System, including methods, apparatus, and kits, for forming emulsions. In an exemplary method of generating droplets, a device may be selected that includes a plurality of emulsion-formation units each including a sample well, a continuous-phase well, a droplet well, and a channel network that fluidically interconnects the wells and creates a droplet-generation region. A discrete volume of sample-containing fluid may be placed into the sample well of each emulsion-formation unit, and a discrete volume of continuous-phase fluid into the continuous-phase well of each emulsion-formation unit. Pressure may be applied to the device with a fluidics assembly after the step of placing, such that the plurality of emulsion-formation units generate droplets in parallel with one another. A pressure signal may be detected from the fluidics assembly. Application of the pressure may be stopped when the pressure signal indicates that a sample well is empty.

In a method for mixing two liquid components of a medium with the aid of a static mixer, the two components are supplied to the static mixer, are mixed therein and are subsequently dispensed from the mixer. In this respect, only one respective component is supplied to the mixer, while the other component is not supplied to the mixer.

Fluidic devices and methods associated with mixing of fluids in fluidic devices are provided. In some embodiments, a method may involve the mixing of two or more fluids in a channel segment of a fluidic device. The fluids may be in the form of, for example, at least first, second and third fluid plugs, composed of first, second, and third fluids, respectively. The second fluid may be immiscible with the first and third fluids. In certain embodiments, the fluid plugs may be flowed in series in the channel segment, e.g., in linear order, causing the first and third fluids to mix without the use of active components such as mixers. The mixing of fluids in a channel segment as described herein may allow for improved performance and simplification in the design and operations of fluidic devices that rely on mixing of fluids.

Method of detecting a signal from droplets for instrument calibration. In the method, a calibration standard for a droplet detection instrument may be received. The calibration standard may have been shipped at least one kilometer when received. The calibration standard may include a mixture of first droplets and second droplets. Each of the first and second droplets may be encapsulated by an immiscible carrier liquid and may have a stabilizing droplet skin that is formed by heating and that includes a skin-forming protein. Each the first droplets may contain a fluorescent dye, and each of the second droplets may contain a fluorescent dye. A fluorescence signal may be detected from a plurality of the first and second droplets with a droplet detection instrument. The fluorescence signal may be stronger for the first droplets than the second droplets.

System, including methods, apparatus, and kits, for forming emulsions. In an exemplary method of generating droplets, a device may be selected that includes a plurality of emulsion-formation units each including a sample well, a continuous-phase well, a droplet well, and a channel network that fluidically interconnects the wells and creates a droplet-generation region. A discrete volume of sample-containing fluid may be placed into the sample well of each emulsion-formation unit, and a discrete volume of continuous-phase fluid into the continuous-phase well of each emulsion-formation unit. Pressure may be applied to the device with a fluidics assembly after the step of placing, such that the plurality of emulsion-formation units generate droplets in parallel with one another. A pressure signal may be detected from the fluidics assembly. Application of the pressure may be stopped when the pressure signal indicates that a sample well is empty.

Fluidic devices and methods associated with mixing of fluids in fluidic devices are provided. In some embodiments, a method may involve the mixing of two or more fluids in a channel segment of a fluidic device. The fluids may be in the form of, for example, at least first, second and third fluid plugs, composed of first, second, and third fluids, respectively. The second fluid may be immiscible with the first and third fluids. In certain embodiments, the fluid plugs may be flowed in series in the channel segment, e.g., in linear order, causing the first and third fluids to mix without the use of active to components such as mixers. The mixing of fluids in a channel segment as described herein may allow for improved performance and simplification in the design and operations of fluidic devices that rely on mixing of fluids.

The present disclosure provides methods and compositions for detecting polynucleotides in a sample and for quantifying polynucleotide load in a sample. The polynucleotides can be associated with a disease, disorder, or condition. In some applications, methylated DNA is quantified, e.g., in order to determine the load of polynucleotides in a sample. The present disclosure also provides methods and compositions for determining the load of fetal polynucleotides in a biological sample, e.g., the load of fetal polynucleotides (e.g., DNA, RNA) in maternal plasma. The present disclosure provides methods and compositions for detecting cellular processes such as cellular viability, growth rates, and infection rates. This disclosure also provides compositions and methods for detecting differences in copy number of a target polynucleotide. In some embodiments, the methods and compositions provided herein are useful for diagnosis of fetal genetic abnormalities, when the starting sample is maternal tissue (e.g., blood, plasma). The methods and materials described apply techniques for allowing detection of small, but statistically significant, differences in polynucleotide copy number.

A device for recording data in nucleic acids that includes a liquid dispenser configured to dispense a carrier drop, a drop collecting element, wherein during operation of the device the carrier drop flies from the liquid dispenser towards the drop collecting element in a trajectory, and at least two other liquid dispensers, arranged such that the carrier drop's trajectory passes by the at least two other liquid dispensers. The at least two other liquid dispensers are configured to dispense two respective drops towards the trajectory of the carrier drop in a synchronized manner, such that the carrier drop sequentially collides with the two drops. Each drop of the two drops aggregately includes a subset of components from a set of nucleic acid components, thereby the subsets of components are located in the carrier drop during flight and before the carrier drop lands on the drop collecting element.

In a method for continuously supplying a metering device with different batches of one and the same liquid medium, a progressive addition of the medium of a new batch takes place during a batch change.