近期，本课题组张敏老师和任沁琦同学分别以通讯作者和共同第一作者与深圳湾实验室坪山生物医药研发转化中心生物部、深圳市人民医院叶喜阳课题组合作，在材料科学和工程技术领域顶级期刊 Advanced Materials （Nature-index期刊，影响因子29.4）上发表题为“Multi-body Biomarker Entrapment System: An All-encompassing Tool for Ultrasensitive Disease Diagnosis and Epidemic Screening”的文章，实现了一种具有通用性生物分子检测能力的生物分子诱捕系统，用于子宫内膜异位症临床诊断，猴痘病毒抗原检测以及三阴性乳腺癌循环肿瘤DNA的高灵敏定量检测。
受到自然界生物的启发，本研究模仿双头蛇特征开发了一种生物分子诱捕系统（Biomolecular Entrapment System, BioES）。该系统由碳纳米管晶体管、四面体DNA纳米结构、Y形核酸悬臂和具有生物识别能力的结合位点组成，具有强大的生物分子捕获能力。基于BioES，本研究实现了对子宫内膜异位症生物标志物ERβ的超灵敏定量，检测限可低至6.74 aM。通过核酸架构工程，本研究探索了不同BioES构型对ERβ识别的机制。在临床实验中，BioES表现出对子宫内膜异位症患者和卵巢囊肿患者具有明显的响应区分度。该系统为子宫内膜异位症的标准化诊断方案开辟了新的途径。
此外，研究将BioES平台从多体进化为多位点模式，通过在不同的识别位点修饰两种抗体Clon 19和Clon 43，首次实现了对猴痘病毒抗原蛋白A35R的超灵敏检测。双重识别位点的协同作用和增强的识别效率使得BioES能够在血清中特异性地识别A35R，检测限降低至991 aM。此外，研究展示了多位点BioES在核酸检测和早期癌症筛查中的实际应用。通过对核酸结合位点的修饰，BioES能够以低至0.21 aM的检测限在血清中捕获与三阴性乳腺癌相关的循环肿瘤DNA（ctDNA）。BioES的研究不仅为临床医学领域带来了新的进展，同时也为公共卫生领域的流行病监测和疾病防控提供了新的工具和方法。
Ultrasensitive identification of biomarkers in biofluids is essential for precise diagnosis of diseases. For the gold standard approaches, polymerase chain reaction and enzyme-linked immunosorbent assay, cumbersome operational steps hinder their point-of-care applications. Here, w e implement a bionic biomarker entrapment system (BioES), which employs a multi-body Y-shaped tetrahedral DNA probe immobilized on carbon nanotube transistors. W e successfully realize clinical identification of endometriosis by detecting an estrogen receptor, ERβ, from the lesion tissue of endometriosis patients and establish a standard diagnosis procedure. The multi-body Y-shaped BioES achieves a theoretical limit of detection (LoD) of 6.74 aM and a LoQ of 141 aM in a complex protein milieu. Furthermore, the BioES is optimized into multi-site recognition module for enhanced binding efficiency, realizing the first identification of monkeypox virus antigen A35R and unamplified detection of circulating tumor DNA of breast cancer in serum. The rigid and compact probe framework with synergy effect enable the BioES to target A35R and DNA with a LoD down to 991 aM and 0.21 aM, respectively. Owing to its versatility for proteins and nucleic acids as well as ease-of-manipulation and ultra-sensitivity, the BioES can be leveraged as an all-encompassing tool for population-wide screening of epidemics and clinical disease diagnosis.
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