# Nanomaterials for Healthcare Biosensing Applications
## 4 Organic Nanomaterial Applications for Healthcare Biosensing
### Covalent Organic Frameworks  
Covalent organic frameworks (COFs) consist of porous polymers linked to each other via covalent bonds in a crystalline assembly. They are capable of integrating organic blocks in an atomically accurate ordered structure with the help of strong covalent linkages [267]. It is possible to control the structure and size of the pores in a COF and such frameworks show high surface area, thermal stability, and permanent porosity [268; 269]. The scope of COFs as components for biosensing was proposed in 2014 [270], wherein amino functionalisation allowed the adsorption of DNA and proteins in the framework. COF-based sensors show promising prospects in the detection of various antibiotics. As COFs are rich in N sites and show high porosity, it is possible to enhance their fluorescence quenching efficacy with the help of adsorption-triggered pre-concentration and rigidifying-induced fluorescence improvement. Tang et al. introduced aggregation-induced emission luminogens such as diphenamidine hydrochloride in a covalent traizine framework nanosheet for the sensitive and highly selective detection of nitrofurans, such as nitrofurazone (LOD: 4.97 ppb), nitrofurantoin (LOD: 8.08 ppb), and furazolidone (LOD: 13.35 ppb) [271]. The limit of detection reduced nearly four-fold when the luminogen was replaced with phenylalanine hydrochloride. In another study, COFs were used as amplifying agents in a nanocomposite with graphene oxide [272]. The nanocomposite was used in conjunction with molecularly imprinted polypyrrole and GCE to generate an electrochemical sensor for the determination of sulfadiazine and acetaminophen. The sensor showed a performance identical to that of an independent high-performance liquid chromatography assay [272]. Recently, Wang and co-workers developed a COF with time bonds generated by the polycondensation of melamine and 1,3,6,8-tetrakis(4-formylphenyl)pyrene [273]. The COF showed an extensive specific surface area (495.5 m\({}^{2}\) g\({}^{-1}\)), large porous cavities, and a structure resembling nanosheets with abundantene, carbonyl, imine, and amine functional groups, along with a high charge carrier mobility which facilitated the immobilization of DNA aptamers. This COF-based aptasensor yielded extremely low LODs for the detection of enrofloxacin (6.07 fg mL\({}^{-1}\)) and ampicillin (0.01 fg mL\({}^{-1}\)) [273]. In addition to antibiotics, COFs are useful for the detection of several disease biomarkers, particularly those indicative of cancer. As a platform, they show high versatility among various detection systems. Therefore, Ai and He developed a chromogenic visual colorimetric system for sensing 3,3'-diaminobenzidine, which is suspected of carcinogenic and mutagenic properties [274]. The sensor utilized the large \(\pi\)-conjugation system present in imine-linked COFs. The high energy electrons enhanced the extinction coefficient of the system and allowed sensitive and selective visual detection down to 5 uM with an LOD of 900 nM in UV-vis assisted colorimetric assay [274]. Similarly, Yan et al. developed an electrochemical sensor for the detection of Michigan cancer foundation cell line (MCF-7) as well as human epidermal growth factor receptor (hEGFR) [275]. The 2D porphyrin-based COF was rich in nitrogen-bearing moieties with large cavities and an excellent aqueous stability, low toxicity, and high bioaffinity encouraged the immobilization of aptamer strands. Electrochemical detection with differential pulse voltammetry and electrochemical impedance spectroscopy allowed low LODs for both the targets with high reproducibility and recyclability [275]. Liang's group developed a similar electrochemical sensor using magnetic COFs for the determination of PSA in buffer as well as serum [276]. The sandwich immunosensor consisted of an AuNP-phosphorene nanocomposite platform for the immobilization of primary antibodies. Secondary antibody functionalised AuNP loaded magnetic COFs along with methylene blue were responsible for electrochemical signal generation.