Spatially Encoded Biological Assays

What is this patent about?

’505 is related to the field of spatially resolved biological assays, specifically those used to determine the distribution of biological molecules within a tissue sample. Traditional methods like in situ hybridization lack the throughput to analyze a large number of targets simultaneously, while techniques like microarrays lose spatial context. This patent addresses the need for high-resolution spatial mapping of numerous biological molecules.

The underlying idea behind ’505 is to combine the spatial resolution of in situ methods with the high-throughput capabilities of sequencing. This is achieved by using spatially encoded probes that interact with target biological molecules in a tissue sample. The location of each probe interaction is encoded by a unique oligonucleotide sequence, allowing the abundance and location of each target to be determined by sequencing the captured probes.

The claims of ’505 focus on a method for determining the spatial distribution of target biological molecules in a tissue sample. This involves allowing target molecules to interact with nucleic acid probes, coupling encoded oligonucleotides (arranged in a known spatial pattern) to these probes, sequencing the coupled oligonucleotides, and then mapping the target molecules back to their original locations within the tissue based on the sequenced oligonucleotide codes.

In practice, the method involves first affixing a tissue sample to a support. Nucleic acid probes are then introduced to interact with the target biological molecules. Next, encoded oligonucleotides, each with a unique sequence corresponding to a specific location, are coupled to the probes. After coupling, the sequences of the encoded oligonucleotides are determined, typically using high-throughput sequencing. Finally, the data is processed to map the presence and abundance of each target molecule to its location in the tissue sample, creating a spatial map of biological activity.

This approach differs from prior methods by enabling highly multiplexed spatial analysis. Instead of analyzing one or a few targets at a time, ’505 allows for the simultaneous detection and localization of many different biological molecules. The use of high-throughput sequencing as a readout provides a digital and quantitative measure of target abundance at each location, overcoming the limitations of traditional imaging-based methods. The combinatorial encoding scheme further enhances the scalability and efficiency of the assay.