# Nanomaterials for Healthcare Biosensing Applications
## 2 Carbon Allotrope-Based Nanomaterial Applications in Healthcare Biosensing
### Nanodiamonds  
In comparison to the carbon allotrope-based nanomaterials previously discussed, nanodiamonds (NDs) are the only ones comprised of sp\({}^{3}\) hybridised carbon centres. NDs represent outstanding properties of bulk diamond, such as wide band gap electronic behaviour, chemical inertness, thermal conductivity, and exceptional mechanical properties to those derived by their high specific area, which can reach 400 m\({}^{2}\) g\({}^{-1}\)[115]. They can be synthesised by grinding microdiamonds under high pressure high temperature (HPHT) conditions or by the detonation of carbonaceous explosives (DND). They can link covalently or non-covalently with biomolecules after simple functionalisation with amines, thiol group halides, or hydroxyl groups. HPHT diamonds are rich in nitrogen impurities, which are amenable to transformation into vacancy-related colour centres, thus forming fluorescent nanodiamonds (FND). The photophysical characteristics of the vacancy centres allow FNDs to act as efficient biosensing, as well as bioimaging probes and contrast agents [116; 117; 118]. NDs have been extensively used in biosensing due to their fluorescent nature and their ability to detect a variety of metal ions. Shellaiah and co-workers developed photoluminescent cysteine (CYA)-modified nanodiamonds for the detection of Hg\({}^{2+}\) ions [119]. CYA forms amide linkages with NDs and possesses free thiol groups capable of trapping mercury ions. The sensor provided a linear response to Hg\({}^{2+}\) samples from 100 nM to 100 uM and revealed an LOD of 153 nM. Instead of functionalisation, NDs can also be doped with nitrogen for the quantification of heavy metal ions. Monodimensional nitrogen doped nanodiamond nanorods (\(N\)-DNR) were used as an electrochemical sensor for detecting Pb\({}^{2+}\) and Cd\({}^{2+}\) simultaneously. CV and square wave anodic stripping voltammetry (SWASV) measurements resulted in a detection range of 0.05-1 uM and 0.01-1.1 uM for Pb\({}^{2+}\) and Cd\({}^{2+}\), respectively. The LODs were found to be 0.05 uM and 0.01 for the corresponding heavy metal ions [120]. Various clinically relevant compounds, including neurotransmitters, pharmaceuticals, and toxins, as well as biomarkers for chronic illnesses such as diabetes, have been detected using NDs [121]. Dai and co-workers electrophoretically deposited NDs on a boron doped diamond (BDD) electrode and subsequently modified it with Ni nanosheets for enzyme free detection of glucose [122]. The electrochemical sensor was functional for measuring glucose in a concentration range of 0.2-1055.4 uM, which provided an LOD of 50 nM. Briones et al. developed a GOx-based glucose sensor prototype to fabricate the first electrochemical nanodiamond lactate biosensor on a gold electrode platform [123]. They substituted GOx with LOx. The neoteric sensor provided a detection range of 0.05 to 0.7 mM and a detection limit of 15 uM. An enzymatic CNT screen printed electrode (CNT-SPE) with a nanocomposite of carboxyl functionalised graphene platelets and graphitised nanodiamonds (f-GNPtlts-GNDs) was reported to successfully detect urea down to 5 ug mL\({}^{-1}\) (Figure 7) [121]. Peltola et al. enhanced dopamine detection using hydroxyl functionalised nanodiamonds (ND\({}_{\text{H}}\)) integrated with tetrahedral amorphous carbon (ta-C) thin films [47]. They made a comparison between variously functionalised NDs and showed that ND\({}_{\text{H}}\) addition to the thin film electrodes lowered the detection limit of the sensor by two orders of magnitude, from 10 uM to 50 nM. The potentiometric method was capable of quantifying dopamine from 50 nM to 1 mM using ND\({}_{\text{H}}\) integrated ta-C films. Simioni et al. constructed an ND-GCE sensor for the detection of pyrazineamide (PZA), an antibiotic for tuberculosis treatment that has serious side effects in cases of overdoses [124]. The electrochemical sensor was functional up to \(4.9\times 10^{-5}\) M of PZA.