Abstract: The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc.

Abstract: The present invention relates generally to vesicles such as liposomes, colloidosomes, and polymersomes, as well as techniques for making and using such vesicles. In some cases, the vesicles may be at least partially biocompatible and/or biodegradable. The vesicles may be formed, according to one aspect, by forming a multiple emulsion comprising a first droplet surrounded by a second droplet, which in turn is surrounded by a third fluid, where the second droplet comprises lipids and/or polymers, and removing fluid from the second droplet, e.g., through evaporation or diffusion, until a vesicle is formed. In certain aspects, the size of the vesicle may be controlled, e.g., through osmolarity, and in certain embodiments, the vesicle may be ruptured through a change in osmolarity. In some cases, the vesicle may contain other species, such as fluorescent molecules, microparticles, pharmaceutical agents, etc., which may be released upon rupture.

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

Abstract: The present disclosure generally relates to systems and methods for detecting viruses, e.g., using microfluidic devices. Certain embodiments are generally directed to systems and methods that are able to detect pathogens such as viruses or bacteria by encapsulating a sample in droplets, and applying amplification reagents to the droplets able to amplify nucleic acids therein, e.g., using loop mediated isothermal amplification (LAMP) or other amplification techniques. In addition, some aspects are generally directed to identifying a species in a sample, e.g., at very low concentrations. In some cases, the sample may be broken into droplets, arid the droplets determined to determine the species.

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

Abstract: The present invention generally relates to microfluidic droplets and, including forming gels within microfluidic droplets. In some aspects, a fluid containing agarose or other gel precursors is transported into a microfluidic droplet, and caused to harden within the droplet, e.g., to form a gel particle contained within the microfluidic droplet. Surprisingly, a discrete gel particle may be formed even if the fluid containing the agarose or other gel precursor, and the fluid contained within the microfluidic droplet, are substantially immiscible. Other aspects of the present invention are generally directed to techniques for making or using such gels within microfluidic droplets, kits containing such gels within microfluidic droplets, or the like.

Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Abstract: The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.

Abstract: The present disclosure generally relates, in certain aspects, to droplet-based microfluidic devices and methods. In certain aspects, target nucleic acids contained within droplets are amplified within droplets in a first step, where multiple primers may be present. However, multiple primers may cause multiple target nucleic acids to be amplified within the droplets, which can make it difficult to identify which nucleic acids were amplified. In a second step, the amplified nucleic acids may be determined. For example, the droplets may be broken and the amplified nucleic acids can be pooled together and sequenced. As an example, new droplets may be formed containing the amplified nucleic acids, and those nucleic acids within the droplets amplified by exposure to certain primers.

Abstract: The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.

Abstract: Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.

Abstract: The present invention generally relates to the manipulation of species using acoustic waves such as surface acoustic waves. In some aspects, a channel such as a microfluidic channel may be provided having two or more outlets, and acoustic waves applied to species within the channel to determine which outlet the species is directed to. For instance, surface acoustic waves may be applied to a species such as a cell or a particle to deflect it from the channel into a groove or other portion that directs it to a different outlet. In some cases, surprisingly, this deflection of species may be in a different direction than the incident acoustic waves on the channel. Other embodiments of the present invention are generally directed to kits including such systems, techniques for producing such systems, or the like.

Abstract: A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.

Abstract: The present invention is generally related to systems and methods for producing a plurality of droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, the fluidic droplets may be rigidified to form rigidified droplets (e.g., gel droplets). In certain embodiments, the droplets may undergo a phase change (e.g., from rigidified droplets to fluidized droplets), as discussed more herein. In some cases, a species may be added internally to a droplet by exposing the droplet to a fluid comprising a plurality of species.

Abstract: Parallel uses of microfluidic methods and devices for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid are described. In some aspects, the present invention relates generally to flow-focusing-type technology, and also to microfluidics, and more particularly parallel use of microfluidic systems arranged to control a dispersed phase within a dispersant, and the size, and size distribution, of a dispersed phase in a multi-phase fluid system, and systems for delivery of fluid components to multiple such devices.

Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Abstract: The present invention generally relates to systems and techniques for manipulating fluids and/or making droplets. In certain aspects, the present invention generally relates to droplet production. The droplets may be formed from fluids from different sources. In one set of embodiments, the present invention is directed to a microfluidic device comprising a plurality of droplet-making units, and/or other fluidic units, which may be substantially identical in some cases. Substantially each of the fluidic units may be in fluidic communication with a different source of a first fluid and a common source of a second fluid, in certain embodiments. In one aspect, substantially the same pressure may be applied to substantially all of the different sources of fluid, which may be used to cause fluid to move from the different sources into the microfluidic device. In some cases, the fluids may interact within the fluidic units, e.g., by reacting, or for the production of droplets within the microfluidic device.

Abstract: Described herein are methods, uses, and kits for droplet-based single cell sequencing of nucleic acids from extracellular vesicles. Specifically, the disclosure provides methods of analyzing protein compositions from individual extracellular vesicles (EVs) from biological samples including pluralities of EVs, the methods comprising labeling the EVs with antibody-DNA conjugates; encapsulating the labeled EVs, barcoded beads, and an extension reagent mix into droplets; within one or more of the droplets, hybridizing the antibody-DNA conjugates with a hybridization region in the barcoded beads; generating RNA from the DNA; synthesizing cDNA from the RNA; amplifying and sequencing the cDNA from one or more individual EVs from the biological sample; and analyzing the sequence of the cDNA from individual EVs to define their protein composition.

Abstract: The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc.

Abstract: The present invention generally relates to polymers and, in particular, to copolymers for stabilizing, e.g., emulsions or droplets. In certain aspects, the copolymers may comprise a relatively hydrophobic monomer and a relatively hydrophilic monomer polymerized together (e.g., randomly) to form the copolymer. Examples of hydrophobic monomers include methacrylates and vinylphenyls; examples of hydrophilic monomers include boronic acids or acid derivatives. Surprisingly, such random copolymers may act as surfactants, e.g., stabilizing droplets within the emulsion. In addition, in some cases, an interfacial film may be produced by exposing the copolymer to a complexing molecule, such as a polyol, that can complex with the copolymer to form the film. In some cases, the film may at least partially surround a droplet, and in certain embodiments, the film may be sufficiently sturdy such that the droplet can be removed from the emulsion.