April 2022

Tech Talk – Plastic Response of Cells: from Embryo Development to Disease Detection

Living cells need to undergo significant shape changes during processes such as cell division, migration and tissue formation. Therefore, it is commonly believed that the deformability of cells is intimately related to their capability in executing different biological duties as well as the progression of diseases. In this talk, I will discuss how irreversible deformation of cells ensures proper axial extension of embryos during their development and how the plastic response of tumor cells can be used in monitoring the progression of cancer. Specifically, I will show that the presence of active intracellular/intercellular contraction will trigger the severing and re-bundling of actin filaments in cells (leading to cellular anisotropy and plasticity), elevate the internal hydrostatic pressure of embryo and eventually drive its elongation. In particular, the gradual re-alignment of F-actins must be synchronized with the development of intracellular forces for the embryo to elongate, which is then further sustained by muscle contraction-triggered plastic deformation of cells. In addition, I will also introduce a microfluidic setup developed in our lab allowing us to impose precisely controlled cyclic deformation on cells and therefore probe their plastic characteristics. Interestingly, we found that significant plastic strain can accumulate rapidly in highly invasive cancer cell lines and circulating tumor cells (CTCs) from late-stage lung cancer patients with a characteristic time of a few seconds. In comparison, very little irreversible deformation was observed in the less invasive cell lines and CTCs from early-stage lung cancer patients, highlighting the potential of using the plastic response of cells as a novel marker in future cancer prognosis and monitoring.

Soft Robotic Manipulator for Intra-operative MRI-guided Transoral Laser Microsurgery

Magnetic resonance (MR) imaging (MRI) provides compelling features for the guidance of interventional procedures, including high-contrast soft tissue imaging, detailed visualization of physiological changes, and thermometry. Laser-based tumor ablation stands to benefit greatly from MRI guidance because 3D resection margins alongside thermal distributions can be evaluated in real time to protect critical structures while ensuring adequate resection margins. However, few studies have investigated the use of projection-based lasers like those for transoral laser microsurgery, potentially because dexterous laser steering is required at the ablation site, raising substantial challenges in the confined MRI bore and its strong magnetic field. Here, we propose an MR-safe soft robotic system for MRI-guided transoral laser microsurgery. Owing to its miniature size (Ø12 × 100 mm), inherent compliance, and five degrees of freedom, the soft robot ensures zero electromagnetic interference with MRI and enables safe and dexterous operation within the confined oral and pharyngeal cavities. The laser manipulator is rapidly fabricated with hybrid soft and hard structures and is powered by microvolume (<0.004 milliter) fluid flow to enable laser steering with enhanced stiffness and lowered hysteresis. A learning-based controller accommodates the inherent nonlinear robot actuation, which was validated with laser path-following tests. Submillimeter laser steering accuracy was demonstrated with a mean error < 0.20 mm. MRI compatibility testing demonstrated zero observable image artifacts during robot operation. Ex vivo tissue ablation and a cadaveric head-and-neck trial were carried out under MRI, where we employed MR thermometry to monitor the tissue ablation margin and thermal diffusion intraoperatively.