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用于芯片上超顺磁珠聚集体分离和检测模型蛋白及双链 DNA 分析物的磁微阵列设计。

Design of micromagnetic arrays for on-chip separation of superparamagnetic bead aggregates and detection of a model protein and double-stranded DNA analytes.

机构信息

School of Chemistry, University College Dublin, Belfield, Dublin, Ireland.

National Virus Reference Laboratory, University College Dublin, Belfield, Dublin, Ireland.

出版信息

Sci Rep. 2021 Mar 5;11(1):5302. doi: 10.1038/s41598-021-84395-3.

DOI:10.1038/s41598-021-84395-3
PMID:33674645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7935980/
Abstract

Magnetically actuated lab-on-a-chip (LOC) technologies have enabled rapid, highly efficient separation of specific biomarkers and cells from complex biological samples. Nonlinear magnetophoresis (NLM) is a technique that uses a microfabricated magnet array (MMA) and a time varying external magnetic field to precisely control the transport of superparamagnetic (SPM) beads on the surface of a chip based on their size and magnetization. We analyze the transport and separation behavior of SPM monomers and dimers on four MMA geometries, i.e., circular, triangular, square and rectangular shaped micromagnets, across a range of external magnetic field rotation frequencies. The measured critical frequency of the SPM beads on an MMA, i.e., the velocity for which the hydrodynamic drag on a bead exceeds the magnetic force, is closely related to the local magnetic flux density landscape on a micromagnet in the presence of an external magnetic field. A set of design criteria has been established for the optimization of MMAs for NLM separation, with particular focus on the shape of the micromagnets forming the array. The square MMA was used to detect a model protein biomarker and gene fragment based on a magnetic bead assembly (MBA) assay. This assay uses ligand functionalized SPM beads to capture and directly detect an analyte through the formation of SPM bead aggregates. These beads aggregates were detected through NLM separation and microscopic analysis resulting in a highly sensitive assay that did not use carrier fluid.

摘要

磁驱动微流控芯片(LOC)技术已经实现了从复杂生物样本中快速、高效地分离特定生物标志物和细胞。非线性磁泳(NLM)是一种利用微制造磁阵列(MMA)和时变外磁场来精确控制超顺磁(SPM)珠在芯片表面上的传输的技术,这基于它们的尺寸和磁化强度。我们分析了 SPM 单体和二聚体在四种 MMA 几何形状(圆形、三角形、方形和矩形微磁铁)上的传输和分离行为,跨越了一系列外磁场旋转频率。MMA 上 SPM 珠的测量临界频率,即珠的速度,其中水动力阻力超过磁力,与微磁铁在外部磁场存在下的局部磁通密度景观密切相关。已经建立了一套用于优化 NLM 分离的 MMA 的设计标准,特别关注形成阵列的微磁铁的形状。使用正方形 MMA 基于磁珠组装(MBA)检测模型蛋白生物标志物和基因片段。该检测使用配体功能化的 SPM 珠通过 SPM 珠聚集体的形成来捕获和直接检测分析物。这些珠聚集体通过 NLM 分离和显微镜分析进行检测,导致一种无需载体流体的高灵敏度检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/7a84a13a40d1/41598_2021_84395_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/d24338e4262d/41598_2021_84395_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/9d2535aa260a/41598_2021_84395_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/af2fbecb15a1/41598_2021_84395_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/a0d9a807dea6/41598_2021_84395_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/e16ee0024a31/41598_2021_84395_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/7a84a13a40d1/41598_2021_84395_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/d24338e4262d/41598_2021_84395_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/9d2535aa260a/41598_2021_84395_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/af2fbecb15a1/41598_2021_84395_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/a0d9a807dea6/41598_2021_84395_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/e16ee0024a31/41598_2021_84395_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854f/7935980/7a84a13a40d1/41598_2021_84395_Fig6_HTML.jpg

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