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。 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.
- paper-based microfluidics chips
- biomedicine
- biomarker
- clinical detection
一、简介1. Introduction
2. 纸基微流控芯片概述Overview of Paper-Based Microfluidic Chips
2.1。纸基微流控芯片的特点. Characteristics of Paper-Based Microfluidic Chips
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, itisalsocalled“芯片实验室labonchip” [ 5、6、7 ]。美国哈佛大学. Whitesides 研究小组于 2007 年提出了纸质微流控分析装置 (μes’research group at Harvard University in the United States proposed the concept of paper-based microfluidic analytical devices ( µ PADs) 的概念in 2007 [ 8 ]。对于. For “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lab on papers”, 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, µ PADs are more economical, safer, and easier to use and transport than other microfluidic chips [ 9、10、11 ]。.2.2. 纸基微流控芯片材料Materials of Paper-Based Microfluidic Chips
纸基材料的设计和制备在确定The design and preparation of a paper-based material plays a decisive role in determining how well the µ 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PADs will perform. There are currently three paper-based materials widely used for the production of paper chips: filter paper [ 12 ]、硝酸纤维素纸, nitrocellulose paper [ 13 ] 和玻璃纤维纸, and glass fiber paper [ 14 ]。它们都有自己的特点和应用（如表. All of them have their own characteristics and applications (described in Table 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 can 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 ]。.| 材料 |
|---|
Material |
| 特征 |
|---|
Characteristics |
| 应用 |
|---|
Applications |
Suitable water absorption, easy to obtain, low cost, poor strength |
Suitable for all kinds of paper chips, the most widely used paper-based materials |
.
Table 2
纸基微流控芯片的制备方法. Preparation method of paper-based microfluidic chips.
| 方法 |
Methods |
优点 |
Advantages |
缺点 |
Disadvantages |
|---|
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 |
| 光刻 |
Photolithography | |
| 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 |
Filter paper |
三、纸基微流控芯片的制备方法3. Preparation Method of Paper-Based Microfluidic Chip
3.1。二维纸片制备. Two-Dimensional Paper Chip Preparation
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 ]。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）[]. This section focuses on common methods for making channels on paper for fluid flow (as described in Table 2) [
17,18,19 ]| 最早的纸片制作方法，精密的通道结构[ | 20 ] |
The earliest method for making paper chips, precise channel structure [ 20 ] |
工艺复杂 产生的纸屑不适合折弯 [ 8 ] |
The process is complicatedThe resulting paper chips are not suitable for bending[ 8 ] |
| 等离子处理技术 |
Plasma treatment technology |
更适合大批量生产，成本低[ 21 |
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 [
48、49、50 ]（如表(described in Table 3
所述）找出不同物质的定性和定量信息。).
| 方法 |
Methods |
优点 |
Advantages |
缺点 |
Disadvantages |
||||
|---|---|---|---|---|---|---|---|---|---|
| 比色法 |
Colorimetric method |
结果直观，肉眼易读，成本低 [ 51 , 52 ] |
Intuitive results, easy to read with the naked eye, low cost [ 51 , 52 ] |
无法实现准确的定量检测[ 53 ] |
Unable to achieve accurate quantitative detection [ 53 ] |
||||
| 电化学法 |
Electrochemical method | ] |
More suitable for mass production and have low cost [ 21 ] |
, 55 ] |
Quantitatively accurate, fast reading [ 54 , 55 ] | 取决于模板，降低了灵活性 [ 22 ] | 定量准确，快速阅读 [ 54 |
Depends on templates, reducing flexibility [ 22 ] |
|
| 依赖电化学工作站，增加成本，降低灵活性 [ | 56 | ] |
Rely on electrochemical workstation, increase cost and reduce flexibility [ 56 ] |
蜡染 |
Wax printing |
||||
| 荧光法 |
Fluorescence method | 加工简单，环保材料 [ 23 , 24 ] |
Simple processing, environmentally friendly materials [ 23 , |
检测限低，非常灵敏 [ 57 , 58 ] |
Low detection limit, very sensitive24 ] |
[ 57 , 58 ] | 依靠喷蜡打印机，加热引起的水平扩散会降低结构精度 [ 25 ] |
Rely on wax spray printers, heating-induced horizontal diffusion reduces structure accuracy [ 25 ] |
|
| 依靠荧光检测设备，易受纸荧光剂信号影响[ | 59 | ] |
Relying on fluorescence detection equipment, easily affected by the signal of paper fluorescent agent [ 59 ] |
喷墨方式 |
Inkjet method |
||||
| 联合电子 |
United electronics | 加工简单，可以用墨水笔绘制，无热扩散，结构更精密 [ 26 , 27 ] |
Simple processing can be drawn with ink pen, no heating diffusion, more precise structure [ 26 , 27 ] |
结合上述方法可以使非专业人士获得准确的结果 [ 60 , 61 ] |
Combining the aforementioned methods enables non-professionals to obtain accurate results [ 60 , 61 ] | 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 [ 28 ] |
Hydrophobic inks can be toxic, ink pens are inaccurate for hand drawing, still rely on inkjet printers [ 28 ] |
||
| 需要安装手机APP甚至更大的设备，降低灵活性[ | 4 ] |
Need to install a mobile APP or even larger devices, reducing flexibility [ 4 ] |
丝网印刷 |
Screen printing |
大批量生产的理想选择，工艺简单，成本低 [ 29 , 30 ] |
Ideal for mass production, simple process, and low cost [ 29 , 30 ] |
依赖模板，大大降低了研究过程中的灵活性 [ 31 ] |
Rely on templates, greatly reducing flexibility during research [ 31 ] |
|
| 激光加工技术 |
Laser processing technology |
可以制备非常精确的结构 [ 32 ] |
Very precise structures can be prepared [ 32 ] |
依靠昂贵的激光设备，难以普及[ 33 ] |
Rely on expensive laser equipment and difficult to popularize[ 33 ] |
||||
| 3D折纸法 |
3D origami method |
3D结构有更多的功能，每一层的直接配准[ 34、35 ] |
3D structure has more functions, direct registration of each layer [ 34、35 ] |
层间需要固定装置，只能使用单一材料 [ 36 ] |
Means of fixing are required between layers, only single material can be used [ 36 ] |
||||
| 3D贴合方式 |
3D lamination method |
3D结构具有更多功能，可以使用多种材料[ 37 ] |
3D structure has more functions, can use a variety of materials [ 37 ] |
层间需要固定方式，需要注册方式[ 38 ] |
Fixed means are required between layers, registration methods are required [ 38 ] |
||||
| 其他 3D 方法 |
Other 3D methods |
创新性强，发展潜力大[ 39 ] |
Highly innovative and has huge development potential [ 39 ] |
特殊用途，难以推广 [ 40 ] |
Special uses, difficult to promote [ 40 ] |
3.2. 三维纸片制备
3.2. Three-Dimensional Paper Chips Preparation
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 [
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[]. 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 [
46 ]。].