Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.

Methods and apparatus for controlling flow in a microfluidic arrangement are disclosed. In one arrangement, a microfluidic arrangement comprises a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate. The microfluidic pattern comprises at least an elongate conduit and a first reservoir. A second liquid is in direct contact with the first liquid and covers the microfluidic pattern. A flow of liquid is driven through the elongate conduit into the first reservoir. The microfluidic pattern and the depth and density of the second liquid are such that the first reservoir grows in volume during the flow of liquid into the first reservoir, without either of the size and shape of an area of contact between the first reservoir and the substrate changing, until an upper portion of the first reservoir detaches from a lower portion of the first reservoir due to buoyancy and rises upwards through the second liquid, thereby allowing the first reservoir to continue to receive liquid from the flow of liquid without any change in the size and shape of the area of contact between the first reservoir and the substrate.

The disclosure relates to a method for operating a microfluidic device that includes providing at least one first medium at a first location of the microfluidic device, transporting at least one first medium from a first location to a second location of the microfluidic device, the at least one first medium being surrounded by at least one second medium in such a way that the at least one first medium only borders on the at least one second medium and on fluid boundaries of the microfluidic device or only on the at least one second medium. The at least one first medium and the at least one second medium cannot be mixed with one another.

The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.

A fluid handling device has an introduction port, a first flow channel which is connected to the introduction port and in which a droplet can move when a fluid including the droplet is caused to flow therein, a first chamber for capturing the droplet moving through the first flow channel, and a second chamber through which the droplet captured by the first chamber can move via the first flow channel. The liquid handling device is capable of switching between a first state in which a droplet moving through the first flow channel is captured by the first chamber, and a second state in which the droplet captured by the first chamber moves to the second chamber via the first flow channel.

The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.

Methods and apparatus for driving flow in a microfluidic arrangement are provided. In one disclosed arrangement, the microfluidic arrangement comprises a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate. The microfluidic pattern comprises at least an elongate conduit and a first reservoir. The area of contact between the substrate and a portion of the first liquid that forms the elongate conduit defines a conduit footprint. The area of contact between the substrate and a portion of the first liquid that forms the first reservoir defines a first reservoir footprint. The size and shape of each of the conduit footprint and the first reservoir footprint are such that a maximum Laplace pressure supportable by the first liquid in the elongate conduit without any change in the conduit footprint is higher than a maximum Laplace pressure supportable by the first liquid in the first reservoir without any change in the first reservoir footprint. A delivery member having an internal lumen leading to a distal opening through which liquid can be delivered is provided. Liquid is pumped into the microfluidic pattern through the distal opening while the distal opening is held in a delivery position. The delivery position is such that the liquid enters the microfluidic pattern via the elongate conduit and drives a flow of liquid into the first reservoir.

A separation device, system and associated method are provided herein for separation of particulates form a base fluid. The separation device comprises a first microchannel comprising a fluid inlet and a mesofluidic collection chamber. The mesofluidic collection chamber has a first side and a second side, wherein the mesofluidic collection chamber is operatively coupled to the first microchannel on the first side, and wherein the mesofluidic collection chamber comprises a first fluid outlet at the second side, such that the fluid inlet, first microchannel, and first fluid outlet are in fluidic communication via the mesofluidic collection chamber.

The invention relates to a microfluidic system comprising: a) a solid support comprising at least a first group of oligonucleotides, i. wherein each oligonucleotide in said group comprises a nucleic acid sequence of a first type, of a second type and/or a further type, ii. wherein said nucleic acid sequence of a first type is a barcode sequence, iii. and oligonucleotides comprising the same barcode sequence are grouped together in a group of oligonucleotides on said solid support, iv. wherein the first and further oligonucleotide groups are spatially separated on said solid support, b) wherein said one or more groups of oligonucleotide groups on said solid support are within separate reservoirs of the microfluidics system, c) wherein the one or more reservoirs are accessible to fluids, cells, chemicals and/or microdroplet by means of channels, and d) wherein each reservoir comprises comprising a group of oligonucleotides on said solid support is also trap for a microfluidic droplet.

A microfluidic chip for focussing a stream of particulate containing fluid comprises a sample microfluidic channel configured to receive the stream of particulate containing fluid, a guidance microfluidic channel having a polygonal cross-sectional area and configured to receive a stream of guidance fluid, and a common microfluidic channel having a polygonal cross sectional area formed by the merging of the sample microfluidic channel and the guidance 10 microfluidic channel at an oblique angle along only part of one or more sides of the guidance microfluidic channel, and a detection zone disposed in the common microfluidic channel having one or more sensors. The merging of the sample microfluidic channel and the guidance microfluidic channel is configured to provide a composite fluid stream containing a focussed beam of particulates that is disposed asymmetrically in the common microfluidic channel 15 adjacent a corner or side of the common microfluidic channel and wherein the one or more sensors are configured for sensing a characteristic of the focussed beam of particulates in the common channel.