness (e.g., from one wall into an interior of the channel in a manner such that the pillar or baffle does not reach an opposing wall). Such pillars and / or baffles may be formed from the same material as the other portions of the channel walls. Topological features, when present, may have a variety of suitable designs. In some embodiments, a channel wall comprises topological features that form a herringbone pattern (e.g., a channel may comprise herringbone- shaped protrusions, such as herringbone- shaped protrusions in which the orientation of the herringbone is parallel to the channel wall). It should be noted that channels of a variety of suitable shapes may comprise topological features (e.g., straight channels, spiral channels).

[0180] When topological features are present in a channel, they may be arranged in a variety of suitable manners. In some embodiments, the topological features in a channel are arranged such that they are spaced from each other at regular intervals (e.g., such that the standard deviation of the spacing between nearest-neighbor topological features is less than 10%, less than 5%, less than 2%, or less than 1% of the average such spacing and / or greater than or equal to 0% of the average such spacing).

[0181] The fluidic chips and cartridges described herein may be manufactured in a variety of suitable manners. In some embodiments, a fluidic chip and / or a fluidic cartridge is manufactured by printing (e.g., 3D printing). The printing may be performed in any suitable direction (e.g., bottom-to-top, while the cartridge is laid flat).

[0182] In some embodiments, a fluidic chip and / or a cartridge has a design and / or is mechanically coupled to a syringe such that it can receive fluid therefrom and / or pass fluid therethrough without undergoing appreciable leaking.

[0183] The syringes, methods, kits, and fluidic assemblies described herein may be employed in combination with a variety of fluids. In some embodiments, they are employed in combination with a fluid that is a liquid and / or comprises a liquid. It is also possible for them to be employed in combination with a fluid that is a gas and / or comprises a gas.

[0184] As noted above, some methods may comprise delivering fluids from barrels into ports in fluidic elements (such as fluidic chips and fluidic cartridges), such as by flowing fluids out of first and second barrels (and / or volumes internal thereto, such as first such volumes) into ports positioned in fluidic elements (such as fluidic chips and fluidic cartridges). In some embodiments, a combination of fluids is delivered from the barrels to the ports that is particularly suitable for forming lipid nanoparticles and / or a method described herein further comprises forming lipid nanoparticles in a fluidic chip. One non-limiting example of a suitable combination of fluids for forming lipid nanoparticles include a first fluid that comprises a lipid stock solution and a second fluid that comprises an aqueous nucleic acid solution. When such fluids are delivered into first and second ports, lipid nanoparticles may form that comprise a lipid originating from the first fluid and / or a nucleic acid cargo originating from the second fluid.

[0185] A variety of suitable lipid stock solutions may be employed, non-limiting examples of which include: (1) DOTAP, DSPC, cholesterol, and DMG-PEG2000; (2) SM-102, DSPC, cholesterol, DMG-PEG2000; and (3) ALC-0315, DSPC, cholesterol, and ALC-0159.

[0186] A variety of suitable aqueous nucleic acid solutions may be employed, such as aqueous buffers (e.g., citrate buffers).

[0187] In some embodiments, a method comprises performing multiplexing. For instance, two or more syringes described herein may be simultaneously employed to deliver fluids to two or more different fluidic elements (e.g., two or more different fluidic chips, two or more different fluidic cartridges). Multiplexing may also, additionally or alternatively, comprise the use of an automated liquid handler. Desirably, multiplexing may result in an advantageously high throughput.

[0188] Some methods described herein may be automated. For instance, actuating a linear actuator, flowing fluid into and / or out of barrels, and / or controlling fluid flow through a fluidic element (e.g., a microfluidic chip) may be automated.

[0189] Automation may comprise the use of software and / or may be capable of proceeding and / or configured to proceed without the input of an operator. In some embodiments, automation is performed with the assistance of a computer and / or processor.

[0190] In some embodiments, a method described herein is carried out with the assistance of a computer and / or a processor, such as via a computer implemented control system. Additionally, some systems and instruments described herein comprise a computer and / or a processor. Such methods, systems, and instruments are not limited in their implementation to any specific computer system described herein, as many other different machines may be used.

[0191] The computer implemented control systems described herein can be part of or coupled in operative association with a syringe, a fluidic chip, a kit, and / or a fluidic assembly, configured and / or programmed to control and adjust operational parameters of a syringe, a fluidic chip, a kit, and / or a fluidic assembly, and / or to analyze, calculate, and / or determine values. In some embodiments, such as when a defined value or threshold is reached, a computer implemented control system can send and receive reference signals to set and / or control operating parameters of an instrument and / or system. In some embodiments, a computer implemented control system can be separate from and / or remotely located with respect to a syringe, a fluidic chip, a kit, and / or a fluidic assembly and / or may be configured to receive data from one or more remote syringes, fluidic chips, kits, and / or fluidic assemblies via indirect and / or portable means, such as via portable electronic data storage devices, such as magnetic disks, or via communication over a computer network, such as the Internet or a local intranet.

[0192] A computer implemented control system may include components and circuitry, such as a processing unit (i.e., a processor), a memory system, input and output devices and interfaces (e.g., an interconnection mechanism), and / or other components, such as transport circuitry (e.g., one or more busses), a video and audio data input / output (I / O) subsystem, special-purpose hardware, and / or other components and circuitry, as described below in more detail. Further, a computer implemented control system may be a multi-processor computer system and / or may include multiple computers connected over a computer network.

[0193] A computer implemented control system may include a processor, for example, a commercially available processor such as one of the series x86, Celeron and Pentium processors, available from Intel, similar devices from AMD and Cyrix, the 680X0 series microprocessors available from Motorola, the PowerPC microprocessor from IBM, and ARM processors. Many other processors are available, and the computer system is not limited to a particular processor.

[0194] In some embodiments, a processor executes a program called an operating system, of which WindowsNT, Windows95 or 98, Windows 7, Windows 8, UNIX, Linux, DOS, VMS, MacOS and OSX, and iOS are examples, which may control the execution of other computer programs and / or may provide scheduling, debugging, input / output control, accounting, compilation, storage assignment, data management and / or memory management, communication control and / or other related services. The processor and operating system together may define a computer platform for which application programs in high-level programming languages are written. The computer implemented control system is not limited to a particular computer platform.

[0195] In some embodiments, a processor is in electronic communication, is capable of being in electronic communication, and / or is configured to be in electronic communication with one or more other components present in a system described herein. For instance, a processor may be in electronic communication with a detector.

[0196] In some embodiments, a processor is programmed to perform one or more methods described herein and / or one or more values are determined with the use of a processor.

[0197] A computer implemented control system may include a memory system, which may include a computer readable and writeable non-volatile recording medium, of which a magnetic disk, optical disk, a flash memory and tape are examples. Such a recording medium may be removable, for example, a floppy disk, read / write CD or memory stick, or may be permanent, for example, a hard drive.

[0198] Such a recording medium may store signals, typically in binary form (i.e., a form interpreted as a sequence of one and zeros). A disk may (e.g., magnetic or optical) have a number of tracks, on which such signals may be stored, typically in binary form, i.e., a form interpreted as a sequence of ones and zeros. Such signals may define a software program, e.g., an application program, to be executed by the microprocessor, or information to be processed by the application program.

[0199] The memory system of the computer implemented control system also may include an integrated circuit memory element, which typically is a volatile, random access memory such as a dynamic random access memory (DRAM) or static memory (SRAM). In operation, a processor may cause programs and data to be read from the non-volatile recording medium into the integrated circuit memory element, which may allow for faster access to the program instructions and data by the processor than the non-volatile recording medium does.

[0200] The processor may manipulate the data within the integrated circuit memory element in accordance with the program instructions. Then, it may copy the manipulated data to the non-volatile recording medium after processing is completed. The computer implemented control system is not limited to a particular memory system.

[0201] At least part of such a memory system described above may be used to store one or more data structures (e.g., look-up tables) or equations described above. For example, at least part of the non-volatile recording medium may store at least part of a database that includes one or more of such data structures. Such a database may be any of a variety of types of databases, for example, a file system including one or more flat-file data structures where data is organized into data units separated by delimiters, a relational database where data is organized into data units stored in tables, an object-oriented database where data is organized into data units stored as objects, another type of database, or any combination thereof.

[0202] The computer implemented control system may include a video and audio data VO subsystem. An audio portion of the subsystem may include an analog-to-digital (A / D) converter, which may receive analog audio information and convert it to digital information. The digital information may be compressed using known compression systems for storage on the hard disk to use at another time. A video portion of the VO subsystem may include a video image compressor / decompressor. Such compressor / decompressors may convert analog video information into compressed digital information, and / or vice-versa. The compressed digital information may be stored on hard disk for use at a later time.

[0203] The computer implemented control system may include one or more output devices. Example output devices include a cathode ray tube (CRT) display, liquid crystal displays (LCD) and other video output devices, printers, communication devices such as a modem or network interface, storage devices such as disk or tape, and audio output devices such as a speaker. Such output devices may comprise an output interface which may output information to an operator, an instrument, a component of a system, and / or a component of a different system capable of receiving and / or configured to receive such information. In some embodiments, the information may take the form of a signal, such as an electronic signal encoding such information, a visual signal informing an operator of such information, and / or an electronic signal encoding instructions.

[0204] In some embodiments, an output interface comprises a display interface. The display interface may display information to an operator. In some embodiments, displaying information comprises providing a numerical indication of the information on the display interface. For instance, a display interface may indicate a concentration of an analyte in a fluid by providing a numerical indication thereof on the display interface. The display interface may, additionally or alternatively, display other information, such as the status of a kit and / or a fluidic assembly and / or one or more of the components of a kit and / or a fluidic assembly (e.g., a syringe, a fluidic chip) and / or signals. Such display interfaces may display information that is contemporaneously obtained.

[0205] The computer implemented control system also may include one or more input devices.

[0206] Example input devices include a keyboard, keypad, track ball, mouse, pen and tablet, communication devices such as described above, and data input devices such as audio and video capture devices and sensors. Such input devices may comprise an input interface which may receive information from an operator, a kit, a component of a kit, a fluidic assembly, a component of a fluidic assembly, and / or a component of a different system capable of providing and / or configured to provide such information. In some embodiments, the information may take the form of a signal. The information may be received over a network or may be directly input into the input interface (e.g., mechanically).

[0207] It should be appreciated that one or more of any type of computer implemented control system may be used to implement various embodiments described herein. Aspects of the invention may be implemented in software, hardware or firmware, or any combination thereof. The computer implemented control system may include specially programmed, special purpose hardware, for example, an application- specific integrated circuit (ASIC). Such special-purpose hardware may be configured to implement one or more of the methods, steps, simulations, algorithms, systems, and system elements described above as part of the computer implemented control system described above or as an independent component.

[0208] The computer implemented control system and components thereof may be programmable using any of a variety of one or more suitable computer programming languages. Such languages may include procedural programming languages, for example, C, Pascal, Fortran and BASIC, object-oriented languages, for example, C++, Java and Eiffel and other languages, such as a scripting language or even assembly language.

[0209] The methods, steps, simulations, algorithms, systems, and system elements may be implemented using any of a variety of suitable programming languages, including procedural programming languages, object-oriented programming languages, other languages and combinations thereof, which may be executed by such a computer system. Such methods, steps, simulations, algorithms, systems, and system elements can be implemented as separate modules of a computer program, or can be implemented individually as separate computer programs. Such modules and programs can be executed on separate computers.

[0210] Such methods, steps, simulations, algorithms, systems, and system elements, either individually or in combination, may be implemented as a computer program product tangibly embodied as computer-readable signals on a computer-readable storage medium, for example, a non-volatile recording medium, an integrated circuit memory element, or a combination thereof. For each such method, step, simulation, algorithm, system, or system element, such a computer program product may comprise computer-readable signals tangibly embodied on the computer-readable storage medium that define instructions (e.g., encoded therein), for example, as part of one or more programs, that, as a result of being executed by a computer, instruct the computer to perform the method, step, simulation, algorithm, system, or system element.

[0211] EXAMPLE 1

[0212] This Example includes photographs of a variety of syringes, fluidic chips, and the use thereof for mixing fluids.

[0213] FIG. 9 depicts an exemplary syringe mechanically coupled to a pipette. FIGs. 10-13 depict exemplary syringes mechanically coupled to exemplary fluidic chips. FIG. 13 depicts the dispensing of fluid from two barrels of an exemplary syringe into the fluidic chip. FIG. 12 also shows a plunger with a conically shaped tip.

[0214] FIG. 14 depicts the mixing of fluids dispensed from an exemplary syringe on an exemplary fluidic chip.

[0215] FIG. 15 depicts an exemplary syringe.

[0216] FIG. 16 depicts an exemplary syringe barrel mechanically coupled to an exemplary fluidic channel.

[0217] EXAMPLE 2

[0218] This Example includes photographs of a variety of syringes, fluidic cartridges, and the use thereof for mixing fluids.

[0219] FIG. 17 depicts the 3D printing of two exemplary fluidic cartridges, each including rectangular channels having a width of 520 microns and a height of 120 microns.

[0220] FIG. 18 depicts two exemplary, 3D-printed fluidic cartridges.

[0221] FIGs. 19 and 20 are mechanical drawings showing the internal channel structure of the two 3D-printed fluidic cartridges shown in FIG. 18. As can be seen in FIG. 19, the fluidic cartridge shown in FIG. 19 includes a spiral channel, and the spiral channel is oriented such that it comprises some portions in which fluid flows therethrough in a direction that is 180° opposite to the net direction of fluid flow through the fluidic cartridge and comprises some portions in which fluid flows therethrough in a direction that is parallel to the net direction of fluid flow through the fluidic cartridge.

[0222] FIGs. 21 and 22 are mechanical drawings showing two views of the internal channel structure of a spiral channel including protrusions that extend through the entirety of the channel thickness. As can be seen from FIG. 22, the protrusions extend between opposing channel walls.

[0223] FIGs. 23 and 24 are mechanical drawings showing two views of the internal channel structure of a straight channel including protrusions that extend through the entirety of the channel thickness. As can be seen from FIG. 24, the protrusions extend between opposing channel walls.

[0224] FIG. 25 depicts an exemplary kit comprising a syringe (labeled therein as a “Dualchannel syringe”) and a fluidic cartridge (labeled therein as a “Microfluidic Mixer”). FIG. 25 also depicts a pipettor with which the components of the kit can be employed.

[0225] FIG. 26 depicts the pipettor, syringe, and fluidic cartridge shown in FIG. 25 after assembly. EXAMPLE 3

[0226] This Example describes the use of a kit described herein to form lipid nanoparticles.

[0227] The kit comprised a syringe and a fluidic cartridge. The syringe comprised two barrels, together having an aspiration volume of 2.5 mF. The syringe further comprised two plungers, each positioned within a barrel. The fluidic cartridge comprised two ports and a spiral channel. The fluidic cartridge was assembled with the syringe so that each port was supplied with fluid by a different barrel from the syringe. The two ports both supplied the fluids supplied thereto to the spiral channel, which mixed these fluids as they flowed through the spiral channel.

[0228] One of the barrels of the syringe was filled with a lipid stock solution comprising DOTAP (dioleoyl- 3 -trimethylammonium propane), DSPC (distearoylphosphatidylcholine), cholesterol, and DMG-PEG2000 (myristoyl diglyceride chemically bonded to polyethylene glycol having a molecular weight of 2000 kg / mol). These components were present at a molar ratio of DGTAP:DSPC:cholesterol:DMG-PEG2000 of 40: 10:48:2. The other barrel of the syringe was filed with a 10 mM citrate buffer having a pH of 4.

[0229] The plungers positioned in the two barrels were lowered, causing the lipid stock solution and the citrate buffer to flow out of the barrels, into and through the first and second ports, and into and through the fluidic cartridge. The mixed lipid stock solution and citrate buffer were flowed out of the fluidic cartridge and into wells in a 48-well plate. The lowering of the barrels was performed at five different rates, each causing a different total flow rate of fluid out of both barrels of the syringe: 14 mL / min, 24 mL / min, 32 mL / min, 46 mL / min, and 58 mL / min.

[0230] Each of the wells was then analyzed to determine the Z-average diameter and the polydispersity index of the nanoparticles generated. As shown in FIG. 27, these nanoparticles had low Z-average diameters and were relatively monodisperse.

[0231] EXAMPLE 4

[0232] This Example describes a kit comprising a syringe and a fluidic cartridge.

[0233] The syringe and fluidic cartridge are shown in FIG. 28 (the latter labeled as an “Inertial Microfluidic Cartridge”). The syringe and fluidic cartridge depicted in FIG. 28 may be employed to perform inertial cell separation by performing the procedure that follows. First, the syringe may be attached to a positive-displacement pipettor, which may be employed to flow a fluid comprising cells (e.g., a sample, as shown in FIG. 28) into the syringe barrel (e.g., from a well in a multi- well plate). Then, the fluidic cartridge may be attached to the barrel. Next, the positive-displacement pipettor may be employed to flow the fluid comprising the cells out of the barrel and through the inertial microfluidic cartridge. During this process, the fluidic cartridge may be positioned such that the cells flow out of Outlet 1 and into a container (e.g., a well in a multi-well plate) and waste flows out of Outlet 2 and into a waste receptacle (e.g., a different well in the same multi-well plate).

[0234] While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present invention is / are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present invention.

[0235] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0236] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0237] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0238] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc. It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0239] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

CLAIMSWhat is claimed is:

1. A fluidic assembly, comprising: a syringe; and a fluidic element, wherein: the syringe comprises a first barrel and a component configured to draw fluid into and / or expel fluid from the first barrel, the fluidic element comprises a first port, and the first barrel and the first port are configured to be mechanically coupled.

2. A kit, comprising: a syringe; and a fluidic element, wherein: the syringe comprises a first barrel and a component configured to draw fluid into and / or expel fluid from the first barrel, the fluidic element comprises a first port, and the first barrel and the first port are configured to be mechanically coupled.

3. A syringe, comprising: a first barrel; a first plunger positioned within the first barrel; a second barrel; a second plunger positioned within the second barrel; and a connector, wherein the connector is configured to mechanically couple the first and second plungers to a linear actuator.

4. A method of operating a syringe, comprising: delivering a mechanical signal to a connector, wherein: the connector is mechanically coupled to a first plunger and a second plunger, the first plunger is positioned within a first barrel, the first barrel comprises an end comprising a first opening, the second plunger is positioned within a second barrel,the second barrel comprises an end having a second opening, the mechanical signal causes the first and second plungers to raise, the raising of the first plunger causes a first fluid to flow through the first opening and into the first barrel, and the raising of the second plunger causes a second fluid to flow through the second opening and into the second barrel.

5. A method of operating a syringe, comprising: delivering a mechanical signal to a connector, wherein: the connector is mechanically coupled to a first plunger and a second plunger, the first barrel comprises an end comprising a first opening, the second plunger is positioned within a second barrel, the second barrel comprises an end having a second opening, the mechanical signal causes the first and second plungers to lower, the lowering of the first plunger causes a first fluid to flow through the first opening and out of the first barrel, and the lowering of the second plunger causes a second fluid to flow through the second opening and out of the second barrel.

6. A method of dispensing fluid from a syringe into a fluidic element, comprising: delivering a first fluid from a first barrel into a first port, wherein: the syringe comprises the first barrel, the fluidic element comprises the first port, and while the first and fluid is being delivered, the first barrel is mechanically coupled to the first port.

7. The fluidic assembly of claim 1 or the kit of claim 2, wherein the syringe further comprises a second barrel and a component configured to draw fluid into and / or expel fluid from the second barrel, the fluidic element comprises a second port, and the second barrel and the second port are configured to be mechanically coupled.

8. The method of claim 6, further comprising delivering a second fluid from a second barrel into a second port, wherein the syringe comprises the second barrel, wherein the fluidic element comprises the second port, and wherein, while the first and second fluids are beingdelivered, the first barrel is mechanically coupled to the first port and the second barrel is mechanically coupled to the second port.

9. The fluidic assembly of claim 1 or the kit of claim 2, wherein the component configured to draw fluid into and / or expel fluid from the first barrel is a first plunger.

10. The fluidic assembly or the kit of claim 7, wherein the component configured to draw fluid into and / or expel fluid from the second barrel is a second plunger.

11. The fluidic assembly or the kit of claim 7, wherein the syringe further comprises a connector, and wherein the connector is configured to mechanically couple the first and second plungers to a linear actuator.

12. A fluidic assembly comprising the syringe of claim 3.

13. A kit comprising the syringe of claim 3.

14. The fluidic assembly of claim 12 or the kit of claim 13, wherein the fluidic assembly or the kit comprises a fluidic element.

15. The fluidic assembly or the kit of claim 14, wherein the fluidic element comprises a first port and a second port.

16. The fluidic assembly or the kit of claim 7, wherein the fluidic element comprises a third port.

17. The fluidic assembly or the kit of claim 7, wherein the first barrel and the first port and configured to be mechanically coupled, and the second barrel and the second port are configured to be mechanically coupled.

18. The method of claim 8, further comprising delivering a mechanical signal to a connector that is mechanically coupled to the first and second plungers.

19. The method of claim 18, wherein the mechanical signal causes the first and second plungers to raise.

20. The method of claim 18, wherein the mechanical signal causes the first and second plungers to lower.

21. The fluidic assembly of claim 1, the kit of claim 2, the syringe of claim 3, or the method of claim 6, wherein the first barrel comprises an end comprising an opening.

22. The syringe of claim 3, the method of claim 8, the fluidic assembly of claim 12, or the kit of claim 13, wherein the first barrel and the second barrel each comprise an end comprising an opening.

23. The fluidic assembly of claim 1, the kit of claim 2, the syringe of claim 3, or the method of any one of claims 4-6, wherein the first barrel comprises an open end.

24. The syringe of claim 3, or the method of any one of claims 4, 5, or 8, wherein the first barrel and the second barrel each comprise an open end.

25. The method of claim 4 or claim 5, further comprising delivering a first fluid from the first barrel into a first port and a second fluid from the second barrel into a second port.

26. The method of claim 4 or claim 5, wherein the syringe comprises the first and second barrels.

27. The method of claim 4 or claim 5, wherein the syringe further comprises the first and second plungers and the connector.

28. The method of claim 25, wherein a fluidic element comprises the first and second ports.

29. The method of claim 25, wherein, while the first and second fluids are being delivered, the first barrel is mechanically coupled to the first port and the second barrel is mechanically coupled to the second port.

30. The syringe of claim 3, the fluidic assembly of claim 12, or the kit of claim 13, wherein the connector is mechanically coupled to the first and second plungers such that, upon receipt of a first mechanical signal from the linear actuator, it delivers a second mechanical signal to both the first and second plunger.

31. The syringe or the kit of claim 30, wherein the second mechanical signal is a linear displacement.

32. The syringe of claim 3, the fluidic assembly of claim 12, or the kit of claim 13, wherein the connector is mechanically coupled to the first and second plungers such that, upon receipt of a first mechanical signal from the linear actuator, it displaces the first and second plungers by the same amount.

33. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein the connector is integrally connected to the first and second plungers.

34. The syringe of claim 3, the method of any one of claims 4, 5, and 8, the fluidic assembly of claim 12, or the kit of claim 13, wherein the first and the second barrels have the same diameter.

35. The syringe of claim 3, the method of any one of claims 4, 5, and 8, the fluidic assembly of claim 12, or the kit of claim 13, wherein the first barrel has a different diameter than the second barrel.

36. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein the first plunger is positioned within the first barrel such that it forms an air-tight seal with the first barrel.

37. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein the second plunger is positioned within the second barrel such that it forms an air-tight seal with the second barrel.

38. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein the first plunger is positioned within the first barrel such that it forms a fluid-tight seal with the first barrel.

39. The syringe, the method, the fluidic assembly, or the kit of claim 38, wherein the fluid-tight seal is effectuated by an o-ring.

40. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein the second plunger is positioned within the second barrel such that it forms a fluid-tight seal with the second barrel.

41. The syringe, the method, the fluidic assembly, or the kit of claim 34, wherein the fluid-tight seal is effectuated by an o-ring.

42. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein raising the first plunger causes the pressure in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger to decrease.

43. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein raising the first plunger causes fluid to flow through the first opening into a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger.

44. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein raising the second plunger causes the pressure in a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger to decrease.

45. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein raising the second plunger causes fluid to flow through the second opening into a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger.

46. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein lowering the first plunger applies a pressure to fluid positioned in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger.

47. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein lowering the first plunger causes fluid positioned in a volume internal to the first barrel and positioned between the end of the first barrel comprising the first opening and the first plunger to flow through the first opening and out of the first barrel.

48. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein lowering the second plunger applies a pressure to fluid positioned in a volume internal to the second barrel and positioned between the end of the second barrel comprising the second opening and the second plunger.

49. The syringe of claim 3, the method of claim 4 or claim 5, the fluidic assembly of claim 12, or the kit of claim 13, wherein lowering the second plunger causes fluid positioned in a volume internal to the second barrel and positioned between the open end of the second barrel and the second plunger to flow through the second opening and out of the second barrel.

50. The syringe of claim 3, the fluidic assembly of claim 12, or the kit of claim 13, wherein receipt by the connector of a first mechanical signal from the linear actuator causes a first volume of fluid to flow through the first opening and out of the first barrel and a second volume of fluid to flow through the second opening and out of the second barrel.

51. The syringe, the fluidic assembly, or the kit of claim 50, wherein the first volume is the same as the second volume.

52. The syringe, the fluidic assembly, or the kit of claim 50, wherein the first volume is different from the second volume.

53. The syringe of claim 3, the fluidic assembly of claim 12, or the kit of claim 13, wherein receipt by the connector of a second mechanical signal from the linear actuator causes a third volume of fluid to flow through the open end of the first barrel and into the first barrel and a fourth volume of fluid to flow into through the open end of the second barrel and into the second barrel.

54. The syringe, the fluidic assembly, or the kit of claim 53, wherein the third volume is the same as the fourth volume.

55. The syringe, the fluidic assembly, or the kit of claim 53, wherein the third volume is different from the fourth volume.

56. The fluidic assembly of claim 1, the kit of claim 2 or the method of any one of claims 4-6 and 8, wherein the first fluid is a liquid and / or comprises a liquid.

57. The fluidic assembly of claim 1, the kit of claim 2 or method of any one of claims 4-6 and 8, wherein the first fluid is a gas and / or comprises a gas.

58. The method of any one of claims 4, 5, and 8, the fluidic assembly of claim 12, or the kit of claim 13, wherein the second fluid is the same type of fluid as the first fluid.

59. The method of any one of claims 4, 5, and 8, the fluidic assembly of claim 12, or the kit of claim 13, wherein the second fluid is a different type of fluid than the first fluid.

60. The syringe of claim 3, the fluidic assembly of claim 12, or the kit claim 13, wherein the syringe is mechanically coupled to a device comprising the linear actuator.

61. The syringe, the fluidic assembly, or the kit of claim 60, wherein the device is a pipette.

62. The syringe of claim 3, the fluidic assembly of claim 12, or the kit of claim 13, wherein the linear actuator is motor-driven, and / or piezo-driven, and / or pressure driven.

63. The fluidic assembly of claim 1 or claim 12, the kit of claim 2 or claim 13, the syringe of claim 3, or the method of any one of claims 4-6 and 8, wherein the syringe is a pipette tip.

64. The fluidic assembly of claim 1, the kit of claim 2, or the method of claim 6 or claim 8, wherein the first port is surrounded by an elastic material, and wherein the mechanical coupling between the first barrel and the first port comprises an elastic expansion of the elastic material around the first barrel.

65. The fluidic assembly, the kit, or the method of claim 64, wherein the second port is surrounded by an elastic material, and wherein the mechanical coupling between the second barrel and the second port comprises an elastic expansion of the elastic material around the second barrel.

66. The fluidic assembly, the kit, or the method of claim 64, wherein the fluidic element is formed from the elastic material.

67. The fluidic assembly, the kit, or the method of claim 64, wherein the elastic material is and / or comprises PDMS.

68. The fluidic assembly of claim 1, the kit of claim 2 or the method of claim 6 or claim 8, wherein the mechanical coupling between the first barrel and the first port comprises a fluid-tight seal.

69. The fluidic assembly or the kit of claim 7, wherein the mechanical coupling between the second barrel and the second port comprises a fluid-tight seal.

70. The fluidic assembly of claim 1, the kit of claim 2 or the method of claim 6, wherein the mechanical coupling between the first barrel and the first port comprises an air-tight seal.

71. The fluidic assembly or the kit of claim 7, wherein the mechanical coupling between the second barrel and the second port comprises an air-tight seal.

72. The fluidic assembly, the kit, the syringe, or the method of claim 63, wherein the pipette tip further comprises a third barrel and a third plunger positioned within the third barrel.

73. The fluidic assembly, the kit, the syringe, or the method of claim 72, wherein the connector is configured to mechanically couple the third plunger to the linear actuator.

74. The method of any one of claims 4, 5, and 8, wherein the first fluid is different from the second fluid.

75. The method of any one of claims 4, 5, 6, and 8, wherein the first fluid comprises a lipid stock solution.

76. The method of any one of claims 4, 5, and 8, wherein the second fluid comprises an aqueous nucleic acid solution.

77. The method of claim 6 or claim 8, wherein the fluidic element is a fluidic chip, and further comprising forming lipid nanoparticles in the fluidic chip.

78. The method of claim 77, wherein the lipid nanoparticles comprise lipids originating from the first fluid.

79. The method of any one of claims 4-6 and 8, further comprising simultaneously performing the method of any preceding claim with two or more syringes and two or more fluidic elements.

80. The fluidic assembly of claim 1, the kit of claim 2, or the method of claim 6 or claim 8, wherein the fluidic element is a fluidic chip, and wherein the first port supplies fluid to a first channel positioned in the fluidic chip.

81. The fluidic assembly, the kit, or the method of claim 80, wherein the first channel forms a spiral.

82. The fluidic assembly, the kit, or the method of claim 80, wherein the first channel is bounded by a plurality of walls, and wherein one or more of the walls in the plurality of walls comprises a plurality of topological features.

83. The fluidic assembly, the kit, or the method of claim 82, wherein the topological features are protrusions.

84. The fluidic assembly, the kit, or the method of claim 80, wherein the second port supplies fluid to a second channel positioned in the fluidic chip.

85. The fluidic assembly, the kit, or the method of claim 84, wherein the second channel divides into two or more subchannels.

86. The fluidic assembly, the kit, or the method of claim 85, wherein the second channel and / or the subchannels therein intersects the first channel at a junction.

87. The fluidic assembly, the kit, or the method of claim 86, wherein, downstream from the junction, fluid flowing into the junction from the first channel is sheathed by fluid flowing into the junction from the second channel and / or one or more of its subchannels.

88. The fluidic assembly, the kit, or the method of claim 80, wherein the fluidic chip further comprises a reservoir configured to receive fluid from the first channel.

89. The fluidic assembly of claim 1, the kit of claim 2, or the method of claim 6 or claim 8, wherein the fluidic element further comprises a mixing element.

90. The fluidic assembly of claim 1, the kit of claim 2, or the method of claim 6 or claim 8, wherein the fluidic element is a fluidic chip.

91. The fluidic assembly of claim 1, the kit of claim 2, or the method of claim 6 or claim 8, wherein the fluidic element is a fluidic cartridge.

92. A fluidic cartridge, comprising: a first port configured to receive a first fluid; anda channel configured to receive the first fluid from the first port, wherein the channel forms a spiral; and a second port configured to receive the first fluid from the channel.

93. The fluidic cartridge of claim 92, wherein the fluidic cartridge comprises a third port configured to receive a second fluid, and wherein the channel is configured to receive the second fluid from the third port.

94. The fluidic cartridge of claim 92 or claim 93, wherein the fluidic cartridge comprises a fourth port configured to receive fluid flowing out of the channel.

95. The fluidic cartridge of claim 92 or claim 93, wherein the channel is configured to mix two fluids supplied thereto via two different ports.

96. The fluidic cartridge of claim 91 or claim 92, wherein the channel is configured to perform inertial separation on a fluid flowing therethrough.

97. The fluidic cartridge of claim 92, wherein the first port is configured to be mechanically coupled to a syringe barrel.

98. The fluidic cartridge of claim 92, wherein the channel is bounded by a plurality of walls, and wherein one or more of the walls in the plurality of walls comprises a plurality of topological features.

99. The fluidic cartridge of claim 98, wherein the topological features are protrusions.

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