The present invention relates to systems and methods for manipulating droplets within a high through put microfluidic system.

Method for handling at least one first microdrop and at least one second microdrop in a microfluidic system including a capillary trap that has a first trapping zone and a second trapping zone, the method including steps consisting of: (i) trapping the first microdrop in the first trapping zone, and (ii) trapping the second microdrop in the second trapping zone, the first and the second trapping zone being arranged such that the first and the second microdrops are in contact with each other, the first and the second trapping zones being adapted such that the trapping forces returned to one of the microdrops are different.

The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“CUP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.

Methods of partition-based analysis. In an exemplary method, a device having a port fluidically connected to a chamber may be selected. A sample-containing fluid may be placed into the port. The sample-containing fluid may be moved from the port to the chamber. Partitions of the sample-containing fluid may be formed. A monolayer of the partitions in the chamber may be created. At least a portion of the monolayer may be imaged.

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 or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.

An electrochemical detection chip includes a first substrate and a second substrate opposite to each other, a plurality of driving electrodes, first detection electrodes and second detection electrodes. The plurality of driving electrodes are arranged on a side of the first substrate facing toward the second substrate and are arranged independently. The first detection electrodes and the second detection electrodes are arranged at a plurality of positions on a side of the second substrate facing toward the first substrate that are directly opposite at least a part of the plurality of driving electrodes, and are spaced apart from each other.

The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Provided herein are methods of splitting droplets containing magnetically responsive beads in a droplet actuator. A droplet actuator having a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at the droplet operations electrodes, is provided. The magnetically responsive beads in the droplet are immobilized using the magnetic field and the plurality of droplet operations electrodes are used to split the droplet into first and second droplets while the magnetically responsive beads remain substantially immobilized.

A system for processing a biological sample includes a substrate comprising a plurality of wells and a plurality of flow channels. The system further includes a flow control system comprising a manifold having a plurality of ports configured to fluidically couple to the plurality of wells, and one or more containment structures configured to contain carrier fluid and fluidically couple to the ports. The flow control system further includes a cradle configured to removably receive the substrate. The flow control system is configured to transmit pressure differential, via the manifold, to the plurality of wells so as to cause a plurality of sample volumes held by at least some wells of the plurality of wells to flow through respective flow channels and cause the carrier fluid to flow through the flow channels and form a plurality of droplets of the plurality of sample volumes separated by the carrier fluid.

The invention generally relates to performing sandwich assays in droplets. In certain embodiments, the invention provides methods for detecting a target analyte that involve forming a compartmentalized portion of fluid including a portion of a sample suspected of containing a target analyte and a sample identifier, a first binding agent having a target identifier, and a second binding agent specific to the target analyte under conditions that produce a complex of the first and second binding agents with the target analyte, separating the complexes, and detecting the complexes, thereby detecting the target analyte.