Interdigitated Multicolored Bioink Micropatterns by Multiplexed Polymer Pen Lithography

Interdigitated Multicolored Bioink Micropatterns by Multiplexed Polymer Pen Lithography
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DOI:
10.1002/smll.201203183
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发表时间:
2013-10-11
期刊:
影响因子:
13.3
通讯作者:
Fuchs, Harald
Fuchs, Harald
中科院分区:
材料科学1区
文献类型:
--
作者:
Brinkmann, Falko;Hirtz, Michael;Fuchs, Harald

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对于微接触印刷(CP)和类似技术来说,多路复用,即在交叉的微尺度图案中应用和集成一种以上的油墨,仍然是一个挑战。另一方面,在生物实验中,在较低的微米范围内,对亚细胞到细胞长度尺度上多于一种蛋白质的交叉模式有强烈的需求。本文提出了一种利用聚合物笔光刻技术(PPL)制造生物活性微阵列和复杂多墨水图案的新方法。通过利用微接触印刷(CP)的优势,结合空间控制和精确重复PPL的能力,以一种创新的方式,为PPL引入了一种新的上墨和书写策略,使每个重复子模式内实现真正的多路复用。此外,一种特定的墨水/衬底平台被证明可以用于固定化功能蛋白和其他生物活性化合物,而不是生物素-链亲和素方法。这种模式策略专门针对细胞生物学家和生物化学家的应用,解决了广泛的相关模式大小,易于模式生成和调整,仅使用生物友好的,无毒的化学物质,以及在模式步骤中的温和处理条件。通过显示成纤维细胞和神经元分别与纤维连接蛋白和层粘连蛋白或层粘连蛋白和ephrin的多重结构的相互作用,证明了制造的cm(2)区域填充的多蛋白模式保留了生物活性。
Multiplexing, i.e., the application and integration of more than one ink in an interdigitated microscale pattern, is still a challenge for microcontact printing (CP) and similar techniques. On the other hand there is a strong demand for interdigitated patterns of more than one protein on subcellular to cellular length scales in the lower micrometer range in biological experiments. Here, a new integrative approach is presented for the fabrication of bioactive microarrays and complex multi-ink patterns by polymer pen lithography (PPL). By taking advantage of the strength of microcontact printing (CP) combined with the spatial control and capability of precise repetition of PPL in an innovative way, a new inking and writing strategy is introduced for PPL that enables true multiplexing within each repetitive subpattern. Furthermore, a specific ink/substrate platform is demonstrated that can be used to immobilize functional proteins and other bioactive compounds over a biotin-streptavidin approach. This patterning strategy aims specifically at application by cell biologists and biochemists addressing a wide range of relevant pattern sizes, easy pattern generation and adjustment, the use of only biofriendly, nontoxic chemicals, and mild processing conditions during the patterning steps. The retained bioactivity of the fabricated cm(2) area filling multiprotein patterns is demonstrated by showing the interaction of fibroblasts and neurons with multiplexed structures of fibronectin and laminin or laminin and ephrin, respectively.