Modifications to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays are disclosed.

Modifications to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays are disclosed.

Provided herein are methods of enhancing spatial resolution of an analyte using sandwich maker system. The methods and systems used herein include a first substrate that includes a plurality of probes that include a capture domain and a spatial domain and a second substrate that includes a plurality of probes comprising a capture domain and a spatial domain.

Provided herein are methods of enhancing spatial resolution of an analyte using sandwich maker system. The methods and systems used herein include a first substrate that includes a plurality of probes that include a capture domain and a spatial domain and a second substrate that includes a plurality of probes comprising a capture domain and a spatial domain.

The disclosure provides aptamer switch polynucleotides whose kinetics and effective binding affinity to a target analyte can be independently tuned. The aptamer switch polynucleotides comprise an aptamer, an intramolecular linker, and a displacement strand.

The disclosure provides aptamer switch polynucleotides whose kinetics and effective binding affinity to a target analyte can be independently tuned. The aptamer switch polynucleotides comprise an aptamer, an intramolecular linker, and a displacement strand.

The present invention provides a method for detecting genome-related information of a cell coexisting with at least one type of test substance, for various types of test substances. More specifically, the present invention provides a method for detecting genome-related information of a cell or a derivative thereof coexisting with at least one type of test substance, including:

preparing a plurality of types of first compartments that contain at least one type of test substance and a first barcode nucleic acid, and a plurality of types of second compartments that contain a cell or a derivative thereof and a second barcode nucleic acid-linked bead;

forming a plurality of types of third compartments in which one first compartment and one second compartment are fused;

hybridizing each of the genome-related nucleic acid and the first barcode nucleic acid with a second barcode nucleic acid to obtain a hybridized complex;

producing an amplified product derived from the hybridized complex; and

detecting genome-related information in the cell after coexistence with the test substance using an expression pattern of the amplified product as an index.

The present invention provides a method for detecting genome-related information of a cell coexisting with at least one type of test substance, for various types of test substances. More specifically, the present invention provides a method for detecting genome-related information of a cell or a derivative thereof coexisting with at least one type of test substance, including:

preparing a plurality of types of first compartments that contain at least one type of test substance and a first barcode nucleic acid, and a plurality of types of second compartments that contain a cell or a derivative thereof and a second barcode nucleic acid-linked bead;

forming a plurality of types of third compartments in which one first compartment and one second compartment are fused;

hybridizing each of the genome-related nucleic acid and the first barcode nucleic acid with a second barcode nucleic acid to obtain a hybridized complex;

producing an amplified product derived from the hybridized complex; and

detecting genome-related information in the cell after coexistence with the test substance using an expression pattern of the amplified product as an index.

Described herein are methods for determining a sequence of a region of interest from an mRNA molecule. Sequenced polynucleotides can include a barcode region, a homopolymer region (e.g., a poly-A region), and a target region associated with the mRNA molecule. According to some methods, the barcode region omits the same base present in the homopolymer region. According to some methods, extension of the primer used for sequencing is stalled within the homopolymer region. According to some methods, sequencing flow cycles and the different barcode regions of the polynucleotides configured are such that the primer is extended to the end of the barcode region across the plurality of polynucleotides before being extended into the homopolymer region. According to some methods, two primers or a cleavable primer is used to separately sequence the barcode region and the target region.

Described herein are methods for determining a sequence of a region of interest from an mRNA molecule. Sequenced polynucleotides can include a barcode region, a homopolymer region (e.g., a poly-A region), and a target region associated with the mRNA molecule. According to some methods, the barcode region omits the same base present in the homopolymer region. According to some methods, extension of the primer used for sequencing is stalled within the homopolymer region. According to some methods, sequencing flow cycles and the different barcode regions of the polynucleotides configured are such that the primer is extended to the end of the barcode region across the plurality of polynucleotides before being extended into the homopolymer region. According to some methods, two primers or a cleavable primer is used to separately sequence the barcode region and the target region.