A Single-Cell Raman Spectroscopy Analysis of Bone Marrow Mesenchymal Stem/Stromal Cells to Identify Inter-Individual Diversity.

The heterogeneity of stem cells represents the main challenge in regenerative medicine development. This issue is particularly pronounced when it comes to the use of primary mesenchymal stem/stromal cells (MSCs) due to a lack of identification markers. Considering the need for additional approaches in MSCs characterization, we applied Raman spectroscopy to investigate inter-individual differences between bone marrow MSCs (BM-MSCs). Based on standard biological tests, BM-MSCs of analyzed donors fulfill all conditions for their characterization, while no donor-related specifics were observed in terms of BM-MSCs morphology, phenotype, multilineage differentiation potential, colony-forming capacity, expression of pluripotency-associated markers or proliferative capacity. However, examination of BM-MSCs at a single-cell level by Raman spectroscopy revealed that despite similar biochemical background, fine differences in the Raman spectra of BM-MSCs of each donor can be detected. After extensive principal component analysis (PCA) of Raman spectra, our study revealed the possibility of this method to diversify BM-MSCs populations, whereby the grouping of cell populations was most prominent when cell populations were analyzed in pairs. These results indicate that Raman spectroscopy, as a label-free assay, could have a huge potential in understanding stem cell heterogeneity and sorting cell populations with a similar biochemical background that can be significant for the development of personalized therapy approaches.

Correlation between morphology and local mechanical and electrical properties of van der Waals heterostructures.

Properties of van der Waals (vdW) heterostructures strongly depend on the quality of the interface between two dimensional (2D) layers. Instead of having atomically flat, clean, and chemically inert interfaces without dangling bonds, top-down vdW heterostructures are associated with bubbles and intercalated layers (ILs) which trap contaminations appeared during fabrication process. We investigate their influence on local electrical and mechanical properties of MoS2/WS2heterostructures using atomic force microscopy (AFM) based methods. It is demonstrated that domains containing bubbles and ILs are locally softer, with increased friction and energy dissipation. Since they prevent sharp interfaces and efficient charge transfer between 2D layers, electrical current and contact potential difference are strongly decreased. In order to reestablish a close contact between MoS2and WS2layers, vdW heterostructures were locally flattened by scanning with AFM tip in contact mode or just locally pressed with an increased normal load. Subsequent electrical measurements reveal that the contact potential difference between two layers strongly increases due to enabled charge transfer, while localI/Vcurves exhibit increased conductivity without undesired potential barriers.

Atomic force microscopy based manipulation of graphene using dynamic plowing lithography.

Tapping mode atomic force microscopy (AFM) is employed for dynamic plowing lithography of exfoliated graphene on silicon dioxide substrates. The shape of the graphene sheet is determined by the movement of the vibrating AFM probe. There are two possibilities for lithography depending on the applied force. At moderate forces, the AFM tip only deforms the graphene and generates local strain of the order of 0.1%. For sufficiently large forces the AFM tip can hook graphene and then pull it, thus cutting the graphene along the direction of the tip motion. Electrical characterization by AFM based electric force microscopy, Kelvin probe force microscopy and conductive AFM allows us to distinguish between the truly separated islands and those still connected to the surrounding graphene.