A therapeutic convection-enhanced macroencapsulation device for enhancing ß cell viability and insulin secretion.

Islet transplantation for type 1 diabetes treatment has been limited by the need for lifelong immunosuppression regimens. This challenge has prompted the development of macroencapsulation devices (MEDs) to immunoprotect the transplanted islets. While promising, conventional MEDs are faced with insufficient transport of oxygen, glucose, and insulin because of the reliance on passive diffusion. Hence, these devices are constrained to two-dimensional, wafer-like geometries with limited loading capacity to maintain cells within a distance of passive diffusion. We hypothesized that convective nutrient transport could extend the loading capacity while also promoting cell viability, rapid glucose equilibration, and the physiological levels of insulin secretion. Here, we showed that convective transport improves nutrient delivery throughout the device and affords a three-dimensional capsule geometry that encapsulates 9.7-fold-more cells than conventional MEDs. Transplantation of a convection-enhanced MED (ceMED) containing insulin-secreting ß cells into immunocompetent, hyperglycemic rats demonstrated a rapid, vascular-independent, and glucose-stimulated insulin response, resulting in early amelioration of hyperglycemia, improved glucose tolerance, and reduced fibrosis. Finally, to address potential translational barriers, we outlined future steps necessary to optimize the ceMED design for long-term efficacy and clinical utility.

A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue.

The precision of the delivery of therapeutics to the desired injection site by syringes and hollow needles typically depends on the operator. Here, we introduce a highly sensitive, completely mechanical and cost-effective injector for targeting tissue reliably and precisely. As the operator pushes the syringe plunger, the injector senses the loss-of-resistance on encountering a softer tissue or a cavity, stops advancing the needle and delivers the payload. We demonstrate that the injector can reliably deliver liquids to the suprachoroidal space-a challenging injection site that provides access to the back of the eye-for a wide range of eye sizes, scleral thicknesses and intraocular pressures, and target sites relevant for epidural injections, subcutaneous injections and intraperitoneal access. The design of this simple and effective injector can be adapted for a broad variety of clinical applications.

Three-dimensional multihelical microfluidic mixers for rapid mixing of liquids.

Rapid mixing of liquids is important for most microfluidic applications. However, mixing is slow in conventional micromixers, because, in the absence of turbulence, mixing here occurs by molecular diffusion. Recent experiments show that mixing can be enhanced by generating transient flow resulting in chaotic advection. While these are planar microchannels, here we show that three-dimensional orientations of fluidic vessels and channels can enhance significantly mixing of liquids. In particular, we present a novel, multihelical microchannel system built in soft gels, for which the helix angle, helix radius, axial length, and even the asymmetry of the channel cross section are easily tailored to achieve the desired mixing. Mixing efficiency increases with helix angle and asymmetry of channel cross section, which leads to orders of magnitude reduction in mixing length over conventional mixers. This new scheme of generating 3D microchannels will help in miniaturization of devices, process intensification, and generation of multifunctional process units for microfluidic applications.

Embedded template-assisted fabrication of complex microchannels in PDMS and design of a microfluidic adhesive.

In this paper, we describe a novel method for fabricating 2-D and 3-D microchannel patterns in a flexible platform of cross-linked poly(dimethylsiloxane) (PDMS). Here, a slender nylon thread formed into different 2-D and 3-D shapes is used as a template that is embedded inside a block of cross-linked PDMS. The cross-linked network is then allowed to swell in a suitable solvent that swells the network selectively but leaves the nylon thread unaltered. The thread is then gently removed from the swollen network leaving behind a microchannel. Channels of a variety of topologically complex orientations like knots, helices, super-helices, and channels of a variety of cross-sections can be generated using this simple method. Finally, we have presented an application by generating inside layers of adhesive in these microchannels, which are observed to enhance the adhesion strength significantly.