# Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs
## 2 Major Challenges and Opportunities  
### Physical Characteristics of the Paper and/or Fiber Materials  
The development of a unique surface for improved biomolecular interaction is critical. It requires specifically tailored physical properties of the paper/fiber that can highly encourage analyte-surface interaction through a multitude of forces. In spite of the significant advances in fabrication strategies, paper-based platforms suffer from a lack of control over their physical properties [4; 77]. Paper segments in most of the developed platforms are selected from commercially available products (Table 1) possessing certain physical characteristics, including capillary flow rate, surface area, porosity, permeability, and wettability. However, these parameters vary significantly from one manufacturer/batch to another, raising the specer of inconsistency [6; 78; 79]. Capillary flow rate defines the movements of the flow along the length of the paper in the different designs of bio-diagnostic devices. It is the key parameter in assay performance, as the concentration of the target analyte correlates with the speed of the flow rate [78]. While paper is an excellent material for leading and transporting fluids without external forces, control over fluid transfer, the consistency of the flow rate, and the precise direction of the flow are some of the main challenges faced by researchers in this area [2]. Recognizing those challenges, a variety of solutions have been offered to provide a higher degree of control over flow rate. In 2010, [PERSON] et al. positioned a digital valve that introduced designed gaps to separate the paper's layers, thus strategically connecting and disconnecting the flow [80]. Other groups reported approaches for controlling fluid transport by changing the geometry of the channels and altering the width, length, and thickness of the junctions in paper-based microfluidic designs [81; 82; 83]. Applications of the fluidic barriers made from soluble materials for carrier flow were also presented in the literature. These bridges wick fluids until complete dissolution disconnects the flow [84; 82; 85]. Other techniques, such as phase-switching [86] and razor-crafting channels [87] have also introduced innovative strategies to address this challenge. These techniques have successfully offered higher sensitivity of the assay, enhanced accommodation of small sample volumes within the channels, and the increased retention of the analyte of interest in the network of the paper [87; 88]. Although relative hydrophilicity and porosity are desirable features in paper-based devices, as they involve capillary forces for leading fluids in specific directions, those characteristics may also introduce background signal and error into the assay [5; 6; 37; 89]. A high degree of hydrophilicity and porosity are not always favorable for protein immobilization and the subsequent detection of analytes as they may induce biomolecule entrapment, which leads to a false positive signal [5; 6; 90]. Due to the incomplete washing process, and because proteins could be trapped within the highly porous hydrophilic paper matrix, paper-based 96-well plates are normally used to perform double sandwich assays, while evoking a considerable false positive signal [5; 6; 37; 89; 91; 92; 93; 94]. In these assays, a secondary labeled antibody could specifically bind to the primary antibody that is attached to the analyte of interest (Table 2 provides examples of double sandwich assays). If, due to the porosity or swelling condition of the paper or fiber platforms, an excessive level of primary antibodies becomes entangled in the paper matrix, secondary antibodies would most likely bind to the primary antibodieswithout direct attribution to the presence of the analyte, hence producing false signals [3; 5; 6; 95].