Cavitation with bubble-bubble interaction is a fundamental feature in therapeutic ultrasound. However, the causal relationships between bubble dynamics, associated flow motion, cell deformation, and resultant bioeffects are not well elucidated. Here, we report an experimental system for tandem bubble (TB; maximum diameter = 50 ± 2 μm) generation, jet formation, and subsequent interaction with single HeLa cells patterned on fibronectin-coated islands (32 × 32 μm) in a microfluidic chip. We have demonstrated that pinpoint membrane poration can be produced at the leading edge of the HeLa cell in standoff distance S d ≤ 30 μm, driven by the transient shear stress associated with TB-induced jetting flow. The cell membrane deformation associated with a maximum strain rate on the order of 10 4 s −1 was heterogeneous. The maximum area strain (e A,M ) decreased exponentially with S d (also influenced by adhesion pattern), a feature that allows us to create distinctly different treatment outcome (i.e., necrosis, repairable poration, or nonporation) in individual cells. More importantly, our results suggest that membrane poration and cell survival are better correlated with area strain integral ( R e 2 A dt) instead of e A,M , which is characteristic of the response of materials under high strain-rate loadings. For 50% cell survival the corresponding area strain integral was found to vary in the range of 56 ∼ 123 μs with e A,M in the range of 57 ∼ 87%. Finally, significant variations in individual cell's response were observed at the same S d , indicating the potential for using this method to probe mechanotransduction at the single cell level.microfluidics | cavitation bioeffects | single-cell analysis | high strain-rate | cell mechanics

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Silica derived from biocompatible silane precursors and containing covalently bound sugar moieties has recently been reported to be a much more biocompatible matrix for protein entrapment than any previously synthesized materials. To better understand the nature of these new materials, the steady-state and time-resolved fluorescence of human serum albumin (HSA) was used to examine the conformation, dynamics, accessibility, thermal stability, and degree of ligand binding after entrapment of the protein into sol−gel-processed glasses derived from either tetraethyl orthosilicate (TEOS) or diglycerylsilane (DGS), which in some cases contained covalently bound gluconamidylsilane (GLS) moieties. It was observed that the initial conformation, accessibility to external analytes, thermal stability, long-term stability, and degree of ligand binding to HSA were best in DGS-derived materials that contained covalently tethered GLS relative to unmodified DGS-derived materials, TEOS, or TEOS/GLS-derived materials. Measurement of protein rotational dynamics showed that entrapment led to an immediate loss of global motion in all materials. However, the restriction of motion was most dramatic in GLS-doped materials, suggesting preferential interactions of the protein with the sugar-coated surfaces. As aging proceeded, both protein dynamics and the degree of ligand binding decreased, with a gradual loss of segmental motion and a significant increase in local motion in the vicinity of the probe, consistent with unfolding and surface adsorption of the protein, leading to loss of function. Overall, our findings suggest that the use of a biocompatible precursor (DGS) and the addition of a covalently bound sugar both contribute to improved protein performance. However, of these two the use of a biocompatible precursor is the most important factor, and in such cases addition of sugars further improves protein performance. In contrast, the use of the sugar-based additive with a nonbiocompatible precursor such as TEOS imparted essentially no benefit, demonstrating the importance of biocompatible processing conditions.

Robot-assisted surgery is of growing interest in the surgical and engineering communities. The use of robots allows surgery to be performed with precision using smaller instruments and incisions, resulting in shorter healing times. However, using current technology, an operator cannot directly feel the operation because the surgeon-instrument and instrument-tissue interaction force feedbacks are lost during needle insertion. Advancements in force feedback and control not only help reduce tissue deformation and needle deflection but also provide the surgeon with better control over the surgical instruments. The goal of this review is to summarize the key components surrounding the force feedback and control during robot-assisted needle insertion. The literature search was conducted during the middle months of 2017 using mainstream academic search engines with a combination of keywords relevant to the field. In total, 166 articles with valuable contents were analyzed and grouped into five related topics. This survey systemically summarizes the state-of-the-art force control technologies for robot-assisted needle insertion, such as force modeling, measurement, the factors that influence the interaction force, parameter identification, and force control algorithms. All studies show force control is still at its initial stage. The influence factors, needle deflection or planning remain open for investigation in future.