Zhang Lin-Lin, Zhong Cheng-Bing, Huang Ting-Jing, Zhang Li-Min, Yan Feng, Ying Yi-Lun
Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 P. R. China
School of Electronic Science and Engineering, Nanjing University Nanjing 210023 P. R. China.
Chem Sci. 2024 Apr 10;15(22):8355-8362. doi: 10.1039/d3sc06795e. eCollection 2024 Jun 5.
Biomarkers are present in various metabolism processes, demanding precise and meticulous analysis at the single-molecule level for accurate clinical diagnosis. Given the need for high sensitivity, biological nanopore have been applied for single biomarker sensing. However, the detection of low-volume biomarkers poses challenges due to their low concentrations in dilute buffer solutions, as well as difficulty in parallel detection. Here, a droplet nanopore technique is developed for low-volume and high-throughput single biomarker detection at the sub-microliter scale, which shows a 2000-fold volume reduction compared to conventional setups. To prove the concept, this nanopore sensing platform not only enables multichannel recording but also significantly lowers the detection limit for various types of biomarkers such as angiotensin II, to 42 pg. This advancement enables direct biomarker detection at the picogram level. Such a leap forward in detection capability positions this nanopore sensing platform as a promising candidate for point-of-care testing of biomarker at single-molecule level, while substantially minimizing the need for sample dilution.
生物标志物存在于各种代谢过程中，需要在单分子水平进行精确细致的分析以实现准确的临床诊断。鉴于对高灵敏度的需求，生物纳米孔已被应用于单生物标志物传感。然而，低含量生物标志物的检测面临挑战，这是由于它们在稀释缓冲溶液中的浓度较低，以及平行检测存在困难。在此，开发了一种液滴纳米孔技术，用于在亚微升尺度上进行低含量和高通量的单生物标志物检测，与传统装置相比，其体积减少了2000倍。为了验证这一概念，这种纳米孔传感平台不仅能够进行多通道记录，还显著降低了各种类型生物标志物（如血管紧张素II）的检测限，低至42皮克。这一进展使得能够在皮克水平直接检测生物标志物。检测能力的这一巨大飞跃将这种纳米孔传感平台定位为单分子水平生物标志物即时检测的有前途的候选者，同时大幅减少了样品稀释的需求。
