# Dynamic Decoration of DNA Scaffolds for High‐Resolution Cancer Cell Subtyping

## TL;DR

A new DNA-based imaging method prevents cell uptake of labels and allows high-resolution detection of cancer cell subtypes with high sensitivity.

## Contribution

A dynamic DNA scaffold platform that uses Boolean logic operations to enable high-fidelity, long-duration cancer cell imaging.

## Key findings

- DNA scaffolds prevent cellular internalization for up to 300 minutes, improving imaging resolution.
- The system can detect cancer cell subtypes with a sensitivity as low as 0.1% in clinical blood samples.
- Integration of logic-gated circuits enables simultaneous identification of distinct cancer cell subtypes.

## Abstract

Precise imaging of cancer cells serves as the foundation for subtype analysis, significantly advancing the development of precision medicine. The unavoidable cellular internalization of fluorescent labels constrains the resolution and timeliness, presenting a significant obstacle. This study introduces a dynamic decorating strategy of DNA scaffolds that enables the execution of four distinct Boolean logic operations through self‐assembly and self‐disassembly. By integrating the in‐built molecular circuit, the proposed assay achieved signal‐amplified detection of low‐abundance nucleic acid inputs. In the application of cell imaging, inputs were labeled with aptamers to operate membrane‐confined self‐assembly or self‐disassembly of DNA scaffolds on the cell surface, enabling simultaneous identification of distinct subtypes of cancer cells with high fidelity. The intrinsic durability of DNA scaffolds successfully prevented cellular internalization for up to 300 min, boosting the long‐duration imaging. Moreover, the assay was capable of profiling a broad spectrum of cancer cell abundances from as low as 0.1% to 10% in clinical blood samples, consistently achieving recognition efficiency exceeding 60%. These findings underscore the transformational potential of DNA scaffold‐based imaging tools in biological research and precision medicine.

This study presents a dual‐mode imaging platform that utilizes self‐assembly and disassembly of DNA scaffolds for high‐resolution cancer cell detection. The structural rigidity of DNA scaffolds effectively prevents cellular internalization for over 300 min. By integrating logic‐gated circuits, the system achieves specific profiling of cancer cell subtypes with a sensitivity down to 0.1%, offering a promising tool for precise diagnosis.