Invention Grant
US09330295B2 Spatial sequencing/gene expression camera 有权
空间测序/基因表达相机

Spatial sequencing/gene expression camera
Abstract:
Methods, articles and systems that provide imagewise mapping or display of gene expression of a biosample, by contacting the biosample, such as a tissue slice or metacommunity, to a detector which captures material from the biosample and processes the captured material. In one embodiment the detector has an array of one or more capture sites at defined positions on the detector, each site carrying an immobilized capture oligonucleotide and a site-indexing oligonucleotide. The array captures mRNA from the biosample contacted thereto, and the captured mRNA is processed to form a sequenceable amount of amplified captured material which includes the site-indexing oligonucleotide, so that when sequenced, detection of the site-indexing oligonucleotide indicates the original capture location on the array, thereby mapping the sequenced material to its capture location and imaging display of gene expression distribution in the original biosample. In some embodiments the site-encoding sequence is integrated with the capture oligonucleotide. In other embodiments, the detector is a modified sequencing flow cell, which is opened to allow the biospecimen to be contacted to a capture surface; processing is performed while the material remains on the capture surface and locations of the resulting sequences correspond to the location of origin of the templates of the biomolecules in the sample. The spatially resolved sequencing, gene expression camera and technology in various embodiments are applied to genome sequences and DNA fragments present in the biosample, for example to study or diagnose developmental, disease, and tumor conditions.
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