Provided are methods, devices, assemblies, and systems for dispensing into the wells of a multi-well device and imaging such wells from multiple Z-planes. Multi-Z imaging of the present methods and systems may allow for the detection of wells of a multi-well device that contain a desired number of cells. Also provided are methods, devices, assemblies, and systems for processing cell-containing wells of a multi-well device identified through the use of multi-Z imaging.

Disclosed herein are methods for producing high density cellular arrays. In some embodiments, the methods comprise: providing a sample comprising a plurality of cells; and introducing the plurality of cells in the sample into microwells of a microwell array to produce a cellular array, wherein the microwell array comprises 500 or more microwells per inch.sup.2, and wherein 25% or more of the microwells of the cellular array comprise a single cell. The disclosed methods can be used for producing a high density synthetic particle array and a high density reagent array.

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

The invention is directed to methods for synthesizing oligonucleotides directly on biomolecules or cells living or fixed. In some embodiments, template-free enzymatic synthesis is implemented under biological conditions with successive cycles of (i) enzymatic addition of a 3′-O-blocked nucleoside triphosphate and (ii) enzymatic deblocking of the incorporated nucleotide to regenerate a free 3′ hydroxyl. The invention has applications in single-cell cDNA library construction and analysis.

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.

An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

The present invention relates to a device comprising or consisting of: (a) a vessel; (b) a magnet inside said vessel; (c) means to trigger movement of said magnet with acoustic to ultrasonic frequency, preferably ultrasonic frequencies.

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

The present disclosure provides methods and systems for generation of compositions comprising two or more sets of molecules. Compositions herein may comprise sets of molecules of different types. Sets of molecules may be generated by attachment to supports. Different types of molecules may be used to generate a large number of unique molecules. One or more types of molecules may be used to identify one or more additional types of molecules. Compositions of the present disclosure may be used in, for example, nucleic acid sequencing.