Mechanical Trap Surface-Enhanced Raman Spectroscopy for Three-Dimensional Surface Molecular Imaging of Single Live Cells.

Reported is a new shell-based spectroscopic platform, named mechanical trap surface-enhanced Raman spectroscopy (MTSERS), for simultaneous capture, profiling, and 3D microscopic mapping of the intrinsic molecular signatures on the membrane of single live cells. By leveraging the functionalization of the inner surfaces of the MTs with plasmonic gold nanostars, and conformal contact of the cell membrane, MTSERS permits excellent signal enhancement, reliably detects molecular signatures, and allows non-perturbative, multiplex 3D surface imaging of analytes, such as lipids and proteins on the surface of single cells. The demonstrated ability underscores the potential of MTSERS to perform 3D spectroscopic microimaging and to furnish biologically interpretable, quantitative, and dynamic molecular maps in live cell populations.

Self-folding single cell grippers.

Given the heterogeneous nature of cultures, tumors, and tissues, the ability to capture, contain, and analyze single cells is important for genomics, proteomics, diagnostics, therapeutics, and surgery. Moreover, for surgical applications in small conduits in the body such as in the cardiovascular system, there is a need for tiny tools that approach the size of the single red blood cells that traverse the blood vessels and capillaries. We describe the fabrication of arrayed or untethered single cell grippers composed of biocompatible and bioresorbable silicon monoxide and silicon dioxide. The energy required to actuate these grippers is derived from the release of residual stress in 3-27 nm thick films, did not require any wires, tethers, or batteries, and resulted in folding angles over 100° with folding radii as small as 765 nm. We developed and applied a finite element model to predict these folding angles. Finally, we demonstrated the capture of live mouse fibroblast cells in an array of grippers and individual red blood cells in untethered grippers which could be released from the substrate to illustrate the potential utility for in vivo operations.

Intrinsically Stretchable Block Copolymer Based on PEDOT:PSS for Improved Performance in Bioelectronic Applications.

The conductive polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is ubiquitous in research dealing with organic electronic devices (e.g., solar cells, wearable and implantable sensors, and electrochemical transistors). In many bioelectronic applications, the applicability of commercially available formulations of PEDOT:PSS (e.g., Clevios) is limited by its poor mechanical properties. Additives can be used to increase the compliance but pose a risk of leaching, which can result in device failure and increased toxicity (in biological settings). Thus, to increase the mechanical compliance of PEDOT:PSS without additives, we synthesized a library of intrinsically stretchable block copolymers. In particular, controlled radical polymerization using a reversible addition-fragmentation transfer process was used to generate block copolymers consisting of a block of PSS (of fixed length) appended to varying blocks of poly(poly(ethylene glycol) methyl ether acrylate) (PPEGMEA). These block copolymers (PSS(1)-b-PPEGMEA(x), where x ranges from 1 to 6) were used as scaffolds for oxidative polymerization of PEDOT. By increasing the lengths of the PPEGMEA segments on the PEDOT:[PSS(1)-b-PPEGMEA(1-6)] block copolymers, ("Block-1" to "Block-6"), or by blending these copolymers with PEDOT:PSS, the mechanical and electronic properties of the polymer can be tuned. Our results indicate that the polymer with the longest block of PPEGMEA, Block-6, had the highest fracture strain (75%) and lowest elastic modulus (9.7 MPa), though at the expense of conductivity (0.01 S cm-1). However, blending Block-6 with PEDOT:PSS to compensate for the insulating nature of the PPEGMEA resulted in increased conductivity [2.14 S cm-1 for Blend-6 (2:1)]. Finally, we showed that Block-6 outperforms a commercial formulation of PEDOT:PSS as a dry electrode for surface electromyography due to its favorable mechanical properties and better adhesion to skin.

Metallic Nanoislands on Graphene for Biomechanical Sensing.

This minireview describes a nanomaterial-based multimodal sensor for performing biomechanical measurements. The sensor consists of ultrathin metallic films on single-layer graphene. This composite material exhibits physical properties that neither material possesses alone. For example, the metal, deposited by evaporation at low (≤10 nm) nominal thicknesses, renders the film highly sensitive to mechanical stimuli, which can be detected using electrical (i.e., resistance) and optical (i.e., plasmonic) modalities. The electrical modality, in particular, is capable of resolving deformations as small as 0.0001% engineering strain, or 1 ppm. The electrical and optical responses of the composite films can be tailored by controlling the morphology of the metallic film. This morphology (granular or island-like when deposited onto the graphene) can be tuned using the conditions of deposition, the identity of the substrate beneath the graphene, or even the replacement of the graphene for hexagonal boron nitride (hBN). This material responds to forces produced by a range of physiological structures, from the contractions of heart muscle cells, to the beating of the heart through the skin, to stretching of the skin due to the expansion of the lungs and movement of limbs. Here, we provide an update on recent applications of this material in fields ranging from cardiovascular medicine (by measuring the contractions of 2D monolayers of cardiomyocytes), regenerative medicine (optical measurements of the forces produced by myoblasts), speech pathology and physical therapy (measuring swallowing function in head and neck cancer survivors), lab-on-a-chip devices (using deformation of sidewalls of microfluidic channels to detect transiting objects), and sleep medicine (measuring pulse and respiration with a wearable, unobtrusive device). We also discuss the mechanisms by which these films detect strain.

Electropneumotactile Stimulation: Multimodal Haptic Actuators Enabled by a Stretchable Conductive Polymer on Inflatable Pockets.

This paper describes a type of haptic device that delivers two modes of stimulation simultaneously and at the same locations on the skin. The two modes of stimulation are mechanical (delivered pneumatically by inflatable air pockets embedded within a silicone elastomer) and electrical (delivered by a conductive polymer). The key enabling aspect of this work is the use of a highly plasticized conductive polymer based on poly(3,4-ethylenedioxythiphene) (PEDOT) blended with elastomeric polyurethane (PU). To fabricate the "electropneumotactile" device, the polymeric electrodes are overlaid directly on top of the elastomeric pneumatic actuator pockets. Co-placement of the pneumatic actuators and the electrotactile electrodes is enabled by the stretchability of the PEDOT:OTs/PU blend, allowing the electrotactiles to conform to underlying pneumatic pockets under deformation. The blend of PEDOT and PU has a Young's modulus of ~150 MPa with little degradation in conductivity following repeated inflation of the air pockets. The ability to perceive simultaneous delivery of two sensations to the same location on the skin are supported by experiments using human subjects. These results show that participants can successfully detect the location of pneumatic stimulation and whether electrotactile stimulation is delivered (yes/no) at a rate significantly above chance (mean accuracy = 94%).

Nanoscale fiber-optic force sensors for mechanical probing at the molecular and cellular level.

There is an ongoing need to develop ultrasensitive nanomechanical instrumentation that has high spatial and force resolution, as well as an ability to operate in various biological environments. Here, we present a compact nanofiber optic force transducer (NOFT) with sub-piconewton force sensitivity and a nanoscale footprint that paves the way to the probing of complex mechanical phenomena inside biomolecular systems. The NOFT platform comprises a SnO2 nanofiber optic equipped with a thin, compressible polymer cladding layer studded with plasmonic nanoparticles (NPs). This combination allows angstrom-level movements of the NPs to be quantified by tracking the optical scattering of the NPs as they interact with the near-field of the fiber. The distance-dependent optical signals can be converted to force once the mechanical properties of the compressible cladding are fully characterized. In this protocol, the details of the synthesis, characterization, and calibration of the NOFT system are described. The overall protocol, from the synthesis of the nanofiber optic devices to acquisition of nanomechanical data, takes ~72 h.