MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, State Key Laboratory of Physical Chemical of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361005, China.
Anal Chem. 2022 Jun 21;94(24):8766-8773. doi: 10.1021/acs.analchem.2c01359. Epub 2022 Jun 7.
Aptamer-functionalized microfluidic interfaces hold great potential for liquid biopsies owing to their programmable nature. However, most previous studies have focused on development of multivalent aptamers to improve binding affinity, while ignoring aptamer orientation on microfluidic interfaces, resulting in suboptimal accessibility and affinity. Herein, we report a ubic NA anostructure ()-programmed strategy to precisely control the orientation and valency of the amer on a microfluidic interface (CDN-Apt-Chip) for enhancing the capture and release of circulating tumor cells (CTCs). We demonstrate that the ordered orientation and multivalent configuration can synergistically increase the binding affinity of aptamers toward CTCs. By using CDN-Apt-Chip, we successfully isolated CTCs from the peripheral blood of T-cell leukemia patients and discriminated T-cell leukemia patients from healthy volunteers. Furthermore, the captured CTCs were nondestructively released via nuclease treatment. We then performed T-cell receptor sequencing on the released cells to demonstrate the compatibility with downstream analysis. Overall, this study provides a new paradigm for interface regulation of functional microfluidic chips and advances the clinical translation of aptamer-based liquid biopsy.
适体功能化微流控界面由于其可编程性，在液体活检中具有很大的潜力。然而，大多数先前的研究都集中在开发多价适体以提高结合亲和力，而忽略了适体在微流控界面上的取向，从而导致可及性和亲和力不理想。在此，我们报告了一种ubic NA 结构（）-程序化策略，用于精确控制微流控界面上适体的取向和价态（CDN-Apt-Chip），以增强对循环肿瘤细胞（CTCs）的捕获和释放。我们证明，有序的取向和多价结构可以协同提高适体与 CTCs 的结合亲和力。通过使用 CDN-Apt-Chip，我们成功地从 T 细胞白血病患者的外周血中分离出 CTCs，并将 T 细胞白血病患者与健康志愿者区分开来。此外，通过核酸酶处理可无损地释放捕获的 CTCs。然后，我们对释放的细胞进行 T 细胞受体测序，以证明与下游分析的兼容性。总的来说，这项研究为功能微流控芯片的界面调控提供了新的范例，并推进了基于适体的液体活检的临床转化。
