This research manuscript introduces Seq-Scope-X, a novel spatial biology platform that achieves subcellular and nanoscale resolution by integrating sequencing technology with tissue expansion. By embedding biological samples in an expandable hydrogel and enlarging them before molecular capture, the method overcomes the physical resolution limits of traditional next-generation sequencing. The authors demonstrate its versatility by mapping transcriptomic and proteomic data across diverse tissues, including the liver, brain, and spleen. Their findings highlight the ability to distinguish between nuclear and cytoplasmic gene expressions, revealing that a cell's internal compartments can display distinct functional states. Additionally, the technology is compatible with DMAA-based chemistry, pushing spatial analysis toward a true nanoscale regime. Ultimately, this approach provides a high-throughput, cost-effective means to explore complex tissue architecture at a level of detail previously reserved for specialized optical microscopy.

References:

• Anacleto A, Cheng W, Feng Q, et al. Seq-Scope-eXpanded: spatial omics beyond optical resolution[J]. Nature Communications, 2026.