# Nanomaterials for Healthcare Biosensing Applications
## 4 Organic Nanomaterial Applications for Healthcare Biosensing
### Molecular Machines
Hou's group developed a sensitive, highly specific, and reusable aptasensor to obtain a sandwich H\(\alpha\)T immunoassay using a DNA machine comprising two distinct biotinylated thrombin aptamers (TBA), each immobilised on a streptavidin functionalised MNP as resonance light scattering (RLS) probes [312]. The novel sensor could offer a detection in a wide concentration range (\(60\) pM-\(6.0\) nM). Cao et al. developed a catalyst-fuelled molecular machine capable of detecting the CD63 exosome [313]. Primarily, CD63 antibodies were immobilised on immune magnetic beads (IMB). Once the exosome bound to the anti-CD63-IMB probe, it was recognised by a CD63 aptamer, which launched the MoMa. The MoMa was propelled due to a cascade toehold-mediated strand displacement reaction (CTMSDR). The products from CTMSDR were then transferred onto a gold electrode functionalised with a dibenzocyclocotype (DBCO). The LOD of the biosensing system was \(1.72\times 10^{4}\) particles mL\({}^{-1}\). The \"proof-of-concept\" method displayed enormous potential for clinical applications due to its highly specific sensing in serum samples. Zhao and co-workers developed a similar 3D DNA machine induced by immunoprecipitation for the detection of serum cystatin C (CstC), a biomarker of nephrological and cardio-vascular diseases, relying on toehold-mediated strand displacement reaction (TMSDR) [314]. They coated a GCE with GO functionalised with a monolayer of rubrene (mRub) and platinum nanoparticles. Further modification with \(\beta\)CD and BSA was performed to obtain a high signal amplification. Fe\({}_{3}\)O\({}_{4}\) functionalised AuNPs were used as a substrate for the construction of a 3D DNA machine composed of thiolated substrate DNA (TSDNA), ferrocene-labeled assistant strands (FcAS), and ferrocene-labeled blocker strand (FcBS). A sandwich immunoblot formed by capture antibody walking DNA (cAbWD) displaced the FcBS to allow the fuel strand (FuSt) to hybridise with TSDNA. The ensuing TMSDR provided energy to the sandwich immunocomplex resulting in an enormous of release of FcAS and FcBS. These strands were magnetically collected and conjugated with the \(\beta\)CD of the electroluminescent system, quenching the signal in proportion with the CstC concentration. The ultrasensitive sensor exhibited a linear response from \(1.0\) fg mL\({}^{-1}\) to \(10\) ng mL\({}^{-1}\) with an LOD of \(0.38\) fg mL\({}^{-1}\). Bagheryan's group prepared a Guquadruplex machine for biosensing meso-5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine (TMPyP4), an anticancer drug [315]. The nanomachine was prepared on an SPCE using a mesoporous structure of (4-(N-methyl-N-(carboxopropyl)amino)-phenyl-4'-(N,N-dibutylamino)phenylsquaraine (SBA)-enriched AuNPs with \(N\)-propylipyrazine-\(N\)-(2-mercaptoethanol-1-one) (NNPNSH). Because of these modifications, the AuNPs were able to bond with thiolated Guquadruplex DNA (SHG\({}_{4}\)DNA) in the presence of TMPyP4. They obtained highly reproducible signals with DPV for TMPyP4 concentrations between 0.1 and 10 uM. Zhen et al. have recently reported an electrochemiluminescence sensor for the detection of folate receptor (FoR), a biomarker which is overexpressed in several types of cancers, using a folic acid (FoA) labelled DNA nanomachine [316]. In the absence of the target biomarker, the strand displacement amplification (SDA) of the nanomachine takes place with the help of NiEnOx and POx, which release peroxide-mimicking DNAzymes responsible for chemiluminescence. However, when FoR was present, the NiEnOx based SDA was prevented. The different signals in the former and latter cases were responsible for a high sensitivity and a low LOD of 1 pM with a quasilinear logarithmic response for concentrations ranging between 5 pM and 50 nM. Russel et al. developed an interesting approach to detect the sepsis biomarker procalcitonin (PCT) [317]. They used self-propelled Janus nanoparticles for the colorimetric determination of particle motion.