Label-Free Single Exosome Detection Using Frequency-Locked Microtoroid Optical Resonators
Label-Free Single Exosome Detection Using Frequency-Locked Microtoroid Optical Resonators
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DOI：
10.1021/acsphotonics.5b00142
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发表时间：
2015-09-01
期刊：
影响因子：
7
通讯作者：
Su, Judith
中科院分区：
文献类型：
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作者：
Su, Judith
最近，外来体由于其作为癌症生物标志物的潜力而引起了人们的兴趣。我们报告的实时，无标记传感的单个外泌体在血清中使用微环光学谐振器。我们使用这种方法通过特异性检测低浓度的肿瘤源性外泌体来测定植入小鼠的肿瘤的进展。我们的方法通过跟踪微环共振频率的变化来测量单个外泌体在功能化二氧化硅微环上的吸附。当外来体落在微环上时，它们在倏逝场中扰动其折射率，从而改变其共振频率。通过数字频率锁定，我们能够快速跟踪这些偏移，精度优于10个attometer（1/10）。从植入肿瘤的小鼠中采集的样本在后几周产生的频率变化比前几周更大。对这些位移的分析显示了单一台阶的分布，其中最大台阶具有类似于1.2 μ m的高度，对应于44 +/-4.8 nm的外泌体尺寸。我们的研究结果证明了微创肿瘤“活检”的发展，消除了寻找和进入肿瘤的需要。
Recently exosomes have attracted interest due to their potential as cancer biomarkers. We report the real-time, label-free sensing of single exosomes in serum using microtoroid optical resonators. We use this approach to assay the progression of tumors implanted in mice by specifically detecting low concentrations of tumor-derived exosomes. Our approach measures the adsorption of individual exosomes onto a functionalized silica microtoroid by tracking changes in resonant frequency of the microtoroid. When exosomes land on the microtoroid, they perturb its refractive index in the evanescent field and thus shift its resonance frequency. Through digital frequency locking, we are able to rapidly track these shifts with accuracies of better than 10 attometers (one part in 10(11)). Samples taken from tumor-implanted mice from later weeks generated larger frequency shifts than those from earlier weeks. Analysis of these shifts shows a distribution of unitary steps, with the maximum step having a height of similar to 1.2 fm, corresponding to an exosome size of 44 +/- 4.8 nm. Our results demonstrate the development of a minimally invasive tumor "biopsy" that eliminates the need to find and access a tumor.