Emerging Tech Talks: Student Lectures 2/20/2019
Our first Spring 2019 Emerging Tech Talk: Student Lectures was organized by our Seminar Series Director Mae Lewis and was held on Wednesday, February 20th, 2019. The speakers were Chi Zhao (BME), Liam Connolly (ME), and Samuel Potter (ME). Here are some photos from the event:
Here are the speakers’ abstracts from the event:
Chi Zhao, Biomedical Engineering
Title: Direct Cytosolic Delivery of Macromolecules via Connectosomes
Abstract: Inefficient transport across the plasma membrane has greatly hindered the clinical success of siRNAs and other hydrophilic macromolecules. To traverse this selective barrier, existing technologies employ cationic lipid carriers. These carriers enter cells through endocytosis where they release siRNAs into the cytoplasm by bursting endosomal membranes. This inefficient and poorly controlled process contributes strongly to the systemic cytotoxicity of existing siRNA therapeutics. Nature, however, has provided an elegant route for direct delivery of siRNAs to the cytoplasm – the gap junction network. This network of transmembrane channels physically connects the cytoplasm of adjacent cells, and thereby provides a direct passageway into the cytoplasm. To harness the potential of this machinery for molecular delivery, here we demonstrate the transport and delivery of macromolecules using Connectosomes, cell-derived plasma membrane vesicles that contain high concentrations of gap junction proteins (A). Specifically, our results illustrate gap junction-mediated loading of both siRNAs and 10 kilodalton dextran into Connectosomes (B) and the subsequent transfer of these macromolecules into the cellular cytoplasm. Using Connectosomes, we achieve potent silencing of green fluorescent protein expression (C). Further, the delivery efficiency of dextran increases by about 40-fold in comparison to the passive cellular uptake of free dextran in solution (D). These results demonstrate the potential of Connectosomes to effectively address the long-standing challenge of crossing the plasma membrane barrier. Moving forward, this increased delivery efficiency will create new opportunities for delivering siRNAs as well as other classes of therapeutic biomolecules, such as short signaling peptides.
Liam Connolly, Mechanical Engineering
Title: A TIP-Based Metrology Framework for Real-Time Process Feedback of Roll-to-Roll Fabricated Nanopatterned Structures
Abstract: This talk will outline the development of a metrology framework and proof-of-concept tool to perform direct, nanometer-scale topography measurements for real-time process control in the roll-to-roll manufacturing of nanopatterened materials, films, and flexible electronic devices. The system leverages a uniquely compact MEMS-based single chip atomic force microscope with custom approach mechanism positioned on a gantry which is actuated by two vertical, double parallelogram flexure mechanism based two-axis nanopositioners. This probe is situated over a stainless-steel, air bearing supported idler roller and its position dynamically compensated for curvature, eccentricity and surface topography of the roller during web movement through the system from an offline map. The proof-of-concept tool performs a single, 400 µm2, non-contact tapping mode scan with nm height resolution on a flexible, 150 µm x 350 mm polycarbonate substrate every 60 seconds in a step-and-scan fashion where web movement occurs during each step. The performance of the sc-AFM gantry nanopositioning system is evaluated and a representative nanofeatured flexible material, the wing of a Queen Butterfly, is used as a test artifact to demonstrate the efficacy of the nanometrology data acquired. This capability represents a wholly new method for in-line metrology in roll-to-roll nanomanufacturing.
Samuel Potter, Mechanical Engineering
Title: Simultaneous Quantification of Structure, Strain, and Stress in Fibrous Soft Biomaterials
Abstract:It has long been hypothesized that the collagen fibers in soft tissues deform following affine kinematics. Such knowledge is crucial for modeling this subclass of biological tissues. Validation of this assumption across a broad class of tissue types and region sizes has been complicated by the difficulty in obtaining sufficiently high-resolution, simultaneous collagen fiber structure information (CFA) and local strain information over large areas during dynamic loading. Polarized Spatial Frequency Domain Imaging (pSFDI) is a recently developed reflectanceimaging modality that can rapidly obtain high-resolution fiber architecture data over wide fields of native tissues. Moreover, the CFA information can also be used as a form of texture for Digital Image Correlation (DIC) to create full-field, pixel resolution displacement fields. These displacement fields are then differentiated and smoothed with Non-Uniform Basis Spline (NURBS) functions. The resulting smoothed strain fields can then be used in combination with the pSFDI fiber architecture information to validate the affine model with pixel-level resolution.Sequential images of pericardial tissue specimens under planar loading were acquired with the pSFDI system to a peak level of 225 kPa equibiaxial stress. The image sets were processed with a custom Matlab program (MathWorks, Natick, MA) to produce maps of the specimen CFA including information on fiber orientation and the degree of anisotropy. These maps were then converted to grayscale images and processed in a custom Python program to calculate the deformation gradient field. Results to date indicated the pSFDI data is a viable DIC texture and is amenable to strain field determination.