# Nanomaterials for Healthcare Biosensing Applications
## 2 Carbon Allotrope-Based Nanomaterial Applications in Healthcare Biosensing
### Carbon Quantum Dots  
Quantum dots are zero-dimensional semiconducting particles with a size of a few nanometres [96]. They have exceptional optical and fluorescent properties. Carbon-based quantum dots are classified into crystalline GQDs and amorphous carbon dots (CD). As GQDs were discussed along with other graphene biosensors in Section 2.3, this section focuses on CDs. In comparison to GQD, CDs are more water soluble and show a superior biocompatibility due to a greater number of carboxylic moieties on their surface [106]. Easy functionalisation with polymers, biomolecules, and various other organic and inorganic molecules as well as surface passivation can enhance their fluorescence and physical properties, making them ideal candidates for medical diagnostics and bioimaging [107]. CDs have also been used in association with other materials to fabricate biosensors with enhanced sensitivity, reliability, and rapidity [2]. CDs have gained extensive scientific interest as the material of choice for the detection of a variety of cancer biomarkers for early stage diagnosis, as well as monitoring tumour proliferation. Abdelhamid and co-workers developed a gold doped CD-cytosensor for the recognition of metallic ions, such as Fe\({}^{3+}\), in cancer cells [108]. The Au-CD nanocomposite displayed a maximum absorbance of 337 nm, making it an ideal candidate for surface enhance laser desorption/ionisation mass spectrometry (SELDI-MS), since the wavelength of an N\({}_{2}\) laser is 337 nm. The sensor was capable of detecting Fe\({}^{3+}\) when chelated with of (MFA) in cancer cells within the range of 1.0-300.0 nM, following cell separation [108]. Another sensor for Fe\({}^{3+}\) detection employed metal-free nitrogen doped CDs [40]. Intrinsic properties of CDs can be modulated by such doping methods. The fluorescent sensor was active for Fe\({}^{3+}\) in a concentration range of 5-20 uM with an LOD of 3.7 uM. CEA detection by optical upstasensors using nitrogen and sulphur co-doped CDs (NS-CD) as well as undoped CDs has been reported. The former study reported a lower LOD of only 94 pg mL\({}^{-1}\) with a broad linear response in 0.3-80 ng mL\({}^{-1}\), likely due to the HRP-AgAu-aptamer label [109]. In the case of the label-free undoped CD aptasensor, a narrower detection range between 0.5-1 ng mL\({}^{-1}\) with a lower sensitivity (LOD: 0.3 ng mL\({}^{-1}\)) was obtained [110]. Mohammadi et al. developed a fluorescence resonance electron transfer (FRET)-based immunoassay for the cancer antigen 15-3 (CA 15-3), a breast cancer biomarker, using a sandwich assay of CD-anti CA15-3 with polyamidoamine (PAMAM) dendrimer and CA 15-3 aptamer co-immobilised AuNPs as the redox probe [111]. The detection range of this sensing assembly was 1.1 uU mL\({}^{-1}\)-5.0 mu mL\({}^{-1}\), with an LOD of 0.9 uU mL\({}^{-1}\). In addition to cancer, CDs have been used for the diagnosis of other fatal and incurable diseases. Liang and co-workers developed a ratiometric fluorescence (RF) assay using CDs and cadmium telluride (CdTE) quantum dots (QD) for the detection of HIV DNA [112]. Mitoxantrone (MTX) was used as a fluorescence quencher for CdTeQDs. A linear detection was achieved from 1.0 to 50.0 nM of DNA concentration. Cho and Park reported an RF sensor using CDs and rhodamine 6G (Rh6G) with immobilised GOx and HRP for glucose detection [113]. In aqueous solution, the sensor provided a linear photoluminescence response between 0.1 and 500 uM with an LOD of 0.04 uM and a good selectivity in the co-existence of many non-specific molecules in blood. The detection of volatile organic biomarkers (VOBs) is a reliable, rapid, inexpensive, and portable method for medical diagnosis. Bhattacharya et al. reported a fluorescent CD biosensor for tuberculosis (TB)-VOBs using breath analysis techniques [114]. They mixed the CDs with methyl nicotinate dissolved in ethyl alcohol and then directed TB-VOBs bubbles through a methyl nicotine solution with a nitrogen flow onto the aforementioned sensor.