The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

A droplet generator apparatus and droplet generation method based on high aspect ratio induced droplet self-breakup are provided. The droplet generator apparatus includes a channel (1) and a nozzle (2) connected to the channel(1), and the aspect ratio of the channel (1) can be 3.0 or greater. The apparatus may further include a blocking rail (10) that is positioned in front of the nozzle (2), a supplying rail(9) that is positioned in front of the nozzle (2), and a supplying trench (8) formed in a space between the nozzle (2) and the supplying rail (9).

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction. In a related aspect of the invention, systems and methods for allowing fluid mixing within droplets to occur are also provided. In still another aspect, the invention relates to systems and methods for sorting droplets, e.g., by causing droplets to move to certain regions within a fluidic system. Examples include using electrical interactions (e.g., charges, dipoles, etc.) or mechanical systems (e.g., fluid displacement) to sort the droplets. In some cases, the fluidic droplets can be sorted at relatively high rates, e.g., at about 10 droplets per second or more. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.

A lipid nanoparticles manufacturing chip includes a first raw material supply flow path, a second raw material supply flow path, and a mixer portion connected to the first raw material supply flow path and the second raw material supply flow path and configured for mixing a first raw material supplied through the first raw material supply flow path and a second raw material supplied through the second raw material supply flow path. The mixer portion includes a first stabilizing unit, and a first mixing unit connected to the first stabilizing unit and configured for mixing the first raw material and the second raw material with each other. Mixing of the first raw material and the second raw material is performed more in the first mixing unit than in the first stabilizing unit.

The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion of washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.

Devices, systems, and their methods of use, for generating droplets are provided. One or more geometric parameters of a microfluidic channel can be selected to generate droplets of a desired and predictable droplet size.

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction. In a related aspect of the invention, systems and methods for allowing fluid mixing within droplets to occur are also provided. In still another aspect, the invention relates to systems and methods for sorting droplets, e.g., by causing droplets to move to certain regions within a fluidic system. Examples include using electrical interactions (e.g., charges, dipoles, etc.) or mechanical systems (e.g., fluid displacement) to sort the droplets. In some cases, the fluidic droplets can be sorted at relatively high rates, e.g., at about 10 droplets per second or more. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.

Apparatus for controlling motion of liquid droplets. A set of electrode pads is arranged to define one or more tracks over which liquid droplets may be induced to move over a sequence of the electrode pads. A surface over the electrode pads is dielectric, smooth, and slippery to the droplets. In some cases, the smooth surface is formed as a thin layer of a second liquid that is immiscible with the liquid of the droplets. The surface has wetting affinity to the liquid that can be individually varied in a controlled manner by application of voltage to respective electrode pads. A control is designed to alter the wetting characteristic of varying-wettability portions of the surface over respective electrode pads to effect induced motion of the droplets over the surface. The apparatus is designed with the smooth hydrophobic surface open, with no overlying or facing electrode or plate above the droplets.

An integrated semiconductor device for manipulating and processing bio-entity samples and methods are described. The device includes a lower substrate, at least one optical signal conduit disposed on the lower substrate, at least one cap bonding pad disposed on the lower substrate, a cap configured to form a capped area, and disposed on the at least one cap bonding pad, a fluidic channel, wherein a first side of the fluidic channel is formed on the lower substrate and a second side of the fluidic channel is formed on the cap, a photosensor array coupled to sensor control circuitry, and logic circuitry coupled to the fluidic control circuitry, and the sensor control circuitry.

An isolation device for isolation of target particles from a plurality of liquid samples includes a plurality of isolation chips and a vacuum system. Each of the plurality of isolation chips includes a sample reservoir, and a first outlet and a second outlet disposed at opposite sides of the sample reservoir. The vacuum system includes a first vacuum pump connected to the first outlet of each of the plurality of isolation chips and a second vacuum pump connected to the second outlet of each of the plurality of isolation chips. The first vacuum pump generates a negative pressure in each of the plurality of isolation chips through a corresponding first outlet. The second vacuum pump generates a negative pressure in each of the plurality of isolation chips through a corresponding second outlet. The target particles are isolated from each of the plurality of liquid samples in a corresponding sample reservoir.