Sub-millimeter scale three-dimensional (3D) structures are disclosed with customizable chemical properties and/or functionality. The 3D structures are referred to as drop-carrier particles. The drop-carrier particles allow the selective association of one solution (i.e., a dispersed phased) with an interior portion of each of the drop-carrier particles, while a second non-miscible solution (i.e., a continuous phase) associates with an exterior portion of each of the drop-carrier particles due to the specific chemical and/or physical properties of the interior and exterior regions of the drop-carrier particles. The combined drop-carrier particle with the dispersed phase contained therein is referred to as a particle-drop. The selective association results in compartmentalization of the dispersed phase solution into sub-microliter-sized volumes contained in the drop-carrier particles. The compartmentalized volumes can be used for single-molecule assays as well as single-cell, and other single-entity assays.

In a channel structure of a channel device, first confluence channels of a plurality of first channels include a plurality of first confluence channels arranged along a second board front surface, first confluence portions of the first channels in each of first boards are configured of a plurality of first confluence portion through-holes that penetrate the first board, and second first-liquid introduction channel and second second-liquid introduction channels of a plurality of second channels are arranged along the second board front surface and are located in an area that is deviated from the first confluence channels in a view in a direction along a stacking direction of the first board and the second board.

The present disclosure provides methods and systems for sample preparation and/or analysis. Samples may be cells, or may be derived from one or more cells. Sample preparation may comprise conducting one or more reactions on a target. Such reactions may be conducted in one or more partitions. One or more reactions may be performed in one or more successive operations.

A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target biological particle containing genomic material, and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid, and provided to a downstream workflow.

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 fluid handling device includes a sample channel configured to carry a sample; a dispersion medium channel configured to carry dispersion medium; a dispersion liquid generation part connected to the sample channel and the dispersion medium channel, and configured to generate dispersion liquid by dividing the sample by the dispersion medium, the dispersion liquid being liquid in which droplets of the sample are dispersed in the dispersion medium; and a dispersion liquid channel connected to the dispersion liquid generation part. The dispersion liquid generation part includes a protrusion.

In an embodiment, the present disclosure pertains to a microfluidic platform composed of a droplet generator having an entry point for donor particles and target particles, a first droplet incubation chamber in fluid communication with the droplet generator, a droplet detection functionality to allow for analysis of the inner content of droplets, and a droplet sorting functionality to allow for the separation of droplets based on the analysis of the inner content of droplets. In another embodiment, the present disclosure pertains to a method for cell-to-cell DNA, RNA, or other genetic material transfer through use of a water-in-oil emulsion microdroplet-based microfluidic platform for automation and high throughput identification or screening of genetic transfer outcomes utilizing the microfluidic platforms as disclosed herein.

The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Systems and methods for detection of a signal from droplets of an emulsion. An exemplary system may comprise a fluid transporter having a tube with an open end for aspirating droplets, a singulator to arrange the droplets in single file and to space the single-file droplets from one another, and a detection channel in optical communication with a detector configured to detect a signal from droplets. In some embodiments, the singulator may have a channel junction at which a stream of droplets in single file is combined with a stream of spacing fluid, and a tapered spacing channel extending downstream from the channel junction toward the detection channel. In some embodiments, the fluid transporter may suck droplet-containing fluid and spacing fluid through the detection channel from respective sources. In some embodiments, droplets may be subjected to a disaggregation routine before they are passed through the detection channel.

Microfluidic devices having a construct formed from perfluoropolyether and poly(ethylene glycol) diacrylate. The construct includes an inlet for receiving a continuous phase fluid, an inlet for receiving a dispersed phase fluid, and a plurality of channels extending through the construct. The plurality of channels are in fluid communication with both the inlet of the continuous phase fluid and the inlet of the dispersed phase fluid. The construct further includes a plurality of microdroplet generators configured to produce microdroplets, each of the microdroplet generators in fluid communication with the plurality of channels. Additionally, the construct includes an outlet formed in the construct and in fluid connection with the plurality of microdroplet generators.