Inventions covered include methods, systems, and compositions for sample processing, involving morphology-adjustable (e.g., tunable on-demand) functionalized particles. In some embodiments, a method can include distributing a set of functionalized particles, in a first morphological state, across a set of partitions; transitioning the set of functionalized particles, at the set of partitions, from the first morphological state to a second morphological state; transitioning the set of functionalized particles, at the set of partitions, from the second morphological state to a third morphological state, and inducing interactions between the set of functionalized particles and a set of targets, within the set of partitions and according to a set of operations with a set of process fluids.

Provided is a method of constructing a sequencing library. The method includes 1) providing a single-stranded DNA fragment from a biological sample; 2) subjecting the single-stranded DNA fragment to whole genomic amplification to obtain a whole genome amplification product; 3) fragmenting the whole genome amplification product using a transposase embedded with two adaptors to obtain a fragmented product with two adaptors respectively at two ends; and 4) amplifying the fragmented product with two adaptors respectively at two ends using a tag sequence and a pair of primers to obtain said sequencing library.

Analyte filter arrays and methods for making an analyte filter array are provided. The arrays are formed using a dispersion of filter particles having selected moieties attached to the surface of the particles and a microarray having complementary moieties formed in an array on a substrate, such that each filter particle is attached to a selected region of the microarray. The moiety on the substrate may be RNA or DNA or other molecule. The substrate may be a surface of a detector array, a membrane that may be placed in registration with the detector array or a stamp used to transfer the filter array to a detector array.

This disclosure provides methods and compositions for long fragment read sequencing. Technology is described for preparing long fragments of genomic DNA, for processing genomic DNA for long fragment read sequencing methods, as well as software and algorithms for processing and analyzing sequence data. Combinatorial oligonucleotide bar codes are used to label fragments from nearby portions of the genome, which facilitate computational assembly of sequence reads to obtain the genome sequence. This improves efficiency and accuracy of sequencing, whereby an entire sequence can be obtained from fragments that constitute a lower coverage amount of the genome.

The microfluidic devices and systems disclosed herein reduce sample loss and help decrease sample processing bottlenecks for applications such as next generation sequencing (NGS). The microfluidic devices include a plurality of reaction modules. Each reaction module may comprise one or more reaction circuits. Each reaction circuit may comprise a single reaction flow channel with each reaction circuit connected by a bridge flow channel. Alternatively, each reaction circuit may comprise two or more reaction flow channels connected by two or more bridge flow channels. The combination of any two bridge flow channels and a portion of the two or more reaction flow channels between the any two bridge flow channels defining may define the reaction circuit. The reaction module may be arranged as nodes connected by bridge flow channels or each reaction module may be arranged in a parallel fashion on the microfluidic device.

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.

The present invention relates to DNA sequencing with reagent cycling on the wiregrid. The sequencing approach suggested with which allows to use a single fluid with no washing steps. Based on strong optical confinement and of excitation light and of cleavage light, the sequencing reaction can be read-out without washing the surface. Stepwise sequencing is achieved by using nucleotides with optically cleavable blocking moietys. After read-out the built in nucleotide is deblocked by cleavage light through the same substrate. This ensures that only bound nucleotides will be unblocked.

Fiducial markers are provided on patterned arrays of the type that may be used for molecular analysis, such as sequencing. The fiducial markers may have configurations 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 fiducial markers may include features and materials that are provided on or in the support of a patterned array and that return at least a portion of incident light by reflection. The fiducial markers may form gratings or other encoding configurations that assist in image processing, alignment, or other aspects of processing of the patterned array.

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.

An integrated circuit includes an interconnection structure, first and second sensing pixels over the interconnection structure, and an isolation layer over the first and second sensing pixels. Each of the first and second sensing pixels includes a bio-sensing device, a temperature-sensing device, one or more heating elements adjacent to the bio-sensing device and the temperature-sensing device, and a sensing film over the bio-sensing device. The isolation layer includes a first opening configured to expose the sensing film of the first sensing pixel without exposing the sensing film of the second sensing pixel and a second opening configured to expose the sensing film of the second sensing pixel without exposing the sensing film of the first sensing pixel.