# Nanomaterials for Healthcare Biosensing Applications
## 4 Organic Nanomaterial Applications for Healthcare Biosensing
### Molecularly Imprinted Polymeric Nanoparticles  
Molecularly imprinted polymers (MIPs) are artificial materials synthesised by the polymerisation of functional monomers and cross-linking agents in the presence of a template molecule. Following the removal of the template, a cavity is generated which corresponds with the size, shape, and functionality of the template molecule. MIPs thus provide superior physical and mechanical stability in addition to selectivity when compared to their biological equivalents. The synthesis and functionalisation of MIPs is easy and can be sustained in harsh environments. MIP-based nanostructures hold great promise for medical diagnosis applications [294; 295; 296]. Owing to bioaccumulation from food and dairy products, various microorganisms develop a tolerance towards antibiotics. Antibiotic tolerance hinders the treatment of infectious diseases, and therefore, it is important to know the amount of antibiotics in common biological fluids. Altitnas reported a nanoMIP-based SPR sensor for vancomycin detection in milk [297]. In this study, itaconic acid (ITA) was polymerised using trimethylolpropane trimethacrylate and ethylene glycol dimethacrylate as cross-linkers. The nanoMIPs were immobilised on an 11-MUA functionalised Au sensor chip. The sensor displayed high specificity and affinity (dissociation constant: \(1.8\times 10^{-9}\) M) for the antibiotic. A linear range from 10 to 125 ng mL\({}^{-1}\) was obtained and the LOD was 4.1 ng mL\({}^{-1}\). Chen et al. developed a surface imprinting strategy for LZM detection [298]. The LZM template was initially immobilised on SiNP and then \(N\)-(4-vinylbenzyl)iminodiacetic acid (VBIDA) was polymerised in the presence of methylenebisacrylamide, \(N\)-isopropylacrylamide, and acrylamide. VBIDA chelated with Cu\({}^{+2}\) ions and recognised LZM due to metal chelate substantivity. The binding kinetics for the enzyme improved significantly due to the surface imprinted nanoparticles. The detection range in this case was 0.1-1.0 mg mL\({}^{-1}\) and LOD was 0.1 mg mL\({}^{-1}\). A similar technique was introduced for the photochemical determination of bilirubin, where bilirubin imprinted Fe\({}_{3}\)O\({}_{4}\)-hydroxyapatite(HAP)-PPy nanoparticles were immobilised on a magnetic glassy carbon electrode (MGCE). The biosensor provided a linear response in the 1.0-17 uM range and the detection limit was 0.007 uM. The sensor was highly selective against many interferents and a good affinity was maintained in serum [299]. Yun and co-workers manufactured a piezoelectric sensor for amantadine, a drug used in the treatment of Parkinson's as well as influenza, using MIP with RGO and AuNPs [300]. Perchlorate (TBAP) was used as a functional monomer in this study. Each step of the sensor fabrication process was optimised. A linear sensor response was recorded between \(1.0\times 10^{-5}\) and \(1.0\times 10^{-3}\) mM with a good sensitivity (LOD: \(5.4\times 10^{-6}\) mM). Denizli's group developed a MIP based QCM sensor for label-free and highly sensitive determination of synthetic cannabinoids, molecules that mimic the main active component tetrahydrocannabinol of marijuana, in urine [301]. The researchers used 2-methacryloyl-(L)-phenylalanine (MAPA) as the functional monomer. A QCM system could achieve a linear response in the range of 0.0005-1.0 ng mL\({}^{-1}\) with LODs ranging from 0.2 to 0.45 pg mL\({}^{-1}\) for four different cannabinoids. The application of computational approaches to MIP-based biosensor development holds great promise. Such integrated techniques assist in monomer selection for a particular MIP based on the affinities and binding energies between the monomers, as shown in Figure 13, and the analyte, thus making it possible to narrow down from more than 21 possible monomers and curtail the experimental time and costs [302]. Computational studies can also play a pivotal role in the selection of templates when the analyte is large and structurally complex, such as proteins, viruses, and bacteria.