Li Junwei, Baird Madison A, Davis Michael A, Tai Wanyi, Zweifel Larry S, Adams Waldorf Kristina M, Gale Michael, Rajagopal Lakshmi, Pierce Robert H, Gao Xiaohu
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Nat Biomed Eng. 2017;1. doi: 10.1038/s41551-017-0082. Epub 2017 Jun 5.
The ability to detect biomarkers with ultrahigh sensitivity radically transformed biology and disease diagnosis. However, owing to incompatibilities with infrastructure in current biological and medical laboratories, recent innovations in analytical technology have not received broad adoption. Here, we report a simple, universal 'add-on' technology (dubbed EASE) that can be directly plugged into the routine practices of current research and clinical laboratories and that converts the ordinary sensitivities of common bioassays to extraordinary ones. The assay relies on the bioconjugation capabilities and ultrafast and localized deposition of polydopamine at the target site, which permit a large number of reporter molecules to be captured and lead to detection-sensitivity enhancements exceeding 3 orders of magnitude. The application of EASE in the enzyme-linked-immunosorbent-assay-based detection of the HIV antigen in blood from patients leads to a sensitivity lower than 3 fg ml. We also show that EASE allows for the direct visualization, in tissues, of the Zika virus and of low-abundance biomarkers related to neurological diseases and cancer immunotherapy.
以超高灵敏度检测生物标志物的能力彻底改变了生物学和疾病诊断。然而，由于与当前生物和医学实验室的基础设施不兼容，分析技术的最新创新尚未得到广泛应用。在此，我们报告了一种简单、通用的“附加”技术（称为EASE），它可以直接插入当前研究和临床实验室的常规操作中，并将普通生物测定的普通灵敏度转化为非凡的灵敏度。该测定依赖于聚多巴胺在靶位点的生物共轭能力以及超快和局部沉积，这使得大量报告分子能够被捕获，并导致检测灵敏度提高超过3个数量级。EASE在基于酶联免疫吸附测定法检测患者血液中HIV抗原的应用中，灵敏度低于3 fg/ml。我们还表明，EASE能够在组织中直接可视化寨卡病毒以及与神经疾病和癌症免疫疗法相关的低丰度生物标志物。
