This disclosure provides methods and devices for the label-free detection of target molecules of interest. The principles of the disclosure are particularly applicable to the detection of biological molecules (e.g., DNA, RNA, and protein) using standard SiO.sub.2-based microarray technology.

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the sample plane to capture a series of images (e.g., of different fields-of-view), and improved imaging system duty cycle, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications.

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the sample plane to capture a series of images (e.g., of different fields-of-view), and improved imaging system duty cycle, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications.

Disclosed herein include systems, methods, compositions, and kits for methods of assigning sequencing data to partitions. There are provided, in some embodiments, methods of associating sequencing data and phenotypic data of single cells. There are provided, in some embodiments, methods of reducing noise in sequencing data. Disclosed herein include partition indexing oligonucleotides comprising a partition indexing sequence. The partition indexing oligonucleotides can be associated with partitions. Partition indexing oligonucleotides situated within the same partition can comprise the same partition indexing sequence. Partition indexing oligonucleotides situated within different partitions comprise different partition indexing sequences.

Disclosed herein include systems, methods, compositions, and kits for methods of assigning sequencing data to partitions. There are provided, in some embodiments, methods of associating sequencing data and phenotypic data of single cells. There are provided, in some embodiments, methods of reducing noise in sequencing data. Disclosed herein include partition indexing oligonucleotides comprising a partition indexing sequence. The partition indexing oligonucleotides can be associated with partitions. Partition indexing oligonucleotides situated within the same partition can comprise the same partition indexing sequence. Partition indexing oligonucleotides situated within different partitions comprise different partition indexing sequences.

Provided are methods and systems for analyzing nucleic acids in a biological sample in a manner that retains the spatial and/or cellular origin of the nucleic acids within the biological sample. Compositions and kits are also provided that enable the methods and systems of the instant disclosure.

Provided are methods and systems for analyzing nucleic acids in a biological sample in a manner that retains the spatial and/or cellular origin of the nucleic acids within the biological sample. Compositions and kits are also provided that enable the methods and systems of the instant disclosure.

In an example method, a series of time-based clustering images is generated for a plurality of library fragments from a genome sample. Each time-based clustering image in the series is sequentially generated. To generate each time-based clustering image in the series: i) a respective sample is introduced to a flow cell, the respective sample including contiguity preserved library fragments of the plurality of library fragments, wherein the contiguity preserved library fragments are attached to a solid support or are attached to each other; ii) the contiguity preserved library fragments are released from the solid support or from each other; iii) the contiguity preserved library fragments are amplified to generate a plurality of respective template strands; iv) the respective template strands are stained; and v) the respective template strands are imaged.

In an example method, a series of time-based clustering images is generated for a plurality of library fragments from a genome sample. Each time-based clustering image in the series is sequentially generated. To generate each time-based clustering image in the series: i) a respective sample is introduced to a flow cell, the respective sample including contiguity preserved library fragments of the plurality of library fragments, wherein the contiguity preserved library fragments are attached to a solid support or are attached to each other; ii) the contiguity preserved library fragments are released from the solid support or from each other; iii) the contiguity preserved library fragments are amplified to generate a plurality of respective template strands; iv) the respective template strands are stained; and v) the respective template strands are imaged.

An objective lens is used for DNA sequencing. An example system includes a flow cell, the objective lens, and a camera. Light from the flow cell is imaged by the camera through the objective lens. The objective lens can provide a long working distance; a flat field curvature; a high numerical aperture; and/or a wide field of view.