Mapping Tiny Features on a Chip with DNA Barcodes

This patent describes a method for precisely locating individual biological features, like cells or molecules, on a prepared surface by using unique DNA tags and imaging techniques.

What it covers

The patent describes a method for finding the exact spot of a "feature" on a "spatial array" (a surface with many tiny spots). First, the array is prepared with features, each having a "capture probe" that includes a unique "spatial barcode" and a constant DNA sequence. Next, a "sequencing probe" with a fluorescent "label" attaches to the spatial barcode. An image is then taken of this label. By looking at the image, a part of the spatial barcode's sequence is figured out. Finally, the feature is linked to its exact location on the array based on where its label appeared in the image. This allows researchers to know not just what a feature is, but precisely where it is.

What it doesn't cover

• —Does not cover methods for determining feature location without using specific DNA spatial barcodes.
• —Does not cover identifying the full genetic sequence of a feature, only a portion of its spatial barcode.
• —Does not cover systems that rely solely on physical coordinates without molecular tags for localization.
• —Does not cover methods where the sequencing probe does not hybridize to a spatial barcode.

The clever bit

The novelty lies in using specific, pre-assigned DNA "spatial barcodes" on a substrate, which are then read out by labeled sequencing probes and imaging to pinpoint the exact location of biological features. This links molecular identity directly to physical coordinates on a chip.

Why it matters

This technology is important for understanding how cells and molecules are organized within tissues, which is crucial for studying diseases like cancer and for drug discovery. By knowing the precise location of different biological components, scientists can gain deeper insights into their functions and interactions. It enables a new level of detail in biological research, moving beyond simply identifying components to mapping their spatial relationships.

Real-world examples

• 1.10x Genomics Visium platform
• 2.NanoString GeoMx Digital Spatial Profiler
• 3.Resolve Biosciences Molecular Cartography