Spatially encoded biological assays

What is this patent about?

’566 is related to the field of spatially encoded biological assays and high-resolution molecular mapping. It addresses the technical challenge of simultaneously measuring the abundance and distribution of numerous biological targets, such as proteins and nucleic acids, within a solid tissue sample. Traditional methods like in situ hybridization or laser capture microdissection often struggle with high levels of multiplexing or suffer from low spatial resolution and labor-intensive workflows.

The underlying idea behind ’566 is the decoupling of target identification from spatial localization through a digital encoding scheme. Instead of relying on physical separation or visual labels alone, the invention uses oligonucleotide-tagged probes that interact with targets in situ. By delivering specific coding tags to defined coordinates on a tissue section—often using a combinatorial grid—the system effectively stamps each target-binding event with a spatial barcode. This allows the sample to be pooled and analyzed via high-throughput sequencing while retaining the ability to map every data point back to its original micro-location.

The claims of ’566 focus on a method for detecting a target protein within a tissue sample by utilizing antibody-based probes. The process involves contacting the tissue with probes where an antibody is coupled to a specific oligonucleotide sequence. A nucleic acid molecule is then generated that combines the probe's identity with location-specific nucleic acid tags. By sequencing this chimeric molecule, the system simultaneously identifies the protein and its precise coordinate within the tissue architecture.

In practice, the invention utilizes instrumentation like acoustic liquid handlers or inkjet printing to deposit reagents in precise patterns, such as an X-Y grid. For protein detection, antibodies bind to their targets, and subsequently, encoding oligonucleotides are ligated or extended to incorporate the spatial tags. This transformational step creates a sequencing-ready library where each strand contains both the 'what' (the antibody's identity) and the 'where' (the grid coordinates).

This approach differs from prior solutions by moving the complexity of spatial resolution from the microscope to the sequencer. By converting spatial information into a digital readout, the invention bypasses the multiplexing limits of fluorescent dyes and the manual labor of microdissection. It enables the simultaneous mapping of thousands of different molecules across a single tissue section, providing a high-fidelity molecular map that integrates the depth of genomic sequencing with the context of classical histology.