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 relates generally to devices, systems, compositions, and methods for the detection of oligonucleotides, nucleic acids, antigens, antibodies, peptides, proteins, and non-biological molecules.

In one example, a flow cell includes a base support and a protrusion over the base support, where the protrusion is a different material than the base support. The flow cell further includes a first functionalized layer over a first portion of the protrusion, a second functionalized layer over a second portion of the protrusion, and first and second primer sets respectively attached to the first and second functionalized layers.

An example flow cell includes a multi-layer stack including a transparent base support; a patterned sacrificial layer over the transparent base support; and a transparent layer over the patterned sacrificial layer. The flow cell further includes first and second functionalized layers over different portions of the transparent layer, wherein at least one of the first and second functionalized layers aligns with a pattern of the patterned sacrificial layer; and first and second primer sets respectively attached to the first and second functionalized layer.

Disclosed is an assay device comprising a high density of wells aligned thereon.

Fiducial markers are provided on patterned arrays of the type that may be used for molecular analysis, such as sequencing. The fiducials may have configurations and layouts that enhance their detection in image or detection data, that facilitate or improve processing, that provide encoding of useful information, and so forth. Examples of the fiducials may include offset layouts that may be useful in detecting the fiducials in different types and approaches in imaging, and that may help to distinguish regions of the array from one another in image data.

Provided in one example is a method of manufacturing a flowcell that includes: forming a core layer, the core layer disposed between a substrate and a nanowell layer, the nanowell layer having nanowells to receive a sample, the core layer having a higher refractive index than the substrate and the nanowell layer; and forming a grating to couple light to the core layer.

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.

In a first aspect, the present disclosure relates to a system for addressing nanoelectrodes in a nanoelectrode array, the system including an array of electrode cells, each electrode cell including: an access transistor having a gate resistively coupled to a word line, a source resistively coupled to a bit line, and a drain, and a storage circuit resistively coupled to the drain and including a nanoelectrode.

Provided is an array including a solid support having a surface, the surface having a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; and a library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library. Methods for making and using the array are also provided.