Christina L. Randall

Tetherless thermobiochemically actuated microgrippers

We demonstrate mass-producible, tetherless microgrippers that can be remotely triggered by temperature and chemicals under biologically relevant conditions. The microgrippers use a self-contained actuation response, obviating the need for external tethers in operation. The grippers can be actuated en masse, even while spatially separated. We used the microgrippers to perform diverse functions, such as picking up a bead on a substrate and the removal of cells from tissue embedded at the end of a capillary (an in vitro biopsy).

Self-folding devices and materials for biomedical applications

Because the native cellular environment is 3D, there is a need to extend planar, micro- and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or unfold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano- to centimeter scale polyhedral containers, scaffolds for cell culture and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.

Directed Growth of Fibroblasts into Three Dimensional Micropatterned Geometries via Self-Assembling Scaffolds

We describe the use of conventional photolithography to construct three dimensional (3D) thin film scaffolds and direct the growth of fibroblasts into three distinct and anatomically relevant geometries: cylinders, spirals and bi-directionally folded sheets. The scaffolds were micropatterned as two dimensional sheets which then spontaneously assembled into specific geometries upon release from the underlying substrate. The viability of fibroblasts cultured on these self-assembling scaffolds was verified using fluorescence microscopy; cell morphology and spreading were studied using scanning electron microscopy. We demonstrate control over scaffold size, radius of curvature and folding pitch, thereby enabling an attractive approach for investigating the effects of these 3D geometric factors on cell behaviour.

Self-loading lithographically structured microcontainers: 3D patterned, mobile microwells.

We demonstrate mass-producible, mobile, self-loading microcontainers that can be used to encapsulate both non-living and living objects, thus forming three-dimensionally patterned, mobile microwells.

Patternable nanowire sensors for electrochemical recording of dopamine

Spatially resolved electrochemical recording of neurochemicals is difficult due to the challenges associated with producing nanometer-scale patternable and integrated sensors. We describe the lithographic fabrication and characterization of patternable gold (Au) nanowire (NW) based sensors for the electrochemical recording of dopamine (DA). We demonstrate a straightforward NW-size-independent approach to align contact pads to NWs. Sensors, with NW widths as small as 30 nm, exhibited considerable insensitivity to scan rates during cyclic voltammetry, a nonlinear increase in oxidation current with increasing NW width, and the selectivity to measure submaximal synaptic concentrations of DA in the presence of interfering ascorbic acid. The electrochemical sensitivity of Au NW electrode sensors was much larger than that of Au thin-film electrodes. In chronoamperometric measurements, the NW sensors were found to be sensitive for submicromolar concentration of DA. Hence, the patternable NW sensors represent an attractive platform for electrochemical sensing and recording.

Self-folding immunoprotective cell encapsulation devices

UNLABELLED Cell encapsulation therapy (CET) provides an attractive means to transplant cells without the need for immunosuppression. The cells are immunoisolated by surrounding them with a synthetic, semipermeable nanoporous membrane that allows selective permeation of nutrients and therapeutics while isolating the cells from hostile immune components. This communication describes the fabrication and in vitro characterization of lithographically structured and self-folded containers for immunoprotective cell encapsulation. Lithographic patterning ensured identical shapes, sizes, tunable porosity, and precise volumetric control, whereas self-folding enabled transformation of two-dimensional porous membranes into cubes, ensuring that pores were present in all three dimensions for adequate diffusion of O(2) and other nutrients to encapsulated cells. We fabricated containers with varying pore sizes and observed that pores sizes of approximately 78 nm were sufficient to significantly inhibit diffusion of IgG (the smallest antibody) and permit adequate diffusion of insulin, highlighting the possibility to utilize these containers to develop a lithographically structured bioartificial pancreas. FROM THE CLINICAL EDITOR In this paper, a novel immunoisolation technique is presented to enable cell transplant survival by surrounding them with a synthetic, semipermeable nanoporous membrane that allows selective permeation of nutrients and therapeutics while isolating the cells from hostile immune components. This method may pave the way to effective pancreatic islet cell transplantation.

Design for a Lithographically Patterned Bioartificial Endocrine Pancreas

Cell encapsulation provides a means to transplant therapeutic cells for a variety of diseases including diabetes. However, due to the large numbers of cells, approximately on the order of a billion, that need to be transplanted for human diabetes therapy, adequate mass transport of nutrients such as oxygen presents a major challenge. Proof-of-concept for the design of a bioartificial endocrine pancreas (BAEP) that is optimized to minimize hypoxia in a scalable and precise architecture is demonstrated using a combination of simulations and experiments. The BAEP is composed of an array of porous, lithographically patterned polyhedral capsules arrayed on a rolled-up alginate sheet. All the important structural variables such as the capsule dimensions, pore characteristics, and spacing can be precisely engineered and tuned. Further, all cells are encapsulated within a single device with a volume not much greater than the total volume of the encapsulated cells, and no cell within the device is located more than 200 μm from the surrounding medium that facilitates efficient mass transport with the surroundings. Compared with gel-based encapsulation methods, our approach offers unprecedented precision and tunability of structural parameters as well as the volume of the encapsulated cells and consequently the amount of secreted insulin. Our work highlights the utility of lithography and self-assembly in the fabrication of micro- and nanostructured three-dimensional structures that simulate the function of natural endocrine organs.