Reagent kits for in vitro devices

Abstract

Methods and apparatuses for transferring fluid from a cartridge (310) into a microfluidic device (320) and loading fluid into the cartridge (310). The cartridge (310) can include a cartridge body and a pipette array having pipette tips (315) to engage with inlets or other cartridges of the microfluidic device, where the pipette tips (315) correspond in position to a plurality of inlets (325) of the microfluidic device (320). Fluid can be loaded into or transferred from the microfluidic device (320) by a plunger system (615). The cartridge can alternatively include a blister (925) having fluid reservoirs and dispensing tips (930), each dispensing tip (930) including a path (927) fluidically coupled to the blister (925). Fluid can be transferred from or loaded into the blister (925) by the dispensing tips (930). A deformable seal (910) can be overlaid on the blister (925) to seal a volume of fluid within the blister (925) and can be deformed to transfer the fluid.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 879,990, filed July 29, 2019, entitled “Reagent Cartridges For In-VitroDevices,” which is jointly assigned and incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] This relates to devices and methods for introducing fluids into an external device, and more specifically to reagent kits for storing and transferring fluids. Background Technology

[0004] With the advancement of diagnostic and DNA sequencing technologies, the miniaturization of in vitro devices has been on the rise, enabling assays and reactions to be performed within small microfluidic devices. These miniaturized in vitro devices are particularly useful in reducing reagent costs and space requirements. They can also be used to automate biochemical analyses that would otherwise be labor-intensive and time-consuming. Microfluidic cartridges are particularly popular in diagnostics and DNA sequencing, where MEMS and lab-on-a-chip devices enable the precise performance and analysis of a large number of biochemical assays on a single cartridge. Microfluidic technology deals with the behavior, precise control, and manipulation of fluids that may be geometrically confined to a very small (typically sub-millimeter) scale, with capillary permeation controlling mass transfer at this scale.

[0005] Polymerase chain reaction (PCR) is a widely used method in molecular biology for amplifying target DNA fragments or creating numerous copies of those fragments. Using PCR, copies of a DNA sequence are amplified exponentially to generate millions of copies of that specific DNA fragment. Techniques like PCR can be useful for applications such as DNA sequencing, diagnostics, or gene editing. PCR may require a variety of different reagents to successfully amplify the target DNA fragment.

[0006] DNA sequencing is the process of determining the sequence of nucleic acids, or the nucleotide sequence in DNA. It includes any method or technique used to determine the sequence of the following four base nucleotides: adenine, guanine, cytosine, and thymine. Knowledge of DNA sequences has become essential for basic biological research and many applied fields, such as medical diagnostics, biotechnology, forensic biology, virology, and biosystematics. Comparing healthy and mutated DNA sequences can diagnose various diseases (including various cancers), characterize antibody libraries, and guide patient treatment. Rapid DNA sequencing methods enable faster and more personalized medical care and allow for the identification and classification of a wider range of organisms. Summary of the Invention

[0007] In this patent, we describe apparatus, systems, and methods for efficiently introducing fluids, such as reagents, into a microfluidic device (e.g., a microfluidic cartridge or any other suitable device in which one or more reactions or assays can be performed) using a kit. The kit may be a separate cartridge from the microfluidic device, which can be used to store or transfer fluids from one location to another. In this patent, we also describe apparatus, systems, and methods for loading fluids into the kit.

[0008] Miniaturization of in vitro devices (e.g., diagnostic devices, DNA sequencing devices, DNA library preparation devices) that integrate biochemical assays into one or more microfluidic devices (e.g., microfluidic cartridges) presents challenges that may not exist for more routine assays. For example, many miniaturized in vitro devices may require immediate or sequential on-demand reagent release based on specific analytical requirements, and may also require reliable storage of reagents in various volumes. We have found that in many cases, it is advantageous for manufacturers to provide solutions to end users with pre-filled reagents, eliminating the need for individual reagent measurements and direct loading into the microfluidic device, especially in cases involving large quantities of reagents that may require precise measurement. However, for many applications, small in vitro devices (e.g., microfluidic cartridges) may be incompatible with reagent storage conditions (e.g., -20°C or -80°C) or packaging processes (e.g., degassing or heat fusion). We have developed kits that can be stored separately from the microfluidic cartridge. When the end user requires reagents, the kit can be coupled to an in vitro diagnostic device (e.g., a microfluidic cartridge) for on-demand reagent delivery.

[0009] Compared to more conventional solutions, the embodiments disclosed herein offer numerous advantages. For example, the kit can be based on a universal plug interface designed to engage with a socket design (e.g., the inlet of a dispensing pipette tip receiving the kit) on an in vitro device (e.g., a microfluidic cartridge) to deliver all or many different reagents using one or more mechanical drives. Such an interface provides convenience and reduces the time and effort required to introduce reagents into the in vitro device. This reduces the need for trained operators, thereby further reducing costs. Relatedly, the predetermined volume provided by the kit also reduces the risk of error. As another example, the kit can provide the flexibility to store several reagents (e.g., up to 30 reagents) in a single cartridge. Thus, these kits can be shipped as “reaction kits” that include all the reagents required for, for example, a specific type of reaction such as PCR, making them convenient and easy to use. The embodiments disclosed herein can also provide other advantages that will become apparent from the following description. As another example, a universal plug-based interface may be able to accommodate different reagent volume configurations (e.g., by adjusting the size of the kit's pipettes or reservoirs), thus providing flexibility for performing different assays on the same microfluidic device. As another example, multiple reagents can be easily and quickly filled into the kit during manufacturing in a one-step sealing process. As another example, the configurations disclosed herein can be adapted to enable the use of low-cost injection-molded parts in the manufacture of the kits. This makes it feasible to use these kits as disposable consumables, which not only increases convenience but also reduces the risk of contamination. As yet another example, in direct contrast to other solutions such as pipettes, manufacturers can fill at least some of the reagents in the kits described herein under highly controlled conditions and ship them with the kits, thus eliminating the need for calibration.

[0010] In some implementations, the kit may include a kit body; a pipette array including a plurality of pipette tips configured to engage a plurality of inlets of a microfluidic cartridge (or other microfluidic device), wherein the positions of the pipette tips correspond to the plurality of inlets of the microfluidic cartridge.

[0011] In some embodiments, the kit may include a pipette array comprising a plurality of pipette tips. The kit may further include a plunger body comprising a plurality of plungers, each plunger configured to engage fluid within a corresponding pipette tip and to displace or load a volume of fluid into or from the corresponding pipette tip. The plungers may be sized to fit within the corresponding pipette tip. The plungers may include an elastomeric coating. Each plunger may be configured to form a seal with its corresponding pipette tip. The plunger body may also include a connector body configured to couple the plurality of plungers, wherein the plunger body may be configured to be secured to the pipette array. Each pipette tip may have a first opening and a second opening, and wherein each pipette tip is configured to contain a volume of fluid that can be transferred from or loaded into the pipette tip through the second opening. The plunger may engage fluid via the first opening.

[0012] In some embodiments, the pipette array may be disposed within a pipette housing. In some embodiments, the pipette housing may include one or more protrusions and / or recesses configured to retain features for aligning plungers with their respective pipette tips. In some embodiments, the pipette housing may include one or more recesses, and the plunger body includes one or more protrusions, wherein the recesses are configured to receive the protrusions.

[0013] In some embodiments, the kit may further include a sealing plate configured to seal one or more second openings of the pipette tip to seal a corresponding fluid within the pipette tip. In some embodiments, the sealing plate may be configured to be attached to a pipette housing. In some embodiments, one or more fluids (e.g., using a sealing plate) may be stored in a sealed container within one or more pipette tips. The sealing plate may include a flexible sealing material attached to a cap base. The cap base may be configured to be removably attached to the pipette housing such that the flexible sealing material is pressed against a distal portion of the pipette tip. For example, the flexible sealing material may be pressed against one or more second openings of the pipette tip, or may include a hole pressed against an outer wall of the pipette tip. The flexible sealing material may include an elastomer. The cap base may include a thermoplastic material.

[0014] In some embodiments, pipette tips may be configured to be positioned above a microfluidic cartridge (or other suitable microfluidic device). Each pipette tip may be configured to engage an inlet opening of the microfluidic cartridge, which is fluidly coupled to a corresponding reservoir of the microfluidic cartridge. In some embodiments, the positioning kit may include aligning a first pipette tip of a plurality of pipette tips with a first inlet opening of the microfluidic cartridge, such that the first inlet opening is configured to receive a first fluid from the first pipette tip. In some embodiments, a first plunger associated with the first pipette tip may be actuated to transfer a first volume of the first fluid from the first pipette tip to a first reservoir via the first inlet opening of the microfluidic cartridge. In some embodiments, the positioning kit may include aligning a first pipette tip with the first inlet opening and further aligning a second pipette tip with a second inlet opening. The first plunger may be actuated to transfer a first volume of the first fluid from a second pipette tip to a second reservoir of the microfluidic device via the second inlet opening. A second plunger can be actuated to transfer a second volume of second fluid from the second pipette tip into the second reservoir of the microfluidic cartridge via a second inlet opening. The first and second plungers can be actuated simultaneously or sequentially. In some embodiments, the first volume may be different from the second volume. In other embodiments, the first volume may be the same as the second volume. In some embodiments, positioning the pipette tip may include lowering the pipette tip into a corresponding inlet, wherein the corresponding inlet may be located on the cap of the microfluidic device.

[0015] In some embodiments, the first plunger may be coupled to a first position lock configured to move the first plunger a user-defined distance and prevent actuation of the first plunger beyond the user-defined distance. In some embodiments, the first plunger may be configured to be actuated by a loading platform configured to move the first plunger a user-defined distance. In some embodiments, each plunger is operable to be actuated individually. In some embodiments, two or more plungers are operable to be actuated concurrently.

[0016] In some embodiments, reagents may be loaded onto a kit. In some embodiments, the kit may be located on a well plate including a first well. Positioning the kit may include immersing a first pipette tip of the kit into a first fluid contained in the first well. A first plunger associated with the first pipette tip may be actuated to transfer a first volume of first fluid from the first well into the first pipette tip. Positioning the kit on the well plate may include aligning the first pipette tip to receive the first fluid from the first well and aligning a second pipette tip to receive the second fluid from a second well of the well plate. A first and second plunger associated with a second pipette tip may be actuated to transfer a second volume of second fluid from the second well into the second pipette tip. In some embodiments, actuating the first plunger may include manually moving the plunger, wherein the pipette tip may include one or more markings indicating fluid volumes to determine the desired volume to be transferred. The first plungers in the second plunger may be actuated simultaneously or sequentially. In some embodiments, the first volume may be different from the second volume. In some embodiments, the first volume may be the same as the second volume. In some implementations, one or more seals (e.g., sealing plates) may be attached to the kit, wherein the seals are configured to seal one or more second openings of one or more pipette tips after one or more desired volumes of fluid have been transferred to each of one or more pipette tips.

[0017] In some implementations, the kit may include a filler fluid reservoir and a filler fluid dispensing tip, wherein the filler fluid reservoir is configured to receive filler fluid and deliver the filler fluid to the filler fluid dispensing tip, and wherein the filler fluid dispensing tip is configured to align with a corresponding filler fluid inlet of the microfluidic device. A user may introduce filler fluid into the filler fluid reservoir, and the filler fluid may be delivered to the corresponding filler fluid inlet by gravity.

[0018] In some embodiments, the kit may include a substrate comprising one or more blister packs, each blister pack including a reservoir configured to contain a volume of fluid. In some embodiments, the blister pack may include the inner surface of a hollow cavity in the substrate. The kit may further include one or more dispensing tips, each dispensing tip including a path for fluid coupling to the blister pack. In some embodiments, fluid may be transferable from the blister pack via the dispensing tip. In some embodiments, fluid may be introduced into the blister pack via the dispensing tip (or via any other suitable entry point, such as a dedicated port). In some embodiments, the kit may further include one or more deformable seals covering the fluid reservoir, wherein the one or more deformable seals can seal the volume of fluid within the one or more blister packs.

[0019] In some embodiments, one or more deformable seals may include a thermoplastic film (e.g., a thermoplastic elastomer film). In some embodiments, the substrate may include a plurality of blister packs organized in the form of a blister array, and wherein one or more deformable seals include a single deformable film covering the blister array. In some embodiments, the plurality of blister packs may include a first blister pack having a first fluid reservoir and a second blister pack having a second fluid reservoir.

[0020] In some embodiments, the kit may further include a base configured to engage one or more openings of one or more dispensing tips and form a seal. In some embodiments, the base may include one or more recesses configured to receive at least a portion of a dispensing tip. In some embodiments, the base may also include one or more sealing pads disposed within one or more recesses, wherein each sealing pad is configured to engage and seal the opening of a corresponding dispensing tip. In some embodiments, one or more deformable seals may include a thermoplastic film. In some embodiments, one or more deformable seals may include a thermoplastic elastomer film. In some embodiments, one or more deformable seals may include a coating configured to reduce gas permeability. In some embodiments, one or more deformable seals may be attached to a substrate by laser welding or thermal lamination. In some embodiments, one or more deformable seals may be attached to a substrate using a pressure-sensitive adhesive.

[0021] In some embodiments, the first blister may be configured to receive a first plunger end and may also be configured to transfer a first volume of fluid from the first blister via a first dispensing tip upon receiving the first plunger end. In some embodiments, the first dispensing tip may be configured to be disposed within the inlet opening of the microfluidic cartridge. In some embodiments, the first plunger end may conform to the shape and size of the fluid reservoir of the first blister. In some embodiments, the substrate may include a plurality of blister packs, wherein the plurality of blister packs may include a first blister pack having a first fluid reservoir and a second blister pack having a second fluid reservoir, and wherein the first plunger end may conform to the shape and size of the fluid reservoir of the first blister, and the second plunger end may conform to the shape and size of the reservoir of the second blister.

[0022] In some embodiments, the kit can be used to introduce fluid into a microfluidic device (e.g., a microfluidic cartridge) by moving a first deformable seal of the kit, wherein the kit includes: a substrate comprising: one or more blister packs, each blister pack including a reservoir configured to contain a volume of fluid; and one or more dispensing tips, each dispensing tip including a channel fluidly coupled to the blister packs, wherein fluid can be transferred from or loaded into the blister packs via the dispensing tip; and one or more deformable seals fixed to the substrate and covering the one or more blister packs for sealing a volume of fluid in the one or more blister packs. In some embodiments, moving the first deformable seal can cause a first volume of first fluid to be transferred from a first blister pack in the one or more blister packs via the first dispensing tip.

[0023] In some embodiments, the integrated cartridge may include: a blister array comprising multiple fluid reservoirs and dispensing tips configured to connect to multiple reagent inlets of the microfluidic cartridge; and one or more deformable seals covering the reservoirs. Deformation of the one or more deformable seals near one of the fluid reservoirs may dispense fluid from one of the dispensing tips associated with the fluid reservoir.

[0024] In some implementations, the first blister pack of the kit may be configured to receive a first volume of fluid from the dispensing needle via an opening in the first dispensing tip.

[0025] This invention summary is provided to illustrate different embodiments of the present disclosure in a simplified form, which will be described in detail below. This invention summary is not intended to limit the scope of the claimed subject matter. Other features, details, utility, and advantages of the claimed subject matter will become apparent from the following detailed description. Attached Figure Description

[0026] Figure 1 An example of a pipette array for the kit is shown.

[0027] Figure 2A It shows Figure 1 A pipette array, which is part of an integrated kit.

[0028] Figure 2B-2C An exemplary pipette tip sealing mechanism is described.

[0029] Figure 3 An example of an integrated kit attached to a microfluidic cartridge is shown.

[0030] Figure 4 Another example of an integrated kit is shown.

[0031] Figure 5A close-up view of an example pipette that engages with the inlet of a microfluidic cartridge is shown.

[0032] Figures 6A-6B An example of using a kit to transfer fluid volume into a microfluidic cartridge is shown.

[0033] Figures 7A-7B An example is given of filling a reagent kit with a certain volume of fluid.

[0034] Figures 8A-8B An example of using a loading platform to help transfer fluid volumes from or load them into the kit is shown.

[0035] Figures 9A-9B An example of an integrated kit with a blister array for convenient fluid transfer is shown.

[0036] Figures 10A-10B An example illustrating the transfer of fluid from a bubble is given.

[0037] Figure 10C An example of a blister array positioned above a microfluidic cell is shown.

[0038] Figure 11 An example of loading fluid into multiple blister packs is shown.

[0039] Figure 12A-12B Other examples of blister packs are shown.

[0040] Figures 13A-13B An example of a kit 1300 having a reservoir 1310 for filler fluid is shown.

[0041] Figure 14 An exemplary method for transferring reagents to a microfluidic device (e.g., a microfluidic cartridge) is shown.

[0042] Figure 15 An exemplary method for loading reagents onto a kit is shown.

[0043] Figure 16 An exemplary method for transferring reagents to a microfluidic cartridge is shown. Detailed Implementation

[0044] It should be understood that, for the sake of simplicity and clarity, the elements shown in the figures are not necessarily drawn to scale. For example, for clarity, the dimensions of some elements are enlarged relative to each other. Furthermore, where deemed appropriate, reference numerals are repeated between figures to indicate corresponding elements.

[0045] In the following detailed description, reference is made to the accompanying drawings, which form a part of the invention, and specific embodiments in which the invention may be implemented are illustrated by way of illustration. The terms “height,” “top,” “bottom,” etc., are used with reference to the orientation in the described drawings. Because components of embodiments of the invention can be positioned in many different orientations, these terms are used for illustrative purposes and not for limitation.

[0046] The term "reagent" refers to a substance used to induce or otherwise promote a reaction. In some embodiments, exemplary reagents may include reagents that can be used to perform PCR (polymerase chain reaction) on a microfluidic cartridge. For example, such reagents may include any combination of buffer solutions, PCR primers, DNA samples, enzymes (e.g., polymerase), oils, and / or solutions containing magnetically responsive beads (e.g., for transporting DNA samples).

[0047] Figure 1 An example of a pipette array for a kit is shown. In some embodiments, the kit may include a pipette array having multiple pipette tips. For example, see reference... Figure 1 The kit may include multiple pipette tips 110 arranged in several rows. The pipette tips may be arranged in a pipette array to correspond in position to, for example, Figure 3 The illustrated microfluidic device (e.g., a microfluidic cartridge) has multiple inlets. In some embodiments, pipette tips may include lumens configured to contain fluids such as reagents. In some embodiments, multiple pipette tips may be configured to engage multiple inlets of the microfluidic cartridge. For example, the tips may be configured to extend into the walls of the inlets. In some embodiments, the pipette array may be part of a pipette housing, which may be a shell configured to integrate with other elements to form an integrated kit. For example, see reference... Figure 1 The pipette tip 110 is part of the pipette housing 100. The pipette housing 100 may have one or more retaining features to integrate and retain other components. In some embodiments, these retaining features may be configured to guide other components relative to the pipette housing 100 and align them in their proper positions. For example, as... Figure 1 As shown, the pipette housing 100 may include recesses 120 and 130, which may be configured to receive one or more protrusions or ridges from other elements, thereby retaining the other elements. Similarly, as... Figure 1 As shown, the pipette housing 100 may include an auxiliary protrusion 131 associated with the recess 130, which can be used to provide additional support when holding the element. In some embodiments, the auxiliary protrusion may extend to provide an increased level of support. As another example, the pipette housing 100 may include one or more protrusions or ridges in the recess for fitting into other elements. In some embodiments, such as Figure 1As shown, the pipette housing may include a protrusion 137 that can be fitted into a groove in which an element is held.

[0048] Figure 2A It shows Figure 1 A pipette array, which is part of an integrated kit. In some implementations, reference... Figure 2A The integrated kit may include a plunger body comprising a plurality of plungers 225. In some embodiments, the plunger body may further include a connector body 220 configured to couple the plurality of plungers 225. Each plunger may be coupled to a pipette for transferring fluid from or introducing fluid into a corresponding pipette tip. Reference Figure 2A As an example, each plunger 225 may include a plunger tip 225a and an actuating end (hidden in) that can be engaged (e.g., pushed and / or pulled) to actuate the plunger 225. Figure 2A (Within the connector body 220). For example, the plunger head 225a may be configured to enter the pipette tip 210 via a first opening 210a and engage the fluid therein. Pushing the actuating end causes the fluid to be transferred through a second opening 210b of the pipette tip 210. As another example, the actuating end may be pulled while the second opening 210b is immersed in the fluid, thereby drawing fluid into the pipette tip 210. In some embodiments, the plunger head 225a may include a widened portion (e.g., an element having a larger surface area than the plunger body) to ensure a tight seal between the plunger and the inner wall of the pipette tip. In some embodiments, multiple plungers may be coupled to a single actuating element, which may be an actuation point that allows multiple plungers to be simultaneously actuated by a single push or pull at the actuating end. For example, two plungers in two different pipette tips can be coupled to a single actuation element that can be pushed (or pulled) to transfer fluid from both pipette tips simultaneously (or load fluid into both pipette tips).

[0049] Any suitable method can be used to push or pull the plunger to transfer a desired volume of fluid from or load a desired volume of fluid into the kit. In some embodiments, the plunger length can range from tens of centimeters. The plunger diameter can range from 1 mm to several millimeters. The dimensions of the pipette tip's lumen can correspond to the plunger's dimensions. The volume of fluid transferred from (or loaded into) the pipette tip can be calculated based on the corresponding plunger movement distance. In some embodiments, a loading platform with a stepper motor having a resolution of, for example, 0.025 mm / step can be used to move the plunger. In this example, the fluid transfer (or loading) increment can be as small as 0.02 μL. Therefore, by moving the plunger a few centimeters, tens of microliters of fluid can be delivered. In some embodiments, the plunger can be manually actuated by the user. For example, the plunger can be coupled to a position lock configured to move the plunger a user-defined distance and prevent the actuation of the first plunger from exceeding the user-defined distance. In this example, the user can specify that the plunger should move a distance of 0.025 mm (or that the plunger should transfer a volume of 0.02 μL of fluid). The user can then actuate the plunger by pushing (or pulling) until it hits the position locking element, resulting in the transfer (or introduction) of 0.02 μL of fluid. In some embodiments, the pipette tip may have markings indicating the fluid volume, allowing the user to manually actuate the plunger to transfer (or load) the desired volume. In some embodiments, the volume within each pipette tip can be pre-measured to include the desired volume, allowing the user to simply push the plunger down to empty the entire contents of the pipette tip. This can be particularly convenient for the user. In some embodiments, different pipette tips may have different internal volumes, resulting in different maximum capacities. For example, the first set of pipettes in a pipette array may have a volume of 10 μL, while the second set may have a volume of 20 μL. In some embodiments, the sizes of different sets of pipettes can be set to accommodate different volumes of reagent as needed. For example, the size of the first set of pipettes can be determined for the first reagent, while the size of the second set of pipettes can be determined for the second reagent.

[0050] In some embodiments, the plunger tip 225a of the plunger may be sized and shaped such that it fits within the cavity of the corresponding pipette tip. In some embodiments, the plunger tip 225a may abut against the inner wall of the corresponding pipette tip to form a seal. The plunger may include a material configured to improve the seal between the plunger and the inner wall of the pipette tip to prevent fluid leakage through the fluid connection end (and) 225a. For example, the plunger may include a stainless steel material having an overmolded elastomeric coating or layer (e.g., TPU) that presses against the inner wall of the pipette tip for a better seal. In some embodiments, the connector body 220 may include a thermoplastic with a low shrinkage rate, such as ABS or PC.

[0051] In some implementations, the kit can be configured to hold the plunger body aligned with the pipette array. For example, as... Figure 2A As shown, the connector body 220 of the plunger body may include one or more protrusions 222 on opposite ends, which can be fitted into corresponding recesses in the pipette housing 240 (e.g., see reference). Figure 1 (Recesses 120 on opposite sides of the pipette housing 100). In this example, the assembler can insert the protrusion 222 into the recess 120 at the top of the pipette housing 100 and slide the connector body 220 downwards into place. Figure 2A In the example shown, the advantage of having this groove protrusion mechanism is that it serves not only to hold the plunger body but also as a guide mechanism for aligning the plunger body. In some embodiments, multiple such connector bodies can be attached to the pipette housing. For example, see reference... Figure 1 The pipette housing 100 includes three sets of recesses 120 that can accommodate up to three individual connector bodies. In some embodiments, the manufacturer or user may choose not to attach the maximum number of connector bodies to the pipette housing. For example, as... Figure 2A As shown, even though the pipette housing 240 may include recesses for three connector bodies 220, the manufacturer may choose to insert only two connector bodies 220 into the pipette housing 240.

[0052] In some implementations, the pipette tips of the integrated kit may be pre-loaded by the manufacturer or other suitable entity and sealed before being sent to the user. This reduces the risk of user error, which could result from filling the pipettes with the necessary fluids. This can be particularly advantageous for situations requiring pipette arrays with multiple different fluids. For example, performing a series of PCR reactions on a microfluidic cartridge may require pipette arrays with multiple different reagents. Manually loading each pipette in the required order increases the likelihood of user error (e.g., loading the wrong reagent into the pipette, loading the wrong volume of reagent). Furthermore, pre-loaded kits significantly improve convenience by eliminating the loading step. In some implementations, the kit may be pre-loaded and sealed by the user at different times for later use. This can be advantageous in some cases because it allows the user to perform many reaction sequences using the kit without having to spend time and effort loading reagents into pipettes for one or more reactions.

[0053] In some embodiments, the sealing mechanism for sealing the fluid inside the pipette tip is a sealing plate configured to seal one or more second openings of the pipette tip. For example, see reference... Figure 2A The reagent storage box 200 includes a sealing plate 230. The sealing plate 230 can be configured to be fixed to the pipette housing 240. For example... Figure 2A In the example shown, the sealing plate includes a flexible sealing material 235 secured to the cap base 232. In this example, the sealing plate includes a retaining feature 237 configured to removably secure the sealing plate 230 to the pipette housing 240. More specifically, in this particular example, the retaining feature 237 can be snapped into a corresponding feature of the pipette housing 240 (e.g., see reference 235). Figure 1 (Recess 130 on the opposite side of the pipette housing 100). In some embodiments, the sealing plate may also include a recess 236. Figure 1 The protrusion 136 of the pipette housing shown fits into the recess 236 to secure the sealing plate. The sealing plate 230 can be configured such that, when secured as the pipette housing 240, it pushes the flexible sealing material 235 against the second opening 210b of the pipette tip, thereby sealing any fluid present inside the pipette tip 210. In some embodiments, the flexible sealing material 235 may comprise an elastomer (e.g., silicone, polyurethane). In some embodiments, the cap base 232 may comprise one or more thermoplastics, such as ABS, PMMA, or PC. In some embodiments, the flexible sealing material 235 may be secured to the cap base by overmolding or by using a double-sided pressure-sensitive adhesive layer.

[0054] Figure 2B-2C A close-up of an exemplary pipette tip sealing mechanism is shown. Figure 2B An exemplary sealing mechanism is shown, which includes a sealing mechanism with Figure 2A The flexible sealing material 235 is similar to the flexible sealing material 235a, and the opening of the pipette tip 210a is pushed against the flexible sealing material 235a to ensure that the fluid therein is sealed. Figure 2C Another exemplary sealing mechanism is shown, which includes a sealing material 235b (which may be flexible or not), the sealing material may include one or more orifices configured to allow the distal portion of one or more pipette tips 210b to be inserted therein. Figure 2C As shown, when the pipette tip 210b is properly inserted, the sealing material 235b can be configured to be radially inwardly pushed against the outer wall of the distal portion of the pipette tip 210b, thereby sufficiently narrowing the pipette tip to seal the fluid within the pipette tip 210b. Figure 2B-2C A separate sealing plate (such as) is not shown. Figure 2B The sealing plate 230 shown is intended to be fixed to the bottom of the sealing materials 235a and 235b.

[0055] Figure 3 An example of an integrated kit 310 attached to a microfluidic cartridge 320 is shown. In some embodiments, reference is made to... Figure 3 The integrated kit 310 can be connected to a microfluidic cartridge such that each pipette tip 315 engages with an inlet opening 325 of the microfluidic cartridge. In some embodiments, each inlet opening 325 can be fluidly coupled to a corresponding reservoir of the microfluidic cartridge. In some embodiments, the integrated kit 310 may include a retaining feature configured to secure the kit 310 to the microfluidic cartridge 320. For example, refer to... Figure 1 The retaining feature may include a groove 130 and an associated auxiliary protrusion 131 on opposite sides of the pipette housing 100, and may be the same retaining feature already used to retain the sealing plate 230. The retaining feature may also include a protrusion 136, which may be configured to fit into a corresponding groove on the microfluidic cartridge. In this example, refer to Figure 2 and... Figure 3 Users can remove the sealing plate 230 and then fix the reagent kit 310 to the microfluidic box 320.

[0056] like Figure 3As illustrated in the example, the integrated kit 310 can provide a universal plug-based interface for insertion into "sockets" (e.g., cavities defined by the walls of inlet opening 325) of multiple different microfluidic devices. The result is a "one-size-fits-all" universal solution for rapidly and efficiently introducing large quantities of suitable reagents into numerous microfluidic devices in any desired combination. For example, a first kit containing a first set of reagents can be inserted into a first microfluidic device configured to perform a bioassay or into a second microfluidic device configured to perform PCR. As another example, a first kit containing a first set of reagents can be inserted into a first microfluidic device to perform a specific type of bioassay, and a second kit containing a second set of reagents can be inserted into the same first microfluidic device to perform a different type of bioassay.

[0057] Figure 4 An example of the integrated kit 400 is shown. Figure 4 The illustrated embodiment includes a cap 470 attached to a pipette body 475. In the illustrated example, the cap 470 is secured to the pipette body 475 by one or more screws 477. Alternatively or additionally, the cap 470 may be laser-welded to the pipette body 475. In some embodiments, the pipette body 475 may be a single injection-molded component and include one or more corresponding cavities. In some embodiments, one or more plungers having an actuating end 430 and a fluid-connecting end 435 may be disposed within one or more corresponding cavities of the pipette body 475. In some embodiments, the plungers may be held aligned with one or more seals 450. The pipette body 475 may have a plurality of outwardly extending pipette tips 450. In this example, a removable sealing plate 460 seals the contents (e.g., reagent 440) of the cavity of the pipette body 475.

[0058] Figure 5 A close-up view of an example of a pipette 510 engaging with the inlet of the microfluidic cartridge 520 is shown. Figure 5 As shown, a pipette tip 510 can be introduced into an inlet defined by a wall 527 that protrudes outward from the cap 525 of the microfluidic cartridge 520. At the bottom of the microfluidic cartridge may be a substrate 530, which may include a reservoir portion for receiving fluid from the pipette tip 510 once it has been positioned. In some embodiments, the pipette tip 510 may be part of a pipette array, in which case it may be one of a plurality of pipette tips that are (e.g., simultaneously) introduced into corresponding inlets of the microfluidic cartridge 520.

[0059] Figures 6A-6B An example of transferring fluid volume into a microfluidic cartridge 620 using kit 610 is shown. Figure 6A As shown, kit 610 can be aligned such that its pipette tip is positioned to engage the inlet of microfluidic cartridge 620. One or more plungers 615 of kit 610 can be pushed down toward microfluidic cartridge 620, which causes fluid to be transferred from the respective pipette tip through the respective inlet into microfluidic cartridge 620. Figure 6B A close-up view of the interior of the example kit is shown, in which (e.g., via an actuation end (not shown)) the top 630 of the plunger is pushed downward from a starting position A to an ending position B. This movement of the plunger may cause fluid 660 that may already be in the pipette tip 640 to be transferred to the reservoir of the microfluidic cartridge 650.

[0060] Figures 7A-7B An example of loading a certain volume of fluid into kit 710 is shown. Figure 7A As shown, kit 710 can be aligned such that its pipette tip is positioned to engage the inlet of well plate 725. One or more of its pipette tips can be immersed in fluid within one or more wells of well plate 725. One or more plungers 715 of kit 710 can be pulled out of the wells of well plate 725, which can cause fluid from the wells to be loaded into the corresponding pipette tip of kit 710. Figure 7B A close-up view of the interior of an exemplary kit is shown, in which (e.g., via an actuation end not shown in the figure) the top 730 of the plunger is pulled upward from a starting position B to an ending position A. This movement of the plunger may cause fluid 760 from the orifice of the orifice plate 750 to be loaded into the pipette tip 740.

[0061] Figures 8A-8B An example of using a loading platform 830 to assist in transferring or loading fluid volumes from or into the kit is shown. In some implementations, such as Figure 8A As shown, the microfluidic cartridge 820 can be placed on the loading stage 832 of the loading platform 830. The kit 810 (which may contain fluid (e.g., reagents) within one or more pipette tips) can be positioned above the microfluidic cartridge 820 such that one or more pipette tips of the kit 810 can engage one or more inlets of the microfluidic cartridge 820. A lever 835 of the loading platform 830 can be actuated to cause rotation of the loading platform 830 mechanism. This can then cause the engagement surface 837 to move downward a distance corresponding to the rotation. The movement of the engagement stage 837 can push the plunger of the kit 810 downward, thereby causing fluid within the pipette of the kit 810 to be displaced into the microfluidic cartridge 820. In some embodiments, such as... Figure 8BAs shown, a well plate 825 can be placed on a loading stage 832. One or more wells in the well plate 825 may include fluid (e.g., a reagent). A kit 810 can be positioned on the well plate such that one or more pipette tips engage with the wells of the well plate 825 (e.g., such that the pipette tips are at least partially immersed in the fluid within the wells). An engagement surface 837 can contact the plunger of the microfluidic cartridge 810. The engagement surface 837 can be configured to grip the plunger of the microfluidic cartridge 810. A lever 835 can be actuated (e.g., along with...) Figure 8A (in the opposite direction shown) to cause the mechanism of loading platform 830 to rotate, which in turn causes mating surface 837 to move upward a distance corresponding to the rotation, thereby pulling the plunger of microfluidic cartridge 810 accordingly. This can ultimately result in fluid from the orifices of well plate 825 being loaded into the pipette tip of kit 810.

[0062] Figures 9A-9B An example of an integrated kit 900 with a blister array 920 for convenient fluid transfer is shown. In this example, the integrated kit includes "blister arrays" configured as fluid reservoirs for containing fluids (e.g., reagents). In some embodiments, the blister array may be a hollow cavity in the surface of a substrate. In some embodiments, the substrate may be made of a thermoplastic with good chemical compatibility (e.g., PC, COP, or PP). Figure 9A As shown, the blister can be a dome-shaped cavity that is hollowed out in the substrate constituting the blister array 920. In some embodiments, such as Figure 9A As shown, blister array 920 may include multiple blister packs (e.g., arranged in one or more rows). In some embodiments, the capacity of the blister packs can be controlled by changing their size (e.g., depth, diameter, etc.) and / or shape. In some embodiments, the blister array may have blister packs with varying capacities. Figure 9A An exemplary embodiment of a blister array is shown, comprising three rows of blister arrays 925a, 925b, and 925c with different configurations. Figure 9A In the illustrated example, each row of these blister packs may have a different size and / or a different shape. For example, as shown... Figure 9B As shown, the diameter of blister 925b can be smaller than the diameter of blister 925c, resulting in a smaller fluid capacity for blister 925b compared to blister 925c. Similarly, in this example, blister 925a can be configured to be shallower than blister 925b and 925c, resulting in a smaller fluid capacity for blister 925a compared to blister 925b and 925c. As another example, blister can be shaped with a circular, elliptical, rectangular, or any other suitable profile. Blisters in a blister array can have any suitable size. For example, the outer diameter of the blister can be from 4 mm to 10 mm.

[0063] In some implementation schemes, such as Figure 9A As shown, each blister can be fluidly coupled to a dispensing nozzle 930, which can provide a path for dispensing fluid located within the blister. In some embodiments, reference... Figure 9B The dispensing pipette tip may have a first opening (e.g., first opening 922c) adjacent to the blister (e.g., blister 925c) and a second opening (e.g., second opening 929c) distant from the blister. In some embodiments, fluid in the blister can be dispensed from the kit through a second opening (e.g., second opening 929c) of a corresponding dispensing channel (e.g., dispensing channel 927c) of the dispensing pipette tip (e.g., dispensing tip 930c). In some embodiments, the channel in each dispensing pipette tip may have an inner diameter of several hundred micrometers. The dispensing pipette tip may have any suitable height. For example, the height of the dispensing pipette tip may be from 8 mm to 25 mm.

[0064] In some embodiments, the kit may include one or more deformable seals that cover or otherwise enclose the fluid container of the blister pack. For example, such as Figure 9A As shown, a deformable seal 910 can cover the blister array 920. As an example, the deformable seal 910 can be a film attached to the blister array by laser welding, thermal lamination, or application of a pressure-sensitive adhesive. In some embodiments, the deformable seal 910 can be a thermoplastic film (e.g., PET, PP, PMMA, COC, COP) or a thermoplastic elastomer film (e.g., silicone, polyurethane). In some embodiments, the blister arrays can be sufficiently spaced (e.g., 1 to several millimeters) to ensure sufficient sealing surface area between the deformable seal 910 and the surface of the blister array. For example, the pitch of the blister arrays can be 4.5 mm to 9 mm. In some embodiments, suitable coding can be added to the film to further reduce the gas permeability of the film, thereby producing better sealing. The film thickness can be in the range of several hundred micrometers. In some embodiments, such as Figure 9A As shown, a single membrane can be used to cover the fluid reservoir of each blister in a blister array. In these embodiments, the membrane's footprint can be the same as the blister array. In some embodiments, one or more deformable seals can seal the volume of fluid within one or more blister arrays.

[0065] In some embodiments, the kit may include a blister base configured to engage one or more openings of one or more dispensing tips of the kit. The blister base can be used to seal fluid within the blister and / or dispensing tips of the kit. For example, see reference... Figure 9AThe kit 900 may include a blister base 940 that can be secured to cover or enclose an opening of the dispensing tip 930. In this example, as shown, the blister base may include a recessed portion sized to receive at least a portion of the dispensing tip 930. In some embodiments, the blister base 940 may include retaining features configured to secure the blister base 940 to the blister array 920. For example, as... Figure 9B As shown, the blister base 940 may include one or more protrusions 945 configured to snap onto the blister array 920. In some embodiments, the blister base may include one or more sealing gaskets disposed within one or more recesses, wherein each sealing gasket is configured to engage and seal an opening of a corresponding dispensing tip. For example, as Figure 9B As shown, a sealing gasket 929c may be disposed within a recess in the blister base 940 corresponding to the blister 925c, and configured to directly contact the second opening 929c of the dispensing channel 927c of the dispensing nozzle 930c. In some embodiments, the sealing gasket may comprise an elastomeric material such as silicone or polyurethane. In some embodiments, the blister base may comprise a thermoplastic such as PET, PE, PS, PP, PMMA, or PC. In some embodiments, the blister base 940 may be removed prior to use to empty the second opening of the dispensing nozzle 930, thereby enabling fluid dispensing from the corresponding blister.

[0066] Figures 10A-10B An example illustrating fluid transfer from blister packs is provided. In some embodiments, the dispensing tips of the blister array (e.g., dispensing tips 1030a and 1030b) can be positioned at a suitable dispensing location (e.g., the inlet of a microfluidic cartridge). From this location, fluid within one or more blister packs (e.g., blister packs 1025a and 1025b) can be transferred into the inlet by deforming a deformable seal of a reservoir covering the blister pack. The blister packs (e.g., blister packs 1025a and 1025b) can deform in any suitable manner. For example, as... Figures 10A to 10BAs shown, plungers 1020a and 1020b can be directed toward the corresponding blister packs 1025a and 1025b until they deform the blister packs, thereby transferring the fluid therein and causing the fluid to exit via dispensing nozzles 1030a and 1030b. In this example, plungers 1020a and 1020b are shaped as ball heads, their dimensions set to fit properly within blister packs 1025a and 1025b, thereby allowing the transfer of an optimal (e.g., maximum) amount of fluid. Components such as plungers can be actuated by a loading platform, or alternatively, can be simply moved manually by a user. In some embodiments, blister packs in a blister array can be deformed individually (e.g., in a prescribed order) by a single plunger, or they can be deformed in groups (or together) by a single plunger structure having a plurality of integrated plungers.

[0067] Figure 10C An example of a bubble array 1020 located above a microfluidic cell 1040 is shown. Figure 10C As shown, in some embodiments, the blister array 1020 can be configured to be fixed to or positioned above the microfluidic cartridge 1040, such that the positions of the dispensing tips of the blister array 1020 correspond to the respective inlets of the microfluidic cartridge 1040. In these embodiments, the blister array 1020 can be initially positioned above the microfluidic cartridge 1040, and then deformable seals above one or more blister packs of the blister array 1020 can be deformed to displace fluid therein into the microfluidic cartridge 1040. For example, a user can deform the first set of blister packs of the blister array 1020 to squeeze the fluid in the first set of blister packs, causing the fluid to transfer from the blister packs and into the respective inlets of the microfluidic cartridge 1040. As another example, a user can deform all the blister packs of the blister array 1020 (e.g., simultaneously) so that the fluid within all the blister packs is (e.g., simultaneously) introduced into the respective inlets of the microfluidic cartridge 1040.

[0068] Figure 11 An example of loading fluid into multiple blister packs 1125 is shown. In some embodiments, fluid (e.g., a reagent) can be loaded into the blister packs by the manufacturer or user (after the blister packs of the blister array have been sealed with one or more deformable seals). In some embodiments, the blister array can then be inverted such that the dispensing tips of the blister array are facing upwards, as shown. Figure 11 As shown, for reference Figure 11Dispensing needle 1140 can be inserted into blister 1125 via dispensing tip 1130. In some embodiments, dispensing needle 1140 may be selected to have a sufficiently small outer diameter to allow insertion into dispensing tip 1130 and to allow gas (e.g., air) in the blister to be expelled while the blister is being filled with fluid from dispensing needle 1140. An inverted blister array can facilitate gas expulsion from the blister when it is filled. Each dispensing needle 1140 may be coupled to a supply cavity containing the desired fluid. After dispensing needle 1140 has been inserted into the appropriate blister 1125, it can load a desired volume of fluid into the blister 1125. Once the blister has been filled, a blister base can be snapped onto the blister array to seal dispensing tip 1130. In some embodiments, the blister may be loaded via a different path (e.g., a dedicated port separate from the dispensing tip).

[0069] In some implementations, the blister array may include blister packs having a maximum storage volume of 50 μL. However, manufacturers may choose to load a number of blister packs smaller than the maximum storage volume. For example, manufacturers may choose to load 20 μL to 30 μL of fluid into the blister packs.

[0070] Figures 12A to 12B Further examples of blister packs 1225 and 1226 are shown. Instead of a reservoir defined by a cavity in the surface of the kit's substrate and a deformable seal covering that cavity, Figure 12A-12B The exemplary blister packs 1225 and 1226 have reservoirs entirely defined by a deformable material. Thus, when... Figures 9A-9B Compared to the blisters 925a-925c shown, these blisters have a larger total surface area of ​​deformable material. When the deformable material deforms, this can result in an enhanced ability to transfer fluid from blisters 1225 and 1226, making it easier to transfer all or most of the fluid inside the blisters. Figure 12A An example of a blister pack oriented in a plane substantially parallel to the substrate surface 1210 of the kit is shown. Although only one blister pack is shown, an entire array of blister packs can be envisioned, with one or all of them configured similarly to blister pack 1225. As indicated by the arrows, elements 1250 (e.g., engagement elements of a loading / unloading stage) can be advanced toward blister pack 1225 to push it against the substrate surface 1210, thereby transferring fluid therein and allowing the fluid to exit blister pack 1225 via dispensing nozzle 1230. Alternatively, a user can manually squeeze blister pack 1225 to achieve the same effect. Figure 12BAn example of a blister pack positioned in a plane substantially perpendicular to the substrate surface 1210 of the kit is shown. Although only one blister pack is shown, an entire array of blister packs can be envisioned, with one or all of them configured similarly to blister pack 1226. As indicated by the arrows, elements 1260a and 1260b (e.g., engagement elements of the loading stage) may be advanced from both sides toward blister pack 1226 to transfer fluid therein, thereby allowing the fluid to exit blister pack 1226 via dispensing nozzle 1230.

[0071] Figures 13A-13B An example of a kit 1300 with a reservoir 1310 for filler fluid is shown. The filler fluid can flow into a microfluidic device and can act as a medium (e.g., in which a reaction or assay occurs). In some embodiments, the filler fluid can be an oil. In some embodiments, the filler fluid can be an oil mixed with one or more other components (e.g., a surfactant). The exemplary kit 1300 includes a filler fluid dispensing tip 1315 through which oil can flow into the microfluidic device. In some embodiments, the kit 1300 may be pre-filled with reagents within a manufacturer-made pipette tip 1320, and the reservoir 1310 may be unfilled. In these embodiments, a user can introduce a volume of filler fluid into the reservoir 1310 after aligning the kit with the microfluidic device. The reservoir 1310 and the filler fluid dispensing tip 1315 may be configured such that gravity causes the filler fluid to exit the reservoir 1310 through the filler fluid dispensing tip 1315. In some embodiments, a funnel may be present between the reservoir 1310 and the filler fluid dispensing tip 1315 to help guide the filler fluid in its outlet. The filler fluid dispensing tip 1315 may be aligned such that the microfluidic device receives the filler fluid into a corresponding reservoir of the microfluidic device, allowing the filler fluid to flow within the microfluidic device. In some embodiments, the kit 1300 may be pre-filled with reagents within the manufacturer's pipette tip 1320 and may also be pre-filled with filler fluid within the reservoir 1310. In these embodiments, the filler fluid dispensing tip 1315 may include a seal at the opening of the filler fluid dispensing tip 1315 (e.g., a movable or puncture-resistant seal that is properly positioned relative to the microfluidic device).

[0072] In some implementations, the various components of the different embodiments described herein can be manufactured using an injection molding process. Such a process can result in low part costs and may make the kit cost-effective for use as a single-use consumable.

[0073] Figure 14An example method 1400 for transferring reagents to a microfluidic device (e.g., a microfluidic cartridge) is shown. The method may begin at step 1410, wherein a kit is placed over the microfluidic device, wherein the kit includes: a pipette housing including a plurality of pipette tips, each pipette tip having a first opening and a second opening; and a plunger body including: a plurality of plungers; and a connector body configured to couple the plurality of plungers; wherein the plunger body is configured to be secured to the pipette housing; the microfluidic device includes a first inlet opening fluidly coupled to a first reservoir of the microfluidic device; wherein positioning the kit includes aligning a first pipette tip of the plurality of pipette tips with the first inlet opening such that the first inlet opening is configured to receive a first fluid from the first pipette tip. At step 1420, a first plunger associated with the first pipette tip may be actuated to transfer a first volume of the first fluid from the first pipette tip to the first reservoir via the first inlet opening. Specific embodiments may be repeated as appropriate. Figure 14 One or more steps of the method. Although this disclosure describes and illustrates Figure 14 The method involves specific steps that occur in a specific order, but this disclosure considers... Figure 14 The method comprises any suitable steps occurring in any suitable order. Furthermore, although this disclosure describes and illustrates exemplary methods for transferring reagents to a microfluidic device, including... Figure 14 This disclosure considers specific steps of the method, but also any suitable method for transferring reagents to a microfluidic device where appropriate, which includes any suitable steps that may include... Figure 14 The method may include all steps, some steps, or none of them. Figure 14 Any step of the method. Furthermore, although this disclosure describes and illustrates the implementation... Figure 14 This disclosure contemplates specific components, devices, or systems for specific steps of a method, and describes the implementation of such methods. Figure 14 Any appropriate combination of any appropriate component, device or system of any appropriate step of the method.

[0074] Figure 15An exemplary method 1500 for loading reagents onto a kit is shown. The method may begin at step 1510, wherein the kit is placed on a well plate, wherein the kit includes: an array of pipette tips, each pipette tip having a first opening and a second opening; and a plunger body including: a plurality of plungers, and a connector body configured to couple the plurality of plungers; wherein the plunger body is configured to be secured to a pipette housing; and the well plate includes a first well; wherein the step of positioning the kit includes immersing a first pipette tip of the plurality of pipette tips into a first fluid contained in the first well. At step 1520, the first plunger associated with a first detection may be actuated to transfer a first volume of first fluid from the first well into the first pipette tip. Specific embodiments may be repeated as appropriate. Figure 15 The method comprises one or more steps. Although this disclosure describes and illustrates specific steps of the method of Figure 2 that occur in a particular order, this disclosure contemplates... Figure 15 The method comprises any suitable steps occurring in any suitable order. Furthermore, although this disclosure describes and illustrates exemplary methods for loading reagents onto a kit, which include... Figure 15 This disclosure considers specific steps of a method for loading reagents onto a kit, which, when appropriate, includes any suitable steps that may include... Figure 15 The method may include all steps, some steps, or none of them. Figure 15 Any step of the method. Furthermore, although this disclosure describes and illustrates the implementation... Figure 15 The method may refer to a specific component, device, or system of a specific step, but this disclosure is contemplated for the execution of... Figure 15 Any appropriate combination of any appropriate component, device or system of any appropriate step of the method.

[0075] Figure 16An example method 1600 for transferring reagents to a microfluidic cartridge is shown. The method may begin at step 1610, wherein a kit is placed over a microfluidic device, wherein the kit includes: a substrate comprising: one or more blister packs, each blister pack including a fluid reservoir configured to contain a volume of fluid; and one or more dispensing tips, each dispensing tip including a channel fluidly coupled to the blister pack, wherein fluid can be transferred from or loaded into the blister pack via the dispensing tip; and one or more deformable seals fixed to the substrate and covering the one or more blister packs for sealing a volume of fluid within the one or more blister packs; the microfluidic device includes a first inlet opening fluidly coupled to a first reservoir of the microfluidic device; wherein positioning the kit includes aligning the first dispensing tip of the one or more dispensing tips with the first inlet opening such that the first inlet opening is configured to receive first fluid from a first blister pack fluidly coupled to the first dispensing tip. At step 1620, one or more of the deformable seals may be displaced to transfer a first volume of first fluid from the first blister pack to the first reservoir via the first inlet opening. Specific implementation schemes can be repeated when appropriate. Figure 16 One or more steps of the method. Although this disclosure describes and illustrates Figure 16 The method involves specific steps that occur in a specific order, but this disclosure considers... Figure 16 The method comprises any suitable steps occurring in any suitable order. Furthermore, although this disclosure describes and illustrates exemplary methods for transferring reagents into a microfluidic cartridge, which include... Figure 16 This disclosure considers specific steps of the method, but also any suitable method for transferring reagents to a microfluidic cartridge where appropriate, including any suitable steps that may include... Figure 16 The method may include all steps, some steps, or none of them. Figure 16 Any step of the method. Furthermore, although this disclosure describes and illustrates the implementation... Figure 16 This disclosure contemplates specific components, devices, or systems for specific steps of a method, and describes the implementation of such methods. Figure 16 Any appropriate combination of any appropriate component, device or system of any appropriate step of the method.

[0076] Although the process described herein is described with respect to a specific number of steps performed in a particular order, it is contemplated that additional steps not explicitly shown and / or described may be included. Furthermore, it is contemplated that fewer steps than shown and described may be included without departing from the scope of the described embodiment (i.e., one or some of the described steps may be optional). Additionally, it is contemplated that the steps described herein may be performed in a different order than that described.

[0077] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and various modifications or changes thereto will be suggested by those skilled in the art and will be included within the spirit and scope of this application and the appended claims. All publications, patents, and patent applications cited herein are incorporated herein by reference in their entirety for all purposes.

[0078] It should be understood that the above description is intended to be illustrative rather than restrictive. Many embodiments will be apparent to those skilled in the art upon reading the above description. Therefore, the scope of the invention should not be determined by reference to the above description, but rather by reference to the full scope of the appended claims and their equivalents.

[0079] While the foregoing disclosure illustrates illustrative aspects of this disclosure, it should be noted that various changes and modifications may be made herein without departing from the scope of this disclosure as defined by the appended claims. The functions, steps, and / or actions of the method claims according to aspects of this disclosure described herein need not be performed in any particular order. Furthermore, although elements of this disclosure may be described or claimed in the singular, plural forms are contemplated unless a limitation on the singular is expressly stated.

[0080] For all the flowcharts in this article, it should be understood that many steps can be combined, executed in parallel, or executed in different orders without affecting the functionality implemented.

Claims

1. A system comprising a cartridge including: a substrate including: a plurality of blisters organized into a blister array, wherein each blister includes a fluid reservoir configured to hold a volume of fluid; and a plurality of dispensing tips, each dispensing tip including a channel fluidly coupled to the blisters, wherein fluid can be dispensed from the blisters through the dispensing tips; and one or more deformable seals covering the fluid reservoirs, wherein the one or more deformable seals seal the volumes of fluid in the plurality of blisters; and a microfluidic device including a plurality of inlet openings and positioned below and in alignment with the cartridge when fluid is removed from the plurality of blisters, the plurality of inlet openings for receiving fluid removed from the plurality of blisters; wherein each dispensing tip is configured to engage one of the inlet openings of the microfluidic device when the microfluidic device is positioned below the cartridge.

2. The system of claim 1, wherein, The blisters include hollow cavities in a surface of the substrate.

3. The system of claim 1, further comprising a base configured to engage and form a seal with one or more openings of the one or more dispensing tips.

4. The system of claim 3, wherein, The base includes one or more recessed portions configured to accommodate at least a portion of the dispensing tips.

5. The system of claim 4, wherein, The base further includes one or more sealing gaskets disposed within the one or more recessed portions, wherein each sealing gasket is configured to engage and seal an opening of a respective dispensing tip.

6. The system of any one of claims 1 to 5, wherein, The one or more deformable seals include a thermoplastic film.

7. The system of any one of claims 1 to 5, wherein, The one or more deformable seals include a thermoplastic elastomer film.

8. The system of any one of claims 1 to 5, wherein, The one or more deformable seals include a coating configured to reduce gas permeability.

9. The system of any one of claims 1 to 5, wherein, The one or more deformable seals are secured to the substrate by laser welding or thermal lamination.

10. The system of any one of claims 1 to 5, wherein, The one or more deformable seals are secured to the substrate using a pressure sensitive adhesive.

11. The system of any one of claims 1 to 5, wherein the one or more deformable seals include a single deformable film covering the blister array.

12. The system of claim 11, wherein, The plurality of blisters includes a first blister having a first fluid reservoir and a second blister having a second fluid reservoir.

13. The system of any one of claims 1 to 5, wherein, The first blister is configured to receive a first volume of fluid from a dispensing needle via an opening of a first dispensing tip.

14. The system of any one of claims 1 to 5, wherein, The first blister is configured to receive a first plunger end and is further configured to transfer a first volume of fluid from the first blister via a first dispensing tip when the first plunger end is received.

15. The system of claim 14, wherein, The first dispensing tip is configured to be disposed within an inlet opening of a microfluidic device.

16. The system of claim 14, wherein, The first plunger end conforms to a shape and size of the fluid reservoir of the first blister.

17. The system of claim 14, wherein, The plurality of blisters includes a first blister having a first fluid reservoir and a second blister having a second fluid reservoir, and wherein the first plunger end conforms to a shape and size of the fluid reservoir of the first blister and a second plunger end conforms to a shape and size of the fluid reservoir of the second blister.

18. A method of transferring reagents to a microfluidic device, comprising: positioning a cartridge on a microfluidic device, wherein: the cartridge comprises: a substrate comprising: one or more blisters, wherein each blister comprises a fluid reservoir configured to hold a volume of fluid; and one or more dispensing tips, each dispensing tip extending from the blister, configured to extend into a wall of a fluid inlet of the microfluidic device, and comprising a channel fluidically coupled to the blister, wherein fluid can be dispensed from the blister through the dispensing tip; and one or more deformable seals secured to the substrate and covering the one or more blisters for sealing the volume of fluid within the one or more blisters; and the microfluidic device comprises a first inlet opening fluidically coupled to a first reservoir of the microfluidic device; wherein positioning the cartridge comprises aligning a first dispensing tip of the one or more dispensing tips with the first inlet opening, such that the first inlet opening is configured to receive a first fluid from a first blister fluidically coupled to the first dispensing tip; and moving one or more of the deformable seals to cause a first volume of the first fluid to be transferred from the first blister through the first inlet opening into the first reservoir.

19. The method of claim 18, wherein, the blister comprises a hollow cavity in a surface of the substrate.

20. The method of claim 18, further comprising removing the base from the kit, wherein, the base is configured to engage one or more openings of the one or more dispensing tips and form a seal.

21. The method of claim 20, wherein, the base comprises one or more recessed portions configured to accommodate at least a portion of the dispensing tips.

22. The method of claim 21, wherein, the base further comprises one or more sealing gaskets disposed within the one or more recessed portions, wherein each sealing gasket is configured to engage and seal an opening of a respective dispensing tip.

23. The method of any one of claims 18-22, wherein, the one or more deformable seals comprise a thermoplastic film.

24. The method of any one of claims 18-22, wherein, the one or more deformable seals comprise a thermoplastic elastomer film.

25. The method of any one of claims 18-22, wherein, the one or more deformable seals comprise a coating configured to reduce gas permeability.

26. The method of any one of claims 18-22, wherein, the one or more deformable seals are secured to the substrate by laser welding or thermal lamination.

27. The method of any one of claims 18-22, wherein, the one or more deformable seals are secured to the substrate using an adhesive.

28. The method of any one of claims 18-22, wherein, the one or more deformable seals are secured to the substrate using a pressure sensitive adhesive.

29. The method of any one of claims 18-22, wherein, the substrate comprises a plurality of blisters organized in a blister array, and wherein the one or more deformable seals comprise a single deformable film covering the blister array.

30. The method of claim 29, wherein, the plurality of blisters comprises a first blister having a first fluid reservoir and a second blister having a second fluid reservoir.

31. The method of any one of claims 18-22, further comprising: inserting a dispensing needle into an opening of a first dispensing tip coupled to a first blister; dispensing a first volume of fluid into the first blister through the dispensing needle.

32. The method of any one of claims 18 to 22, wherein, moving the one or more deformable seals comprises applying a first plunger end against the one or more deformable seals.

33. The method of any one of claims 18-22, wherein the microfluidic device is a cartridge.

34. The method of claim 32, wherein, The first plunger end conforms to the shape and size of the fluid reservoir of the first blister.

35. The method of claim 32, wherein, The substrate includes a plurality of blisters, wherein the plurality of blisters includes a first blister having a first fluid reservoir and a second blister having a second fluid reservoir, and wherein the first plunger end conforms to the shape and size of the fluid reservoir of the first blister and a second plunger end conforms to the shape and size of the fluid reservoir of the second blister.

36. A method of transferring reagents to a microfluidic device, comprising: moving a first deformable seal of a cartridge, wherein the cartridge comprises: a substrate comprising: one or more blisters, wherein each blister includes a fluid reservoir configured to contain a volume of fluid; and one or more dispensing tips, each dispensing tip extending from the blister, configured to extend into a wall of a fluid inlet of a microfluidic device, and including a channel fluidically coupled to the blister, wherein fluid can be dispensed from the blister through the dispensing tip; and one or more deformable seals affixed to the substrate and covering the one or more blisters for sealing the volume of fluid within the one or more blisters; wherein moving the first deformable seal causes a first volume of a first fluid to be transferred from a first blister of the one or more blisters through a first dispensing tip.

37. The method of claim 36, further comprising placing the cartridge over a microfluidic device, and wherein the first volume of the first fluid is transferred into the microfluidic device through a first inlet opening.

38. The method of claim 37, wherein, The first volume of the first fluid is transferred into a first reservoir via the first inlet opening.

39. An integrated reagent storage cartridge, comprising: an array of blisters including a plurality of fluid reservoirs and dispensing tips configured to connect to a plurality of reagent inputs of a microfluidic device, each dispensing tip extending from one fluid reservoir and configured to extend into a wall of a fluid inlet of the microfluidic device; one or more deformable seals covering the fluid reservoirs; wherein deformation of the one or more deformable seals proximate to one of the fluid reservoirs causes fluid to be dispensed from one of the dispensing tips associated with the fluid reservoir.

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