Abstract: A cannula insertion device is disclosed. The device includes a needle carriage, a rail device on which the needle carriage is slidable, a yoke having a channel, a linkage connected to the needle carriage and extending into the channel, a torsion spring with one end connected to the linkage, and locking device for locking the torsion spring in tension and maintaining the needle carriage and the linkage in a locked position prior to activation. Upon release of the locking device, the tension of the torsion spring is released, which causes the linkage to move in the channel and slide the needle carriage along the rail device. A catheter carriage may also be provided for actuation by the linkage.

Abstract: Provided is a method of generating droplets that includes aspirating a first liquid into a tube, positioning the tube over a receiving liquid, and ejecting the first liquid to generate a plurality of droplets that contact the receiving liquid and remain discrete even after contacting the receiving liquid. Whereas many other droplet generators require complex microfluidics, the present methods allow generation of droplets without the need for microfluidics. The methods can be performed with existing commercially available macro-fluidic liquid handling devices. The methods can be used for digital PCR, digital MDA, enzyme screening, single cell analysis, and other applications involving droplets.

Abstract: A rotary pump for a fluid metering system is provided. The rotary pump reciprocates, and is reversed by a signal from a limit switch that is deflected by an actuator arm on a rotating sleeve of the pump system. The sleeve receives a gasket that forms a seal between the sleeve and the housing, the gasket having an opening surrounding a side hole of the sleeve to permit fluid to pass through the side hole between a pump volume and an inlet port or outlet port of the housing.

Abstract: Provided herein are compositions, systems, kits, and methods for detecting the presence or absence of a target protein in a discrete entity comprising: a) generating a discrete entity (e.g., microdroplet) comprising: i) a first cell that may secrete, or surface express, a target protein, ii) a quenched oligonucleotide probe, iii) first antibody-oligonucleotide conjugate or a particle-oligonucleotide conjugate, and a second antibody-oligonucleotide conjugate that bind the target protein in proximity to each to form an oligonucleotide template structure (OTS), and a nickase enzyme that cleaves the quenched oligonucleotide probe when it is hybridized to the OTS such that a detectable dye (e.g., fluorescent dye) is released and generates a signal; and b) detecting the presence or absence of the signal from the detectable dye.

Abstract: The present invention provides compositions, systems, kits, and methods for combining a. single myeloma cell and a single B-cell (e.g., from an animal exposed to a desired antigen) via discrete entity (e.g., droplet) microfluidics. In certain embodiments, a microfluidic device is used to merge a discrete entity containing a B-cell, and a discrete entity containing a myeloma cell, and a discrete entity containing gellable material, at a merger region via a trapping element in order to generate a combined discrete entity. In further embodiments, the combined discrete entity is treated such that a gelled discrete entity is formed.

Abstract: A pump subsystem for fluid delivery (e.g., in a wearable patch pump) is provided wherein pumping action is generated by linear piston movement that pulls a plug, which is interconnected to the piston between two mechanical extremes or end stops in a telescopic or variable volume fluid chamber. Such interconnection enables piston and plug to move a certain distance with respect to each other that corresponds to a predefined swept volume of the pump subsystem. Telescoping-like effect of relative piston and plug movement provides for intake and discharge of fluid with respect to the fluid chamber. Movement of plug within piston can be enabled by the friction of seals placed on the plug, which serve to provide resistance to piston motion and therefore force translation motion of the plug to lag relative to the piston translation motion during portions of the pump cycle.

Abstract: Methods for on-demand printing discrete entities including, e.g., cells, media or reagents to substrates are provided. In certain aspects, the methods include manipulating qualities of the entities or biological components thereof. In some embodiments, the methods may be used to create arrays of microenvironments and/or for two and three-dimensional printing of tissues or structures and/or for in situ printing for microsurgeries. Systems and devices for practicing the subject methods are also provided.

Abstract: The present invention provides compositions, systems, kits, and methods for combining a. single myeloma cell and a single B-cell (e.g., from an animal exposed to a desired antigen) via discrete entity (e.g., droplet) microfluidics. In certain embodiments, a microfluidic device is used to merge a discrete entity containing a B-cell, and a discrete entity containing a myeloma cell, and a discrete entity containing gellable material, at a merger region via a trapping element in order to generate a combined discrete entity. In further embodiments, the combined discrete entity is treated such that a gelled discrete entity is formed.

Abstract: The present invention provides compositions, systems, kits, and methods for analyzing the interaction of T-cells and neoantigen presenting cells (and other cells) via discrete entity (e.g., droplet) microfluids. In certain embodiments, a microfluidic device is used to merge a discrete entity containing a T-cell, and a discrete entity containing a neoantigen presenting cell, at a merger region via a trapping element in order to generate a combined discrete entity. In particular embodiments, at least one thousand of such combined discrete entities are formed in about one second. In some embodiments, whether the receptor on the T-cell sufficiently binds the neoantigen to activate the T-Cell is detected (e.g., via detection of cytokine or granzyme B release). In certain embodiments, provided herein are methods for identifying polyfunctional T-cells or NK-cells, as well as methods of screening for such cells that would be cytotoxic if injected into a subject.

Abstract: A catheter insertion device (18) includes a housing (12) with a base (14), a catheter (28), an introducer needle (30) and an actuator (26) mounted within the housing. The catheter (28) and needle (30) are coupled to the actuator (26) and movable between a first position where the catheter and needle are retracted within the housing and a second position where the catheter and needle extend from the housing, and where the needle retracts into the actuator when the catheter and needle reach the second position. The actuator (26) has a detent (84) that engages a first recess (76) to require a predetermined force to depress the actuator (26) which is greater than the force necessary to slide the actuator (26) to the second position where the detent (84) engages a second recess (80) in the housing (12) to hold the actuator in the deployed position.

Abstract: Methods for selectively combining discrete entities including, e.g. cells, reagents, drugs, hydrogels, extracellular matrices beads, particles, biological materials, media, or a combination thereof, are provided. In certain aspects, the methods include sorting a plurality of discrete entities and trapping two or more discrete entities for a time sufficient for the two or more discrete entities to combine to form a combined discrete entity. In certain aspects, the methods include making the plurality of discrete entities. In certain aspects, the methods include detecting or analyzing the discrete entities, e.g. via optical detection. In certain aspects, the methods include manipulating or analyzing the combined discrete entity or a component therein, e.g. imaging, sequencing, culturing, e.g., three-dimensional culturing, and measuring cell-cell interactions. Systems and devices for practicing the subject methods are also provided.

Abstract: A button safety cap for a patch pump or other fluid infusion device prevents accidental activation of an activation button of a catheter insertion device. The button safety cap includes a stabilizing surface adapted to stabilize the patch pump when the patch pump is oriented for filling a reservoir port.

Abstract: The present invention provides compositions, systems, and methods for barcoding cells, beads, and secreted proteins in discrete entities (e.g. droplets) to allow sequencing data from such components that are separated during processing to be associated via the common barcodes. In some embodiments, the barcodes are tethered to the cell surface via a lipid, cholesterol, or antibody, or are attached to a surface molecule that moves from one cell to another via trogocytosis. In certain embodiments, such methods allow cell-cell interactions or secreted proteins in the discrete entity to be monitored.

Abstract: A button safety cap for a patch pump or other fluid infusion device prevents accidental activation of an activation button of a catheter insertion device. The button safety cap includes a stabilizing surface adapted to stabilize the patch pump when the patch pump is oriented for filling a reservoir port.

Abstract: A catheter insertion device (10) includes a housing (12) with a base (14), a catheter (28), an introducer needle (30) and an actuator (26) mounted within the housing. The catheter (28) and needle (30) are coupled to the actuator (26) and movable between a first position where the catheter and needle are retracted within the housing and a second position where the catheter (28) and needle (30) extend from the housing, and where the needle retracts into the actuator when the catheter and needle reach the second position. A spring (90) is provided in the housing (12) or the actuator (26) where the spring (90) is released after deployment of the device to retract the needle (20) with respect to the catheter (28).

Abstract: A catheter insertion device (10) includes a housing (12) with a base (14), a catheter (28), an introducer needle (30) and an actuator (26) mounted within the housing. The catheter (28) and needle (30) are coupled to the actuator (26) and movable between a first position where the catheter and needle are retracted within the housing and a second position where the catheter (28) and needle (30) extend from the housing, and where the needle retracts into the actuator when the catheter and needle reach the second position. A spring (90) is provided in the housing (12) or the actuator (26) where the spring (90) is released after deployment of the device to retract the needle (20) with respect to the catheter (28).

Abstract: A method of constructing a cured composite assembly includes positioning a composite assembly within a bonding tool, wherein the composite assembly comprises an uncured composite spar and a skin and performing a curing cycle on the composite assembly to simultaneously cure the uncured composite spar and bond the skin to the cured composite spar.

Abstract: Manual insertion device has retraction spring (202) and hollow septum configuration (224) implemented using barrel-shaped guides (108, 110) and a guiding boss (210) in insertion device housing (106), and provides a fluid path through alignment of septum openings, side-port openings and catheter openings upon complete catheter insertion. Button (200) causes manual insertion of introducer needle (204) and catheter (220) of a first barrel (108) into a skin surface, and loading of retraction spring (202) disposed in an adjacent second barrel (110). Once introducer needle (204) and catheter (220) are fully inserted, the introducer needle hub (206) is released and automatically retracted by release of the retraction spring (202), leaving the catheter (220) in the user's body. Septums (218, 224) and side-port openings (216, 228) in the button (200) and introducer needle (204) are thus aligned, creating an uninterrupted fluid path between a reservoir or pump and catheter (220).

Abstract: Manual insertion device has retraction spring (202) and hollow septum configuration (224) implemented using barrel-shaped guides (108, 110) and a guiding boss (210) in insertion device housing (106), and provides a fluid path through alignment of septum openings, side-port openings and catheter openings upon complete catheter insertion. Button (200) causes manual insertion of introducer needle (204) and catheter (220) of a first barrel (108) into a skin surface, and loading of retraction spring (202) disposed in an adjacent second barrel (110). Once introducer needle (204) and catheter (220) are fully inserted, the introducer needle hub (206) is released and automatically retracted by release of the retraction spring (202), leaving the catheter (220) in the user's body. Septums (218, 224) and side-port openings (216, 228) in the button (200) and introducer needle (204) are thus aligned, creating an uninterrupted fluid path between a reservoir or pump and catheter (220).

Abstract: A cannula insertion device is disclosed. The device includes a needle carriage, a rail device on which the needle carriage is slidable, a yoke having a channel, a linkage connected to the needle carriage and extending into the channel, a torsion spring with one end connected to the linkage, and locking device for locking the torsion spring in tension and maintaining the needle carriage and the linkage in a locked position prior to activation. Upon release of the locking device, the tension of the torsion spring is released, which causes the linkage to move in the channel and slide the needle carriage along the rail device. A catheter carriage may also be provided for actuation by the linkage.