The present invention relates to methods, devices, instruments, processes, and systems for the highly specific, targeted molecular analysis of regions of human genomes and transcriptomes from the blood, i.e. from cell free circulating DNA, exosomes, microRNA, lncRNA, circulating tumor cells, or total blood cells. The technology enables highly sensitive identification and enumeration of mutation, expression, copy number, translocation, alternative splicing, and methylation changes using spatial multiplexing and combined nuclease, ligation, polymerase, and sequencing reactions. Such technology may be used for non-invasive early detection of cancer, non-invasive cancer prognosis, and monitoring both treatment efficacy and disease recurrence of cancer.

A system and a method for on-chip dilution of a calibration solution are provided. An exemplary system includes a microfluidic ejector chip. The microfluidic ejector chip includes a calibration reservoir to contain a calibration standard and a dilution reservoir to contain a dilution solvent. A first fluid control device couples the calibration reservoir to a mixing chamber, and a second fluid control device couples a dilution reservoir to the mixing chamber. The mixing chamber is fluidically coupled to a microfluidic ejector.

The application relates to microfluidic apparatus and methods of use thereof. Provided in one example is a microfluidic device comprising: a first fluidic input and a second fluidic input; and a fluidic intersection channel to receive fluid from the first fluidic input and the second fluidic input, wherein the fluidic intersection channel opens into a first mixing chamber on an upper region of a first side of the first mixing chamber, wherein the first mixing chamber has a length, a width, and a depth, wherein the depth is greater than about 1.5 times a depth of the fluidic intersection channel; an outlet channel on an upper region of a second side of the first mixing chamber, wherein the outlet channel has a depth that is less than the depth of the first mixing chamber, and wherein an opening of the outlet channel is offset along a width of the second side of the first mixing chamber relative to the fluidic intersection.

According to one embodiment, a fluid controller includes a fluid channel deforming portion and a mixing portion provided downstream from the fluid channel deforming portion. The fluid channel deforming portion includes an upstream end portion, a first channel, a second channel and a channel terminating portion. At least one of the first and second channels is deformed between the upstream end portion and the channel terminating portion. A region of the second channel in a second cross-section, is increased more than a region of the second channel in the first cross-section, between the upstream end portion ad the channel terminating portion. The mixing portion mixes a plurality of fluids flowing through the fluid channel deforming portion.

A microfluidic valve provided herein is configured to mix or capable of mixing a sample and/or a reagent in addition to controlling liquid flow. In one embodiment, the microfluidic valve comprises a rotor (3) and one or more micro-structures (2) that move with the rotation of the rotor (3). In one embodiment, the one or more micro-structures (2) stir and/or mix content in a mixing chamber (5) formed by the rotor (3), a base (1), and a sleeve (4) of the microfluidic valve. A microfluidic chip or chip system comprising one or more of the microfluidic valves, and methods of use, are also provided.

The present disclosure relates to a microfluidic concentrating particlizers including a particle generator, a particle concentrator, and a fluid movement network. The particle generator includes a sample inlet microchannel and a reagent inlet microchannel. The sample inlet microchannel is operable to direct a source sample. The reagent inlet microchannel is operable to direct reagent. The source sample and reagent come in contact to form a sample fluid dispersion including sample-modified particulates and fluid. The particle concentrator includes a filtering chamber fluidly coupled to the particle generator to concentrate sample-modified particulates relative to the fluid. The fluid movement network includes multiple pumps to generate fluidic flow through both the particle generator and the particle concentrator.

The application relates to microfluidic apparatus and methods of use thereof. Provided in one example is a microfluidic device comprising: a first fluidic input and a second fluidic input; and a fluidic intersection channel to receive fluid from the first fluidic input and the second fluidic input, wherein the fluidic intersection channel opens into a first mixing chamber on an upper region of a first side of the first mixing chamber, wherein the first mixing chamber has a length, a width, and a depth, wherein the depth is greater than about 1.5 times a depth of the fluidic intersection channel; an outlet channel on an upper region of a second side of the first mixing chamber, wherein the outlet channel has a depth that is less than the depth of the first mixing chamber, and wherein an opening of the outlet channel is offset along a width of the second side of the first mixing chamber relative to the fluidic intersection.

The application relates to microfluidic apparatus and methods of use thereof. Provided in one example is a microfluidic device comprising: a first fluidic input and a second fluidic input; and a fluidic intersection channel to receive fluid from the first fluidic input and the second fluidic input, wherein the fluidic intersection channel opens into a first mixing chamber on an upper region of a first side of the first mixing chamber, wherein the first mixing chamber has a length, a width, and a depth, wherein the depth is greater than about 1.5 times a depth of the fluidic intersection channel; an outlet channel on an upper region of a second side of the first mixing chamber, wherein the outlet channel has a depth that is less than the depth of the first mixing chamber, and wherein an opening of the outlet channel is offset along a width of the second side of the first mixing chamber relative to the fluidic intersection.

Distribution valve comprising: a stationary element comprising a first valve bearing surface, said stationary element comprising a plurality of first fluid ports and at least one second fluid port, each of said fluid ports emerging at said first valve bearing surface and being in fluidic communication with a corresponding conduit provided in said stationary element; a movable element comprising a second valve bearing surface in contact with said first bearing surface, said movable element being arranged to be movable with respect to said stationary element and being arranged to bring at least one of said first ports into fluidic communication with said second port in function of the relative position of said movable element with respect to said stationary element;
characterised in that: said stationary element comprises a mixing chamber in fluidic communication with one of said first fluid ports.

In another embodiment, the mixing chamber can be provided in the movable element rather than in the stationary element.

Articles and methods involving fluidic devices are generally provided. In some embodiments, a fluidic device comprises a first layer comprising first and second regions that are disconnected from each other in the first layer and a second layer comprising a channel in fluidic communication with the first and second regions. The device may also comprise a third layer comprising a channel in fluidic communication with the first and second regions. One or more portions of a channel and/or one or more reagents may comprise reagent. In some embodiments, a method comprises flowing two or more fluid samples towards each other through a channel. The fluids may meet at an interface and/or may react at an interface.