Spatially encoded biological assays

What is this patent about?

’113 is related to the field of spatially encoded biological assays and high-resolution molecular mapping. In traditional genomics and proteomics, the spatial context of biological molecules is often lost during sample homogenization, making it difficult to understand how gene expression or protein distribution varies across different cell types within a complex tissue. The invention addresses the need for a scalable, multiplexed system that can simultaneously identify the presence, abundance, and precise location of numerous biological targets within a solid sample.

The underlying idea behind ’113 is the decoupling of target detection from spatial localization through a programmable encoding scheme. Instead of relying on physical separation or manual microdissection, the invention utilizes probes that bind to specific biological targets and are subsequently linked to unique coding tags. These tags act as digital coordinates, allowing researchers to pool assay products for high-throughput analysis while retaining the ability to map every data point back to its original position in the tissue architecture.

The claims of ’113 focus on a method for determining the presence or abundance of a target protein at a specific region of interest within a tissue sample. This process involves delivering a plurality of probes—each consisting of a capture agent like an antibody conjugated to an oligonucleotide—to the sample. A critical step in the claimed method is the use of imaging to identify the specific region of interest, followed by the removal and sequencing of the oligonucleotides from that targeted area to quantify the protein targets present.

In practice, the system works by applying these conjugated probes to a tissue section affixed to a support. After the capture agents bind to their respective protein targets, the sample is imaged to define the boundaries of specific histological features or cell populations. The oligonucleotides associated with the bound probes are then recovered from these defined regions. By determining the sequence of these oligonucleotides, the system generates a digital readout that correlates the frequency of specific sequences with the concentration of proteins at the imaged location.

This approach differs from prior methods by combining the high-multiplexing capabilities of next-generation sequencing with the visual precision of microscopy. Unlike laser capture microdissection, which is labor-intensive and difficult to scale, or standard in situ hybridization, which is limited in the number of targets it can detect simultaneously, this invention allows for the analysis of thousands of different proteins or transcripts in a single workflow. It effectively transforms a physical tissue sample into a searchable digital map of molecular activity.