promoting cardiomyocyte maturity as indicated by sarcomere size, gene expression, metabolism, and Ca 2+ waves. Similarly, Khodabukus et al. [2] found electrical stimulation (70 mA amplitude, 2 ms, and 1 or 10 Hz) improved protein expression, force generation, calcium handling, and fatty acid oxidation in human skeletal muscles, which demonstrated the enhancement in maturation, structure, and metabolism. However, there are still concerns about the effectiveness of external stimuli. For example, in a review summarized by Love et al., [3] electrical stimulations can trigger an increase, decrease, or neutral effect on cell proliferation and apoptosis. This is perhaps due to non-optimized electrical and material parameters: voltage, type, number of pauses, frequency, duration, treatment period, and cell type. Thus, the underlying mechanism has not thoroughly been studied and understood.Simple detection or verification methods are necessary to fully decipher the mechanism and optimize the function of electric stimuli. Currently used techniques such as gene expression and Ca 2+ detection methods are mature but complex. Mechanical measurement methods (e.g., tensile, hardness, bending, burst testing) have been explored, which were nonideal for soft non-uniform cardiac tissues due to their [4] small size, viscoelasticity, hierarchical and porous structures, hydration levels, complex compositions, and high surface roughness. Novel methods, including patch-clamp, indentation, [5] optical tweezer, [6] multifunctional membrane, [7] and voltagesensitive dye, have also been applied for mechanic and beating properties' measurement. However, these methods are invasive; and the results exhibit high variations and deviations due to the viscoelasticity and non-uniformity characteristics of soft biomaterials. [6] Compared to invasive mechanical measuring methods, digital image correlation (DIC) [8] is a non-invasive and comprehensive method to detect cardiac beating mechanics, measuring nano-and micro-deformation of the tested object through the change of gray value patterned subsets. For example, Shradhanjali et al. [9] designed an adaptive reference-DIC method to study the mechanics of cardiomyocyte contraction.The mechanism of DIC analysis involves tracking and imaging micro-deformation of the tested object through detecting the corresponding subsets' differences between the reference and deformed images. [8] More specifically, it detects the correlations among all the subsets in the reference and Electrical pacing/stimulations (EP) have been widely adopted to promote the maturation of hiPSC-derived cardiomyocytes. However, there is a debate about their functions and effectiveness due to non-optimized pacing conditions. Here, the effectiveness of EP (13 V cm −1 , 2 ms in width, and 5 Hz frequency) on cardiac tissue beating mechanics are analyzed using digital image correlation (DIC). The cardiac tissues with and without EP at tissue culture time from day 2 to 11 (D2-D11) are characterized and compared. The results indicate EP dec...

SERS-active flexible nanopipettes can be used to conduct long-term reliable intracellular single-cell analysis.

Magneto-electric nanoparticles (MENPs), composed of a piezoelectric shell and a ferromagnetic core, exhibited enhanced cell uptake and controlled drug release due to the enhanced localized electric field (surface charge/potential) and the generation of acoustics, respectively, upon applying alternating current (AC) magnetic (B)-field stimulation. This research, for the first time, implements an electrochemical single-entity approach to probe AC B-field induced strain mediated surface potential enhancement on MENP surface. The surface potential changes at the single-NP level can be probed by the open circuit potential changes of the floating carbon nanoelectrode (CNE) during the MENP-CNE collision events. The results confirmed that the AC B-field (60 Oe) stimulation caused localized surface potential enhancement of MENP. This observation is associated with the presence of a piezoelectric shell, whereas magnetic nanoparticles were found unaffected under identical stimulation.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show immature features, but these are improved by integration into 3D cardiac constructs. In addition, it has been demonstrated that physical manipulations such as electrical stimulation (ES) are highly effective in improving the maturation of human-engineered cardiac tissue (hECT) derived from hiPSC-CMs. Here, we continuously applied an ES in capacitive coupling configuration, which is below the pacing threshold, to millimetersized hECTs for 1−2 weeks. Meanwhile, the structural and functional developments of the hECTs were monitored and measured using an array of assays. Of particular note, a nanoscale imaging technique, scanning ion conductance microscopy (SICM), has been used to directly image membrane remodeling of CMs at different locations on the tissue surface. Periodic crest/valley patterns with a distance close to the sarcomere length appeared on the membrane of CMs near the edge of the tissue after ES, suggesting the enhanced transverse tubulation network. The SICM observation is also supported by the fluorescence images of the transverse tubulation network and α-actinin. Correspondingly, essential cardiac functions such as calcium handling and contraction force generation were improved. Our study provides evidence that chronic subthreshold ES can still improve the structural and functional developments of hECTs.