Affordable Microfluidic Bead-Sorting Platform for Automated Selection of Porous Particles Functionalized with Bioactive Compounds

Affordable Microfluidic Bead-Sorting Platform for Automated Selection of Porous Particles Functionalized with Bioactive Compounds
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经济实惠的微流珠分选平台,用于自动选择生物活性化合物功能化的多孔颗粒

DOI:
10.1038/s41598-019-42869-5
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发表时间:
2019
期刊:
影响因子:
4.6
通讯作者:
San-Miguel, Adriana
San-Miguel, Adriana
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Saberi-Bosari, Sahand;Omary, Mohammad;Lavoie, Ashton;Prodromou, Raphael;Day, Kevin;Menegatti, Stefano;San-Miguel, Adriana

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快速准确地评价固定在多孔颗粒上的生物活性化合物的能力在药物、诊断试剂、配体和催化剂的发现中至关重要。生物活性化合物的固相筛选的现有选择,虽然非常有效和完善,但对于概念验证和早期阶段的工作来说,成本过高,限制了其在新研究领域的适用性和灵活性。在这里,我们提出了一个低成本的基于微流体的平台,能够自动筛选小的多孔珠从固相肽库具有高灵敏度和特异性,以确定具有高结合亲和力的生物靶标的线索。无偏计算机辅助图像处理和分析工具的集成为该平台提供了通过具有不同荧光图案的珠进行分选的灵活性。微流控装置的定制设计有助于处理不同直径(约100-300 µm)的珠粒。作为一种微流控装置,这种便携式新型平台可以与各种分析仪器集成以进行筛选。在这项研究中,该系统利用荧光显微镜和无监督图像分析,可以以高达125个珠子/小时的分选速度(比受过训练的操作员快约3.5倍)运行,提供>90%的产量和>90%的珠子分选准确度。值得注意的是,该装置已被证明成功地筛选模型固相肽库,显示出选择珠携带结合靶蛋白(人IgG)的肽的能力。
The ability to rapidly and accurately evaluate bioactive compounds immobilized on porous particles is crucial in the discovery of drugs, diagnostic reagents, ligands, and catalysts. Existing options for solid phase screening of bioactive compounds, while highly effective and well established, can be cost-prohibitive for proof-of-concept and early stage work, limiting its applicability and flexibility in new research areas. Here, we present a low-cost microfluidics-based platform enabling automated screening of small porous beads from solid-phase peptide libraries with high sensitivity and specificity, to identify leads with high binding affinity for a biological target. The integration of unbiased computer assisted image processing and analysis tools, provided the platform with the flexibility of sorting through beads with distinct fluorescence patterns. The customized design of the microfluidic device helped with handling beads with different diameters (~100–300 µm). As a microfluidic device, this portable novel platform can be integrated with a variety of analytical instruments to perform screening. In this study, the system utilizes fluorescence microscopy and unsupervised image analysis, and can operate at a sorting speed of up to 125 beads/hr (~3.5 times faster than a trained operator) providing >90% yield and >90% bead sorting accuracy. Notably, the device has proven successful in screening a model solid-phase peptide library by showing the ability to select beads carrying peptides binding a target protein (human IgG).
从随机肽库中筛选出的 IgY 结合肽作为 IgY 纯化的配体
DOI: --
发表时间: 2017
影响因子: 2.1
作者:
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发表时间: 2016
期刊: Bioinform.
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DOI: 10.1039/c4lc01246a
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期刊: Lab on a chip
影响因子: 6.1
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DOI: --
发表时间: 2014
期刊:
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Micky Fu Xiang Lee;E. Chan;B. Tey
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DOI: 10.1021/cc900059q
发表时间: 2009-09-01
影响因子: --
作者:
Hintersteiner, Martin;Buehler, Christof;Auer, Manfred
通讯作者: Auer, Manfred