微流控
选择(遗传算法)
离解(化学)
化学
纳米技术
计算生物学
噬菌体展示
计算机科学
肽库
组合化学
生物物理学
材料科学
生物
肽
生物化学
人工智能
肽序列
物理化学
基因
作者
Junxia Wang,Liang Li,Yingkun Zhang,Kaifeng Zhao,Xiaofeng Chen,Haicong Shen,Yuanqiang Chen,Jia Song,Yu-qiang Ma,Chaoyong James Yang,Hong-ming Ding,Zhi Zhu
标识
DOI:10.1073/pnas.2211538119
摘要
Efficient molecular selection is a prerequisite for generating molecular tools used in diagnosis, pathology, vaccinology, and therapeutics. Selection efficiency is thermodynamically highly dependent on the dissociation equilibrium that can be reached in a single round. Extreme shifting of equilibrium towards dissociation favors the retention of high-affinity ligands over those with lower affinity, thus improving the selection efficiency. We propose to synergize dual effects by deterministic lateral-displacement microfluidics, including the collision-based force effect and the two-dimensional (2D) separation-based concentration effect, to greatly shift the equilibrium. Compared with previous approaches, this system can remove more low- or moderate-affinity ligands and maintain most high-affinity ligands, thereby improving affinity discrimination in selection. This strategy is demonstrated on phage display in both experiment and simulation, and two peptides against tumor markers ephrin type-A receptor 2 (EphA2) and CD71 were obtained with high affinity and specificity within a single round of selection, which offers a promising direction for discovery of robust binding ligands for a wide range of biomedical applications.
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