**4. Conclusions and Future Perspectives**

This review summarised recent progress in nano-biosensors for non-invasively monitoring of stem cell differentiation. Various nano- and micromaterials, such as AuNPs, AgNPs, UCNPs, autofluorescence probes, nucleic acids, microfluidic systems and microelectrode arrays, were reviewed and compared. Furthermore, their advantageous use to improve the biosensors' performance, including sensitivity and selectivity, for monitoring stem cell differentiation was appraised. In the case of electrochemical sensors, the electrochemically active surface area was found to be a crucial parameter; this is because the redox reaction of target analytes occurs on the electrode surface via electron transfer. Moreover, various nanomaterials were identified that could be applied to improve the electrochemically active surface. Furthermore, specific micro-scaled systems were identified that could be utilised to enhance the advantage of existing nanomaterials, providing more sensitive and selective sensing capabilities toward target molecules. The literature scrutinised supported that many nanomaterials have been applied in optical sensing to enhance the optical signal intensity to target analytes specifically or to make the analysis process simpler and faster. In addition to excellent sensing capabilities, various nanobiosensors have functioned as stem cell cultivation platforms by providing cell-friendly surfaces. In conclusion, electrochemical or optical nano-biosensors capable of monitoring stem cell differentiation in a non-invasive, non-destructive, and label-free sensing system could be used to control stem cell differentiation and develop practical and efficient stem cell therapies.



**Table 1.** *Cont.*


**Table 1.** *Cont.*



goldnanoparticles; Au-Ni, gold-nickel; AuStar, gold nanostar; BC, breast cancer; BCIP, 5-bromo-4-chloro-3-indolyl phosphate; CPNTs, carboxylated polypyrrole nanotubes; cTnI, cardiac troponin I; DA, dopamine; DAnergic neurons, dopaminergic neurons; DNA, deoxyribonucleic acid; DTCC, disseminated tumour cell clusters; E4031, N-[4-[1-[2-(6-methylpyridin-2-yl)ethyl]piperidine-4-carbonyl]phenyl]; FAD, flavin ade-nine dinucleotide; Fe3O4, iron (II, III) oxide; FN, fibronectin; GABA, γ-aminobutyric acid; GDNF, glial cell-derived neurotrophic factor; HER-2, human epidermal growth factor receptor-2; miR, microRNA; MMP13, metalloproteinase 13; NAD(P)H, nicotinamide adenine dinucleotide (phosphate); OC, osteocalcin; Pdots, polymer dots, RGD, Arg-Gly-Asp ligand; rGO, reduced graphene oxide; t-ZnO, tetrapod zinc oxide; UCNPs, upconversion nanoparticles. **Author Contributions:** M.-J.K., Y.-W.C. and T.-H.K. wrote and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by the Chung-Ang University Graduate Research Scholarship in 2022 and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C4002217).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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