Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.
Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.
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DOI：
10.1002/smll.201601829
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Liu JT
中科院分区：
文献类型：
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作者：
Wang YW;Doerksen JD;Kang S;Walsh D;Yang Q;Hong D;Liu JT
需要术中影像技术来指导保乳手术，并降低术后病理分析中发现手术边缘残留肿瘤的患者再次切除的高发生率。可行性研究表明，利用局部应用表面增强拉曼散射（SERS）纳米颗粒（NPs），结合靶向与非靶向NPs的比例成像，可以快速可视化新切除乳腺组织表面过度表达的多种癌症细胞表面生物标志物。为了可靠和快速地对大量生物标志物（具有5种或更多NP风味）进行多路拉曼编码分子成像（REMI），已经开发了一种增强的染色方法，其中将组织表面循环浸入NP染色溶液并进行高频机械振动。这种浸渍和机械振动（DMV）方法促进了SERS NPs在新鲜组织表面的对流，从而加速了它们与各自的生物标志物靶标的结合。通过使用定制开发的自动DMV染色设备，我们展示了在新鲜人乳腺组织表面同时成像4种细胞表面癌症生物标志物的能力，5种风味的SERS NPs（4种靶向和1种非靶向对照）的混合物局部应用5分钟，以0.5 mm的空间分辨率和bbb50 cm2/min的光栅扫描成像速率成像。
There is a need for intraoperative imaging technologies to guide breast-conserving surgeries and to reduce the high rates of re-excision for patients in which residual tumor is found at the surgical margins during post-operative pathology analyses. Feasibility studies have shown that utilizing topically applied surface-enhanced Raman scattering (SERS) nanoparticles (NPs), in conjunction with the ratiometric imaging of targeted vs. untargeted NPs, enables the rapid visualization of multiple cell-surface biomarkers of cancer that are over-expressed at the surfaces of freshly excised breast tissues. In order to reliably and rapidly perform multiplexed Raman-encoded molecular imaging (REMI) of large numbers of biomarkers (with 5 or more NP flavors), an enhanced staining method has been developed in which tissue surfaces are cyclically dipped into a NP-staining solution and subjected to high-frequency mechanical vibration. This dipping and mechanical vibration (DMV) method promotes the convection of the SERS NPs at fresh tissues surfaces, which accelerates their binding to their respective biomarker targets. By utilizing a custom-developed device for automated DMV staining, we demonstrate the ability to simultaneously image 4 cell-surface biomarkers of cancer at the surfaces of fresh human breast tissues with a mixture of 5 flavors of SERS NPs (4 targeted and 1 untargeted control) topically applied for 5 min and imaged at a spatial resolution of 0.5 mm and a raster-scanned imaging rate of >5 cm2/min.