Design of Hierarchical Beads for Efficient Label‐Free Cell Capture

Abstract

materials with diverse nanoshell structures can be emerging candidates to prepare hierarchical materials owing to the unique bio-interfaces, [1b,7] but present core-shell materials are usually in the nanoscale or sub-micrometer size limiting their general application. [3c,8] Considering the above aspects, assembling of hierarchical core-shell materials with microsizes for mass production is still very challenging and calling for applicationdriven design toward practical use.Cell analysis plays a key role in biomedical research for diagnostic purpose. [9] In real case cell analysis, cell capture tends to be essential owing to the high complexity of biological specimens. [9b,c,10] To date, there are two main categories including prelabeling [10a,11] and labelfree [9a,12] process for cell capture. Compared to the labeling process that needs specific probes (such as antibodies), label-free cell capture represents the next generation tool and usually requires smart materials or devices. [6c,13] Ideal materials and devices for efficient label-free cell capture may offer: 1) surface topology with strong adherence to cell membranes; [14] 2) surface chemistry with high biocompatibility and affinity; [3c,12a,15] 3) specific size to avoid cellular endocytosis; [16] and 4) structural stability during the whole cell capture process. [6c,11b,12a,17] Until now, most existing label-free techniques only addressed parts of these issues and usually applied in imaging or delivery. Therefore, it would be desirable to construct newer materials and devices as efficient platforms for label-free cell capture.In this work, we designed hierarchical beads for efficient label-free cell capture, as shown in Figure 1a. We coated silica nanoparticles (size of ≈15 nm) onto silica spheres (size of ≈200 nm) to achieve nanoscale surface roughness, and then combined the rough silica spheres with microbeads (≈150-1000 µm in diameter) to assemble hierarchical structures. We built complex hierarchical beads via electrostatic interaction, covalent bonding, and nanoparticle adherence. Further after functionalization by hyaluronic acid (HA), the hierarchical microbeads displayed desirable surface hydrophilicity, biocompatibility, and chemical/structural stability. Due to the controlled surface topology and chemistry, the functionalized microbeads showed high cell capture efficiency of 87.9-98.7% in a label-free manner. Our work contributed to the design of Defined hierarchical materials promise cell analysis and call for applicationdriven design in practical use. The further issue is to develop advanced materials and devices for efficient label-free cell capture with minimum instrumentation. Herein, the design of hierarchical beads is reported for efficient label-free cell capture. Silica nanoparticles (size of ≈15 nm) are coated onto silica spheres (size of ≈200 nm) to achieve nanoscale surface roughness, and then the rough silica spheres are combined with microbeads (≈150-1000 µm in diameter) to assemble hierarchical structures. These hierarch...

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“…[10c, 11] Furthermore, label-free methodw ithout pre-labelling process represents the next-generation tool for its simple procedures and requires smart design for practical use. [12] Hence, label-free electrochemical detection based on ligand-protein binding may contributet on ovel high-efficacy sensors towardd isease diagnostics.…”