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纸基微流控芯片: Comparison
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Please note this is a comparison between Version 1 by Bo Liu and Version 3 by Vivi Li.

Traditional detectors mostly consist of complex structures that are difficult to use. However, paper-based microfluidic chips combine the advantages of small size, high efficiency, easy processing and environmental protection. Paper-based microfluidic chips for biomedical applications focus on efficiency, accuracy, integration and innovation. As a result, continuous progress has been observed in the transition from single-channel to multi-channel detection and from qualitative to quantitative detection. These developments have improved the efficiency and accuracy of single cells and biochemical markers detection. Paper-based microfluidic chips can provide insights into multiple fields, including biomedicine and other related fields.传统探测器大多由难以使用的复杂结构组成。然而，纸基微流控芯片结合了小型、高效、易于加工和环保的优点。用于生物医学应用的纸基微流控芯片专注于效率、准确性、集成和创新。因此，在从单通道检测到多通道检测的转变以及从定性检测到定量检测的转变中，观察到了不断的进步。这些发展提高了单细胞物质检测的效率和准确性。纸基微流控芯片可以提供对多个领域的洞察，包括生物医学和其他相关领域。 

  • paper-based microfluidics chips
  • biomedicine
  • biomarker
  • clinical detection

1. Introduction一、简介

医学与工程的完美结合，带动了许多生物技术的发展，如标记检测、基因扩增、细胞培养等。但在专业实验室，使用专业仪器，成本增加，相关实验难度加大，制约学科发展。因此，生物医学研究已慢慢转向制造经济、易于使用、环保且效果显着的新设备。
The perfect integration of medicine and engineering has led to the development of many biotechnologies, such as marker detection, gene amplification, cell culture, etc. In professional laboratories, however, professional instruments are used, which raises costs, makes relevant experiments more difficult, and restricts discipline development. So, biomedical research has slowly moved toward making new devices that are economical, easy to use, environmentally friendly, and yield great results. In 1990, microfluidics was first proposed for microfluidic control in microelectromechanical systems 年，微流控技术首次被提出用于微机电系统 (MEMS) [1].中的微流控控制 Microfluidic[ chips1 were]。微流控芯片最初应用于化学分析 initially[ applied2 for]。在不同类型的微流控芯片中，纸基微流控芯片由于其发展成为理想的生物医学设备的潜力，近年来在生物医学领域受到关注[ chemical3 analysis [2]. Among different types of microfluidic chips, paper-based4 microfluidic chips have recently gained attention in the biomedical field because of their potential for developing into ideal biomedical devices [3][4]. ]。

2. Overview of Paper-Based Microfluidic Chips纸基微流控芯片概述

2.1. Characteristics of Paper-Based Microfluidic Chips

2.1。纸基微流控芯片的特点

Microfluidic chips are small and lightweight devices with highly integrated detection. It integrates sample preparation, reaction, separation, detection, and other components at the micron scale level with fine processing technology. As a result, it can carry out complex physical and chemical processes as well as complete the whole experimental analysis, from adding samples to reading results. Therefore, it is also called 微流控芯片是具有高度集成检测的小而轻的设备。它将微米级的样品制备、反应、分离、检测等组件与精细加工技术融为一体。因此，它可以进行复杂的物理和化学过程，并完成从添加样品到读取结果的整个实验分析。因此，它也被称为“lab芯片实验室” on[ chip”5、6、7 ]。美国哈佛大学 [5][6][7]. Whitesides’ research group at Harvard University in the United States proposed the concept of paper-based microfluidic analytical devices 研究小组于 2007 年提出了纸质微流控分析装置 (μPADs) in 2007的概念 [ [8]. For 8]。对于“lab on papers纸上实验室”,，滤纸用作微流控芯片的基材，而不是无机或聚合物材料。使用纸基微流控芯片有几个优点：纸本身具有毛细管效应，可以引导试剂流动而无需额外的电源。纸相对便宜，易于获得和加工，因此降低了芯片制备成本。同样，体积小，体积轻，便于运输和储存。由于它比其他合成材料更容易降解，因此减少了对芯片使用的环境限制，更加环保。因此， μPAD比其他微流控芯片更经济、更安全、更易于使用和运输[ filter paper is used as a substrate for microfluidic chips instead of inorganic or polymeric materials. There are several advantages to using paper-based microfluidic chips: the paper itself has a capillary effect, which can guide reagent flow without requiring additional power sources. Paper is relatively inexpensive, easy to obtain and process, so chip preparation cost is reduced. Similarly, the size is small and the volume is light, making it easy to transport and store. As it degrades more easily than other synthetic materials, it reduces the environmental restrictions on chips’ use and is more environmentally friendly. Thus, μPADs are more economical, safer, and easier to use and transport than other microfluidic chips [9][10][11].9、10、11 ]。

2.2. Materials of Paper-Based Microfluidic Chips

2.2. 纸基微流控芯片材料

The纸基材料的设计和制备在确定 design and preparation of a paper-based material plays a decisive role in determining how well the μPADs will perform.μPAD 的性能方面起着决定性的作用。目前有三种纸基材料广泛用于生产纸屑：滤纸 [ There12 are]、硝酸纤维素纸 currently[ three13 paper-based] materials widely和玻璃纤维纸 [ used14 for the production of paper chips: filter paper [12], nitrocellulose paper [13], and glass fiber paper [14]. All of them have their own characteristics and applications (described in Table ]。它们都有自己的特点和应用（如表1),所示），也可以单独使用或相互组合使用，以实现整体功能。此外，纸的厚度和纸的孔隙率等参数也会影响流体速度。在进行更详细的流体控制计算时应考虑这些参数 and[ can15 also be used alone or combined with each other to achieve the overall function. Furthermore, parameters such as the thickness of the paper and the porosity of the paper also affect fluid velocity. These parameters should be taken into consideration when performing more detailed fluid control calculations [15].]。
Table表 1.纸基微流控芯片材料 Materials[ 12 of, paper-based13 microfluidic, chips14 [12][13][14].]。

Material

材料

Characteristics

特征

Applications
应用

Filter paper

Suitable water absorption, easy to obtain, low cost, poor strength

Suitable for all kinds of paper chips, the most widely used paper-based materials

Nitrocellulose paper

It can bind and fix protein, and high cost

Detection based on Western blot reaction, colloidal gold test paper reaction zone

Glass fiber paper

Stable properties, not easy to break, high temperature resistance, corrosion resistance

Detection based on chemical reactions

过滤纸吸水性好，容易获得，成本低，强度差适用于各种纸屑，应用最广泛的纸基材料
Other
其他
3D
methods
方法 Highly创新性强，发展潜力大[ innovative and has huge development potential [39]39 ] Special特殊用途，难以推广 uses,[ difficult to promote [40]40 ]

3.2. Three-Dimensional Paper Chips Preparation

3.2. 三维纸片制备

In fact, three-dimensional paper chips are just a superposition of two-dimensional paper chips, but they achieve the goal of “1 + 1 > 2”. By providing a multilayer structure and vertical flow channels, the flux of the paper chip is increased and the layers of the paper chip are enriched, allowing for a more controlled detection reaction in time and space, one of the new directions for paper chip development [41][42]. In comparison to 2D paper chips, 3D paper chips are more difficult to fabricate at a higher cost, but they are more convenient, accurate, and sensitive [43].

实际上，三维纸屑只是二维纸屑的叠加，但达到了“1+1>2”的目的。通过提供多层结构和垂直流道，增加了纸片的通量，丰富了纸片的层数，使检测反应在时间和空间上更加可控，是纸片发展的新方向之一。44、45 ]。_ 与 2D 纸芯片相比，3D 纸芯片更难以更高的成本制造，但它们更方便、更准确、更灵敏[ 46 ]。

4. Analysis Method of Paper-Based Microfluidic Chip

4. 纸基微流控芯片分析方法

The paper-based microfluidic chip focuses on the results being presented in a visual way. Using colorimetry, electrochemistry, and fluorescence, the paper chip can find out both qualitative and quantitative information about different substances based on their physical, biological, and chemical properties [44][45][46] (described in Table

纸基微流控芯片专注于以视觉方式呈现的结果。使用比色法、电化学和荧光法，纸芯片可以根据不同物质的物理、生物和化学特性[ 48、49、50 ]（如表 3

).

所述）找出不同物质的定性和定量信息。
Table表 3. Analysis Method of paper-based microfluidic chips.纸基微流控芯片分析方法
Methods方法 Advantages优点 Disadvantages缺点
Colorimetric method比色法 Intuitive结果直观，肉眼易读，成本低 results,[ easy to read with the naked eye, low cost [47]51[48] , 52 ] Unable无法实现准确的定量检测[ to achieve accurate quantitative detection
硝酸纤维素纸可结合和固定蛋白质，成本高基于蛋白质印迹反应的检测，胶体金试纸反应区
玻璃纤维纸性能稳定、不易断裂、耐高温、耐腐蚀基于化学反应的检测

3. Preparation Method of Paper-Based Microfluidic Chip三、纸基微流控芯片的制备方法

3.1. Two-Dimensional Paper Chip Preparation

3.1。二维纸片制备

Paper-based chips differ from glass, plastic, or other materials-based chips. For example, the hydrophilic channels flanked by hydrophobic barriers in paper-based microfluidic devices guide liquid flow and the reaction is etched on the substrate. As technology develops, paper chip preparation methods become more sophisticated. Paper in a broad sense includes various analytical devices prepared by simple splicing or stacking of paper-derived materials. Fluid control is undoubtedly a top priority in paper chip design [16]. This section focuses on common methods for making channels on paper for fluid flow (as described in Table 2) [17][18][19].

纸基芯片不同于玻璃、塑料或其他材料基芯片。例如，纸基微流体装置中的亲水通道两侧是疏水屏障，引导液体流动，反应被蚀刻在基板上。随着技术的发展，纸片制备方法变得更加复杂。广义的纸包括纸源材料通过简单的拼接或堆叠制备的各种分析装置。流体控制无疑是纸片设计的重中之重[ 16 ]。本节重点介绍在纸上制作流体流动通道的常用方法（如表2所述）[ 17,18,19 ]。
Table表 2. Preparation method of paper-based microfluidic chips.纸基微流控芯片的制备方法
Methods方法 Advantages优点 Disadvantages缺点
Photolithography光刻 The最早的纸片制作方法，精密的通道结构[ earliest method for making paper chips, precise channel structure [20]20 ] The process is complicated工艺复杂

The产生的纸屑不适合折弯 resulting[ paper chips are not suitable for bending [49][8]8 ]
53 ] Plasma treatment technology等离子处理技术 More更适合大批量生产，成本低[
Electrochemical method电化学法suitable for mass production and have low cost [21]21 ] Quantitatively定量准确，快速阅读 accurate,[ fast reading [50]54[51] , 55 ]Depends取决于模板，降低了灵活性 on[ templates, reducing flexibility [22]22 ]
Rely依赖电化学工作站，增加成本，降低灵活性 on[ electrochemical workstation, increase cost and reduce flexibility [52]56 ] Wax printing蜡染 Simple加工简单，环保材料 processing,[ environmentally friendly materials [23]23[24] , 24 ]
Fluorescence method荧光法 Low检测限低，非常灵敏 detection[ limit, very sensitive [53]57[54] , 58 ]Rely依靠喷蜡打印机，加热引起的水平扩散会降低结构精度 on[ wax spray printers, heating-induced horizontal diffusion reduces structure accuracy [25]25 ]
Relying依靠荧光检测设备，易受纸荧光剂信号影响[ on fluorescence detection equipment, easily affected by the signal of paper fluorescent agent [55]59 ] Inkjet method喷墨方式 Simple加工简单，可以用墨水笔绘制，无热扩散，结构更精密 processing[ can be drawn with ink pen, no heating diffusion, more precise structure [26]26
United electronics联合电子[27] , 27 ] Combining结合上述方法可以使非专业人士获得准确的结果 the[ aforementioned methods enables non-professionals to obtain accurate results [56]60[57] , 61 ]Hydrophobic疏水性墨水可能有毒，墨水笔手绘不准确，仍然依赖喷墨打印机 inks[ can be toxic, ink pens are inaccurate for hand drawing, still rely on inkjet printers [28]28 ]
Need to install a mobile 需要安装手机APP甚至更大的设备，降低灵活性[ or even larger devices, reducing flexibility [4]4 ] Screen printing丝网印刷 Ideal大批量生产的理想选择，工艺简单，成本低 for[ mass production, simple process, and low cost [29]29[30] , 30 ] Rely依赖模板，大大降低了研究过程中的灵活性 on[ templates, greatly reducing flexibility during research [31]31 ]
Laser processing technology激光加工技术 Very可以制备非常精确的结构 precise[ structures can be prepared [32]32 ] Rely依靠昂贵的激光设备，难以普及[ on expensive laser equipment and difficult to popularize [33]33 ]
3D origami method折纸法 3D structure has more functions, direct registration of each layer [34][35]结构有更多的功能，每一层的直接配准[ 34、35 ] Means层间需要固定装置，只能使用单一材料 of[ fixing are required between layers, only single material can be used [36]36 ]
3D lamination method贴合方式 3D结构具有更多功能，可以使用多种材料[ structure has more functions, can use a variety of materials [37]37 ] Fixed层间需要固定方式，需要注册方式[ means are required between layers, registration methods are required [38]38 ]
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