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.

Disclosed herein are systems and methods for serial flow emulsion processes. Systems and methods as described herein result in reduced cross-contamination.

The invention provides methods for assessing one or more predetermined characteristics or properties of a microfluidic droplet within a microfluidic channel, and regulating one or more fluid flow rates within that channel to selectively alter the predetermined microdroplet characteristic or property using a feedback control.

This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls, and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced. In another set of embodiments, a fluidic stream may be manipulated in some fashion, for example, to create tubes (which may be hollow or solid), droplets, nested tubes or droplets, arrays of tubes or droplets, meshes of tubes, etc. In some cases, droplets produced using certain embodiments of the invention may be charged or substantially charged, which may allow their further manipulation, for instance, using applied external fields. Non-limiting examples of such manipulations include producing charged droplets, coalescing droplets (especially at the microscale), synchronizing droplet formation, aligning molecules within the droplet, etc. In some cases, the droplets and/or the fluidic streams may include colloids, cells, therapeutic agents, and the like.

The present invention generally relates to microfluidics, and, in particular, to systems and methods for coalescing or fusing droplets. In certain aspects, two or more droplets within a microfluidic channel are brought together and caused to coalesce without using electric fields or charges. For example, in certain embodiments, droplets stabilized with a surfactant may be disrupted, e.g., by exposing the droplets to a solvent able to alter the surfactant, which may partially destabilize the droplets and allow them to coalesce. In some instances, the droplets may also be physically disrupted to facilitate coalesce. In addition, in some cases, the positions of one or more droplets may be controlled within a channel using a groove in a wall of the channel. For example, a droplet may at least partially enter the groove such that the position of the droplet is at least partially controlled by the groove.

A system for analyzing a biological sample may include at least one sample acquisition stage comprising a sample acquisition device for acquiring the biological sample from a sample source; a droplet generator device for forming a droplet wrapped in an immiscible carrier fluid, wherein the wrapped droplet comprises at least the biological sample and a reagent, the droplet generator configured to receive the biological sample transferred from the sample acquisition device; a collection vessel for collecting the wrapped sample droplet from the droplet generator, the vessel configured to contain a carrier fluid for receiving and protecting the sample droplet; and an analysis system for analyzing the wrapped sample droplet and detecting products of a polymerase chain reaction.

The present invention discloses polymer surfaces with T-shaped microstructure and their fabrication method and applications. The polymer surfaces with the T-shaped microstructure are characterized in that T-shaped microposts arrange orderly on them, and nanobulges arrange orderly on the top surfaces of the micronails of the T-shaped microposts. A flexible insert is designed and manufactured according to the geometry of the T-shaped microposts, and nanogrooves are manufactured on the cavity surface of an injection mold according to the geometry of the nanobulges on the top surfaces of the micronails. The flexible insert is mounted on the injection mold cavity. An injection molding machine is used to inject the molten polymer into the injection mold cavity. Then the polymer surfaces with the T-shaped microposts, on the top surfaces of the micronails of which the nanobulges arrange orderly, are molded. The polymer surfaces with the T-shaped microstructure exhibit robust Cassie-Baxter state and moderate surface adhesion to water droplets, and can be used for quantitative collection, lossless transportation or micromixing of microdroplets.

Microfluidic methods for barcoding nucleic acid target molecules to be analyzed, e.g., via nucleic acid sequencing techniques, are provided. Also provided are microfluidic, droplet-based methods of preparing nucleic acid barcodes for use in various barcoding applications. The methods described herein facilitate high-throughput sequencing of nucleic acid target molecules as well as single cell and single virus genomic, transcriptomic, and/or proteomic analysis/profiling. Systems and devices for practicing the subject methods are also provided.

Systems and methods for continuous flow polymerase chain reaction (PCR) are provided. The system comprises an injector, a mixer, a coalescer, a droplet generator, a detector, a digital PCR system, and a controller. The injector takes in a sample, partitions the sample into sample aliquots with the help of an immiscible oil phase, dispenses waste, and sends the sample aliquot to the mixer. The mixer mixes the sample aliquot with a PCR master mix and diluting water, dispenses waste, and sends the sample mixture (separated by an immiscible oil) to the coalescer. The coalescer coalesces the sample mixture with primers dispensed from a cassette, dispenses waste, and sends the reaction mixture (separated by an immiscible oil) to the droplet generator. The droplet generator converts the sample mixture into an emulsion where aqueous droplets of the reaction mixture are maintained inside of an immiscible oil phase and dispenses droplets to the digital PCR system. The digital PCR system amplifies target DNAs in the droplets. The detector detects target DNAs in the droplets. The controller controls the system to run automatically and continuously.

The invention provides a device, method, and system for high throughput detection of nucleic acid expression in individual cells. Cells are encapsulated in aqueous microdroplets which are merged with a biocompatible matrix, allowing on-chip fluorescence in situ hybridization on both adherent and non-adherent cells. The invention also provides multiplexed detection of nucleic acids, proteins, and cellular activity. The device and methods can be used to assess cellular interactions and to test the effects of antitumor agents.