The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in loading of polymerase enzyme complexes into a predetermined number of reaction sites, including nanoscale wells.

A device for synthesis of macromolecules is disclosed. In one aspect, the device comprises an ion-releaser having a synthesis surface comprising an array of synthesis locations arranged for synthesis of the macromolecules. The ion-releaser also includes an ion-source electrode, which is arranged to contain releasable ions and is arranged to be in contact with each of the synthesis locations of the synthesis surface, thereby release ions to the synthesis locations. The ion-releaser further comprises activating electrodes, which are arranged to be in contact with the ion-source electrode, wherein each one of the activating electrodes is arranged in association with one of the synthesis locations via the ion-source electrode. The ion-releaser is arranged to release at least a portion of the releasable ions from the ion-source electrode to one of the synthesis locations, by activation of the activating electrode associated with the synthesis location.

A system includes a synthesizer unit having a fluid input to receive fluids and a communication input to receive commands to synthesize data-encoded DNA sequences and cleave the DNA. A first flexible chemistry reaction chamber module may be fluidically coupled to the synthesizer unit to receive the data-encoded DNA sequences and amplify the sequences. A deposition unit may be fluidically coupled to the first flexible chemistry reaction chamber module to receive the amplified DNA sequences and encapsulate the amplified DNA sequences into one or more wells in a storage plate for storage and retrieval to and from a plate storage unit. Retrieved DNA may be processed and read by further units.

The invention relates to a method for analyzing molecular properties and/or reaction conditions, comprising a step of providing a first store having a first surface, wherein a specific selection of sample molecules is directly or indirectly bonded to the surface in a defined arrangement, a step of producing at least two transfer stores, wherein at least two additional surfaces are provided, and a reaction step, selected from the group comprising a transfer reaction, an amplification reaction, and/or a derivatization reaction, whereby product molecules can arise and said product molecules and/or the sample molecules bond to the surfaces, wherein there is a clear spatial association between the sample molecules of the first store and the product molecules and/or sample molecules of the transfer stores and the first store, the transfer stores, the sample molecules, the product molecules, the transfer reaction, the amplification reaction, and/or the derivatization reaction is analyzed.

A rigid mask protects selective portions of a chip including a plurality of wells for biochemical reactions. The rigid mask includes a supporting portion and a plurality of legs, where each leg is provided with a rigid stem and a plate. The plurality of legs are arranged and fixed with respect to the supporting portion in a way aligned to the spatial arrangement of the wells, and are configured in such a way that, when each leg is inserted into the corresponding well, the respective plate covers at least in part the bottom of the well, protecting it during a chemical/physical treatment of side walls of the wells.

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.

Systems and methods are disclosed for enhancing the consistency of performance of assays, such as multiplexed assays, by printing features in a particular pattern, such that the outer edge of the pattern has a shape that is substantially similar to the shape of the test well. For example, the pattern is a ring pattern, such that the outer edge of the ring pattern is circular or oval along the bottom of multiplexed wells. The assay substrates prepared according to the methods described result in more accurate, precise, and sensitive chemical and/or biological analyses.

An example of a flow cell includes a substrate, a plurality of chambers defined on or in the substrate, and a plurality of depressions defined in the substrate and within a perimeter of each of the plurality of chambers. The depressions are separated by interstitial regions. Primers are attached within each of the plurality of depressions, and a capture site is located within each of the plurality of chambers.

Provided herein are systems and methods for nucleic acid sequencing by synthesis in a plurality of wells using detectably labeled chain terminating nucleotides with photolabile blocking groups and pulses of photocleaving light. In certain embodiments, the systems and methods provides a plurality of deblock-scan cycles comprising an initial deblock time period followed by a scanning light period, wherein at least one of the following occurs in each deblock-scan cycle: 1) the deblock time period is shorter than the scan time period; 2) the deblock time period is only long enough to deblock the photolabile groups that are part of a primer in less than all of the plurality of wells; or 3) the deblock time period is between 25 and 150 mSec and the scan time is at least 200 mSec. Such shorter deblock time periods help prevent the addition of more than one nucleotide to the primer prior to scanning (e.g., accuracy is enhanced).

An apparatus and method for performing analysis and identification of molecules have been presented. In one embodiment, a portable molecule analyzer includes a sample input/output connection to receive a sample, a nanopore-based sequencing chip to perform analysis on the sample substantially in real-time, and an output interface to output result of the analysis.