This application provides fluidic devices, such as microfluidic devices, which can be used for the creation and/or manipulation of droplets in droplet-based microfluidic systems, as well as systems and methods for using the same. The microfluidic devices can be used to generate droplets, extract or inject volume to droplets, and/or split droplets. Also provided are methods for generating nucleosomes, and isolated DNA from nucleosomes (or from non-nucleosomes), for example using the disclosed devices.

Devices, systems, and their methods of use, for generating droplets are provided. One or more geometric parameters of a microfluidic channel can be selected to generate droplets of a desired and predictable droplet size.

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

Described herein are apparatuses and methods for the processing and/or measurements of chemical or biochemical samples on a digital microfluidic device. Also described are methods to configure and operate the modules for efficient processing and measurements of the samples on the device. The apparatus can be used in applications such as DNA/RNA/protein/cell concentration/purification, real-time PCR, isothermal amplification, immunoassay, cell-based assay, library preparation for NGS sequencing, etc.

Engineered nanoscale multicomponent particles are introduced and are called “quants.” Methods and apparatuses for producing such multicomponent nanoparticles are provided. A single quant can be manufactured to contain a variety of different internal component molecules. Likewise, a plurality of such quants may be manufactured wherein the plurality of quants are suspended in an aqueous solution. Typically, quants are produced in quantity and concentration adequate to support human scale therapeutics. In some embodiments, millions or billions of quants are suspended in a volume of aqueous solution for delivery to a patient. When manufactured to the same specification, the plurality of quants are uniform in size, uniform in chemical composition, and therefore uniform in functionality. Functional uniformity is an essential aspect of quants, manifested in design and production. By controlling the variables of manufacture, such as particle size and composition, and by redefining a drug dose as the measured number of quants delivered (as opposed to measuring a drug dose by the mass of its active ingredient), the performance of these nanoparticle-based drugs introduce significant efficiencies and much higher value products to the expanding therapeutics market.

In a first aspect, the present invention relates to a method of producing a library of microorganisms, the method comprising the steps of: a. providing a first fluid comprising at least one single cell, b. dispersing said first fluid comprising at least one single cell in a second fluid, thereby obtaining a plurality of single-layer microfluidic droplets, wherein at least one single- layer microfluidic droplet comprises at least one single cell, wherein the second fluid is immiscible with the first fluid, c. optionally, adding to said at least one single-layer microfluidic droplet a third fluid comprising a sensing compound, wherein the third fluid is miscible with said first fluid, and wherein the third fluid is immiscible with said second fluid, d. injecting said at least one single-layer microfluidic droplet optionally comprising the sensing compound into a fourth fluid, wherein said fourth fluid is immiscible with said second fluid, thereby obtaining at least one double-layer microfluidic droplet, e. dispensing said at least one double-layer microfluidic droplet into a culture medium based on the viability of the cell, f. incubating said culture medium, thereby obtaining said library. In a second aspect, the present invention relates to a system comprising: a. a first microfluidic chip for producing a plurality of single-layer microfluidic droplets wherein at least one single-layer microfluidic droplet comprises at least one single cell, b. a first microfluidic device for collecting said plurality of single-layer microfluidic droplets, c. a second device for adding a sensing compound into said at least one single-layer microfluidic droplet comprising at least one single cell, d. a second microfluidic chip for producing a double-layer microfluidic droplet, and e. a dispensing unit. In a third aspect, the present invention relates to the use of the method according to the first aspect of the present invention in a system according to the second aspect of the present invention.

Methods for selectively adding one or more reagents are provided. In certain aspects, the methods include selectively merging one or more droplets of a plurality of droplets with one or more droplets of a plurality of reagent droplets based on detection of a property. Systems, devices and kits for practicing the subject methods are also provided. The subject disclosure may find use in a wide variety of applications, such as increasing the accuracy and/or efficiency of single-cell sequencing, detection of cancer or other diseases, monitoring disease progression, analyzing the DNA or RNA content of cells, and other applications in which it is desired to detect and/or quantify specific target cells.

A method of encapsulating a solid sample in a droplet, the method including flowing a continuous phase through a first fluid channel at a first flow rate; flowing a dispersed phase through a second fluid channel at a second flow rate, the dispersed phase including a plurality of particles, cells or beads; trapping the plurality of particles, cells or beads in a mixing region that receives the dispersed phase and the continuous phase; and reducing the first flow rate to encapsulate the trapped particles, cells or beads in droplets of the dispersed phase generated when the dispersed phase and the continuous phase exit the mixing region through an orifice.

This relates to acoustic microfluidic systems that can generate emulsions/droplets or encapsulate particles of interest (including mammalian cells, bacteria cells, or other cells) into droplets upon detection of the particles of interest flowing in a stream of particles. The systems operate on the detect/decide/deflect principle wherein the deflection step, in a single operation, not only deflects particles of interest from a stream of particles but also encapsulates the particles of interest in an emulsion droplet. The microfluidic systems have an abrupt transition in the channel geometry from a shorter channel to a taller channel (i.e., in the shape of a ‘step’) to break the stream of the dispersed phase into a droplet upon acoustic actuation. When there is no acoustic wave present, no droplets/emulsions are generated and the stream of particles proceeds uninterrupted. The rapid actuation and post-actuation recovery employed by the microfluidic systems taught herein ensure that the vast majority of selected particles are properly deflected, that few or no empty droplets are produced, and that total throughput remains high.

The present disclosure provides a microfluidic chip and a droplet separation method, and belongs to the field of biological chip technology. The microfluidic chip includes a first liquid tank and a second liquid tank opposite to each other and a channel layer therebetween. The channel layer includes a plurality of microfluidic channels separated from each other, first ends of the microfluidic channels are communicated with the first liquid tank, and second ends are communicated with the second liquid tank. The first liquid tank contains sample solution to be detected, and the second liquid tank contains encapsulating liquid. The sample solution to be detected entering the first liquid tank may be separated into a plurality of sample droplets through the microfluidic channels, the separated sample droplets enter the second liquid tank, so that the encapsulating liquid is encapsulated on a surface of each of the plurality of sample droplets.