To transform from reactive to proactive healthcare, there is an increasing need for low-cost and portable assays to continuously perform health measurements. The paper-based analytical devices could be a potential fit for this need. To miniaturize the multiplex paper-based microfluidic analytical devices and minimize reagent use, a fabrication method with high resolution along with low fabrication cost should be developed. Here, we present an approach that uses a desktop pen plotter and a high-resolution technical pen for plotting high-resolution patterns to fabricate miniaturized paper-based microfluidic devices with hundreds of detection zones to conduct different assays. In order to create a functional multiplex paper-based analytical device, the hydrophobic solution is patterned on the cellulose paper and the reagents are deposited in the patterned detection zones using the technical pens. We demonstrated the effect of paper substrate thickness on the resolution of patterns by investigating the resolution of patterns on a chromatography paper with altered effective thickness. As the characteristics of the cellulose paper substrate such as thickness, resolution, and homogeneity of pore structure affect the obtained patterning resolution, we used regenerated cellulose paper to fabricate detection zones with a diameter as small as 0.8 mm. Moreover, in order to fabricate a miniaturized multiplex paper-based device, we optimized packing of the detection zones. We also showed the capability of the presented method for fabrication of 3D paper-based microfluidic devices with hundreds of detection zones for conducting colorimetric assays.

中文翻译：

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使用低成本和高通量笔式绘图仪方法提高纸基微流控技术的空间分析分辨率极限。

为了从反应式医疗转变为主动式医疗，对低成本和便携式测定法不断进行健康测量的需求日益增长。基于纸张的分析设备可能满足此需求。为了使多层纸基微流体分析装置小型化并最小化试剂的使用，应当开发高分辨率和低制造成本的制造方法。在这里，我们提出一种使用台式笔式绘图仪和高分辨率技术笔来绘制高分辨率图案的方法，以制造具有数百个检测区域的小型纸质微流体设备，以进行不同的分析。为了创建功能多样的纸质分析设备，疏水性溶液在纤维素纸上构图，然后使用工业笔将试剂沉积在构图的检测区域中。我们通过研究有效厚度改变的色谱纸上图案的分辨率，证明了纸基材厚度对图案分辨率的影响。由于纤维素纸基材的特性（例如厚度，分辨率和孔结构的均匀性）会影响所获得的图案分辨率，因此我们使用再生纤维素纸来制作直径小至0.8 mm的检测区域。此外，为了制造小型的基于纸张的多路复用设备，我们优化了检测区域的包装。