Accelerated Digital Biodetection Using Magneto-plasmonic Nanoparticle-Coupled Photonic Resonator Absorption Microscopy
Accelerated Digital Biodetection Using Magneto-plasmonic Nanoparticle-Coupled Photonic Resonator Absorption Microscopy
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DOI：
10.1021/acsnano.1c08569
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发表时间：
2022-01-18
期刊：
影响因子：
17.1
通讯作者：
Cunningham, Brian T.
中科院分区：
文献类型：
--
作者：
Che, Congnyu;Xue, Ruiyang;Cunningham, Brian T.
体液中循环microRNA （miRNA）生物标志物的快速、超灵敏和选择性定量越来越多地应用于早期癌症诊断、预后和治疗监测。虽然纳米颗粒标签可以在没有酶扩增的情况下以数字分辨率和亚飞摩尔检测限检测核酸或蛋白质生物标志物，但这些检测的响应时间通常由扩散限制的分析物或纳米标签到生物传感器表面的运输所主导。在这里，我们提出了一种磁激活捕获和数字计数（mAC+DC）方法，该方法利用磁等离子体纳米粒子（MPNPs）来加速单分子传感，通过足趾介导的链位移来检测miRNA。带有固定目标特异性探针的尖状Fe3O4@Au MPNPs通过与miRNA靶标结合而被“激活”，然后通过磁性驱动通过散装流体向光子晶体（PC）上的纳米颗粒捕获探针传输。通过将MPNP的局部表面等离子体共振与PC引导的共振进行光谱匹配，每个捕获的MPNP在局部淬灭PC的反射效率，从而使捕获的MPNP能够以高对比度单独显示，以便计数。我们展示了直接从未经处理的人血清中定量miR-375癌症生物标志物，反应时间为1分钟，检测限为61.9 aM，动态范围宽（100 aM至10 pM），并且具有单碱基错配选择性。该方法非常适合微创生物标志物定量，在短时间内的即时检测中具有潜在的应用前景。
Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection via toeholdmediated strand displacement. Spiky Fe3O4@Au MPNPs with immobilized target-specific probes are "activated" by binding with miRNA targets, followed by magnetically driven transport through the bulk fluid toward nanoparticle capture probes on a photonic crystal (PC). By spectrally matching the localized surface plasmon resonance of the MPNPs to the PC-guided resonance, each captured MPNP locally quenches the PC reflection efficiency, thus enabling captured MPNPs to be individually visualized with high contrast for counting. We demonstrate quantification of the miR-375 cancer biomarker directly from unprocessed human serum with a 1 min response time, a detection limit of 61.9 aM, a broad dynamic range (100 aM to 10 pM), and a single-base mismatch selectivity. The approach is well-suited for minimally invasive biomarker quantification, enabling potential applications in point-of-care testing with short sample-to-answer time.