# Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs
## 1 Introduction  
There is an increasing demand in the field of bio-sensing for inexpensive, reliable, portable, rapid, and high throughput analytical devices. The World Health Organization (WHO) defined seven key guidelines for the development of diagnostics platforms suitable for resource-limited areas as major needs for extreme point of care (EPOC): \"(i) affordability, (ii) sensitivity, (iii) specificity, (iv) user-friendliness, (v) rapid and robust, (vi) equipment-free, and (vii) deliverable to those in need for such technologies\" [1]. These seven requirements recommended by WHO rightfully accumulate to the acronym \"ASSURED\" [1]. Through diverse applications, in areas such as tissue engineering, controlled drug release, dressings for wound healing, molecular separation, preservation of bioactive compounds, environmental analysis, and food and beverage quality control, etc., paper and fiber-based platforms are now of great importance in healthcare [2; 3; 4]. By addressing WHO's guidelines, paper/fiber-based bio-analytical platforms have attracted considerable attention for their effective application in remote/rural and resource-limited areas serving EPOC [5]. Paper and fiber-based materials are generally cost effective, while offering a large, available surface area for biomolecular interaction due to their highly porous structures. Different types of reagent can be stored within their network and benefit from the power-free fluid transport environment occurring through capillary action [2]. Analytical applications of paper in science date to the early 17 th century with the use of cellulose papers for chromatographic purposes [6] and pH sensing [7; 8]. A paper-based dipstickfor quantifying glucose in urine was first introduced to the scientific community in the 1950s, followed by commercialization of the product for a diabetes test one decade later [9]. Historically used for filtration purposes, nitrocellulose membranes were first proposed for molecular recognition in the 1970s [10]. The following decades marked a significant expansion in the application of paper materials for serological lateral flow tests, particularly as pregnancy tests emerged and evolved [11]. Recent advances, particularly in visual bio-diagnostics and hand-held bio-analytical devices, have opened a new and exciting chapter in the development of paper/fiber materials within embedded platforms [12]. Various paper-based bio-sensing platforms were designed and fabricated in recent decades, including dot-immunobinding assays (DIAs), microfluidic paper-based analytical devices (\(\upmu\)PADs), lateral flow immunoassay (LFIA), laminated paper-based analytical devices (LPADs), immunospot, nitrocellulose pads (NC-PADs) and paper-based ELISA (P-ELISA) well plates [2; 3; 4]. Fabrication of these platforms involves a wide variety of techniques, including plotting [13; 14], wax-printing [15; 16; 17; 18; 19], inkjet-printing [20; 21], flexographic printing [22], computer-controlled knife cutting [23], laser cutting [24; 25], vapor-phase polymer deposition [26; 27; 28], photolithography [29; 30; 31; 32; 33; 34], spraying [35], electrospinning [5; 6; 36] and coating [37], among others (Table 1) [2; 21]. Different aspects of paper-based bio-diagnostic devices, including fabrication strategies, applications for the recognition of various biomolecular entities, the storability as well as the marketability of the paper-based products have been extensively reviewed [2; 38; 39; 40; 41; 23; 21]. Considerable potentials of fiber materials in analytical fields offered a vibrant area of research to the scientific community initiated by the introduction of textile materials for chromatographic stationary phases [42]. The high-performance liquid chromatography (HPLC) technique has drawn a great deal of attention toward polymer fibers for separation purposes [43].