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Rapid biochemical functionalization of technical surfaces by means of a photobleaching-based maskless projection lithography process

机译:基于光漂白的无掩模投影光刻工艺的技术表面的快速生化功能化

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MEMS/MOEMS based systems are increasingly applied in the biological and biomedical context, e.g. in form of biosensors or substrates for monitoring biological responses such as cell migration. For such applications, technical surfaces have to be provided with suitable biochemical functionalization. Typical functionalization procedures include wet-chemical techniques based on self-assembled monolayers of thiols on gold or silanes on glass. These processes create binary patterns and are often of limited use if spatially constrained non-binary patterns like surface bound biochemical gradients have to be provided. In order to create gradients or patterns, methods such as direct spotting or dip pen nanolithography can be used. Here, gradients can be emulated by varying the spot density or the concentration of the solutions employed. However, these methods are serial in nature and are thus of limited use if large surface areas have to be patterned. We present a technique to generate gradients of biochemical function by a photobleaching-based process allowing fast large-scale patterning. The process is based on photobleaching resulting in light-induced coupling of a fluorescently tagged biomolecule to a technical surface by concerted bleaching of the fluorophore. We custom designed a maskless projection lithography system based on a digital mirror device that allows the rapid creation of 8-bit grayscale protein patterns on any technical surface from digital data (e.g. bitmap files). We demonstrate how this process can be used to obtain patterns of several cm2 lateral size at micrometer resolution within minutes.
机译:基于MEMS / MOEMS的系统越来越多地应用于生物学和生物医学背景中,例如,以生物传感器或基材的形式,用于监测生物反应,例如细胞迁移。对于这种应用,必须提供具有合适的生化功能化的技术表面。典型的官能化程序包括基于玻璃上的金或硅烷的自组装单层的湿化学技术。如果必须提供表面结合的生物化学梯度,则这些过程创造二进制模式并且通常是有限的使用。为了创建梯度或图案,可以使用诸如直接斑点或浸渍笔纳米光刻的方法。这里,可以通过改变所用溶液的光斑密度或浓度来仿真梯度。然而,这些方法本质上是连续的,因此如果必须图案化大表面积,则是有限的使用。我们提出了一种通过基于光漂白的过程产生生物化学功能梯度的技术,允许快速大规模图案化。该方法基于光漂白,通过荧光团的齐彻漂白,通过齐节地漂白使荧光标记的生物分子与荧光标记的生物分子的光诱导偶联。我们定制设计基于数字镜像的无掩模投影光刻系统,该系统允许从数字数据(例如位图文件)的任何技术表面上快速创建8位灰度蛋白质模式。我们展示了如何使用该过程在分钟内以微米分辨率在微米分辨率下获得几Cm2横向尺寸的图案。

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