Provided herein are multiplexible particle systems and related methods of making and using the multiplexible particle systems. A plurality of monodisperse polymer particle populations are provided, wherein each population has a unique electrical parameter for multiplexed detection by flow through a spatially confined electric field, and the distribution of the electrical parameter within each population is sufficiently narrow for reliable multiplex detection. The density difference between populations may be relatively uniform, such as within 30%, including within 30% of a suspending solution density for when the particles are flowed through a confined electric field and detected in a multiplex manner by a change in the electric parameter measured by a counting device. Relatively uniform density of particles is important for ensuring minimal settling while the plurality of particle populations flow together under a single flow regime. The multiplexible particle systems are used in applications including multiplex detection or quantification, electrically barcoding, sorting, and counting.

The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid.

Methods to fabricate tightly packed arrays of nanoparticles are disclosed, without relying on organic ligands or a substrate. In some variations, a method of assembling particles into an array comprises dispersing particles in a liquid solution; introducing a triggerable pH-control substance capable of generating an acid or a base; and triggering the pH-control substance to generate an acid or a base within the liquid solution, thereby titrating the pH. During pH titration, the particle-surface charge magnitude is reduced, causing the particles to assemble into a particle array. Other variations provide a device for assembling particles into particle arrays, comprising a droplet-generating microfluidic region; a first-fluid inlet port; a second-fluid inlet port; a reaction microfluidic region, disposed in fluid communication with the droplet-generating microfluidic region; and a trigger source configured to trigger generation of an acid or a base from at least one pH-control substance contained within the reaction microfluidic region.

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

An apparatus for biological reactions is provided. The apparatus includes a substrate and a plurality of reaction sites within the substrate. A surface of the substrate is configured to have a first hydrophilicity and each surface of the plurality of reaction sites is configured to have a second hydrophilicity to load a substantial number of reaction sites with a sample volume. The sample volume of each loaded reaction site is substantially confined to its respective reaction site. The sample volume is configured to undergo a biological reaction within the reaction site.

Methods and devices for the formation and/or merging of droplets in microfluidic systems are provided. In certain embodiments a microfluidic droplet merger component is provided that comprises a central channel comprising a plurality of elements disposed and spaced to create a plurality of lateral passages that drain a carrier fluid out of a fluid stream comprising droplets of a first fluid contained in the carrier fluid; and a deformable lateral membrane valve disposed to control the width of said center channel.

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the sunset. The amount of target can be determined based on the detected number.

The present invention provides microfluidic technology enabling rapid and economical manipulation of reactions on the femtoliter to microliter scale.

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.