Circulating tumor DNA (ctDNA) is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments. Currently ctDNA detection relies on sequencing. Here, a platform termed three-dimensional-coded interlocked DNA rings (3D-coded ID rings) was created for multiplexed ctDNA identification. The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring. The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease; the cutting then triggers rolling circle amplification on the reporter ring. The signals are further integrated with internal 3D codes for multiplexed readouts. ctDNAs from non-invasive clinical specimens including plasma, feces, and urine were detected and validated at a sensitivity much higher than those obtained through sequencing. This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing. We envision that our platform will facilitate the implementation of future personalized/precision medicine.

循环肿瘤 DNA (ctDNA) 是一种重要的生物标志物，不仅对肿瘤的早期检测很重要，而且对于个性化治疗也非常宝贵。目前ctDNA检测依赖于测序。在这里，一个叫做三维的平台——编码互锁 DNA 环（3D 编码 ID 环）用于多重 ctDNA 鉴定。ID 环提供 ctDNA 识别环，与报告环物理互锁。ctDNA 与识别环的特异性结合通过限制性核酸内切酶启动目标响应性切割；切割然后触发报告环上的滚环放大。这些信号进一步与内部 3D 代码集成，用于多路读取。检测和验证来自非侵入性临床标本（包括血浆、粪便和尿液）的 ctDNA 的灵敏度远高于通过测序获得的灵敏度。这种 3D 编码 ID 环平台无需测序即可同时检测任何多个 DNA 片段。